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                                                                    EXHIBIT 10.3

                           THOMAS & BETTS CORPORATION
                      1993 MANAGEMENT STOCK OWNERSHIP PLAN
                        (AS AMENDED THROUGH JUNE 5, 2001)

     1.   PURPOSE. The purpose of the Thomas & Betts Corporation 1993 Management
Stock Ownership Plan (the "Plan") is to promote the long-term success of Thomas
& Betts Corporation (the "Corporation") by providing its officers and selected
employees with incentives for continued service with the Corporation, its
subsidiaries and affiliates. Both by encouraging such officers and employees to
become owners of the common stock of the Corporation through stock options and
by providing actual ownership through share awards, the Plan promotes
participants' identification with the Corporation's shareholders. The
Corporation believes the Plan will assist in attracting and retaining in its
employ outstanding people with the training, experience and ability to lead the
Corporation.

     2.   TERM. The Plan shall be effective as of May 5, 1993 and shall remain
in effec t until terminated by the Corporation's Board of Directors (the
"Board"). After termination of the Plan, no future awards may be granted, but
previously granted awards shall remain outstanding in accordance with their
applicable terms and conditions and the terms and conditions of the Plan.

     3.   PLAN ADMINISTRATION. A committee appointed by the Board (the
"Committee") shall be responsible for administering the Plan. The Committee
shall be comprised of three or more members of the Board, each of whom meets the
definitions of an "outside director," as such term is defined under Internal
Revenue Code Section 162(m), and a "non-employee director," as such term is
defined in Rule 16b-3(b)(3) of the Securities Exchange Act of 1934 (the "1934
Act"), or any successor rule. The Committee shall have full and exclusive power
to interpret the Plan and to adopt such rules, regulations and guidelines for
carrying out the Plan as it may deem necessary or proper, all of which power
shall be exercised in the best interests of the Corporation and in keeping with
the objectives of the Plan. These powers include, but are not limited to,
selecting award recipients, establishing terms and conditions of awards, and
adopting modifications, amendments, procedures, sub-plans and the like as are
necessary to comply with the laws and regulations of other countries in which
the Corporation operates in order to assure the viability of awards granted
under the Plan to participants employed in such other countries. Except for the
power to amend this Plan as provided in Section 13, the Committee may delegate
to the Chief Executive Officer or to other senior officers of the Corporation
its duties under the Plan pursuant to such conditions or limitations as the
Committee may establish, except that only the Committee may make any awards to
or determinations regarding grants to employees who are subject to Section 16 of
the 1934 Act. [Amended by Human Resources Committee June 5, 2001 to reflect
appropriate terminology and reference under Rule 16b-3 and appropriate reference
under Code.]

     4.   ELIGIBILITY. Any employee of the Corporation, including any entity
that is directly or indirectly controlled by the Corporation or any entity in
which the Corporation has a significant equity interest, as determined by the
Committee, shall be eligible to receive one or more awards under the Plan;
PROVIDED, HOWEVER, only employees of the Corporation or a parent

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or subsidiary of the Corporation shall be eligible to receive an award of an
incentive stock option ("ISO").

     5.   SHARES OF COMMON STOCK SUBJECT TO THE PLAN.

          (a)  For each calendar year, up to one and one-quarter percent (1
1/4%) of the issued and outstanding common stock of the Corporation, $0.10 par
value (the "Common Stock") as of the first day of such year shall be available
for issuance as grants or awards under the Plan. In addition, the aggregate
number of (i) any shares of Common Stock which as of the effective date of the
Plan are reserved for issuance under the 1990 Stock Option Plan (the "Prior
Plan") and which are not thereafter issued; (ii) any shares available for
issuance as grants or awards under the Plan in previous years but not actually
issued; (iii) any shares which have been exchanged by a participant as full or
partial payment to the Corporation in connection with any award under the Plan;
and (iv) any shares subject to any grant or award that is forfeited or
terminated without issuance of the shares or other consideration, shall again be
available for issuance under the Plan. [Amended by Human Resources Committee
June 5, 2001 to reflect 1998 charter amendment.]

          (b)  In no event, however, except as subject to adjustment as provided
in Section 6, shall more than 3,000,000 (three million) shares of Common Stock
be cumulatively available for issuance pursuant to the exercise of ISOs awarded
under the Plan. [Amended by Human Resources Committee June 5, 2001 to reflect
1996 stock split.]

          (c)  Any award of restricted stock pursuant to Section 7(c) that is
not subject to criteria other than continuous service with the Corporation will
be counted as two shares for purposes of determining the number of shares
available for issuance as grants or awards in any calendar year.

          (d)  In instances where a stock appreciation right ("SAR") or other
award is settled in cash or any form other than shares, then the shares covered
by these settlements shall not be deemed issued and shall remain available for
issuance under the Plan. Further, the payment of cash dividends and dividend
equivalents in conjunction with outstanding awards shall not be counted against
the shares available for issuance. Any shares that are issued by the
Corporation, and any awards that are granted by, or become obligations of, the
Corporation through the assumption by the Corporation or an affiliate of, or in
substitution for, outstanding awards previously granted by an acquired company
shall not, except in the case of awards granted to employees who are subject to
Section 16 of the 1934 Act, be counted against the shares available for issuance
under the Plan.

          (e)  Any shares issued under the Plan will consist of authorized and
unissued shares and no fractional shares shall be issued under the Plan. Cash
may be paid in lieu of any fractional shares in settlements of awards under the
Plan.

          (f)  Except for a grant that meets all of the requirements for
performance-based compensation set forth in Treasury Regulation Section
1.162-27(e), without regard to Section 1.162-27(e)(2)(vi), and subject to
adjustment as provided in Section 6, no officer or employee may receive, in
any given year, grants of stock options or SARs which, singly or in the
aggregate,

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cover more than 200,000 shares of the Common Stock. [Amended by shareholders May
7, 1997; clarification made by Human Resources Committee June 5, 2001.]

     6.   ADJUSTMENTS AND REORGANIZATIONS. In the event of any stock dividend,
stock split, combination or exchange of shares, merger, consolidation, spin-off
or other distribution (other than normal cash dividends) of Corporation assets
to shareholders, or any other change affecting shares, such proportionate
adjustments, if any, as the Committee in its discretion may deem appropriate to
reflect such change shall be made with respect to (i) the aggregate number of
shares that may be issued under the Plan; (ii) each outstanding award made under
the Plan; (iii) the price per share for any outstanding stock options, SARs and
stock awards under the Plan; and (iv) the limitation on awards set forth in
Section 5(f). [Amended by Human Resources Committee June 5, 2001 to conform to
amendment made to Section 5(f).]

     In the event that the Corporation undergoes a change of control (as defined
below), or in the event the Corporation merges, consolidates or amalgamates with
another company, or in the event of a liquidation or reorganization of the
Corporation, all outstanding awards under the Plan shall be immediately vested
and the Committee, as constituted before such change of control, in its sole
discretion, may provide for appropriate adjustments and settlements of such
awards either at the time of the award or at a subsequent date; PROVIDED,
HOWEVER, that outstanding awards shall become immediately vested pursuant to
this Section 6 in the event of a merger, consolidation or amalgamation only if
the Corporation is not the surviving company. [Clarification made by Human
Resources Committee June 5, 2001.]

     For purposes of this Plan, a "change of control" of the Corporation shall
mean a change of control of a nature that would be required to be reported in
response to Item 1(a) of the Current Report on Form 8-K, as in effect on the
date hereof, pursuant to Section 13 or 15(d) of the 1934 Act; provided that,
without limitation, such a "change of control" shall be deemed to have occurred
if: (i) a third person, including a "group" as such term is used in Section
13(d)(3) of the 1934 Act, becomes the beneficial owner, directly or indirectly,
of 25% or more of the combined voting power of the Corporation's outstanding
voting securities ordinarily having the right to vote for the election of
directors of the Corporation; or (ii) individuals who, as of the date hereof,
constitute the Board of Directors of the Corporation (the "Board" generally and
as of the date hereof the "Incumbent Board") cease for any reason to constitute
at least a majority of the Board, provided that any person becoming a director
subsequent to the date hereof whose election, or nomination for election by the
Corporation's shareholders, was approved by a vote of at least three-quarters of
the directors comprising the Incumbent Board (other than an election or
nomination of an individual whose initial assumption of office is in connection
with an actual or threatened election contest relating to the election of the
directors of the Corporation, as such terms are used in Rule 14a-11 of
Regulation 14A promulgated under the 1934 Act) shall be, for purposes of this
Plan, considered as though such person were a member of the Incumbent Board.

     7.   AWARDS. The Committee shall determine the type or types of award(s) to
be granted to each participant. Awards may be granted singly, in combination or
in tandem. Awards may also be made in combination or in tandem with, in
replacement of, as alternatives, or in payment for grants or rights under any
other employee or compensation plan of the Corporation, including the plan of
any acquired entity.

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          (a)  STOCK OPTION. This is an award consisting of a right to purchase
a specified number of shares of Common Stock during a specified period as
determined by the Committee. The purchase price of each option shall be not less
than 100% of Fair Market Value (as defined in Section 10) on the date of grant,
except that, in the case of a stock option granted retroactively in tandem with
or in substitution for another award, the exercise or designated price may be no
lower than the Fair Market Value on the date such other award was granted. A
stock option may be in the form of an ISO which, in addition to being subject to
applicable terms, conditions, and limitations established by the Committee,
complies with Section 422 of the Internal Revenue Code of 1986, as amended (the
"Code"). Any ISO granted pursuant to the Plan must be granted within ten years
from the date the Plan is approved by the Corporation's shareholders. The price
at which shares of Common Stock may be purchased under a stock option shall be
paid in full at the time of the exercise in cash or such other method as
provided by the Committee at the time of grant, including tendering Common
Stock, surrendering a stock award valued at Fair Market Value on the date of
surrender, surrendering a cash award, or any combination thereof. If the option
price is paid by tendering Common Stock acquired by exercise of an option such
Common Stock shall have been owned by the optionee for at least six months prior
to such payment. The Committee may grant stock options that provide for the
award of a new option when the exercise price has been paid by tendering shares
of Common Stock, such new option to be for the number of shares tendered, with
the exercise price set at the Fair Market Value on the date of option exercise.
[Amended by Human Resources Committee June 5, 2001 to eliminate two-year ISO
holding period for payment of option price and add a six-month holding period
for accounting purposes.]

          (b)  STOCK APPRECIATION RIGHT. This is an award consisting of a right
to receive a payment in cash and/or Common Stock equal to the excess of the Fair
Market Value of a specified number of shares of Common Stock on the date the SAR
is exercised over the Fair Market Value of such shares on the date of grant as
set forth in the applicable award agreement except that, in the case of an SAR
granted retroactively in tandem with or in substitution for another award, the
exercise or designated price may be no lower than the Fair Market Value of the
Common Stock on the date such other award was granted.

          (c)  STOCK AWARD. This is an award made in stock or denominated in
units of stock. All or part of any stock award may be subject to conditions and
restrictions established by the Committee and set forth in the award agreement,
which may include, but are not limited to, continuous service with the
Corporation, achievement of specific business objectives, and other measurements
of individual, business unit or Corporation performance.

     8.   DIVIDENDS AND DIVIDEND EQUIVALENTS. The Committee may provide that
awards under the Plan earn dividends or dividend equivalents. Such dividends or
dividend equivalents may be paid currently or may be credited to a participant's
account. Any crediting of dividends or dividend equivalents shall be subject to
such restrictions and conditions as the Committee may establish, including
reinvestment in additional shares or share equivalents.

     9.   DEFERRALS AND SETTLEMENTS. Payment of awards may be in the form of
cash, stock, other awards, or in combinations thereof as the Committee shall
determine, and with such restrictions as it may impose. The Committee may
require, or permit participants to elect, that the issuance of shares or the
settlement of cash awards be deferred under such rules and

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procedures as it may establish. It may also provide that deferred settlements
include the payment or crediting of interest on the deferred amounts or the
payment or crediting of dividend equivalents on deferred settlements denominated
in shares.

     10.  FAIR MARKET VALUE. "Fair Market Value" for all purposes under the Plan
shall mean the average of the high and low prices of Common Stock as reported on
the composite tape for securities listed on the New York Stock Exchange for the
date in question, or if no sales of Common Stock were made on said Exchange on
that date, the average of the high and low prices of Common Stock as reported on
said composite tape for the preceding day on which sales of Common Stock were
made on said Exchange.

     11.  TRANSFERABILITY AND EXERCISABILITY. Unless otherwise determined by the
Committee with respect to nonqualified stock options, all awards under the Plan
shall be nontransferable and shall not be assignable, alienable, saleable or
otherwise transferable by the participant other than by will or the laws of
descent and distribution, by designation of a beneficiary after death, or
pursuant to a qualified domestic relations order (as defined by the Code).
[Amended by Human Resources Committee June 5, 2001 to correct typographical
error.]

     12.  AWARD AGREEMENTS. Awards under the Plan shall be evidenced by
agreements that set forth the terms, conditions and limitations for each award
which may include the term of an award (except that in no event shall the term
of any ISO exceed a period of ten years from the date of its grant), the
provisions applicable in the event the participant's employment terminates, and
the Corporation's authority to unilaterally or bilaterally amend, modify,
suspend, cancel or rescind any award. The Committee need not require the
execution of any such agreement by the recipient, in which case the delivery of
the award to the respective participant will constitute the participant's
acceptance and agreement to the terms of the award.

     13.  PLAN AMENDMENT. The Committee may amend the Plan as it deems necessary
or appropriate to better achieve the purpose of the Plan, except that no such
amendment shall be made without the approval of the Corporation's shareholders
that would increase the number of shares available for issuance in accordance
with Sections 5 and 6 of the Plan or otherwise cause the Plan not to comply with
Rule 16b-3 or any successor rule under the 1934 Act, or any other legal
requirement.

     14.  TAX WITHHOLDING. The Corporation shall have the right to deduct from
any settlement of an award made under the Plan, including the delivery or
vesting of shares, a sufficient amount to cover withholding of any federal,
state or local taxes required by law, or to take such other action as may be
necessary to satisfy any such withholding obligations. The Committee may permit
a recipient of an award to tender shares of Common Stock to the Corporation to
be used to satisfy required tax withholding, and such Common Stock shall be
valued at the Fair Market Value as of the settlement date of the applicable
award.

     15.  OTHER CORPORATION BENEFIT AND COMPENSATION PROGRAMS. Unless otherwise
specifically determined by the Committee, settlements of awards received by
participants under the Plan shall not be deemed a part of a participant's
regular, recurring compensation for purposes of calculating payments or benefits
from any corporation benefit plan or severance

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program or the severance pay law of any country. Further, the Corporation may
adopt other compensation programs, plans or arrangements as it deems appropriate
or necessary.

     16.  UNFUNDED PLAN. Unless otherwise determined by the Committee, the Plan
shall be unfunded and shall not create (or be construed to create) a trust or a
separate fund or funds. The Plan shall not establish any fiduciary relationship
between the Corporation and any participant or other person. To the extent any
person holds any rights by virtue of a grant awarded under the Plan, such right
(unless otherwise determined by the Committee) shall be no greater than the
right of an unsecured general creditor of the Corporation.

     17.  FUTURE RIGHTS. No person shall have any claim or rights to be granted
an award under the Plan, and no participant shall have any rights under the Plan
to be retained in the employ of the Corporation.

     18.  GOVERNING LAW. The validity, construction and effect of the Plan and
any actions taken or relating to the Plan shall be determined in accordance with
the laws of the State of Tennessee and applicable federal law.

     19.  SUCCESSORS AND ASSIGNS. The Plan shall be binding on all successors
and assigns of a participant, including, without limitation, the estate of such
participant and the executor, administrator or trustee of such estate, or any
receiver or trustee in bankruptcy or representative of the participant's
creditors.

     20.  RIGHTS AS A SHAREHOLDER. Except as otherwise provided in the award
agreement, a participant shall have no rights as a shareholder until he or she
becomes the holder of record.

     21.  ANNUAL LIMIT ON ISO GRANTS. The aggregate fair market value
(determined on the date the option is granted) of Common Stock subject to ISOs
granted to an optionee in any calendar year shall not exceed any limitation
imposed by the Code.

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                                                                   EXHIBIT 10.3A

                                 GRANT AGREEMENT

                             INCENTIVE STOCK OPTION

Thomas & Betts Corporation (the "Corporation"), for and in consideration of the
provisions and conditions as stated herein and in the Corporation's 1993
Management Stock Ownership Plan (the "Plan") and other good and valuable
consideration, does hereby grant to the employee (one of the key employees of
the Corporation) identified in the attached Notice of Grant of Stock Option (the
"Optionee") this option to purchase from the Corporation the number of shares of
Common Stock of the Corporation at the price per share set forth in the Notice
of Grant of Stock Option, which option, except as provided in Paragraph 4, is
intended to qualify as an incentive stock option ("ISO") as that term is defined
in Section 422(b) of the Internal Revenue Code of 1986, as amended (the "Code").

The option granted pursuant to this Grant Agreement (the "Option") shall be
subject to the following conditions:

(1)  Subject to the provisions of Paragraph 4, the Option shall become
     exercisable in three installments in accordance with the following schedule
     and after the expiration of the following periods of time:

<Table>
<Caption>
                                   Portion of            Period from which
          Installment             Option Grant            Option Granted
          -----------             ------------            --------------
<S>                                <C>                      <C>
          First                    One-third                12 months
          Second                   One-third                24 months
          Third                    One-third                36 months
</Table>

     If the Optionee does not purchase the full number of shares which he has at
     any time become entitled to purchase, he may purchase all or any part of
     those shares at any subsequent time during the term of this Option.

(2)  The Option herein granted to the extent that it is exercisable may be
     exercised by giving written notice to the Corporate Human Resources
     Department or other designated person of the Corporation at its principal
     office no later than the Expiration Date (as defined in Paragraph 3). Such
     notice shall include a statement of the number of shares with respect to
     which this Option is being exercised and the exercise date, and shall be
     accompanied by full tender of the purchase price payable which may be made
     in whole or in part either in cash or by the exchange of such number of
     whole shares of Thomas & Betts Corporation Common Stock owned by the
     Optionee whose fair market value as of the close of the business day
     immediately preceding the specified Exercise Date does not exceed the
     purchase price payable; PROVIDED, HOWEVER, that the following holding
     period shall have been satisfied with respect to shares to be exchanged:
     (i) if the shares to be exchanged were acquired under an ISO, such ISO
     shall have been granted at least two years prior thereto; and

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     (ii) if the shares to be exchanged were acquired by exercise of an option,
     such Common Stock shall have been owned by the Optionee for at least one
     year prior to such payment, and FURTHER PROVIDED that the Committee shall
     have the right, upon prior notice to the holders of options, to modify,
     suspend or cancel the right to pay the purchase price in whole or in part
     by exchange of shares at any time in the event the Committee determines
     that there has been a change in tax or accounting consequences to the
     Corporation or to any Optionee. Nothing in this agreement shall confer upon
     the Optionee any rights as a stockholder prior to the time of the delivery
     to the Optionee of a stock certificate for the shares purchased under this
     agreement.

(3)  Unless this Option expires earlier in accordance with any provision of
     Paragraph 4, this Option shall expire on the date which is ten (10) years
     from the Date of Grant (the "Expiration Date").

(4)  If, prior to the Expiration Date, the Optionee (i) becomes totally and
     permanently disabled as determined by the Corporation in its sole
     discretion, (ii) retires, (iii) dies, or (iv) otherwise terminates or is
     terminated as an employee of the Corporation, this Option shall be
     exercisable under the circumstances and for the time periods set forth
     below, but only to the extent such time periods do not extend beyond the
     Expiration Date:

     (a)  If the Optionee's employment terminates or is terminated for any
          reason other than (i) retirement, (ii) the Optionee becoming totally
          and permanently disabled, (iii) death, or (iv) under the circumstances
          described in Paragraph 4(b), this Option may be exercised within
          thirty (30) days of the date of such termination to the extent
          exercisable in accordance with the provisions of Paragraph 1;

     (b)  If the Optionee retires at his normal or later retirement date or,
          with the consent of the Corporation, takes early retirement, this
          Option may be exercised in full, notwithstanding the provisions of
          Paragraph 1, at any time within six (6) years of the date of
          retirement; provided, however, that if such exercise occurs more than
          three (3) months after the date of such retirement, the Option shall
          be treated as a Nonqualified Stock Option;

     (c)  If the Optionee becomes totally and permanently disabled, this Option
          may be exercised in full, notwithstanding the provisions of Paragraph
          1, at any time within six (6) years of the date the Optionee's service
          as an employee is terminated within the meaning of the Code by reason
          of being totally and permanently disabled; provided, however, that if
          such Exercise occurs more than one (1) year after the date the
          Optionee's employment is terminated due to such disability, this
          Option shall be treated as a Nonqualified Stock Option;

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     (d)  If the Optionee dies while he is employed or within three (3) years of
          his retirement in accordance with subparagraph (c) above, this Option
          may be exercised in full, notwithstanding the provisions of Paragraph
          1, at any time within three (3) years of the Optionee's date of death
          by the legal representative of the Optionee or any person who acquires
          this Option by bequest or inheritance; provided, however, if the
          Optionee's date of death is more than three (3) months from the date
          of such retirement, this Option shall be treated as a Nonqualified
          Stock Option, and

     (e)  For purpose of this Paragraph 4, a sick leave or other bona fide leave
          of absence granted in accordance with the Corporation's usual
          procedure which does not operate to interrupt continuous employment
          for other benefits granted by the Corporation shall not be considered
          a termination of employment or interruption of continuous employment
          hereunder and an employee who is granted such a leave of absence shall
          be considered to be continuously employed during such period of leave;
          provided, that if the Code or the regulations promulgated thereunder
          establish a more restrictive rule defining termination of employment
          applicable to the option granted herein, such rule shall be
          substituted here for.

(5)  The Optionee agrees, by the acceptance of this Option, for himself and his
     executors and administrators, that if a registration statement under the
     Securities Act of 1933 is not in effect at the time of the exercise of any
     portion of this Option, with respect to the sale by the Corporation and the
     resale by the Optionee of the shares issuable upon such exercise, it shall
     be a condition precedent to the right to purchase such shares that the
     notice of exercise shall be accompanied by a written representation that
     the Optionee or his executor or administrator is acquiring such shares for
     his own or such executor's or administrator's account for investment and
     not with a view to the distribution thereof.

(6)  The Corporation shall be not be required to issue or deliver any
     certificate or certificates for shares of stock purchased upon the exercise
     of this Option until the admission of such shares to listing on any stock
     exchange on which the Corporation's stock may then be listed and until the
     Corporation takes such steps as may be required by law and applicable
     regulations, including rules and regulations of the Securities and Exchange
     Commission and any stock exchange as above mentioned, or until, in the
     opinion of counsel for the Corporation, any such listing or registration or
     other steps are not required.

(7)  The shares issued may be authorized but unissued stock, or treasury stock.
     and the number of shares with respect to which this Option may be
     exercised, and the price payable with respect thereto, shall be properly
     adjusted if the Corporation shall at any time declare a stock split, issue
     any stock dividend, or make a reclassification of such stock, so that the
     Optionee or his executors, administrators, legatees or distributees
     entitled hereunder shall not be in any

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     way in a better or worse position as to the number of shares acquired and
     the aggregate amount paid therefore, solely from having exercised this
     option with respect to any of said shares after, rather than before, such
     stock split, stock dividend, or reclassification.

(8)  The granting of this Option shall not constitute or be evidence of any
     agreement or understanding, express or implied, on the part of the
     Corporation or any of its subsidiaries to employ the Optionee for any
     specified period. The Company continues to retain the absolute right to
     terminate the employment relationship with the Optionee at any time, with
     or without good cause.

(9)  This Option shall be binding upon the Corporation and its successors and
     assigns, and upon the Optionee and his administrators and executors.

(10) Whenever the Corporation is required to issue or transfer shares of its
     Common Stock to Optionee pursuant hereto, the Corporation shall have the
     right to require the Optionee to remit to the Corporation an amount
     sufficient to satisfy all federal, state and local withholding tax
     requirements, if any.

(11) The Optionee agrees, by the acceptance of this Option, to the amendment of
     this Grant Agreement, the Notice of Grant of Stock Option and the form of
     exercise of option provided by the Corporation, in any manner requested by
     the Corporation pursuant to advice from the Securities and Exchange
     Commission at any time during the term of this Option, and to execute any
     and all instruments relative thereto when so requested by the Corporation.

(12) Throughout this agreement, the masculine gender shall be deemed to include
     the feminine.

(13) This Option is not transferable by the Optionee otherwise than by will or
     by the laws of descent and distribution and during the lifetime of the
     Optionee it is exercisable only by the Optionee.
<Page>

                                                                   EXHIBIT 10.3B

                                 GRANT AGREEMENT

                            NONQUALIFIED STOCK OPTION

Thomas & Betts Corporation (the "Corporation"), for and in consideration of the
provisions and conditions as stated herein and in the Corporation's 1993
Management Stock Ownership Plan (the "Plan") and other good and valuable
consideration, does hereby grant to the employee (one of the key employees of
the Corporation) identified in the attached Notice of Grant of Stock Option (the
"Optionee") this option to purchase from the Corporation the number of shares of
Common Stock of the Corporation at the price per share set forth in the Notice
of Grant of Stock Option, which option is not intended to qualify as an
incentive stock option ("ISO") as that term is defined in Section 422(b) of the
Internal Revenue Code of 1986, as amended (the "Code")

The option granted pursuant to this Grant Agreement (the "Option") shall be
subject to the following conditions:

(1)  Subject to the provisions of Paragraph 4, the Option shall become
     exercisable in three installments in accordance with the following schedule
     and after the expiration of the following periods of time:

<Table>
<Caption>
                                   Portion of            Period from which
          Installment             Option Grant            Option Granted
          -----------             ------------            --------------
<S>                                <C>                      <C>
          First                    One-third                12 months
          Second                   One-third                24 months
          Third                    One-third                36 months
</Table>

     If the Optionee does not purchase the full number of shares which he has at
     any time become entitled to purchase, he may purchase all or any part of
     those shares at any subsequent time during the term of this Option.

(2)  The Option herein granted to the extent that is exercisable may be
     exercised by giving written notice to the Corporate Human Resources
     Department or other designated person of the Corporation at its principal
     office no later than the

<Page>

     Expiration Date (as defined in Paragraph 3). Such notice shall include a
     statement of the number of shares with respect to which this Option is
     being exercised and the exercise date, and shall be accompanied by full
     tender of the purchase price payable which may be made in whole or in part
     either in cash or by the exchange of such number of whole shares of Thomas
     & Betts Corporation Common Stock owned by the Optionee whose fair market
     value as of the close of the business day immediately preceding the
     specified Exercise Date does not exceed the purchase price payable;
     PROVIDED, HOWEVER, that the following holding periods shall have been
     satisfied with respect to shares to be exchanged: (i) if the shares to be
     exchanged were acquired by exercise of an ISO, such ISO shall have been
     granted at least two years prior thereto; and (ii) if the shares to be
     exchanged were acquired by exercise of an option, such Common Stock shall
     have been owned by the Optionee for at least one year prior to such
     payment, and FURTHER PROVIDED that the Committee shall have the right, upon
     prior notice to the holders of options, to modify, suspend or cancel the
     right to pay the purchase price in whole or in part by exchange of shares
     at any time in the event the Committee determines that there has been a
     change in tax or accounting consequences to the Corporation or to any
     Optionee. Nothing in this agreement shall confer upon the Optionee any
     rights as a stockholder prior to the time of the delivery to the Optionee
     of a stock certificate for the shares purchased under this agreement.

(3)  Unless this Option expires earlier in accordance with any provision of
     Paragraph 4, this Option shall expire on the date which is ten (10) years
     from the Date of Grant (the "Expiration Date").

(4)  If, prior to the Expiration Date, the Optionee (i) becomes totally and
     permanently disabled as determined by the Corporation in its sole
     discretion, (ii) retires, (iii) dies, or (iv) otherwise terminates or is
     terminated as an employee of the Corporation, this Option shall be
     exercisable under the circumstances and for the time periods set forth
     below, but only to the extent such time periods do not extend beyond the
     Expiration Date:

     (a)  If the Optionee's employment terminates or is terminated for any
          reason other than (i) retirement, (ii) the Optionee becoming totally
          and permanently disabled, or (iii) death, this Option may be exercised
          within thirty (30) days of the date of such termination to

<Page>

          the extent exercisable in accordance with the provisions of Paragraph
          1.

     (b)  If the Optionee retires at his normal or later retirement date or,
          with the consent of the Corporation, takes early retirement, this
          Option may be exercised in full, notwithstanding the provisions of
          Paragraph 1, at any time within six (6) years of the date of
          retirement;

     (c)  If the Optionee becomes totally and permanently disabled, this Option
          may be exercised in full, notwithstanding the provisions of Paragraph
          1, at any time within six (6) years of the date the Optionee's service
          as an employee is terminated within the meaning of the Code by reason
          of being totally and permanently disabled;

     (d)  If the Optionee dies while he is employed or within three (3) years of
          his retirement in accordance with subparagraph (b) above, this Option
          may be exercised in full, notwithstanding the provisions of Paragraph
          1, at any time within three (3) years of the Optionee's date of death
          by the legal representative of the Optionee or any person who acquires
          this Option by bequest or inheritance; and

     (e)  For purpose of this Paragraph 4, a sick leave or other bona fide leave
          of absence granted in accordance with the Corporation's usual
          procedure which does not operate to interrupt continuous employment
          for other benefits granted by the Corporation shall not be considered
          a termination of employment or an interruption of continuous
          employment hereunder and an employee who is granted such a leave of
          absence shall be considered to be continuously employed during such
          period of leave; provided, that if the Code or the regulations
          promulgated thereunder establish a more restrictive rule defining
          termination of employment applicable to the option granted herein,
          such rule shall be substituted herefor.

<Page>

(5)  The Optionee agrees, by the acceptance of this Option, for himself and his
     executors and administrators, that if a registration statement under the
     Securities Act of 1933 is not in effect at the time of the exercise of any
     portion of this Option, with respect to the sale by the Corporation and the
     resale by the Optionee of the shares issuable upon such exercise, it shall
     be a condition precedent to the right to purchase such shares that the
     notice of exercise shall be accompanied by a written representation that
     the Optionee or his executor or administrator is acquiring such shares for
     his own or such executor's or administrator's account for investment and
     not with a view to the distribution thereof.

(6)  The Corporation shall not he required to issue or deliver any certificate
     or certificates for shares of stock purchased upon the exercise of this
     Option until the admission of such shares to listing on any stock exchange
     on which the Corporation's stock may then be listed and until the
     Corporation takes such steps as may be required by law and applicable
     regulations, including rules and regulations of the Securities and Exchange
     Commission and any stock exchange as above mentioned, or until, in the
     opinion of counsel for the Corporation, any such listing or registration or
     other steps are not required.

(7)  The shares issued may be authorized but unissued stock, or treasury
     stock,and the number of shares with respect to which this Option may be
     exercised, and the price payable with respect thereto, shall be properly
     adjusted if the Corporation shall at any time declare a stock split, issue
     any stock dividend, or make a reclassification of such stock, so that the
     Optionee or his executors, administrators, legatees or distributees
     entitled hereunder shall not be in any way in a better or worse position as
     to the number of shares acquired and the aggregate amount paid therefore,
     solely from having exercised this option with respect to any of said shares
     after, rather than before, such stock split, stock dividend, or
     reclassification.

(8)  The granting of this Option shall not constitute or be evidence of any
     agreement or understanding, express or implied, on the part of the
     Corporation or any of its subsidiaries to employ the Optionee for any
     specified period. The Company continues to retain the absolute right to
     terminate the employment relationship with the Optionee at any time, with
     or without good cause.

(9)  This Option shall be binding upon the Corporation and its successors and
     assigns, and upon the Optionee and his administrators and executors.

(10) Whenever the Corporation is required to issue or transfer shares of its
     Common Stock to Optionee pursuant hereto, the Corporation shall have the
     right to require

<Page>

     the Optionee to remit to the Corporation an amount sufficient to satisfy
     all federal, state and local withholding tax requirements, if any.

(11) The Optionee agrees, by the acceptance of this Option, to the amendment of
     this Grant Agreement, the Notice of Grant of Stock Option and the form of
     exercise of option provided by the Corporation in any manner requested by
     the Corporation pursuant to advice from the Securities and Exchange
     Commission at any time during the term of this Option, and to execute any
     and all instruments relative thereto when so requested by the Corporation.

(12) Throughout this agreement, the masculine gender shall be deemed to include
     the feminine.

(13) This Option is not transferable by the Optionee otherwise than by will or
     by the laws of descent and distribution and during the lifetime of the
     Optionee it is exercisable only by the Optionee.
<Page>

                                                                   EXHIBIT 10.3C

                                 GRANT AGREEMENT

                             INCENTIVE STOCK OPTION

Thomas & Betts Corporation (the "Corporation"), for and in consideration of the
provisions and conditions as stated herein and in the Corporation's 1993
Management Stock Ownership Plan (the "Plan") and other good and valuable
consideration, does hereby grant to the employee (one of the key employees of
the Corporation) identified in the attached Notice of Grant of Stock Option (the
"Optionee") this option to purchase from the Corporation the number of shares of
Common Stock of the Corporation at the price per share set forth in the Notice
of Grant of Stock Option, which option, except as provided in Paragraph 4, is
intended to qualify as an incentive stock option ("ISO") as that term is defined
in Section 422(b) of the Internal Revenue Code of 1986, as amended (the "Code").

The option granted pursuant to this Grant Agreement (the "Option") shall be
subject to the following conditions:

(1)  Subject to the provisions of Paragraph 4, the Option shall become
     exercisable in three installments in accordance with the following schedule
     and after the expiration of the following periods of time:

<Table>
<Caption>
                                   Portion of            Period from which
          Installment             Option Grant            Option Granted
          -----------             ------------            --------------
<S>                                <C>                      <C>
          First                    One-third                12 months
          Second                   One-third                24 months
          Third                    One-third                36 months
</Table>

     If the Optionee does not purchase the full number of shares which he has at
     any time become entitled to purchase, he may purchase all or any part of
     those shares at any subsequent time during the term of this Option.

(2)  The Option herein granted to the extent that it is exercisable may be
     exercised by giving written notice to the Corporate Human Resources
     Department or other designated person of the Corporation at its principal
     office no later than the Expiration Date (as defined in Paragraph 3). Such
     notice shall include a statement of the number of shares with respect to
     which this Option is being exercised and the exercise date, and shall be
     accompanied by full tender of the purchase price payable which may be made
     in whole or in part either in cash or by the exchange of such number of
     whole shares of Thomas & Betts Corporation Common Stock owned by the
     Optionee whose fair market value as of the close of the business day
     immediately preceding the specified Exercise Date does not exceed the
     purchase price payable; PROVIDED, HOWEVER, that the following holding
     periods shall have been satisfied with respect to shares to be exchanged:
     (i) if the shares to be exchanged were acquired under an ISO, such ISO
     shall have been granted at least two years prior thereto; and (ii) if the
     shares to be exchanged were acquired by exercise of an option, such Common
     Stock shall have been owned by the

<Page>

     Optionee for at least one year prior to such payment; and FURTHER PROVIDED
     that the Committee shall have the right, upon prior notice to the holders
     of options, to modify, suspend or cancel the right to pay the purchase
     price in whole or in part by exchange of shares at any time in the event
     the Committee determines that there has been a change in tax or accounting
     consequences to the Corporation or to any Optionee. Nothing in this
     agreement shall confer upon the Optionee any rights as a stockholder prior
     to the time of the delivery to the Optionee of a stock certificate for the
     shares purchased under this agreement.

(3)  Unless this Option expires earlier in accordance with any provision of
     Paragraph 4, this Option shall expire on the date which is ten (10) years
     from the Date of Grant (the "Expiration Date").

(4)  If, prior to the Expiration Date, the Optionee (i) becomes totally and
     permanently disabled as determined by the Corporation in its sole
     discretion, (ii) retires, (iii) dies, or (iv) otherwise terminates or is
     terminated as an employee of the Corporation, this Option shall be
     exercisable under the circumstances and for the time periods set forth
     below, but only to the extent such time periods do not extend beyond the
     Expiration Date:

     (a)  If the Optionee's employment terminates or is terminated for any
          reason other than (i) retirement, (ii) the Optionee becoming totally
          and permanently disabled, (iii) death, or (iv) under the circumstances
          described in Paragraph 4(b), this Option may be exercised within
          thirty (30) days of the date of such termination to the extent
          exercisable in accordance with the provisions of Paragraph 1;

     (b)  In the event that (i) the Optionee has an employment agreement with
          the Corporation which provides for his continued employment following
          a change in control ("Employment Agreement") and (ii) a "Change in
          Control," as defined in Section 2 of such Employment Agreement,
          occurs, this Option shall become fully exercisable upon the "Effective
          Date," as defined in Section 1(a) of such Employment Agreement,
          notwithstanding any provision in Paragraph 1 to the contrary,
          provided, however, that to the extent (if any) that the limitation set
          forth in Code Section 422(d) is exceeded, the Option shall be treated
          as a Nonqualified Stock Option; in addition, if such Optionee's
          employment with the Corporation is thereafter terminated under the
          circumstances described in Section 7(d) of such Employment Agreement,
          this Option shall remain exercisable at any time prior to the
          Expiration Date, provided, however, that if such exercise occurs more
          than three (3) months after the date of such Optionee's termination of
          employment, the Option shall be treated as a Nonqualified Stock
          Option;

     (c)  If the Optionee retires at his normal or later retirement date or,
          with the consent of the Corporation, takes early retirement, this
          Option may be

<Page>

          exercised in full, notwithstanding the provisions of Paragraph 1, at
          any time within six (6) years of the date of retirement; provided,
          however, that if such exercise occurs more than three (3) months after
          the date of such retirement, the Option shall be treated as a
          Nonqualified Stock Option;

     (d)  If the Optionee becomes totally and permanently disabled, this Option
          may be exercised in full, notwithstanding the provisions of Paragraph
          1, at any time within six (6) years of the date the Optionee's service
          as an employee is terminated within the meaning of the Code by reason
          of being totally and permanently disabled; provided, however, that if
          such Exercise occurs more than one (1) year after the date the
          Optionee's employment is terminated due to such disability, this
          Option shall be treated as a Nonqualified Stock Option;

     (e)  If the Optionee dies while he is employed or within three (3) years of
          his retirement in accordance with subparagraph (c) above, this Option
          may be exercised in full, notwithstanding the provisions of Paragraph
          1, at any time within three (3) years of the Optionee's date of death
          by the legal representative of the Optionee or any person who acquires
          this Option by bequest or inheritance; provided, however, if the
          Optionee's date of death is more than three (3) months from the date
          of such retirement, this Option shall be treated as a Nonqualified
          Stock Option, and

     (f)  For purpose of this Paragraph 4, a sick leave or other bona fide leave
          of absence granted in accordance with the Corporation's usual
          procedure which does not operate to interrupt continuous employment
          for other benefits granted by the Corporation shall not be considered
          a termination of employment or interruption of continuous employment
          hereunder and an employee who is granted such a leave of absence shall
          be considered to be continuously employed during such period of leave;
          provided, that if the Code or the regulations promulgated thereunder
          establish a more restrictive rule defining termination of employment
          applicable to the option granted herein, such rule shall be
          substituted herefor.

(5)  The Optionee agrees, by the acceptance of this Option, for himself and his
     executors and administrators, that if a registration statement under the
     Securities Act of 1933 is not in effect at the time of the exercise of any
     portion of this Option, with respect to the sale by the Corporation and the
     resale by the Optionee of the shares issuable upon such exercise, it shall
     be a condition precedent to the right to purchase such shares that the
     notice of exercise shall be accompanied by a written representation that
     the Optionee or his executor or administrator is acquiring such shares for
     his own or such executor's or administrator's account for investment and
     not with a view to the distribution thereof.

<Page>

(6)  The Corporation shall be not be required to issue or deliver any
     certificate or certificates for shares of stock purchased upon the exercise
     of this Option until the admission of such shares to listing on any stock
     exchange on which the Corporation's stock may then be listed and until the
     Corporation takes such steps as may be required by law and applicable
     regulations, including rules and regulations of the Securities and Exchange
     Commission and any stock exchange as above mentioned, or until, in the
     opinion of counsel for the Corporation, any such listing or registration or
     other steps are not required.

(7)  The shares issued may be authorized but unissued stock, or treasury stock.
     and the number of shares with respect to which this Option may be
     exercised, and the price payable with respect thereto, shall be properly
     adjusted if the Corporation shall at any time declare a stock split, issue
     any stock dividend, or make a reclassification of such stock, so that the
     Optionee or his executors, administrators, legatees or distributees
     entitled hereunder shall not be in any way in a better or worse position as
     to the number of shares acquired and the aggregate amount paid therefore,
     solely from having exercised this option with respect to any of said shares
     after, rather than before, such stock split, stock dividend, or
     reclassification.

(8)  The granting of this Option shall not constitute or be evidence of any
     agreement or understanding, express or implied, on the part of the
     Corporation or any of its subsidiaries to employ the Optionee for any
     specified period. The Company continues to retain the absolute right to
     terminate the employment relationship with the Optionee at any time, with
     or without good cause.

(9)  This Option shall be binding upon the Corporation and its successors and
     assigns, and upon the Optionee and his administrators and executors.

(10) Whenever the Corporation is required to issue or transfer shares of its
     Common Stock to Optionee pursuant hereto, the Corporation shall have the
     right to require the Optionee to remit to the Corporation an amount
     sufficient to satisfy all federal, state and local withholding tax
     requirements, if any.

(11) The Optionee agrees, by the acceptance of this Option, to the amendment of
     this Grant Agreement, the Notice of Grant of Stock Option and the form of
     exercise of option provided by the Corporation, in any manner requested by
     the Corporation pursuant to advice from the Securities and Exchange
     Commission at any time during the term of this Option, and to execute any
     and all instruments relative thereto when so requested by the Corporation.

(12) Throughout this agreement, the masculine gender shall be deemed to include
     the feminine.

<Page>

(13) This Option is not transferable by the Optionee otherwise than by will or
     by the laws of descent and distribution and during the lifetime of the
     Optionee it is exercisable only by the Optionee.
<Page>

                                                                   EXHIBIT 10.3D

                                 GRANT AGREEMENT

                            NONQUALIFIED STOCK OPTION

Thomas & Betts Corporation (the "Corporation"), for and in consideration of the
provisions and conditions as stated herein and in the Corporation's 1993
Management Stock Ownership Plan (the "Plan") and other good and valuable
consideration, does hereby grant to the employee (one of the key employees of
the Corporation) identified in the attached Notice of Grant of Stock Option (the
"Optionee") this option to purchase from the Corporation the number of shares of
Common Stock of the Corporation at the price per share set forth in the Notice
of Grant of Stock Option, which option is not intended to qualify as an
incentive stock option ("ISO") as that term is defined in Section 422(b) of the
Internal Revenue Code of 1986, as amended (the "Code").

The option granted pursuant to this Grant Agreement (the "Option") shall be
subject to the following conditions:

(1)  Subject to the provisions of Paragraph 4, the Option shall become
     exercisable in three installments in accordance with the following schedule
     and after the expiration of the following periods of time:

<Table>
<Caption>
                                   Portion of            Period from which
          Installment             Option Grant            Option Granted
          -----------             ------------            --------------
<S>                                <C>                      <C>
          First                    One-third                12 months
          Second                   One-third                24 months
          Third                    One-third                36 months
</Table>

If the Optionee does not purchase the full number of shares which he has at any
time become entitled to purchase, he may purchase all of any part of those
shares at any subsequent time during the term of this Option.

(2)  The Option herein granted to the extent that it is exercisable may be
     exercised by giving written notice to the Corporate Human Resources
     Department or other designated person of the Corporation at its principal
     office no later than the Expiration Date (as defined in Paragraph 3). Such
     notice shall include a statement of the number of shares with respect to
     which this Option is being exercised and the exercise date, and shall be
     accompanied by full tender of the purchase price payable which may be made
     in whole or in part either in cash or by the exchange of such number of
     whole shares of Thomas & Betts Corporation Common Stock owned by the
     Optionee whose fair market value as of the close of the business day
     immediately preceding the specified Exercise Date does not exceed the
     purchase price payable; PROVIDED, HOWEVER, that the following holding
     periods shall have been satisfied with respect to shares to be exchanged;
     (i) if the shares to be exchanged were acquired by exercise by an ISO, such
     ISO shall have been granted at least two years prior thereto; and (2) if
     the shares to be exchanged were acquired by exercise of an option, such
     Common Stock shall have been owned by the Optionee for at least one year
     prior to such payment; and further provided that the Committee shall have
     the right, upon prior notice to the holders of options, to modify, suspend
     or cancel the right to pay the purchase price in whole or in part by
     exchange of shares at any time in the event the Committee determines

<Page>

     that there has been a change in tax or accounting consequences to the
     Corporation or to Optionee. Nothing in this agreement shall confer upon the
     Optionee any rights as a stockholder prior to the time of the delivery to
     the Optionee of a stock certificate for the shares purchased under this
     agreement.

(3)  Unless this Option expires earlier in accordance with any provision of
     Paragraph 4, this Option shall expire on the date which is ten (10) years
     from the Date of Grant (the "Expiration Date").

(4)  If, prior to the Expiration Date, the Optionee (i) becomes totally and
     permanently disabled as determined by the Corporation in its sole
     discretion, (ii) retires, (iii) dies, or (iv) otherwise terminates or is
     terminated as an employee of the Corporation, this option shall be
     exercisable under the circumstances and for the time periods set forth
     below, but only to the extent such time periods do not extend beyond the
     Expiration Date:

     (a)  If the Optionee's employment terminates or is terminated for any
          reason other than (i) retirement, (ii) the Optionee becoming totally
          and permanently disabled, (iii) death, or (iv) under the circumstances
          described in Paragraph 4(b), this Option may be exercised within
          thirty (30) days of the date of such termination to the extent
          exercisable in accordance with the provisions of Paragraph 1;

     (b)  In the event that (i) the Optionee has an employment agreement with
          the Corporation which provides for his continued employment following
          a change in control ("Employment Agreement") and (ii) a "Change in
          Control," as defined in Section 2 of such Employment Agreement,
          occurs, this Option shall become fully exercisable upon the "Effective
          Date," as defined in Section 1(a) of such Employment Agreement,
          notwithstanding any provision in Paragraph 1 to the contrary; in
          addition, if such Optionee's employment with the Corporation is
          thereafter terminated under the circumstances described in Section
          7(d) of such Employment Agreement, this Option shall remain
          exercisable at any time prior to the Expiration Date;

     (c)  If the Optionee retires at his normal or later retirement date or,
          with the consent of the Corporation, takes early retirement, this
          Option may be exercised in full, notwithstanding the provisions of
          Paragraph 1, at any time within six (6) years of the date of
          retirement;

     (d)  If the Optionee becomes totally and permanently disabled, this Option
          may he exercised in full, notwithstanding the provisions of Paragraph
          1, at any time within six (6) years of the date the Optionee's service
          as an employee is terminated within the meaning of the Code by reason
          of being totally and permanently disabled;

     (e)  If the Optionee dies while he is employed or within three (3) years of
          his retirement in accordance with subparagraph (c) above, this Option
          may be exercised in full, notwithstanding the provisions of Paragraph
          1, at any time within three (3) years of the Optionee's date of death
          by the legal representative of the Optionee or any

<Page>

          person who acquires this Option by bequest or inheritance; and

     (f)  For purpose of this Paragraph 4, a sick leave or other bona fide leave
          of absence granted in accordance with the Corporation's usual
          procedure which does not operate to interrupt continuous employment
          for other benefits granted by the Corporation shall not be considered
          a termination of employment or interruption of continuous employment
          hereunder and an employee who is granted such a leave of absence shall
          be considered to be continuously employed during such period of leave;
          provided, that if the Code or the regulations promulgated thereunder
          establish a more restrictive rule defining termination of employment
          applicable to the option granted herein, such rule shall be
          substituted here for.

(5)  The Optionee agrees, by the acceptance of this Option, for himself and his
     executors and administrators, that if a registration statement under the
     Securities Act of 1933 is not in effect at the time of the exercise of any
     portion of this Option, with respect to the sale by the Corporation and the
     resale by the Optionee of the shares issuable upon such exercise, it shall
     be a condition precedent to the right to purchase such shares that the
     notice of exercise shall be accompanied by a written representation that
     the Optionee or his executor or administrator is acquiring such shares for
     his own or such executor's or administrator's account for investment and
     not with a view to the distribution thereof.

(6)  The Corporation shall be not be required to issue or deliver any
     certificate or certificates for shares of stock purchased upon the exercise
     of this Option until the admission of such shares to listing on any stock
     exchange on which the Corporation's stock may then be listed and until the
     Corporation takes such steps as may be required by law and applicable
     regulations, including rules and regulations of the Securities and Exchange
     Commission and any stock exchange as above mentioned, or until, in the
     opinion of counsel for the Corporation, any such listing or registration or
     other steps are not required.

(7)  The shares issued may be authorized but unissued stock, or treasury stock,
     and the number of shares with respect to which this Option may be
     exercised, and the price payable with respect thereto, shall be properly
     adjusted if the Corporation shall at any time declare a stock split, issue
     any stock dividend, or make a reclassification of such stock, so that the
     Optionee or his executors, administrators, legatees or distributees
     entitled hereunder shall not be in any way in a better or worse position as
     to the number of shares acquired and the aggregate amount paid therefore,
     solely from having exercised this option with respect to any of said shares
     after, rather than before, such stock split, stock dividend, or
     reclassification.

(8)  The granting of this Option shall not constitute or be evidence of any
     agreement or understanding, express or implied, on the part of the
     Corporation or any of its subsidiaries to employ the Optionee for any
     specified period. The Company continues to retain the absolute right to
     terminate the employment relationship with the Optionee at any time, with
     or without good cause.

(9)  This Option shall be binding upon the Corporation and its successors and
     assigns, and upon the Optionee and his administrators and executors.

<Page>

(10) Whenever the Corporation is required to issue or transfer shares of its
     Common Stock to Optionee pursuant hereto, the Corporation shall have the
     right to require the Optionee to remit to the Corporation an amount
     sufficient to satisfy all federal, state and local withholding tax
     requirements, if any.

(11) The Optionee agrees, by the acceptance of this Option, to the amendment of
     this Grant Agreement, the Notice of Grant of Stock Option and the form of
     exercise of option provided by the Corporation, in any manner requested by
     the Corporation pursuant to advice from the Securities and Exchange
     Commission at any time during the term of this Option, and to execute any
     and all instruments relative thereto when so requested by the Corporation.

(12) Throughout this agreement, the masculine gender shall be deemed to include
     the feminine.

(13) This Option is not transferable by the Optionee otherwise than by will or
     by the laws of descent and distribution and during the lifetime of the
     Optionee it is exercisable only by the Optionee.<Page>

                                MASTER AGREEMENT

         RELATING TO THE CROSS LICENSE OF CERTAIN INTELLECTUAL PROPERTY
                                AND COLLABORATION
                                 BY AND BETWEEN
                                 HYBRIDON, INC.
                             a Delaware corporation

                                       AND
                           ISIS PHARMACEUTICALS, INC.
                             a Delaware corporation

                            DATED AS OF MAY 24, 2001

<Page>

                                TABLE OF CONTENTS
<Table>
<Caption>
                                                                                                   PAGE
<S>                                                                                               <C>
ARTICLE 1 - DEFINED TERMS............................................................................1

    1.1     Definitions..............................................................................1

ARTICLE 2 - COLLABORATION AND LICENSE AGREEMENT AND OTHER CONSIDERATION..............................6

    2.1     Execution of Collaboration and License Agreement.........................................6
    2.2     Additional Hybridon Consideration........................................................7
    2.3     Additional Isis Consideration...........................................................11
    2.4     Restrictive Legend......................................................................16

ARTICLE 3 - REPRESENTATIONS AND WARRANTIES OF HYBRIDON..............................................17

    3.1     Organization and Good Standing; Power...................................................17
    3.2     Authorization...........................................................................17
    3.3     No Violation............................................................................17
    3.4     No Consent Required.....................................................................18
    3.5     Issuance................................................................................18
    3.6     Litigation..............................................................................18
    3.7     Investment Representations..............................................................18
    3.8     SEC Filings.............................................................................19
    3.9     Brokers or Finders......................................................................19

ARTICLE 4 - REPRESENTATIONS AND WARRANTIES OF ISIS..................................................20

    4.1     Organization and Good Standing; Power...................................................20
    4.2     Authorization...........................................................................20
    4.3     No Violation............................................................................20
    4.4     No Consent Required.....................................................................21
    4.5     Issuance................................................................................21
    4.6     Litigation..............................................................................21
    4.7     Investment Representations..............................................................21
    4.8     SEC Filings.............................................................................22
    4.9     Brokers or Finders......................................................................22

ARTICLE 5 - CLOSING DELIVERIES OF ISIS..............................................................22

ARTICLE 6 - CLOSING DELIVERIES OF HYBRIDON..........................................................23

ARTICLE 7 - REGISTRATION RIGHTS.....................................................................23

    7.1     Hybridon Registration Obligations.......................................................23
    7.2     Isis Registration Obligations...........................................................25
    7.3     Filing Requirements.....................................................................26
    7.4     Limitation on Registration Obligations..................................................27

                                       -i-
<Page>

ARTICLE 8 - POST EFFECTIVE COVENANTS................................................................28

    8.1     Isis's Voting Restrictions..............................................................28
    8.2     Hybridon's Voting Restrictions..........................................................28
    8.3     Restrictions on Isis's Sale of its Hybridon Common Stock................................28
    8.4     Restrictions on Hybridon's Sale of its Isis Common Stock................................29
    8.5     Certain Transactions Prohibited.........................................................29
    8.6     Waiver of Restrictions..................................................................30
    8.7     Reservation of Shares...................................................................30
    8.8     Change in Control of Hybridon...........................................................30
    8.9     Change in Control of Isis...............................................................30

ARTICLE 9 - INDEMNIFICATION AND CONTRIBUTION........................................................30

    9.1     Indemnification.........................................................................30

ARTICLE 10 - TERM AND EVENTS OF DEFAULT.............................................................32

    10.1    Term....................................................................................32
    10.2    Events of Default.......................................................................32
    10.3    Remedies Upon an Event of Default.......................................................33
    10.4    Survival................................................................................33
    10.5    Failure to Make Master Agreement Deliveries.............................................33

ARTICLE 11 - MISCELLANEOUS PROVISIONS...............................................................34

    11.1    Adjustments for Dividends, Splits, Reorganizations, Reclassifications, Etc..............34
    11.2    Successors and Assigns..................................................................35
    11.3    Notices.................................................................................35
    11.4    Entire Agreement; Amendments; Attachments...............................................36
    11.5    Severability............................................................................36
    11.6    Investigation of the Parties............................................................36
    11.7    Expenses................................................................................36
    11.8    Governing Law...........................................................................37
    11.9    Section Headings........................................................................37
    11.10   Counterparts............................................................................37
    11.11   Waiver and Modification.................................................................37
    11.12   No Waiver...............................................................................37
    11.13   Further Assurances......................................................................37
    11.14   Dispute Resolution......................................................................37
    11.15   No Consequential Damages................................................................37
    11.16   Confidentiality.........................................................................38
</Table>

                                       -ii-
<Page>

                                MASTER AGREEMENT

         This Master Agreement (this "MASTER AGREEMENT") dated as of May 24,
2001, is entered into by and between Hybridon, Inc., a Delaware corporation with
its principal place of business at Cambridge, Massachusetts ("HYBRIDON"), and
Isis Pharmaceuticals, Inc., a Delaware corporation with its principal place of
business at Carlsbad, California ("ISIS").

                                   WITNESSETH:

         WHEREAS, each of Hybridon and Isis owns or licenses intellectual
property that it wishes to license to the other; and

         WHEREAS, as partial consideration for such license of intellectual
property, Hybridon and Isis each intends to issue shares of common stock to the
other and Isis intends to pay Hybridon a cash payment contemporaneously with the
execution of this Master Agreement; and

         WHEREAS, each of the parties has expended significant efforts and
resources in the research and development of antisense technology and the
payments to be made under this Master Agreement to each party hereto will allow
each party hereto to recoup such expenditures; and

         WHEREAS, the parties hereto wish to enter into a binding agreement with
respect to the specific transactions and agreements set forth in this Master
Agreement; and

         WHEREAS, each of the parties to this Master Agreement desires to make
certain representations, warranties and agreements in connection with the
transactions contemplated hereby and also to prescribe various conditions
thereto.

         NOW, THEREFORE, in consideration of the foregoing recitals, the
provisions and the respective agreements hereinafter set forth, and other good
and valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, the parties agree as follows:

                                    ARTICLE 1

                                  DEFINED TERMS

         1.1   DEFINITIONS. Capitalized terms used herein and not otherwise
defined shall have the meanings set forth below:

         "AFFILIATE" means, with respect to a person or entity, any corporation,
company, partnership, joint venture or other entity which controls, is
controlled by, or is under common control with such person or entity. For
purposes of this definition, "control" shall mean (a) in the case of corporate
entities, direct or indirect ownership of fifty percent (50%) or more of the
stock

                                       -1-
<Page>

or shares having the right to vote for the election of directors, and (b) in
the case of non-corporate entities, direct or indirect ownership of fifty
percent (50%) or more of the equity interest with the power to direct the
management and policies of such non-corporate entities.

         "AVERAGE CLOSING PRICE" means the Closing Prices of either Isis Common
Stock or Hybridon Common Stock, as the context requires, averaged over any
number of trading days as specified in this Master Agreement.

         "CHANGE IN CONTROL TRANSACTION" means (a) any sale or transfer of all
or substantially all of the assets of a Party to another individual, corporation
or entity ("Type A"), (b) any merger, consolidation, reorganization, share
exchange or business combination of a Party into or with another corporation or
entity, with the result that, upon conclusion of the transaction, the voting
securities of such Party immediately prior thereto do not represent (either by
remaining outstanding or by being converted into voting securities of the
surviving entity) more than 40% of the combined voting power of the voting
securities of the continuing or surviving corporation or entity of such
consolidation, merger, reorganization, share exchange or business combination
("Type B"), (c) any direct or indirect acquisition of securities in which a
"person" or "group" (as used in Rule 13d-1 of the Exchange Act) directly or
indirectly acquires beneficial or record ownership of voting securities of a
Party representing at least 60% of the outstanding voting securities of such
Party ("Type C"), or (d) any event that results in the securities of a Party
issued or issuable under SECTION 2.2 (including SECTION 2.2(c)) or SECTION 2.3
(including SECTION 2.3(c)), as the case may be, no longer being a class of
securities registered with the Commission pursuant to Section 12 of the Exchange
Act ("Type D").

         "CLOSING PRICE" means the midpoint of the high and low sale price of a
share of the Hybridon Common Stock or the Isis Common Stock, as applicable, on
any given day as reported on the Stock Market on which such security is traded.

         "COMMISSION" means the Securities and Exchange Commission.

         "EFFECTIVE DATE" means the date on which this Master Agreement is
executed by the Parties.

         "EXCHANGE ACT" means the Securities Exchange Act of 1934, as amended.

         "HYBRIDON COMMON STOCK" means the common stock, $.001 par value per
share, of Hybridon.

         "HYBRIDON INTELLECTUAL PROPERTY" shall have the meaning set forth in
the License Agreement.

         "HYBRIDON MARKET PRICE" means the Market Price of Hybridon Common
Stock.

                                       -2-
<Page>

         "HYBRIDON MAXIMUM PRICE" means $3 for the first Hybridon Tranche
Period, $4 for the second Hybridon Tranche Period and $5 for the third Hybridon
Tranche Period, each as may be adjusted from time to time pursuant to
SECTION 11.1.

         "HYBRIDON MINIMUM PRICE" means $1, as may be adjusted from time to time
pursuant to SECTION 11.1.

         "HYBRIDON RESTRICTED STOCK" means all shares of Hybridon Common Stock
issued to Isis pursuant to this Master Agreement and all shares of capital stock
which may, from time to time, be issued in respect of any such shares of capital
stock, including, without limitation, all shares issued as a stock dividend, as
a result of a stock split or pursuant to any reorganization, recapitalization,
merger, consolidation or similar event.

         "HYBRIDON TRANCHE PAYMENT" means the stock issuance to be made by
Hybridon to Isis with respect to a Hybridon Tranche Period or, if permitted, the
cash to be paid by Hybridon to Isis in lieu of such stock issuance.

         "HYBRIDON TRANCHE PAYMENT DATE" means, as to a Hybridon Tranche Period,
the next business day following the last day of the Hybridon Tranche Period or,
if prior to such day, the date on which the Hybridon Tranche Payment for such
Hybridon Tranche Period becomes payable pursuant to SECTION 2.2(b).

         "HYBRIDON TRANCHE PERIOD" means any one of the three successive
twelve-month periods commencing on the Effective Date.

         "ISIS COMMON STOCK" means the common stock, $.001 par value per share,
of Isis.

         "ISIS INTELLECTUAL PROPERTY" shall have the meaning set forth in the
License Agreement.

         "ISIS MARKET PRICE" means the Market Price of the Isis Common Stock.

         "ISIS MAXIMUM PRICE" means $14 for the first Isis Tranche Period,
$20 for the second and third Isis Tranche Period, and $26 for the fourth Isis
Tranche Period, each as may be adjusted from time to time pursuant to
SECTION 11.1.

         "ISIS MINIMUM PRICE" means $7, as may be adjusted from time to time
pursuant to SECTION 11.1.

         "ISIS RESTRICTED STOCK" means all shares of Isis Common Stock issued to
Hybridon pursuant to this Master Agreement and all shares of capital stock which
may, from time to time, be issued in respect of any such shares of capital
stock, including, without limitation, all shares issued as a stock dividend, as
a result of a stock split or pursuant to any reorganization, recapitalization,
merger, consolidation or similar event.

                                       -3-
<Page>

         "ISIS TRANCHE PAYMENT" means the stock issuance to be made by Isis to
Hybridon with respect to an Isis Tranche Period or, if permitted, the cash to be
paid by Isis to Hybridon in lieu of such stock issuance.

         "ISIS TRANCHE PAYMENT DATE" means, as to a Isis Tranche Period, the
next business day following the last day of the Isis Tranche Period or if prior
to such day, the date on which the Isis Tranche Payment becomes payable pursuant
to SECTION 2.3(b).

         "ISIS TRANCHE PERIOD" means any one of the four successive six-month
periods commencing on the Effective Date.

         "LOST PROFITS" means the product of (i) the number of shares of stock
that should have been (but were not) issued to the non-breaching Party (the
"UNISSUED STOCK") on the date specified in this Master Agreement (the "REQUIRED
ISSUANCE DATE") and (ii) the excess, if any, of (a) the highest Closing Price on
any date during the period from and including the Required Issuance Date (or the
trading day immediately preceding the Required Issuance Date if the required
Issuance Date is not a trading day on the Stock Market on which the stock of the
breaching Party trades) up to the date the Unissued Stock is actually issued to
the non-breaching Party (the "ACTUAL ISSUANCE DATE"), over (b) the Closing Price
on the Actual Issuance Date (or the trading day immediately preceding the Actual
Issuance Date if the Actual Issuance Date is not a trading day on the Stock
Market on which the stock of the breaching Party trades). In the event that the
breaching Party shall have distributed any dividends in cash, stock or other
property on or after the Required Issuance Date and on or prior to the Actual
Issuance Date, or fixed a record date for the determination of stockholders
entitled to receive a distribution of any dividends in cash, stock or other
property which record date occurs on or after the Required Issuance Date and on
or prior to the Actual Issuance Date, then Lost Profits shall also include the
total dividends in cash, stock or other property which the non-breaching Party
would have been otherwise entitled to receive if the Unissued Stock had been
issued to the non-breaching Party on the Required Issuance Date.

         "MARKET PRICE" means the Average Closing Price of Isis Common Stock or
Hybridon Common Stock, as the case may be, for the 20 trading days immediately
preceding a specified date.

         "PARTY" means Hybridon or Isis and "PARTIES" means Hybridon and Isis.
As used in this Master Agreement, references to third parties do not include a
Party or its Affiliates.

         "PER SHARE TRANSACTION VALUE" means

                  (a)   in the case of Type A Change in Control Transaction,
the value, as determined in good faith by the board of directors of the Party
whose assets are being sold, of the distributions which the holder of one share
of Hybridon or Isis Common Stock, as the case may be, would be entitled to
receive (including the dilutive effect of the Hybridon or Isis Common Stock to
be issued under Section 2.2(b)(iv) or Section 2.3(b)(iv), as the case may be,
and of all

                                       -4-
<Page>

other shares of Hybridon or Isis Common Stock which may be issued upon the
conversion or exercise of securities of Hybridon or Isis, as the case
may be, the issuance of which would be dilutive in light of the amount
that will be available for distribution upon liquidation) if the Party selling
its assets were to be liquidated upon consummation of the Change in Control
Transaction, PROVIDED, HOWEVER, that in determining Per Share Transaction Value
under this subparagraph (a) no consideration shall be given to any earn-outs or
any other future payments to be determined after the consummation of the Change
in Control Transaction, except any payments of amounts held in escrow; or

                  (b)   in the case of a Type B Change in Control Transaction,

                           (i)   if the agreement of merger or other instrument
         governing the consideration to be issued provides for a cash purchase
         price exclusively, the cash purchase price that shall be paid in
         exchange for one share of Hybridon or Isis Common Stock, as the case
         may be, pursuant to the terms of the agreement of merger or other
         instrument governing the consideration to be issued;

                           (ii)   if the agreement of merger or other
         instrument governing the consideration to be issued provides for a
         fixed exchange ratio exclusively pursuant to which each share of
         Hybridon or Isis Common Stock, as the case may be, will be exchanged
         in the Change in Control Transaction solely for capital stock of the
         acquiror or other surviving entity (the acquiror or other surviving
         entity, the "Surviving Entity"), the value of the shares of capital
         stock of the Surviving Entity exchanged for one share of Hybridon or
         Isis Common Stock, as the case may be, pursuant to the terms of the
         agreement of merger or other instrument governing the consideration to
         be issued, which value shall be determined by multiplying:

                                    (A)   the average of the midpoint of the
                  high and low sale price of a share of such Surviving Entity's
                  capital stock on the Stock Market on which such capital stock
                  is traded for the 20 trading days immediately preceding the
                  date the Change in Control Transaction is consummated (or, if
                  the Surviving Entity is not traded on a Stock Market, the fair
                  market value of a share of such Surviving Entity's capital
                  stock on the date immediately preceding the date the Change in
                  Control Transaction is consummated, as determined in good
                  faith by the board of directors of the Party which is a party
                  to the Change in Control Transaction), by

                                    (B)   the number of shares of such
                  Surviving Entity's capital stock to be exchanged in the Change
                  in Control Transaction for each share of Hybridon or Isis
                  Common Stock, pursuant to the terms of the agreement of merger
                  or other instrument governing the consideration to be issued;

                           (iii)   if the agreement of merger or other
         instrument governing the consideration to be issued provides that the
         number of shares of capital stock of the Surviving Entity to be issued
         in exchange for one share of Hybridon or Isis Common

                                       -5-
<Page>

         Stock, as the case may be, shall be determined based on a fixed dollar
         amount of the Surviving Entity's capital stock, the fixed dollar value
         attributed by the parties to the Change in Control Transaction to one
         share of Hybridon or Isis Common Stock, as the case may be, pursuant
         to the terms of the agreement of merger or other instrument governing
         the consideration to be issued; or

                           (iv)   if the agreement of merger or other
         instrument governing the consideration to be issued provides that the
         consideration to be exchanged in the Change in Control Transaction for
         one share of Hybridon or Isis Common Stock, as the case may be, shall
         consist of any combination of cash, stock (including stock issued
         pursuant to a fixed exchange ratio or a fixed dollar value) or other
         property of the Surviving Entity, the value of the consideration to be
         exchanged in the Change in Control Transaction for one share of
         Hybridon or Isis Common Stock, as the case may be, as determined in
         good faith by the Board of Directors of the Party which is a party to
         the Change in Control Transaction, which determination shall reflect
         the valuation methodologies provided in clauses (i), (ii) and/or (iii)
         above to the extent that an element or elements of the consideration is
         covered by clauses (i), (ii) and/or (iii);

         PROVIDED, HOWEVER, that in determining Per Share Transaction Value
         under this subparagraph (b) no consideration shall be given to any
         earn-outs or any other future payments to be determined after the
         consummation of the Change in Control Transaction, except any payments
         of amounts held in escrow; or

                  (c)   in the case of a Type C Change in Control Transaction,
the Market Price as of the date that such Change in Control Transaction
becomes effective.

         "RESTRICTION PERIOD" shall mean ten (10) years or such lesser period as
is provided for in SECTION 8.8, in the case of Hybridon, or in SECTION 8.9, in
the case of Isis.

         "SECURITIES ACT" means the Securities Act of 1933, as amended.

         "STOCK MARKET" means the New York Stock Exchange, the American Stock
Exchange, the Nasdaq National Market, or the OTC Bulletin Board.

         "TRANSACTION DOCUMENTS" means this Master Agreement, the License
Agreement, and any other document or agreement executed in connection herewith
or therewith on the Effective Date.

                                    ARTICLE 2

           COLLABORATION AND LICENSE AGREEMENT AND OTHER CONSIDERATION

         2.1   EXECUTION OF COLLABORATION AND LICENSE AGREEMENT. Subject to
and upon the terms and conditions set forth in this Master Agreement, and in
reliance upon the respective

                                       -6-
<Page>

representations and warranties made herein by each of the Parties on the
Effective Date, each of Hybridon and Isis shall execute and deliver to the
other the Collaboration and License Agreement attached hereto as EXHIBIT A
(the "LICENSE AGREEMENT").

         2.2   ADDITIONAL HYBRIDON CONSIDERATION.

                  (a)   HYBRIDON TRANCHE PAYMENTS. In consideration for the
agreements contained in this Master Agreement, and the licenses contemplated by
the License Agreement, unless paid or issued earlier pursuant to SECTION 2.2(b),
on the next business day following the end of each Hybridon Tranche Period,
Hybridon shall issue to Isis a number of shares of Hybridon Common Stock equal
to $2,000,000 divided by the Hybridon Market Price as of the last day of such
Hybridon Tranche Period; provided however, that if such Hybridon Market Price is
greater than the Hybridon Maximum Price applicable to such Hybridon Tranche
Period then such Hybridon Market Price shall be deemed to be the Hybridon
Maximum Price applicable to such Hybridon Tranche Period for purposes of
calculating the number of shares issuable hereunder for such Hybridon Tranche
Period; and provided further, that if such Hybridon Market Price is less than
the Hybridon Minimum Price, then such Hybridon Market Price shall be deemed to
be the Hybridon Minimum Price for purposes of calculating the number of shares
issuable hereunder for such Hybridon Tranche Period.

                  (b)   ACCELERATION OF HYBRIDON TRANCHE PAYMENTS.

                           (i)   ACCELERATION EVENTS DURING FIRST HYBRIDON
         TRANCHE PERIOD. If at any time after the Effective Date the Hybridon
         Market Price as of any date on or before the last day of the first
         Hybridon Tranche Period:

                                    (A)   is greater than $5.00, then within
                  ten (10) business days of such date, Hybridon shall issue to
                  Isis 1,566,667 shares of Hybridon Common Stock less any
                  shares previously issued or then issuable to Isis pursuant to
                  SECTIONS 2.2(b)(i)(B) or (C), in lieu of all Hybridon Tranche
                  Payments, and upon such date Hybridon shall have no further
                  obligations under this SECTION 2.2 other than to issue
                  the shares of Hybridon Common Stock that are otherwise
                  issuable as of such date and as provided for under this
                  SECTION 2.2(b)(i)(A).

                                    (B)   is greater than $4.00, but not
                  greater than $5.00, then within ten (10) business days of such
                  date, Hybridon shall issue to Isis 1,166,667 shares of
                  Hybridon Common Stock less any shares previously issued or
                  then issuable to Isis pursuant to SECTION 2.2(b)(i)(C), in
                  lieu of the first and second Hybridon Tranche Payments, and
                  upon such date Hybridon shall have no further obligations
                  under SECTION 2.2 with respect to the first and second
                  Hybridon Tranche Periods, under this SECTION 2.2(b)(i)(B) or
                  under SECTION 2.2(b)(i)(C) other than to issue the shares of
                  Hybridon Common Stock that are otherwise issuable as of such
                  date and as provided for under this SECTION 2.2(b)(i)(B).

                                       -7-
<Page>

                                    (C)   is greater than $3.00, but not
                  greater than $4.00, then within ten (10) business days of such
                  date, Hybridon shall issue to Isis 666,667 shares of Hybridon
                  Common Stock in lieu of the first Hybridon Tranche Payment and
                  upon such date Hybridon shall have no further obligations
                  under SECTION 2.2 with respect to the first Hybridon Tranche
                  Period or under this SECTION 2.2(b)(i)(C) other than to issue
                  the shares of Hybridon Common Stock provided for under this
                  SECTION 2.2(b)(i)(C).

                           (ii)   ACCELERATION EVENTS DURING SECOND HYBRIDON
         TRANCHE PERIOD. If the Hybridon Market Price as of any date which ends
         after the last day of the first Hybridon Tranche Period and on or
         before the last day of the second Hybridon Tranche Period:

                                    (A)   is greater than $5.00, then within
                  ten (10) business days of such date, Hybridon shall issue to
                  Isis 900,000 shares (or 400,000 shares if shares have been
                  previously issued or are then issuable to Isis pursuant to
                  SECTION 2.2(b)(i)(B)) of Hybridon Common Stock less any shares
                  previously issued or then issuable to Isis pursuant to
                  SECTION 2.2(b)(ii)(B), in lieu of all remaining Hybridon
                  Tranche Payments, and upon such date Hybridon shall have no
                  further obligations under this SECTION 2.2 other than to issue
                  the shares of Hybridon Common Stock that are otherwise
                  issuable as of such date and as provided for under this
                  SECTION 2.2(b)(ii)(A).

                                    (B)   is greater than $4.00, but not
                  greater than $5.00, and no shares have been previously issued
                  or are then issuable to Isis pursuant to SECTION 2.2(b)(i)(B),
                  then within ten (10) business days of such date, Hybridon
                  shall issue to Isis 500,000 shares of Hybridon Common Stock in
                  lieu of the second Hybridon Tranche Payment, and upon such
                  date Hybridon shall have no further obligations under
                  SECTION 2.2 with respect to the second Hybridon Tranche
                  Period or under this SECTION 2.2(b)(ii)(B) other than to issue
                  the shares of Hybridon Common Stock provided for under this
                  SECTION 2.2(b)(ii)(B).

                                    (C)   is less than $1.00, then within
                  ten (10) business days of such date, Hybridon shall, at its
                  option, either: (x) issue to Isis 4,000,000 shares (or
                  2,000,000 shares if shares have been previously issued or are
                  then issuable to Isis pursuant to either SECTION 2.2(b)(i)(B)
                  or SECTION 2.2(b)(ii)(B)) of Hybridon Common Stock or (y) pay
                  to Isis $4,000,000 (or $2,000,000 if shares have been
                  previously issued or are then issuable to Isis pursuant to
                  either SECTION 2.2(b)(i)(B) or 2.2(b)(ii)(B)), in lieu of all
                  remaining Hybridon Tranche Payments, and upon such date
                  Hybridon shall have no further obligations under this SECTION
                  2.2 other than to issue the shares of Hybridon Common Stock
                  that are otherwise issuable as of such date and to issue the
                  shares of Hybridon Common Stock or pay the cash provided for
                  under this SECTION 2.2(b)(ii)(C).

                                       -8-
<Page>

                           (iii)   ACCELERATION EVENTS DURING THIRD HYBRIDON
         TRANCHE PERIOD. If the the Hybridon Market Price as of any date which
         ends after the last day of the second Hybridon Tranche Period and on or
         before the last day of the third Hybridon Tranche Period:

                                    (A)   is greater than $5.00, then within
                  ten (10) business days of such date, Hybridon shall issue to
                  Isis 400,000 shares of Hybridon Common Stock in lieu of all
                  remaining Hybridon Tranche Payments, and upon such date
                  Hybridon shall have no further obligations under this SECTION
                  2.2 other than to issue the shares of Hybridon Common Stock
                  that are otherwise issuable as of such date and as provided
                  for under this SECTION 2.2(b)(iii)(A).

                                    (B)   is less than $1.00, then within
                  ten (10) business days of such date, Hybridon shall, at its
                  option, either (x) issue to Isis 2,000,000 shares of Hybridon
                  Common Stock or (y) pay to Isis $2,000,000, in lieu of all
                  remaining Hybridon Tranche Payments, and upon such date
                  Hybridon shall have no further obligations under this SECTION
                  2.2 other than to issue the shares of Hybridon Common Stock
                  that are otherwise issuable as of such date and to issue the
                  shares of Hybridon Common Stock or pay the cash provided for
                  under this SECTION 2.2(b)(iii)(B).

                           (iv)   ACCELERATION FOR CHANGE IN CONTROL
         TRANSACTIONS. In the event of a Type A, Type B or Type C Change in
         Control Transaction that will be consummated prior to the third
         Hybridon Tranche Payment Date (such consummation date, the "HYBRIDON
         CLOSING DATE"), then immediately prior to such Hybridon Closing Date
         (or in the event of a Type C Change in Control Transaction, within five
         business days of such Hybridon Closing Date), in lieu of ALL OTHER
         remaining payments or share issuance obligations under this SECTION 2.2
         (other than those Hybridon Tranche Payments for which the applicable
         Hybridon Tranche Payment Date is prior to the Hybridon Closing Date),
         Hybridon shall issue to Isis such number of shares of Hybridon Common
         Stock as is equal to the following:

                                    $2,000,000 DIVIDED BY the Per Share
                                    Transaction Value of such Change in Control
                                    Transaction, PROVIDED, HOWEVER, that if the
                                    Per Share Transaction Value is less than the
                                    Hybridon Minimum Price, then the $2,000,000
                                    shall instead be DIVIDED BY the Hybridon
                                    Minimum Price, and, PROVIDED FURTHER, that
                                    if the Per Share Transaction Value is
                                    greater than the Hybridon Maximum Price
                                    applicable to the third Hybridon Tranche
                                    Period, then the $2,000,000 shall instead be
                                    DIVIDED BY such Hybridon Maximum Price.

                                       -9-
<Page>

                           PLUS, IF AND ONLY IF the Hybridon Closing Date is
                           prior to the second Hybridon Tranche Payment Date:

                                    an additional $2,000,000 DIVIDED BY the Per
                                    Share Transaction Value of such Change in
                                    Control Transaction, PROVIDED, HOWEVER, that
                                    if the Per Share Transaction Value is less
                                    than the Hybridon Minimum Price, then the
                                    $2,000,000 shall instead be DIVIDED BY the
                                    Hybridon Minimum Price and PROVIDED FURTHER
                                    that if the Per Share Transaction Value is
                                    greater than the Hybridon Maximum Price
                                    applicable to the second Hybridon Tranche
                                    Period, then the $2,000,000 shall instead be
                                    DIVIDED BY such Hybridon Maximum Price.

                           PLUS, IF AND ONLY IF the Hybridon Closing Date will
                           be or is prior to the first Hybridon Tranche Payment
                           Date:

                                    an additional $2,000,000 DIVIDED BY the Per
                                    Share Transaction Value of such Change in
                                    Control Transaction, PROVIDED, HOWEVER, that
                                    if the Per Share Transaction Value is less
                                    than the Hybridon Minimum Price, then the
                                    $2,000,000 shall instead be DIVIDED BY the
                                    Hybridon Minimum Price and PROVIDED FURTHER
                                    that if the Per Share Transaction Value is
                                    greater than the Hybridon Maximum Price
                                    applicable to the first Hybridon Tranche
                                    Period, then the $2,000,000 shall instead be
                                    DIVIDED BY that Hybridon Maximum Price.

                           (v)   TYPE D CHANGE IN CONTROL TRANSACTION. On
         each Hybridon Tranche Payment Date from and after the occurrence of a
         Type D Change in Control Transaction, Hybridon shall pay to Isis
         $2,000,000 in cash in lieu of the shares of Hybridon Common Stock that
         Hybridon would otherwise be required to issue to Isis on such Hybridon
         Tranche Payment Date.

                           (vi)   Notwithstanding the other provisions of
         this SECTION 2.2(b), if Hybridon would be obligated under this Master
         Agreement to issue a number of shares of Hybridon Common Stock as would
         subject such issuance to the approval of Hybridon's stockholders under
         the rules and regulations of any Stock Market on which the Hybridon
         Common Stock is then traded, Hybridon may elect to not seek or obtain
         such approval and instead may issue such lesser number of shares as
         would not require such approval and may satisfy the balance of its
         obligation by a cash payment.

                  (c)   SUCCESSOR ENTITIES. In the event that Hybridon
consummates a merger, consolidation, reorganization, share exchange or business
combination which does not qualify as a Change in Control Transaction and
Hybridon is not the surviving corporation or entity following the consummation
of such merger, consolidation, reorganization, share exchange or

                                       -10-
<Page>

business combination, then Hybridon shall cause such surviving corporation or
entity to comply with and be bound by and subject to (i) the provisions of
SECTIONS 2.2(a) and (b), including requiring the surviving corporation or
entity to issue common stock of such surviving corporation or entity to Isis,
and (ii) the registration obligations and other provisions of this Master
Agreement related to the stock so issued by such surviving corporation or
entity, to the same extent as such provisions were applicable to Hybridon
prior to the consummation of such merger, consolidation, reorganization,
share exchange or business combination.

         2.3   ADDITIONAL ISIS CONSIDERATION.

                  (a)   INITIAL CASH PAYMENT AND ISIS TRANCHE PAYMENTS. In
consideration for the agreements contained in this Master Agreement and the
licenses contemplated by the License Agreement, Isis shall: (i) unconditionally,
and irrespective of any breach of this Master Agreement or the License Agreement
by Hybridon, on or prior to 5:00 p.m. (Boston time), on Friday, June 1, 2001,
pay to Hybridon by wire transfer in immediately available funds, the sum of
Fifteen Million Dollars ($15,000,000), and (ii) unless paid or issued earlier
pursuant to SECTION 2.3(b), on the next business day following the end of each
Isis Tranche Period, issue to Hybridon such number of shares of Isis Common
Stock equal to $5,000,000 ($4,500,000 in the case of the fourth Isis Tranche
Period), divided by the Isis Market Price as of the last day of such Isis
Tranche Period; provided, however, that if such Isis Market Price is greater
than the Isis Maximum Price applicable to such Isis Tranche Period, then such
Isis Market Price shall be deemed to be the Isis Maximum Price applicable to
such Isis Tranche Period for purposes of calculating the number of shares
issuable hereunder for such Isis Tranche Period; and provided, further, that if
such Isis Market Price is less than the Isis Minimum Price applicable to such
Isis Tranche Period, then such Isis Market Price shall be deemed to be the Isis
Minimum Price applicable to such Isis Tranche Period for purposes of calculating
the number of shares issuable hereunder for such Isis Tranche Period. The
Parties acknowledge and agree that all payments to be made to Hybridon by Isis
pursuant to this Master Agreement will allow Hybridon to recoup the expenditures
incurred by Hybridon in the research and development of antisense technology
undertaken by Hybridon.

                  (b)   ACCELERATION OF ISIS TRANCHE PAYMENTS

                           (i)   ACCELERATION EVENTS DURING FIRST ISIS
         TRANCHE PERIOD. If at any time after the Effective Date the Isis Market
         Price as of any date which ends on or before the last day of the first
         Isis Tranche Period:

                                    (A)   is greater than $26.00, then
                  within ten (10) business days of such date, Isis shall issue
                  to Hybridon 1,030,220 shares of Isis Common Stock less any
                  shares previously issued or then issuable to Hybridon pursuant
                  to SECTION 2.3(b)(i)(B) or SECTION 2.3(b)(i)(C), in lieu of
                  all Isis Tranche Payments, and upon such date Isis shall have
                  no further obligations under this SECTION 2.3 other than to

                                       -11-
<Page>

                  issue the shares of Isis Common Stock that are otherwise
                  issuable on such date and as provided for under this
                  SECTION 2.3(b)(i)(A).

                                    (B)   is greater than $20.00, but not
                  greater than $26.00, then within ten (10) business days of
                  such date, Isis shall issue to Hybridon 857,143 shares of Isis
                  Common Stock less any shares previously issued or then
                  issuable to Hybridon pursuant to SECTION 2.3(b)(i)(C), in lieu
                  of the first, second and third Isis Tranche Payments, and upon
                  such date Isis shall have no further obligations under
                  SECTION 2.3 with respect to the first, second and third
                  Isis Tranche Periods, under this SECTION 2.3(b)(i)(B) or
                  under SECTION 2.3(b)(i)(C) other than to issue the shares of
                  Isis Common Stock that are otherwise issuable on such date
                  and as provided for under this SECTION 2.3(b)(i)(B).

                                    (C)   is greater than $14.00, but not
                  greater than $20.00, then within ten (10) business days of
                  such date, Isis shall issue to Hybridon 357,143 shares of Isis
                  Common Stock in lieu of the first Isis Tranche Payment, and
                  upon such date Isis shall have no further obligations under
                  SECTION 2.3 with respect to the first Isis Tranche Period or
                  under this SECTION 2.3(b)(i)(C) other than to issue the
                  shares of Isis Common Stock provided for under this
                  SECTION 2.3(b)(i)(C).

                                    (D)   is less than $3.00, then within
                  ten (10) business days of such date, Isis shall, at its option
                  either: (x) issue to Hybridon 2,785,714 shares less any shares
                  previously issued or are then issuable to Hybridon pursuant to
                  SECTION 2.3(b)(i)(B) or SECTION 2.3(b)(i)(C), or (y) pay to
                  Hybridon $19,500,000 (or $4,500,000 if shares have been
                  previously issued or are then issuable to Hybridon pursuant to
                  SECTION 2.3(b)(i)(B) or $14,500,000 if shares have been
                  previously issued or are then issuable to Hybridon pursuant to
                  SECTION 2.3(b)(i)(C)), in lieu of all remaining Isis Tranche
                  Payments, and upon such date Isis shall have no further
                  obligations under this SECTION 2.3 other than to issue the
                  shares of Isis Common Stock that are otherwise issuable on
                  such date and to issue the shares of Isis Common Stock or pay
                  the cash provided for under this SECTION 2.3(b)(i)(D).

                           (ii)   ACCELERATION EVENTS DURING SECOND ISIS
         TRANCHE PERIOD. If the Isis Market Price as of any date which ends
         after the last day of the first Isis Tranche Period and on or before
         the last day of the second Isis Tranche Period:

                                    (A)   is greater than $26.00, then within
                  ten (10) business days of such date, Isis shall issue
                  to Hybridon 673,077 shares (or 173,077 shares in the event
                  shares have been previously issued or are then issuable
                  to Hybridon pursuant to SECTION 2.3(b)(i)(B) or
                  SECTION 2.3(b)(ii)(B)) of Isis Common Stock in lieu of
                  all remaining Isis Tranche Payments, and upon such date
                  Isis shall have no further obligations under this SECTION 2.3
                  other than to issue the shares of Isis

                                       -12-
<Page>

                  Common Stock that are otherwise issuable on such date and as
                  provided for under this SECTION 2.3(b)(ii)(A).

                                    (B)   is greater than $20.00, but less
                  than $26.00, and no shares have been previously issued or are
                  then issuable to Hybridon pursuant to SECTION 2.3(b)(i)(B),
                  then within ten (10) business days of such date, Isis shall
                  issue to Hybridon 500,000 shares of Isis Common Stock in lieu
                  of the second and third Isis Tranche Payments, and upon such
                  date Isis shall have no further obligations under SECTION 2.3
                  with respect to the second and third Isis Tranche Periods
                  or under this SECTION 2.3(b)(ii)(B) other than to issue
                  shares of Isis Common Stock provided for under this
                  SECTION 2.3(b)(ii)(B).

                                    (C)   is less than $3.00, then within
                  ten (10) business days of such date, Isis shall, at its
                  option, either: (x) issue to Hybridon 2,071,429 shares (or
                  642,857 shares if shares have been previously issued
                  or are then issuable to Hybridon pursuant to either
                  SECTION 2.3(b)(i)(B) or SECTION 2.3(b)(ii)(B)) of Isis
                  Common Stock or (y) pay to Hybridon $14,500,000 (or
                  $4,500,000 if shares have been previously issued or are
                  then issuable to Hybridon pursuant to either
                  SECTION 2.3(b)(i)(B) or SECTION 2.3(b)(ii)(B)), in lieu
                  of all remaining Isis Tranche Payments, and upon such
                  date Isis shall have no further obligations under this
                  SECTION 2.3 other than to issue the shares of Isis Common
                  Stock that are otherwise issuable on such date and to
                  issue the shares of Isis Common Stock or pay the cash
                  provided for under this SECTION 2.3(b)(ii)(C).

                           (iii)   ACCELERATION EVENTS DURING THIRD ISIS
         TRANCHE PERIOD. If the Isis Market Price as of any date which ends
         after the last day of the second Isis Tranche Period and on or before
         the last day of the third Isis Tranche Period:

                                    (A)   is greater than $26.00, then
                  within ten (10) business days of such date, Isis shall issue
                  to Hybridon 423,077 shares (or 173,077 shares if shares have
                  been previously issued or are then issuable to Hybridon
                  pursuant to SECTION 2.3(b)(i)(B), SECTION 2.3(b)(ii)(B) or
                  SECTION 2.3(b)(iii)(B)) of Isis Common Stock, in lieu of all
                  remaining Isis Tranche Payments, and upon such date Isis shall
                  have no further obligations under this SECTION 2.3 other than
                  to issue the shares of Isis Common Stock that are otherwise
                  issuable on such date and as provided for under this
                  SECTION 2.3(b)(iii)(A).

                                    (B)   is greater than $20.00, but not
                  greater than $26.00, and no shares have been previously
                  issued or are then issuable to Hybridon pursuant to
                  SECTION 2.3(b)(i)(B) or SECTION 2.3(b)(ii)(B), then within
                  ten (10) business days of such date, Isis shall issue to
                  Hybridon 250,000 shares of Isis Common Stock in lieu of the
                  third Isis Tranche Payments, and upon such date Isis shall
                  have no further obligations under SECTION 2.3 with
                  respect to the third Isis Tranche Period

                                       -13-
<Page>

                  or under this SECTION 2.3(b)(iii)(B) other than to issue
                  the shares of Isis Common Stock provided for under this
                  SECTION 2.3(b)(iii)(B).

                                    (C)   is less than $7.00, then within
                  ten (10) business days of such date, Isis shall, at its
                  option, either: (x) issue to Hybridon 1,357,143 shares (or
                  642,857 shares if shares have been previously issued or are
                  then issuable to Hybridon pursuant to SECTION 2.3(b)(i)(B),
                  SECTION 2.3(b)(ii)(B) or SECTION 2.3(b)(iii)(B)) of Isis
                  Common Stock or (y) pay to Hybridon $9,500,000 (or $4,500,000
                  if shares have been previously issued or are then
                  issuable to Hybridon pursuant to SECTION 2.3(b)(i)(B),
                  SECTION 2.3(b)(ii)(B) or SECTION 2.3(b)(iii)(B)), in lieu of
                  all remaining Isis Tranche Payments, and upon such date Isis
                  shall have no further obligations under this SECTION 2.3 other
                  than to issue the shares of Isis Common Stock that are
                  otherwise issuable on such date and to issue the shares of
                  Isis Common Stock or pay the cash provided for under this
                  SECTION 2.3(b)(iii)(C).

                           (iv)   ACCELERATION EVENTS DURING FOURTH ISIS
         TRANCHE PERIOD. If the Isis Market Price as of any date which ends
         after the last day of the third Isis Tranche Period and on or before
         the last day of the fourth Isis Tranche Period:

                                    (A)   is greater than $26.00, then
                  within ten (10) business days of such date, Isis shall issue
                  to Hybridon 173,077 shares of Isis Common Stock in lieu of all
                  remaining Isis Tranche Payments, and upon such date Isis shall
                  have no further obligations under this SECTION 2.3 other than
                  to issue the share of Isis Common Stock that are otherwise
                  issuable on such date and as provided for under this SECTION
                  2.3(b)(iv)(A).

                                    (B)   is less than $7.00, then within
                  ten (10) business days of such date, Isis shall, at its option
                  either: (x) issue to Hybridon 642,857 shares of Isis Common
                  Stock or (y) pay Hybridon $4,500,000, in lieu of all remaining
                  Isis Tranche Payments, and upon such date Isis shall have no
                  further obligations under this SECTION 2.3 other than to issue
                  the shares of Isis Common Stock that are otherwise issuable on
                  such date and to issue the shares of Isis Common Stock or pay
                  the cash provided for under this SECTION 2.3(b)(iv)(B).

                           (v)   ACCELERATION FOR CHANGE IN CONTROL
         TRANSACTIONS. In the event of a Type A, Type B or Type C Change in
         Control Transaction that will be consummated prior to the fourth Isis
         Tranche Payment Date (such consummation date, the "ISIS CLOSING DATE"),
         then immediately prior to such Isis Closing Date (or in the event of a
         Type C Change in Control Transaction, within five business days of such
         Isis Closing Date), in lieu of ALL OTHER remaining payments or share
         issuance obligations under this SECTION 2.3 (other than those Isis
         Tranche Payments for which the applicable Isis Tranche Payment Date is
         prior to the Isis Closing Date), Isis shall issue to Hybridon such
         number of shares of Isis Common Stock as is equal to the following:

                                       -14-
<Page>

                                    $4,500,000 DIVIDED BY the Per Share
                                    Transaction Value, PROVIDED, HOWEVER, that
                                    if the Per Share Transaction Value is less
                                    than the Isis Minimum Price applicable to
                                    the fourth Isis Tranche Period, then the
                                    $4,500,000 shall instead be DIVIDED BY the
                                    Isis Minimum Price applicable to the fourth
                                    Isis Tranche Period, and, PROVIDED FURTHER,
                                    that if the Per Share Transaction Value is
                                    greater than the Isis Maximum Price
                                    applicable to the fourth such Isis Tranche
                                    Period, then the $4,500,000 shall instead be
                                    DIVIDED BY such Isis Maximum Price.

                           PLUS, IF AND ONLY IF the Isis Closing Date will be or
                           is prior to the third Isis Tranche Payment Date:

                                    an additional $5,000,000 DIVIDED BY the Per
                                    Share Transaction Value, PROVIDED, HOWEVER,
                                    that if Per Share Transaction Price is less
                                    than the Isis Minimum Price applicable to
                                    the third Isis Tranche Period, then the
                                    $5,000,000 shall instead be DIVIDED BY the
                                    Isis Minimum Price applicable to the third
                                    Isis Tranche Period, and, PROVIDED FURTHER,
                                    that if the Per Share Transaction Value is
                                    greater than the Isis Maximum Price
                                    applicable to the third Isis Tranche Period,
                                    then the $5,000,000 shall instead be DIVIDED
                                    BY such Isis Maximum Price.

                           PLUS, IF AND ONLY IF the Isis Closing Date will be or
                           is prior to the second Isis Tranche Payment Date:

                                    an additional $5,000,000 DIVIDED BY the Per
                                    Share Transaction Price, PROVIDED, HOWEVER,
                                    that if the Per Share Transaction Price is
                                    less than the Isis Minimum Price applicable
                                    to the second Isis Tranche Period, then the
                                    $5,000,000 shall instead be DIVIDED BY the
                                    Isis Minimum Price applicable to the second
                                    Isis Tranche Period, and, PROVIDED FURTHER,
                                    that if the Per Share Transaction Value is
                                    greater than the Isis Maximum Price
                                    applicable to the second Isis Tranche
                                    Period, then the $5,000,000 shall instead be
                                    DIVIDED BY such Isis Maximum Price.

                           PLUS, IF AND ONLY IF the Isis Closing Date will be or
                           is prior to the first Isis Tranche Payment Date:

                                    an additional $5,000,000 DIVIDED BY the Per
                                    Share Transaction Price, PROVIDED, HOWEVER,
                                    that if Per Share Transaction Price is less
                                    than the Isis Minimum Price applicable to
                                    the first Isis Tranche Period, then the
                                    $5,000,000 shall instead be DIVIDED BY the
                                    Isis Minimum Price applicable to the first
                                    Isis Tranche Period, and,

                                       -15-
<Page>

                                    FURTHER PROVIDED, that if the Per Share
                                    Transaction Value is greater than the Isis
                                    Maximum Price applicable to the first Isis
                                    Tranche Period, then the $5,000,000 shall
                                    instead be DIVIDED BY such Isis Maximum
                                    Price.

                           (vi)   TYPE D CHANGE IN CONTROL TRANSACTION. On
         each Isis Tranche Payment Date from and after the occurrence of a Type
         D Change in Control Transaction, Isis shall pay to Hybridon $5,000,000
         ($4,500,000 in the case of the fourth Isis Tranche Payment Date) in
         lieu of the shares of Isis Common Stock that Isis would otherwise be
         required to issue to Hybridon on such Isis Tranche Payment Date.

                           (vii)   Notwithstanding the other provisions of
         this SECTION 2.3(b), if Isis would be obligated under this Master
         Agreement to issue a number of shares of Isis Common Stock as would
         subject such issuance to the approval of Isis's stockholders under the
         rules and regulations of the Stock Market on which the Isis Common
         Stock is then traded, Isis may elect to not seek or obtain such
         approval and instead may issue such lesser number of shares as would
         not require such approval and may satisfy the balance of its obligation
         by a cash payment.

                  (c)   SUCCESSOR ENTITIES. In the event that Isis
consummates a merger, consolidation, reorganization, share exchange or business
combination which does not qualify as a Change in Control Transaction and Isis
is not the surviving corporation or entity following such merger, consolidation,
reorganization, share exchange or business combination, then Isis shall cause
such surviving corporation or entity to comply with and be bound by and subject
to (i) the provisions of SECTIONS 2.3(a) and (b), including requiring the
surviving corporation or entity to issue common stock of such surviving
corporation or entity to Hybridon, and (ii) the registration obligations and
other provisions of this Master Agreement related to the stock so issued by Isis
or such surviving corporation or entity, all to the same extent as such
provisions were applicable to Isis prior to the merger, consolidation,
reorganization, share exchange or business combination.

         2.4    RESTRICTIVE LEGEND. Each certificate for the shares of
Hybridon Common Stock or Isis Common Stock, whichever is applicable, issuable
under this ARTICLE 2 shall be stamped or otherwise imprinted with legends in
substantially the following form:

                  "THE SECURITIES REPRESENTED BY THIS CERTIFICATE HAVE BEEN
         ACQUIRED FOR INVESTMENT AND HAVE NOT BEEN REGISTERED UNDER THE
         SECURITIES ACT OF 1933. NEITHER THESE SECURITIES NOR ANY INTEREST
         THEREIN MAY BE SOLD, PLEDGED, HYPOTHECATED, TRANSFERRED OR OTHERWISE
         DISPOSED OF IN THE ABSENCE OF SUCH REGISTRATION AND IN COMPLIANCE WITH
         APPLICABLE STATE SECURITIES LAWS OR THE DELIVERY OF AN OPINION
         REASONABLY SATISFACTORY TO THE COMPANY STATING THAT THERE IS A VALID
         EXEMPTION THEREFROM

                                       -16-
<Page>

         UNDER SUCH ACT AND THE RULES AND REGULATIONS THEREUNDER AND SUCH STATE
         SECURITIES LAWS."

                                    ARTICLE 3

                   REPRESENTATIONS AND WARRANTIES OF HYBRIDON

         As an inducement to Isis to enter into and perform its obligations
under this Master Agreement and License Agreement, Hybridon hereby represents
and warrants to Isis as of the date hereof as follows:

         3.1   ORGANIZATION AND GOOD STANDING; POWER. Hybridon is a
corporation duly organized, validly existing and in good standing under the
laws of the State of Delaware and has full power and authority to execute and
deliver this Master Agreement and the other Transaction Documents to which it
is a party, to perform its obligations hereunder and thereunder and to
consummate the transactions contemplated hereby and thereby.

         3.2   AUTHORIZATION. The execution and delivery by Hybridon of
this Master Agreement and the other Transaction Documents to which it is a
party, the performance by Hybridon of its obligations hereunder and thereunder,
and the consummation by Hybridon of the transactions contemplated hereby and
thereby have been duly authorized by all necessary corporate action on the part
of Hybridon. This Master Agreement and the other Transaction Documents have been
duly executed and delivered by Hybridon and constitute the legal, valid and
binding obligations of Hybridon, enforceable against Hybridon in accordance with
their respective terms, except (a) that enforcement may be limited by (i)
applicable bankruptcy, insolvency, reorganization, arrangement, moratorium or
other similar laws affecting creditors' rights, and (ii) general equity
principles and limitations on the availability of equitable relief, including
specific performance, and (b) that any rights to indemnity or contribution
hereunder or thereunder may be limited by state and federal securities laws and
by public policy considerations.

         3.3   NO VIOLATION. The execution, delivery and performance by
Hybridon of this Master Agreement and the other Transaction Documents to which
it is a party and the consummation by Hybridon of the transactions contemplated
hereby and thereby do not and will not:

                  (a)   conflict with, result in the breach, modification,
termination or violation of, or loss of any benefit under, constitute a default
under, accelerate the performance required by, result in or give rise to a right
to amend or modify the terms of, result in the creation of any lien upon any
assets or properties, or in any manner release any party thereto from any
obligation under, any mortgage, note, bond, indenture, contract, agreement,
lease, license or other instrument or obligation to which Hybridon is a party or
by which Hybridon's assets or property are bound;

                                       -17-
<Page>

                  (b)   conflict with, violate or result in any loss of
benefit under, any permit, concession, franchise, order, judgment, writ,
injunction, regulation, statute or decree; to which it is subject, or

                  (c)   conflict with or violate any provision of the
Certificate of Incorporation or Bylaws, each as heretofore amended, of Hybridon,

         except where, in the case of (a) and (b) above, such event would not,
individually or in the aggregate with other such events, adversely affect the
rights of Isis under this Master Agreement and the Transaction Documents or
subject Isis to any material liability (contingent or otherwise).

         3.4   NO CONSENT REQUIRED. No consent, approval, order or
authorization of, or declaration, filing or registration with, any person,
entity or governmental authority is required to be made or obtained by Hybridon
in connection with the authorization, execution, delivery or performance of this
Master Agreement, the other Transaction Documents to which it is a party or the
transactions contemplated hereby or thereby, except for the filing of
registration statements and other reports with the Commission, filings related
to compliance with the Securities Act, the Exchange Act and state securities
laws and any filings with the Stock Market on which the Hybridon Common Stock is
traded.

         3.5   ISSUANCE. The shares of Hybridon Restricted Stock to be
delivered by Hybridon hereunder have been duly authorized and, when issued and
delivered in accordance with the terms of this Master Agreement, will be validly
issued, fully paid and non-assessable and will not be issued in violation of any
preemptive rights, rights of first refusal or similar rights.

         3.6   LITIGATION. There is no litigation or governmental or
administrative proceeding or investigation pending or, to the knowledge of
Hybridon, threatened in writing against Hybridon or its Affiliates which,
individually or in the aggregate, reasonably would be expected to have a
material adverse effect on the Hybridon Intellectual Property or which would
prevent or hinder Hybridon from performing its obligations under this Master
Agreement or the other Transaction Documents to which it is a party.

         3.7   INVESTMENT REPRESENTATIONS.

                  (a)   Hybridon is capable of evaluating the merits and
risks of an investment in Isis Restricted Stock. Hybridon has not been formed
solely for the purpose of entering into the transactions contemplated in this
Master Agreement and is acquiring the Isis Restricted Stock for investment for
its own account, not as a nominee or agent, and not with the view to, or for
resale, distribution or fractionalization thereof (except in connection with a
registered offering), in whole or in part, and no other person has a direct or
indirect interest, beneficial or otherwise in the Isis Restricted Stock, except
in compliance with securities laws.

                                       -18-
<Page>

                  (b)   Hybridon acknowledges its understanding that the
private placement and sale to Hybridon of the Isis Restricted Stock to it is
exempt from registration under the Securities Act by virtue of the provisions of
Regulation D. In furtherance thereof, Hybridon represents and warrants that it
is an "accredited investor" as that term is defined in Regulation D.

                  (c)   Hybridon agrees that it shall not sell or otherwise
transfer any of the Isis Restricted Stock without registration under the
Securities Act unless it shall deliver to Isis an opinion of counsel reasonably
satisfactory to Isis that an exemption from registration is available. Hybridon
fully understands and agrees that it must bear the total economic risk of its
purchase of Isis Restricted Stock for an indefinite period of time because,
among other reasons, the Isis Restricted Stock will not have been registered
under the Securities Act or under the securities laws of any applicable state or
other jurisdiction and, therefore, cannot be resold, pledged, assigned or
otherwise disposed of unless subsequently registered under the Securities Act
and under applicable state securities laws or unless an exemption from such
registration is available. Hybridon understands that Isis is under no obligation
to register the Isis Restricted Stock on its behalf with the exception of
certain registration rights as set forth herein. Hybridon understands the lack
of liquidity and the restrictions on transfer on the Isis Restricted Stock and
that the acquisition of Isis Restricted Stock is suitable only for a person or
entity of adequate financial means that has no need for liquidity of its
investment and that can afford a total loss of its investment.

         3.8   SEC FILINGS. Except for the filing of its Annual Report on
Form 10-K for the year ended December 31, 1999, which was not timely filed,
since January 1, 1998, Hybridon has filed with the Commission all forms,
reports, schedules, statements, exhibits and other documents (collectively, the
"SEC FILINGS") required to be filed by Hybridon pursuant to Section 13, 14 or
15(d) of the Exchange Act on or before the date required to be filed with the
Commission. At the time filed, Hybridon's SEC Filings, including without
limitation, any financial statements, exhibits and schedules included therein or
documents incorporated therein by reference, to Hybridon's knowledge, (i) did
not contain any untrue statement of a material fact or omit to state a material
fact required to be stated therein or necessary in order to make the statements
therein, in light of the circumstances under which they were made, not
misleading and (ii) complied in all material respects with the applicable
requirements of the Securities Act or the Exchange Act, as the case may be.

         3.9   BROKERS OR FINDERS. There have been no investment bankers,
brokers or finders used by Hybridon in connection with the transactions
contemplated by the Transactions Documents and no such persons or entities are
entitled to a fee or compensation in respect thereof.

                                       -19-
<Page>

                                    ARTICLE 4

                     REPRESENTATIONS AND WARRANTIES OF ISIS

         As an inducement to Hybridon to enter into and perform its obligations
under this Master Agreement and the License Agreement, Isis hereby represents
and warrants to Hybridon as of the date hereof as follows:

         4.1   ORGANIZATION AND GOOD STANDING; POWER. Isis is a corporation
duly organized, validly existing and in good standing under the laws of the
State of Delaware and has full power and authority to execute and deliver this
Master Agreement and the other Transaction Documents to which it is a party, to
perform its obligations hereunder and thereunder and to consummate the
transactions contemplated hereby and thereby.

         4.2   AUTHORIZATION. The execution and delivery by Isis of this
Master Agreement and the other Transaction Documents to which it is a party, the
performance by Isis of its obligations hereunder and thereunder, and the
consummation by Isis of the transactions contemplated hereby and thereby have
been duly authorized by all necessary corporate action on the part of Isis. This
Master Agreement and the other Transaction Documents have been duly executed and
delivered by Isis and constitute the legal, valid and binding obligations of
Isis, enforceable against Isis in accordance with their respective terms, except
(a) that enforcement may be limited by (i) applicable bankruptcy, insolvency,
reorganization, arrangement, moratorium or other similar laws affecting
creditors' rights, and (ii) general equity principles and limitations on the
availability of equitable relief, including specific performance, and (b) that
any rights to indemnity or contribution hereunder or thereunder may be limited
by state and federal securities laws and by public policy considerations.

         4.3   NO VIOLATION. The execution, delivery and performance by
Isis of this Master Agreement and the other Transaction Documents to which it is
a party and the consummation by Isis of the transactions contemplated hereby and
thereby do not and will not:

                  (a)   conflict with, result in the breach, modification,
termination or violation of, or loss of any benefit under, constitute a default
under, accelerate the performance required by, result in or give rise to a right
to amend or modify the terms of, result in the creation of any lien upon any
assets or properties, or in any manner release any party thereto from any
obligation under, any material mortgage, note, bond, indenture, contract,
agreement, lease, license or other instrument or obligation to which Isis is a
party or Isis's assets or property are bound;

                  (b)   conflict with, violate or result in any loss of
benefit under, any permit, concession, franchise, order, judgment, writ,
injunction, regulation, statute or decree to which it is subject; or

                  (c)   conflict with or violate any provision of the
Certificate of Incorporation or Bylaws, each as heretofore amended, of Isis,

                                       -20-
<Page>

         except where, in the case of (a) and (b) above, such event would not,
individually or in the aggregate with other such events, adversely affect the
rights of Hybridon under this Master Agreement and the other Transaction
Documents or subject Hybridon to any material liability (contingent or
otherwise).

         4.4   NO CONSENT REQUIRED. No consent, approval, order or
authorization of, or declaration, filing or registration with, any person,
entity or governmental authority is required to be made or obtained by Isis in
connection with the authorization, execution, delivery or performance of this
Master Agreement, the other Transaction Documents to which it is a party or the
transactions contemplated hereby or thereby, except for the filing of
registration statements and other reports with the Commission, filings related
to compliance with the Securities Act, the Exchange Act and state securities
laws and any filings with the Stock Market on which the Isis Common Stock is
listed.

         4.5   ISSUANCE. The shares of Isis Restricted Stock to be
delivered by Isis hereunder have been duly authorized and, when issued and
delivered in accordance with the terms of this Master Agreement, will be validly
issued, fully paid and non-assessable and will not be issued in violation of any
preemptive rights, rights of first refusal or similar rights.

         4.6   LITIGATION. There is no litigation or governmental or
administrative proceeding or investigation pending or, to the knowledge of the
Isis, threatened in writing against Isis or its Affiliates which, individually
or in the aggregate, reasonably would be expected to have a material adverse
effect on the Isis Intellectual Property or which would prevent or hinder Isis
from performing its obligations under this Master Agreement or the other
Transaction Documents to which it is a party.

         4.7   INVESTMENT REPRESENTATIONS.

                  (a)   Isis is capable of evaluating the merits and risks
of an investment in Hybridon Restricted Stock. Isis has not been formed solely
for the purpose of entering into the transactions contemplated in this Master
Agreement and is acquiring the Hybridon Restricted Stock for investment for its
own account, not as a nominee or agent, and not with the view to, or for resale,
distribution or fractionalization thereof, (except in connection with a
registered offering), in whole or in part, and no other person has a direct or
indirect interest, beneficial or otherwise in the Hybridon Restricted Stock.

                  (b)   Isis acknowledges its understanding that the
private placement and sale to Isis of the Hybridon Restricted Stock to it is
exempt from registration under the Securities Act by virtue of the provisions of
Regulation D. In furtherance thereof, Isis represents and warrants that it is an
"accredited investor" as that term is defined in Regulation D.

                  (c)   Isis agrees that it shall not sell or otherwise
transfer any of the Hybridon Restricted Stock without registration under the
Securities Act unless it shall deliver to Hybridon an opinion of counsel
reasonably satisfactory to Isis that an exemption from registration is

                                       -21-
<Page>

available. Isis fully understands and agrees that it must bear the total
economic risk of its purchase of Hybridon Restricted Stock for an indefinite
period of time because, among other reasons, the Hybridon Restricted Stock will
not have been registered under the Securities Act or under the securities laws
of any applicable state or other jurisdiction and, therefore, cannot be resold,
pledged, assigned or otherwise disposed of unless subsequently registered under
the Securities Act and under applicable state securities laws or unless an
exemption from such registration is available. Isis understands that Hybridon is
under no obligation to register the Hybridon Restricted Stock on its behalf with
the exception of certain registration rights as set forth herein. Isis
understands the lack of liquidity and the restrictions on transfer on the
Hybridon Restricted Stock and that the acquisition of Hybridon Restricted Stock
is suitable only for a person or entity of adequate financial means that has no
need for liquidity of its investment and that can afford a total loss of its
investment.

         4.8   SEC FILINGS. Since January 1, 1998, Isis has filed with the
Commission all SEC Filings required to be filed by Isis pursuant to Section 13,
14 or 15(d) of the Exchange Act on or before the date required to be filed with
the Commission. At the time filed, Isis's SEC Filings, including without
limitation, any financial statements, exhibits and schedules included therein or
documents incorporated therein by reference, to Isis's knowledge, (i) did not
contain any untrue statement of a material fact or omit to state a material fact
required to be stated therein or necessary in order to make the statements
therein, in light of the circumstances under which they were made, not
misleading and (ii) complied in all material respects with the applicable
requirements of the Securities Act or the Exchange Act, as the case may be.

         4.9   BROKERS OR FINDERS. There have been no investment bankers,
brokers or finders used by Isis in connection with the transactions contemplated
by the Transactions Documents and no such persons or entities are entitled to a
fee or compensation in respect thereof.

                                    ARTICLE 5

                           CLOSING DELIVERIES OF ISIS

         Isis hereby unconditionally agrees, irrespective of any breach of this
Master Agreement or the License Agreement by Hybridon, to deliver to Hybridon at
or prior to 5:00 p.m. (Boston time) on Friday, June 1, 2001:

                  (a)   An executed counterpart of the License Agreement;

                  (b)   A certificate of the appropriate officer of Isis
certifying as to the resolutions adopted by the board of directors authorizing
the execution, delivery, and performance by Isis of this Master Agreement and
the License Agreement and the consummation of the transactions contemplated
hereby and thereby;

                                       -22-
<Page>

                  (c)   An opinion of counsel to Isis which shall address
the Isis Common Stock to be issued under this Master Agreement in regards to its
due authorization and, when issued, its being legally and validly issued, fully
paid and non-assessable.

                  (d)   The cash payment referred to in SECTION 2.3(a) above.

                                    ARTICLE 6

                         CLOSING DELIVERIES OF HYBRIDON

         Isis shall have received at or prior to the Effective Date:

                  (a)   An executed counterpart of the License Agreement;

                  (b)   A certificate of the appropriate officer of
Hybridon certifying as to the resolutions adopted by the board of directors
authorizing the execution, delivery, and performance by Hybridon of this Master
Agreement and the License Agreement and the consummation of the transactions
contemplated hereby and thereby; and

                  (c)   An opinion of counsel to Hybridon which shall
address the Hybridon Common Stock to be issued under this Master Agreement in
regards to its due authorization, and, when issued, its being legally and
validly issued, fully paid and non-assessable.

                                    ARTICLE 7

                               REGISTRATION RIGHTS

         7.1   HYBRIDON REGISTRATION OBLIGATIONS.

                  (a)   For each issuance of Hybridon Common Stock hereunder,
Hybridon shall, at its own expense:

                           (i)   prepare and file, within ten (10) business
         days of each such issuance of Hybridon Common Stock, with the
         Commission a registration statement to register for resale on the Stock
         Market on which Hybridon's Common Stock is then traded, the Hybridon
         Common Stock so issued and use its best efforts to cause such
         registration statement to be declared effective by the Commission as
         promptly as practicable; and

                           (ii)   prepare and file with the Commission such
         amendments and supplements to such registration statement and the
         prospectus used in connection therewith as may be necessary to keep
         such registration statement effective until the first anniversary of
         the date of such issuance of Hybridon Common Stock, or, if earlier,
         until such time as Isis shall have completed the distribution of all
         Hybridon Common Stock

                                       -23-
<Page>

         covered by the registration statement, and comply with the
         provisions of the Securities Act with respect to the disposition of
         all securities covered by such registration statement during such
         effective period in accordance with the intended methods of
         disposition by Isis, and cause the prospectus to be supplemented by
         any required prospectus supplement, and as so supplemented to be
         filed pursuant to Rule 424 under the Securities Act. Hybridon is
         entitled to withdraw such registration statement at such time as it
         no longer is required to keep such registration statement effective
         under this clause (ii) and following such withdrawal Isis shall have
         no further right to offer or sell any Hybridon Common Stock pursuant
         to such registration statement; and

                           (iii)   provide a transfer agent and registrar for
         all Hybridon Common Stock so issued to Isis not later than the
         effective date of such registration statement.

                  (b)   Isis will furnish to Hybridon in writing such
information as Hybridon may reasonably require from Isis, and otherwise
reasonably cooperate with Hybridon, in connection with any registration
statement to be filed pursuant to subparagraph (a) above.

                  (c)   Subject to SECTION 9.1, Hybridon will indemnify
Isis against any and all claims, losses, damages and liabilities (or actions in
respect thereof) arising out of or based on any untrue statement (or alleged
untrue statement) of any material fact contained in any prospectus, offering
circular or other document incident to any registration, qualification or
compliance (or in any related registration statement, notification or the like)
or any omission (or alleged omission) to state therein any material fact
required to be stated therein or necessary to make the statements therein, in
light of the circumstances in which they were made, not misleading, or any
violation by Hybridon of any rule or regulation promulgated under federal and
state securities laws applicable to Hybridon and relating to any action or
inaction required of Hybridon in connection with any such registration,
qualification or compliance, and Hybridon will reimburse Isis for any legal and
any other expenses reasonably incurred in connection with investigating or
defending any such claim, loss, damage, liability or action; provided, however,
that Hybridon will not be liable in any such case to the extent that any such
claim, loss, damage or liability arises out of or is based on any untrue
statement or omission based upon written information furnished to Hybridon in an
instrument duly executed by Isis for use in such prospectus, offering circular
or other document (or in any related registration statement, notification or the
like).

                  (d)   Subject to SECTION 9.1, Isis will indemnify
Hybridon against any and all claims, losses, damages and liabilities (or actions
in respect thereof) arising out of or based on any untrue statement (or alleged
untrue statement) of any material fact contained in any prospectus, offering
circular or other document incident to any registration, qualification or
compliance (or in any related registration statement, notification or the like)
or any omission (or alleged omission) to state therein any material fact
required to be stated therein or necessary to make the statement therein, in
light of the circumstance in which they were made, not misleading, and Isis will
reimburse Hybridon for any legal and any other expenses reasonably

                                       -24-
<Page>

incurred in connection with investigating or defending any such claim, loss,
damage, liability or action; provided, however, that this paragraph (e) shall
apply only if (and only to the extent that) such statement or omission was made
in reliance upon written information furnished to Hybridon in an instrument
duly executed by Isis for use in such prospectus, offering circular or other
document (or related registration statement, notification or the like) or any
amendment or supplement thereto; and, provided further, that Isis's liability
hereunder with respect to any particular registration shall be limited to an
amount equal to the net proceeds received by Isis from the Hybridon Common Stock
 sold by Isis under such registration statement.

         7.2   ISIS REGISTRATION OBLIGATIONS.

                  (a)   For each issuance of Isis Common Stock hereunder,
Isis shall, at its own expense:

                           (i)   prepare and file, within ten (10) business
         days of each such issuance of Isis Common Stock, with the Commission a
         registration statement to register for resale on the Stock Market on
         which Isis's Common Stock is then traded, the Isis Common Stock so
         issued and use its best efforts to cause such registration statement to
         be declared effective by the Commission as promptly as practicable;

                           (ii)   prepare and file with the Commission such
         amendments and supplements to such registration statement and the
         prospectus used in connection therewith as may be necessary to keep
         such registration statement effective until the first anniversary of
         the date of such issuance of Isis Common Stock, or, if earlier, until
         such time as Hybridon shall have completed the distribution of all Isis
         Common Stock covered by the registration statement, and comply with the
         provisions of the Securities Act with respect to the disposition of all
         securities of all Isis Common Stock covered by such registration
         statement during such effective period in accordance with the intended
         methods of disposition by Hybridon, and cause the prospectus to be
         supplemented by any required prospectus supplement, and as so
         supplemented to be filed pursuant to Rule 424 under the Securities Act.
         Isis is entitled to withdraw such registration statement at such time
         as it no longer is required to keep such registration statement
         effective under this clause (ii) and following such withdrawal Hybridon
         shall have no further right to offer or sell any Isis Common Stock
         pursuant to such registration statement; and

                           (iii)   provide a transfer agent and registrar for
         all Isis Common Stock so issued to Hybridon not later than the
         effective date of such registration statement.

                  (b)   Hybridon will furnish to Isis in writing such
information as Isis may reasonably require from Hybridon, and otherwise
reasonably cooperate with Isis in connection with any registration to be filed
pursuant to subparagraph (a) above.

                  (c)   Subject to SECTION 9.1, Isis will indemnify Hybridon
against any and all claims, losses, damages and liabilities (or actions
in respect thereof) arising out of or based on

                                       -25-
<Page>

any untrue statement (or alleged untrue statement) of any material fact
contained in any prospectus, offering circular or other document incident to
any registration, qualification or compliance (or in any related registration
statement, notification or the like) or any omission (or alleged omission) to
state therein any material fact required to be stated therein or necessary to
make the statements therein, in light of the circumstances in which they were
made, not misleading, or any violation by Isis of any rule or regulation
promulgated under federal and state securities laws applicable to Isis and
relating to any action or inaction required of Isis in connection with any
such registration, qualification or compliance, and Isis will reimburse
Hybridon for any legal and any other expenses reasonably incurred in
connection with investigating or defending any such claim, loss, damage,
liability or action; provided, however, that Isis will not be liable in any
such case to the extent that any such claim, loss, damage or liability arises
out of or is based on any untrue statement or omission based upon written
information furnished to Isis in an instrument duly executed by Hybridon for
use in such prospectus, offering circular or other document (or in any
related registration statement notification or the like).

                  (d)   Subject to SECTION 9.1, Hybridon will indemnify
Isis against any and all claims, losses, damages and liabilities (or actions in
respect thereof) arising out of or based on any untrue statement (or alleged
untrue statement) of any material fact contained in any prospectus, offering
circular or other document incident to any registration, qualification or
compliance (or in any related registration statement, notification or the like)
or any omission (or alleged omission) to state therein any material fact
required to be stated therein or necessary to make the statement therein, in
light of the circumstances in which they were made, not misleading, and Hybridon
will reimburse Isis for any legal and any other expenses reasonably incurred in
connection with investigating or defending any such claim, loss, damage,
liability or action; provided, however, that this paragraph (e) shall apply only
if (and only to the extent that) such statement or omission was made in reliance
upon written information furnished to Isis in an instrument duly executed by
Hybridon for use in such prospectus, offering circular or other document (or
related registration statement, notification or the like) or any amendment or
supplement thereto; and, provided further, that Hybridon's liability hereunder
with respect to any particular registration shall be limited to an amount equal
to the net proceeds received by Hybridon from the Isis Common Stock sold by
Hybridon in such registration.

         7.3   FILING REQUIREMENTS. With a view to making available to each
of the Parties the benefits of Rule 144 promulgated under the Securities Act
("RULE 144") and any other rule or regulation of the SEC that may at any time
permit such Parties to sell their respective shares of Hybridon Common Stock or
Isis Common Stock issued under this Master Agreement to the public without
registration or pursuant to a registration on Form S-3, each of Hybridon and
Isis covenants and agrees to take commercially reasonable efforts to: (i) make
and keep public information available, as those terms are understood and defined
in Rule 144; (ii) file with the Commission in a timely manner all reports and
other documents required of such Party under the Securities Act and the Exchange
Act, and (iii) furnish to the other Party upon the other Party's request, (A) a
copy of such Party's most recent annual or quarterly report, and (B) such other

                                       -26-
<Page>

information as may be reasonably requested by the other Party in order to avail
the other Party of any rule or regulation of the Commission that permits the
selling pursuant to a registration statement. Notwithstanding the foregoing, a
Party's covenants and agreements under this SECTION 7.3 shall terminate and be
of no further force or effect from and after such time as the other Party may
resell all of the Common Stock of such Party issued to the other Party under
this Master Agreement pursuant to paragraph (k) of Rule 144 under the Securities
Act or, if earlier, such date as the other Party shall have sold or otherwise
distributed all of such Common Stock.

         7.4   LIMITATION ON REGISTRATION OBLIGATIONS. Notwithstanding
anything in this Master Agreement to the contrary, if either Party (the
"Blocking Party") shall furnish to the other Party (the "Selling Party") a
certificate signed by the President or Chief Executive Officer of the Blocking
Party, stating that its Board of Directors has made the good faith determination
(i) that continued use by the Selling Party, of a registration statement filed
pursuant to ARTICLE 7 for purposes of effecting offers or sales of Common Stock
of a Blocking Party, pursuant thereto would require, under the Securities Act,
premature disclosure in the registration statement (or the prospectus relating
thereto) of material, nonpublic information concerning the Blocking Party, its
business or prospects or any of its proposed material transactions, (ii) that
such premature disclosure would be materially adverse to the Blocking Party,
then (x) the Blocking Party may postpone the filing or effectiveness of such
registration statement, or (y) suspend the right of the Selling Party to use the
registration statement (and the prospectus relating thereto) for purposes of
effecting offers or sales of Common Stock of the Blocking Party pursuant
thereto. Notwithstanding the foregoing, neither Party shall under any
circumstances be entitled to exercise its right to postpone the filing or
effectiveness of, or suspend the use of, a registration statement more than two
(2) times in any twelve (12) month period, and the aggregate number of days
during which the filing or effectiveness of, or the suspension of the use of,
the registration statement may be postponed or suspended shall not exceed ninety
(90) days in any such (12) month period. Each Party hereby covenants and agrees
that it will not sell any Isis Common Stock or Hybridon Common Stock, as the
case may be, pursuant to a registration statement filed under this ARTICLE 7
during a period in which the ability to sell thereunder is suspended as set
forth in this SECTION 7.4 and will maintain in confidence the fact and content
of any notice provided under this SECTION 7.4.

         The effectiveness of a registration statement may not be postponed and
the rights of a Selling Party to sell shares under a registration statement may
not be suspended under this SECTION 7.4 unless the Blocking Party has similarly
suspended distribution rights under any other effective registration statement
of which it is the registrant (except for registration statements on Form S-8)
and has similarly suspended the rights of its officers and directors to trade in
its securities for at least the same 90 day period.

                                       -27-
<Page>

                                    ARTICLE 8

                            POST EFFECTIVE COVENANTS

         8.1   ISIS'S VOTING RESTRICTIONS. Isis agrees that, at all times
during the Restriction Period, at any meeting or vote by written consent in lieu
thereof of the stockholders of Hybridon, however called, Isis shall cause all
outstanding shares of Hybridon Restricted Stock that are beneficially owned by
Isis or its Affiliates as of the record date fixed for such meeting or on the
date of a vote by written consent to be voted in accordance with and in the same
proportion as the votes of the other stockholders of Hybridon, not including
abstentions. By way of example, if at Hybridon's annual meeting, stockholders
holding at least 70% of the combined voting power of Hybridon's voting
securities then outstanding, excluding Isis, vote in favor of a proposal, 10%
against and 20% abstain, then Isis shall be required to vote 87.5% of its
Hybridon Common Stock in favor of such proposal and 12.5% against.

         8.2   HYBRIDON'S VOTING RESTRICTIONS. Hybridon agrees that, at all
times during the Restriction Period, at any meeting or vote by written consent
in lieu thereof of the stockholders of Isis, however called, Hybridon shall
cause all outstanding shares of Isis Restricted Stock that are beneficially
owned by Hybridon or its Affiliates as of the record date fixed for such meeting
or on the date of a vote by written consent to be voted in accordance with and
in the same proportion as the votes of the other stockholders of Isis, not
including abstentions. By way of example, if at Isis's annual meeting,
stockholders holding at least 70% of the combined voting power of Isis's voting
securities then outstanding, excluding Hybridon, vote in favor of a proposal,
10% against and 20% abstain, then Hybridon shall be required to vote 87.5% of
its Isis Common Stock in favor of such proposal and 12.5% against.

         8.3   RESTRICTIONS ON ISIS'S SALE OF ITS HYBRIDON COMMON STOCK.
During the Restriction Period, Isis may only sell, assign, transfer or otherwise
dispose of , or engage in any short selling or hedging transaction in respect of
(for purposes of SECTIONS 8.3 and 8.4, "sell"), any of the Hybridon Restricted
Stock, whether in a private or public sale, pursuant to the conditions and
restrictions in this SECTION 8.3, PROVIDED, HOWEVER, that nothing in this
SECTION 8.3 shall prohibit Isis from transferring the Hybridon Restricted Stock
to an Affiliate of Isis that has agreed, in writing with Hybridon, to be bound
by the terms of this ARTICLE 8. During the Restriction Period, Isis shall not
sell in any 180-day period a number of shares of Hybridon Restricted Stock in
excess of one percent (1%) of the total outstanding shares of Hybridon Common
Stock determined on an as-converted basis (which shall be calculated by adding
the total number of shares of Hybridon Common Stock outstanding and the total
number of shares of Hybridon Common Stock issuable upon conversion of
outstanding convertible securities of Hybridon (excluding options and
warrants)); PROVIDED, HOWEVER, that in the event the Hybridon Market Price as of
a specified date is less than the Hybridon Minimum Price, then in the following
180 day period, Isis shall be allowed to sell a number of shares of Hybridon
Restricted Stock that does not exceed three percent (3%) of the total
outstanding shares of Hybridon Common Stock determined on an as-converted basis.
For the purposes of this SECTION 8.3, (i) the number of

                                       -28-
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outstanding shares of Hybridon Common Stock and the number of outstanding
shares of Hybridon Common Stock issuable upon conversion of outstanding
convertible securities of Hybridon (excluding options and warrants) shall be
the actual numbers at the time if known by Isis or, if not known, the stated
numbers of such shares reflected in Hybridon's most recent filing of a Form
10-Q or Form 10-K.

         8.4   RESTRICTIONS ON HYBRIDON'S SALE OF ITS ISIS COMMON STOCK.
During the Restriction Period, Hybridon may only sell any of the Isis Restricted
Stock, whether in a private or public sale, pursuant to the conditions and
restrictions in this SECTION 8.4, PROVIDED, HOWEVER, that nothing in this
SECTION 8.4 shall prohibit Hybridon from transferring the Isis Restricted Stock
to an Affiliate of Hybridon that has agreed, in writing with Isis, to be bound
by the terms of this ARTICLE 8. During the Restriction Period, Hybridon shall
not sell in any 180-day period a number of shares of Isis Restricted Stock in
excess of one percent (1%) of the total outstanding shares of Isis Common Stock
determined on an as-converted basis (which shall be calculated by adding the
total number of shares of Isis Common Stock outstanding and the total number of
shares of Isis Common Stock issuable upon conversion of outstanding convertible
securities of Isis (excluding options and warrants)); provided, however, that in
the event the Isis Market Price as of a specified date is less than the Isis
Minimum Price for the Isis Tranche Period during which such date occurs, then in
the following 180 day period, Hybridon shall be allowed to sell a number of
shares of Isis Restricted Stock that does not exceed three percent (3%) of the
total outstanding shares of Isis Common Stock determined on an as-converted
basis. For the purposes of this SECTION 8.4, the number of outstanding shares of
Isis Common Stock and the number of shares of Isis Common Stock issuable upon
conversion of outstanding convertible securities of Isis (excluding options and
warrants) shall be the actual numbers at the time if known by Hybridon or, if
not known, the stated numbers of such shares reflected in Isis's most recent
filing of a Form 10-Q or Form 10-K.

         8.5   CERTAIN TRANSACTIONS PROHIBITED. Notwithstanding any
provision herein to the contrary, for so long as a Party shall hold Isis
Restricted Stock or Hybridon Restricted Stock, as the case may be such Party
agrees that it will not and will cause its Affiliates to not: (i) except
pursuant to SECTION 2.2 and SECTION 2.3, whichever is applicable, acquire,
directly or indirectly, by purchase or otherwise, of record or beneficially, any
capital stock of the other Party, any securities of the other Party convertible
into capital stock of the other Party (which for purposes of this Master
Agreement shall include without limitation convertible notes), or any rights,
options or warrants to acquire capital stock of the other Party; (ii) "solicit"
proxies with respect to voting securities of the other Party under any
circumstances or become a "participant" in any "election contest" relating to
the election of directors of the other Party, as such terms are defined in
Regulation 14A under the Exchange Act; (iii) deposit any voting securities of
the other Party in a voting trust or subject them to a voting agreement or other
agreement of similar effect; (iv) initiate, propose or otherwise solicit
stockholders of the other Party for the approval of one or more stockholder
proposals at any time, or induce or attempt to induce any other person to
initiate any stockholder proposal; (v) present, or propose to present, publicly
or otherwise, to the other Party, its Board of Directors or its stockholders any
proposal or offer for a merger, tender or

                                       -29-
<Page>

exchange offer or other form of business combination involving the other
Party, or effect, propose to effect or cause to occur any of the foregoing;
(vi) take any action individually or jointly with any person, corporation,
entity or group or assist any person, corporation, entity or group in taking
any action such Party could not take individually under the terms of this
Master Agreement, or (vii) take any action which would be reasonably likely
to require such Party to make a public announcement regarding a possible
transaction involving such Party.

         8.6   WAIVER OF RESTRICTIONS. Notwithstanding anything to the
contrary set forth herein, either Party may, at any time and from time to time,
waive in writing any of the conditions or restrictions contained in this
ARTICLE 8. Each Party agrees to keep any request for a waiver and the approval
or denial thereof confidential under the terms of Section 7.1 of the License
Agreement.

         8.7   RESERVATION OF SHARES.

                  (a)   BY HYBRIDON. Hybridon will at all times reserve and
keep available, solely for issuance and delivery pursuant to this Master
Agreement, such number of shares of Hybridon Common Stock equal to the maximum
number of shares of Hybridon Restricted Stock as from time to time may be
issuable under this Master Agreement assuming the Hybridon Market Price is the
Hybridon Minimum Price.

                  (b)   BY ISIS. Isis will at all times reserve and keep
available, solely for issuance and delivery pursuant to this Master Agreement,
such number of shares of Isis Common Stock equal to the maximum number of shares
of Isis Restricted Stock as from time to time may be issuable under this Master
Agreement assuming the Isis Market Price is the Isis Minimum Price.

         8.8   CHANGE IN CONTROL OF HYBRIDON. In the event of a Change in
Control Transaction by Hybridon, then Isis's obligations in SECTIONS 8.1, 8.3
and 8.5 shall terminate and the Hybridon Common Stock restricted pursuant
thereto shall be released from such restrictions.

         8.9   CHANGE IN CONTROL OF ISIS. In the event of a Change in
Control Transaction by Isis, then Hybridon's obligations in SECTIONS 8.2, 8.4
and 8.5 shall terminate and the Isis Common Stock restricted pursuant thereto
shall be released from such restrictions.

                                    ARTICLE 9

                        INDEMNIFICATION AND CONTRIBUTION

         9.1   INDEMNIFICATION. The following provisions shall govern the
rights and the duties of the Parties in the event a Party seeks indemnity from
the other Party under the provisions of either SECTIONS 7.1 or 7.2, or both, as
the case may be.

                                       -30-
<Page>

                  (a)   Each party entitled to indemnification (the
"INDEMNIFIED PARTY") shall give notice to the party required to provide
indemnification (the "INDEMNIFYING PARTY") promptly after such Indemnified Party
has actual knowledge of any claim as to which indemnity may be sought, and shall
permit the Indemnifying Party to assume the defense of any such claim or any
litigation resulting therefrom; PROVIDED, that counsel for the Indemnifying
Party, who shall conduct the defense of such claim or litigation, shall be
approved by the Indemnified Party (whose approval shall not be unreasonably
withheld); and, PROVIDED, FURTHER, that the failure of any Indemnified Party to
give notice as provided herein shall not relieve the Indemnifying Party of its
obligations except to the extent that the Indemnifying Party is adversely
affected by such failure. The Indemnified Party may participate in such defense
at such party's expense; PROVIDED, HOWEVER, that the Indemnifying Party shall
pay such expense if representation of such Indemnified Party by the counsel
retained by the Indemnifying Party would be inappropriate due to actual or
potential conflicting interests between the Indemnified Party and any other
party represented by such counsel in such proceeding; PROVIDED FURTHER that in
no event shall the Indemnifying Party be required to pay the expenses of more
than one law firm per jurisdiction as counsel for the Indemnified Party. The
Indemnifying Party also shall be responsible for the expenses of such defense if
the Indemnifying Party does not elect to assume such defense. No Indemnifying
Party, in the defense of any such claim or litigation shall, except with the
consent of each Indemnified Party, consent to entry of any judgment or enter
into any settlement which does not include as an unconditional term thereof the
giving by the claimant or plaintiff to such Indemnified Party of a release from
all liability in respect of such claim or litigation, and no Indemnified Party
shall consent to entry of any judgment or settle such claim or litigation
without the prior written consent of the Indemnifying Party which consent shall
not be unreasonably withheld.

                  (b)   In order to provide for just and equitable
contribution in circumstances in which the indemnification provided for in
SECTIONS 7.1 and 7.2 is due in accordance with its terms but for any reason is
held to be unavailable to an Indemnified Party in respect to any expenses,
losses, claims, damages and liabilities referred to herein, then the
Indemnifying Party shall, in lieu of indemnifying such Indemnified Party,
contribute to the amount paid or payable by such Indemnified Party as a result
of such losses, claims, damages or liabilities to which such Party may be
subject in such proportion as is appropriate to reflect the relative fault of
the Indemnified Party on the one hand and the Indemnifying Party on the other in
connection with the statements or omissions which resulted in such losses,
claims, damages or liabilities, as well as any other relevant equitable
considerations. The relative fault of the Indemnified Party and the Indemnifying
Party shall be determined by reference to, among other things, whether the
untrue or alleged untrue statement of a material fact or the omission to state a
material fact related to information supplied by the Indemnified Party or the
Indemnifying Party and the parties' relative intent, knowledge, access to
information and opportunity to correct or prevent such statement or omission.
Each Party agrees that it would not be just and equitable if contribution
pursuant to this SECTIONS 9.1(b) were determined by pro rata allocation or by
any other method of allocation which does not take account of the equitable
considerations referred to above. Notwithstanding the provisions of this
paragraph, (a) in no case shall any Party be liable or responsible for any

                                       -31-
<Page>

amount in excess of the net proceeds received by such Party from the offering of
the securities of the other Party registered on its behalf under either SECTION
7.1 or 7.2, as the case may be, and (b) the Party filing the registration
statement shall be liable and responsible for any amount in excess of such
proceeds; PROVIDED, HOWEVER, that no person guilty of fraudulent
misrepresentation (within the meaning of Section 11(f) of the Securities Act)
shall be entitled to contribution from any person who was not guilty of such
fraudulent misrepresentation. Any Party entitled to contribution will, promptly
after receipt of notice of commencement of any action, suit or proceeding
against such Party in respect of which a claim for contribution may be made
against another Party under this paragraph, notify such Party from whom
contribution may be sought, but the omission to so notify such Party from whom
contribution may be sought shall not relieve such Party from any other
obligation may have thereunder or otherwise under this paragraph except to the
extent that such Party is adversely affected by such failure. No Party shall be
liable for contribution with respect to any action, suit, proceeding or claim
settled without its prior written consent, which consent shall not be
unreasonably withheld.

                                   ARTICLE 10

                           TERM AND EVENTS OF DEFAULT

         10.1   TERM. This Master Agreement shall commence upon execution and
remain in effect for ten years.

         10.2   BREACH OF NONPAYMENT AND FAILURE TO COMPLY WITH ARBITRATION
ORDER.

                  (a)   BREACH OF NONPAYMENT. In the event a Party is in
breach of any its obligations under either SECTION 2.2 or SECTION 2.3, then the
non-breaching Party may give written notice to the breaching Party of such
breach. Within ten (10) business days of the receipt by the breaching Party of
such written notice, the breaching Party shall cure the breach, PROVIDED,
HOWEVER, that if the breaching Party believes that a bona fide dispute exists as
to the amount of any payment, then the breaching Party may, not later than five
business days following the notice of the breach, (i) provide the non-breaching
Party with a written notice setting forth the nature of the dispute and the
amount in dispute, and (ii) at the same time, pay to the non-breaching Party the
amount of the payment which is not in dispute. Failure to either cure such
breach OR take the actions required under subsection (i) or (ii) above,
whichever action is applicable, shall be an "EVENT OF DEFAULT".

                  If part or all of a payment is in dispute hereunder, either
Party may submit the dispute to arbitration pursuant to SECTION 11.14, in which
case the non-payment of the disputed portion shall not be deemed a breach during
the pendency of the arbitration. If the final arbitration order or ruling issued
in the arbitration proceeding resolves the dispute against the breaching Party
and orders the breaching Party to pay all or part of the disputed portion to the
non-breaching Party, then the arbitrator shall include in its award, in addition
to such other remedies as it deems appropriate, the following against the
breaching Party: (A) attorneys' fees

                                       -32-
<Page>

of the non-breaching Party, the fees of the arbitrator and the costs and
expenses of the arbitration, (B) any Lost Profits, and (C) in the case the
arbitrator finds that a cash payment was due, an amount equal to interest at
a rate equal to the lower of 1.5% per month, compounded monthly, or the
highest rate permitted by law on the amount of cash determined to have been
due commencing on the due date determined by the arbitrator through the date
of actual payment.

                  (b)   FAILURE TO COMPLY WITH ARBITRATION ORDER. If an
arbitrator has rendered a ruling pursuant to Article VIII of the License
Agreement that a Party has materially breached this Master Agreement or the
License Agreement, which ruling specified the remedies imposed on such breaching
Party for such breach, including, without limitation, a ruling on a dispute as
to breach of SECTION 2.2 or 2.3 as contemplated by SECTION 10.2(a) (the "ADVERSE
RULING"), and the breaching Party has failed to comply with the terms of the
Adverse Ruling within the time period specified therein for compliance, or if
such compliance cannot be fully achieved by such date, the breaching Party has
failed to commence compliance and to use diligent efforts to achieve full
compliance as soon thereafter as is reasonably possible, then such failure shall
be deemed an "EVENT OF DEFAULT".

         10.3   REMEDIES UPON AN EVENT OF DEFAULT. Upon the occurrence of an
Event of Default and written notice to the defaulting Party, (i) the defaulting
Party shall have no further rights under this Master Agreement (except, in the
event that the licenses and sublicenses granted by the defaulting Party under
the License Agreement remain in effective under SECTION 9.2(d) of the License
Agreement, the right to receive Common Stock and cash of the non-defaulting
Party pursuant to SECTION 2.2 or 2.3, whichever is applicable and the right to
have such stock registered, and the provisions relating thereto under SECTION
7), but shall continue to be liable for all of its obligations under this Master
Agreement, including but not limited to the obligation to issue Isis or Hybridon
Common Stock or pay cash to the non-defaulting Party pursuant to SECTION 2.2 or
2.3, whichever is applicable, and (ii) the non-defaulting Party shall have no
further obligations under this Master Agreement other than its obligation to
issue Isis or Hybridon Common Stock or pay cash to the defaulting Party pursuant
to SECTION 2.2 or 2.3, whichever is applicable, and the obligations to register
such stock and the other obligations under SECTION 7 relating thereto, but shall
continue to have all of its rights under this Master Agreement, including but
not limited to the right to receive Common Stock and cash of the defaulting
Party pursuant to SECTION 2.2 or 2.3, whichever is applicable and the benefits
of any voting restrictions and trading restrictions imposed under ARTICLE 8 on
the other party, the benefits of any registration provisions under ARTICLE 7 and
rights arising out of any breach of representations or warranties or other
covenants of the defaulting Party under the Agreement.

         10.4   SURVIVAL. The terms and conditions in SECTIONS 7.1(a)(ii),
7.1(c), 7.1(d), 7.2(a)(ii), 7.2(c), 7.2(d) AND 7.4, ARTICLE 9 and
SECTIONS 10.2, 10.3 and 11.14 shall survive termination or expiration of
this Master Agreement.

         10.5   FAILURE TO MAKE MASTER AGREEMENT DELIVERIES. Notwithstanding
any provision in this Master Agreement or the License Agreement to the
contrary, if Isis breaches Section

                                       -33-
<Page>

2.3(a)(i) or Article 5 of this Master Agreement, Hybridon shall have the
right, at its sole election, effective immediately upon written notice to
Isis, to terminate this Master Agreement AB INITIO. The Parties hereby agree
that termination of this Master Agreement as provided in this Section 10.5
shall not be the exclusive remedy of Hybridon in the event of a breach of
Section 2.3(a)(i) or Article 5 of this Master Agreement by Isis and that,
without regard to the arbitration provisions of Article VIII of the License
Agreement, Hybridon shall be entitled to declare such breach to be an Event
of Default under this Master Agreement and to seek any and all remedies to
which Hybridon may be entitled at law or in equity, including without
limitation seeking to enforce the provisions of Section 2.3(a)(i) and Article
5 of this Master Agreement (and Section 10.3 of this Master Agreement if the
breach is declared by Hybridon to be an Event of Default). In the event of
any action by Hybridon under this Section 10. 5 for payment under Section
2.3(a)(i) and Article 5 of this Master Agreement or otherwise, Hybridon shall
be entitled to reimbursement of attorney's fees and other collection costs
incurred by Hybridon and an amount equal to interest at the rate equal to the
lower of 1.5% per month, compounded monthly, or the highest rate permitted by
law on the amount of cash due commencing on the due date through the date of
actual payment.

                                   ARTICLE 11

                            MISCELLANEOUS PROVISIONS

         11.1   ADJUSTMENTS FOR DIVIDENDS, SPLITS, REORGANIZATIONS,
RECLASSIFICATIONS, ETC.

                  (a)   If after the date hereof (i) the outstanding shares
of the Isis Common Stock or Hybridon Common Stock, as the case may be (for
purposes of this SECTION 11.1(a), the "Subject Stock") shall be subdivided or
split into a greater number of shares or a dividend in Subject Stock shall be
paid in respect of such Subject Stock, (ii) the outstanding shares of Subject
Stock are combined, (iii) a Party shall pay a dividend in securities of the
Party (other than Subject Stock) or of the property (including cash) on the
Subject Stock, or (iv) there shall occur any merger, consolidation, capital
reorganization or reclassification in which the Subject Stock is converted or
exchanged for securities, cash or other property (other than as part of a Change
of Control Transaction), all dollar amounts and share quantities in this Master
Agreement, as well as the class or series of stock constituting the Subject
Stock, shall be adjusted to reflect such stock splits, stock dividend,
combination, other dividend, merger, consolidation, capital reorganization or
reclassification consistent with the economic intent of the parties, PROVIDED,
HOWEVER, there shall be no adjustments to the amount of any cash payments which
either Party may be obligated to make or have the election to make in lieu of
the issuance of shares of Subject Stock. After any event referenced in clauses
(i) through (iv) is consummated, if applicable, all references herein to Isis
Common Stock or Hybridon Common Stock, as the case may be, shall be deemed to
refer to the capital stock or property (including cash) into or for which the
Subject Stock was converted or exchanged, with the necessary changes in detail.
All calculations under this SECTION 11.1 shall be made to the nearest cent or
whole number amount for shares.

                                       -34-
<Page>

                  (b)   Upon the happening of any event referenced in
clauses (i) through (iv) in SECTION 11.1(a), the Party whose Common Stocks is so
affected shall forthwith give written notice thereof to the other Party stating
the adjusted figures and setting forth in reasonable detail the method of
calculation and the facts upon which such calculation is based.

         11.2   SUCCESSORS AND ASSIGNS. This Master Agreement shall be binding
upon and inure to the benefit of the Parties and their respective successors and
assigns, except that neither Party may assign its respective obligations
hereunder, including an assignment by merger or by operation of law, without the
prior written consent of the other Party, unless such assignment is in
connection with the sale or transfer of all or substantially all of the business
or assets of the assigning Party. Any attempted assignment in contravention of
this provision shall be void.

         11.3   NOTICES. All notices, requests, consents and other
communications hereunder shall be in writing and shall be delivered by hand,
by facsimile, or by certified mail, postage prepaid, return receipt requested:

                  (a)   If to Hybridon, at the address set forth below:

                                 Hybridon, Inc.
                                 345 Vassar Street
                                 Cambridge, MA 02139
                                 Attention:  President
                                 Telephone:  617-679-5500
                                 Facsimile:  617-679-5592

                        WITH A COPY TO:

                                 James Pollock, Esq.
                                 Holland & Knight, LLP
                                 10 St. James Avenue
                                 Boston, MA 02116
                                 Telephone:  (617) 523-2700
                                 Facsimile:  (617) 523-6850

                  (b)   If to Isis:

                                 Isis Pharmaceuticals, Inc.
                                 2292 Faraday Avenue
                                 Carlsbad, CA 92008
                                 Attention:  President
                                 Telephone:  (760) 931-9200
                                 Facsimile:  (760) 931-9639l

                                       -35-
<Page>

                        WITH A COPY TO:

                                 L. Kay Chandler, Esq.
                                 Cooley Godward LLP
                                 4365 Executive Drive, Suite 1100
                                 San Diego, CA 92121
                                 Telephone:  (858) 550-6000
                                 Facsimile:  (858) 453-3555

         Any notice or other communication so addressed and so delivered shall
be deemed to have been received on the date of hand delivery or facsimile or, if
sent by certified mail, return receipt requested, on the date of mailing.

         11.4   ENTIRE AGREEMENT; ATTACHMENTS.

                  (a)   This Master Agreement and all exhibits hereto,
together with the Transaction Documents, represent the entire understanding and
agreement between the Parties with respect to the subject matter hereof and
supersede all prior oral and written and all contemporaneous oral negotiations,
commitments and understandings between the Parties.

                  (b)   If the provisions of the License Agreement are
inconsistent with the provisions of this Master Agreement, the provisions of
the License Agreement shall prevail. The Exhibits are hereby incorporated as
integral parts of this Master Agreement.

         11.5   SEVERABILITY. Any provision of this Master Agreement which is
invalid, illegal or unenforceable in any jurisdiction shall, as to that
jurisdiction, be ineffective to the extent of such invalidity, illegality or
unenforceability, without affecting in any way the remaining provisions hereof
in such jurisdiction or rendering that or any other provision of this Master
Agreement invalid, illegal or unenforceable in any other jurisdiction. The
language in this Master Agreement is acknowledged by the Parties to be language
chosen by the Parties to express their mutual consent, and no rule of strict
construction against any Party shall apply to any term or provision hereof.

         11.6   INVESTIGATION OF THE PARTIES. All representations and warranties
contained herein which are made to the best knowledge of a Party shall require
that such Party investigate and inquire with respect thereto to the extent that
a reasonable business person would make such investigation and inquiry in light
of the circumstances at the time, without regard to this transaction.

         11.7   EXPENSES. Except as otherwise expressly provided herein,
Hybridon, on the one hand, and Isis on the other hand, will pay all fees and
expenses (including, without limitation, legal and accounting fees and
expenses) incurred by them in connection with the transactions contemplated
hereby.

                                       -36-
<Page>

         11.8   GOVERNING LAW. This Master Agreement shall be governed by and
construed in accordance with the laws of the State of Delaware, without regard
to the conflict of laws rules of any jurisdiction.

         11.9   SECTION HEADINGS. The section headings are for the convenience
of the Parties and in no way alter, modify, amend, limit, or restrict the
contractual obligations of the Parties.

         11.10   COUNTERPARTS. This Master Agreement may be executed in one
or more counterparts, each of which shall be deemed to be an original, but all
of which shall be one and the same document. A copy or facsimile of a signature
shall be binding upon the signatory as if it were an original signature.

         11.11   WAIVER AND MODIFICATION. A Party may only waive the failure
of another Party to comply with any of such Party's obligations, agreements or
conditions as set forth herein expressly in writing. To the extent permitted by
law, this Master Agreement may be amended or modified in whole or in part by an
agreement in writing executed on behalf of the Parties at any time.

         11.12   NO WAIVER. No failure on the part of any Party to exercise,
and no delay in exercising (except where a specific time period is specified)
any right shall operate as a waiver thereof, nor shall any single or partial
exercise by any Party of any right preclude any other future exercise thereof or
the exercise of any other right. No investigation, review or audit by either
party of the other prior to or after the date hereof shall stop or prevent
either Party from exercising any right hereunder or be deemed to be a waiver of
any such right.

         11.13   FURTHER ASSURANCES. At any time and from time to time after
the Effective Date, each party shall promptly execute and deliver such
instruments of transfer, conveyance, assignment and confirmation, and take all
such other action as the other Party may reasonably request to carry out the
purpose and intent of this Master Agreement.

         11.14   DISPUTE RESOLUTION.

                  (a)   Any Party must submit any dispute under this Master
Agreement to arbitration pursuant to the terms and conditions set forth in
Article VII of the License Agreement.

                  (b)   Nothing in this SECTION 11.14 shall prevent either
Party from seeking from a court of competent jurisdiction a preliminary
injunction, temporary restraining order or similar relief in order to prevent or
limit an irreparable harm that may occur in the absence thereof.

         11.15   NO CONSEQUENTIAL DAMAGES. NEITHER PARTY HERETO WILL BE
LIABLE FOR SPECIAL, INCIDENTAL OR CONSEQUENTIAL DAMAGES ARISING OUT OF THIS
AGREEMENT OR THE EXERCISE OF ITS RIGHTS HEREUNDER, REGARDLESS OF ANY NOTICE OF
SUCH DAMAGES.

                                       -37-
<Page>

         11.16   CONFIDENTIALITY. The Parties hereto agree that the
provisions of the License Agreement relating to confidentiality are incorporated
herein by reference.

                          [Remainder of page intentionally omitted]

                                       -38-
<Page>

         IN WITNESS WHEREOF, the parties hereto have caused this Master
Agreement to be executed as of the date first written above.

                                 HYBRIDON, INC.

                                 By: /s/ Sudhir Agrawal
                                    ----------------------------------------
                                 Title: President & CSO
                                       -------------------------------------

                                 By: /s/ R. Andersen
                                    ----------------------------------------
                                 Title: CFO
                                       -------------------------------------

                                 ISIS PHARMACEUTICALS, INC.

                                 By: /s/ B. Lynne Parshall
                                    ----------------------------------------
                                 Title: Exective Vice President
                                       -------------------------------------

                                       -39-
<Page>

                                    EXHIBIT A

                                LICENSE AGREEMENT

                                              *Text Omitted and Filed Separately
                                               Confidential Treatment Requested
                                           Under 17 C.F.R. Sections 200.80(b)(4)
                                                              200.83 and 240b-2

                       COLLABORATION AND LICENSE AGREEMENT

                                 BY AND BETWEEN

                           ISIS PHARMACEUTICALS, INC.

                                       AND

                                 HYBRIDON, INC.

<Page>

                                TABLE OF CONTENTS
<Table>
<Caption>

                                                                            PAGE
                                                                            ----

<S>                                                                           <C>
ARTICLE I  DEFINITIONS.........................................................1

   SECTION 1.1  "AFFILIATE"....................................................1

   SECTION 1.2  "AMINO PATENT RIGHTS"..........................................2

   SECTION 1.3  "ANTISENSE PRODUCTS"...........................................2

   SECTION 1.4   "ANTISENSE TECHNOLOGY"........................................2

   SECTION 1.5  "CONFIDENTIAL INFORMATION".....................................2

   SECTION 1.6  "DOCKET 104"...................................................2

   SECTION 1.7  "DOCKET 105"...................................................3

   SECTION 1.8  "DRUG POTENTIATION PATENT RIGHTS"..............................3

   SECTION 1.9  "EXHIBIT K PATENTS"............................................3

   SECTION 1.10  "FACILITATOR PATENT RIGHTS"...................................3

   SECTION 1.11  "FINDERON PATENT RIGHTS"......................................3

   SECTION 1.12  "HYBRIDON ANTISENSE DRUG".....................................4

   SECTION 1.13  "HYBRIDON ANTISENSE PATENT RIGHTS"............................4

   SECTION 1.14  "HYBRIDON EXCLUDED PATENT RIGHTS".............................5

   SECTION 1.15  "HYBRIDON INTELLECTUAL PROPERTY"..............................5

   SECTION 1.16  "IMMUNE STIMULATION PATENT RIGHTS"............................5

   SECTION 1.17  "ISIS INTELLECTUAL PROPERTY RIGHTS"...........................5

   SECTION 1.18  [*]

   SECTION 1.19  "MOTIFS"......................................................6

   SECTION 1.20  "NAKED SUBLICENSE"............................................6

   SECTION 1.21  "NON-PARENT AFFILIATE"........................................6

   SECTION 1.22  "OPTIMIZATION"................................................6

   SECTION 1.23  "PARTY".......................................................6

   SECTION 1.24  "RIBOZYMES"...................................................6

   SECTION 1.25  "RIBOZYME TECHNOLOGY".........................................6

   SECTION 1.26  "RNASEH DEPENDENT MECHANISMS OF ACTION".......................7

   SECTION 1.27  "SUBLICENSE INCOME"...........................................7

*Confidential Treatment Requested    - i -
<Page>

   SECTION 1.28  "SUBLICENSEE".................................................7

   SECTION 1.29  "SUBSIDIARY"..................................................7

   SECTION 1.30  "THIRD PARTY LICENSE AGREEMENTS"..............................8

   SECTION 1.31  "TULLIS NET SALES"............................................8

   SECTION 1.32  "TULLIS PATENTS"..............................................8

   SECTION 1.33  "TULLIS PRODUCT"..............................................8

   SECTION 1.34  "UMASS PATENT RIGHTS".........................................8

   SECTION 1.35  "VALID CLAIM".................................................8

ARTICLE II  GRANT OF RIGHTS BY HYBRIDON........................................9

   SECTION 2.1  LICENSE GRANT..................................................9

   SECTION 2.2  SUBLICENSING RIGHT............................................11

   SECTION 2.3  NO IMPLIED LICENSES; RETAINED RIGHTS..........................13

   SECTION 2.4  COMMERCIALIZATION EFFORTS.....................................13

   SECTION 2.5  LICENSE AGREEMENTS TO WHICH HYBRIDON IS A PARTY...............13

   SECTION 2.6  METHYLGENE LICENSE AGREEMENT..................................14

   SECTION 2.7  ORIGENIX LICENSE AGREEMENT....................................14

   SECTION 2.8  AFFILIATES....................................................14

ARTICLE III  GRANT OF RIGHTS BY ISIS..........................................14

   SECTION 3.1  LICENSE GRANT.................................................14

   SECTION 3.2  SUBLICENSING RIGHT............................................14

   SECTION 3.3  TULLIS PATENTS................................................15

   SECTION 3.4  SCOPE OF LICENSE..............................................16

   SECTION 3.5  NO IMPLIED LICENSES...........................................17

   SECTION 3.6  LIMITATION ON LICENSE GRANT WITH RESPECT TO TARGET
                     VALIDATION AND GENE FUNCTIONALIZATION ACTIVITIES.........17

   SECTION 3.7  NOTICE OF HYBRIDON ANTISENSE DRUGS............................17

   SECTION 3.8  AFFILIATES....................................................18

                                     - ii -
<Page>

ARTICLE IV PAYMENT OBLIGATIONS................................................18

   SECTION 4.1  CONSIDERATION FOR LICENSES OF HYBRIDON INTELLECTUAL
                      PROPERTY AND ISIS INTELLECTUAL PROPERTY.................18

   SECTION 4.2  CONSIDERATION FOR SUBLICENSE OF TULLIS PATENTS................18

   SECTION 4.3  ISIS SUBLICENSE INCOME........................................19

   SECTION 4.4  RECORDS; AUDITS...............................................19

   SECTION 4.5  PAYMENT CURRENCY..............................................19

   SECTION 4.6  LATE PAYMENTS; COLLECTIONS....................................19

ARTICLE V  COLLABORATION......................................................20

ARTICLE VI INTELLECTUAL PROPERTY PROTECTION...................................20

   SECTION 6.1  PATENT PROSECUTION AND COOPERATION............................20

   SECTION 6.2  ENFORCEMENT OF HYBRIDON ANTISENSE PATENT RIGHTS...............24

ARTICLE VII  CONFIDENTIALITY..................................................27

   SECTION 7.1  CONFIDENTIAL INFORMATION......................................27

ARTICLE VIII  DISPUTE RESOLUTION..............................................28

ARTICLE IX TERM AND TERMINATION...............................................29

   SECTION 9.1  TERM..........................................................29

   SECTION 9.2  TERMINATION OF LICENSES AND SUBLICENSES FOR BREACH............30

   SECTION 9.3  TERMINATION OF SUBLICENSE OF TULLIS PATENTS...................31

   SECTION 9.4  SURVIVAL......................................................31

   SECTION 9.5  SUBLICENSE SURVIVAL...........................................31

   SECTION 9.6  FAILURE TO MAKE MASTER AGREEMENT DELIVERIES...................32

ARTICLE X MISCELLANEOUS PROVISIONS............................................32

   SECTION 10.1  INDEMNIFICATION..............................................32

   SECTION 10.2  GOVERNING LAW................................................33

   SECTION 10.3  ASSIGNMENT...................................................33

   SECTION 10.4  ENTIRE AGREEMENT; AMENDMENTS.................................33

   SECTION 10.5  NOTICES......................................................33

   SECTION 10.6  FORCE MAJEURE................................................35

   SECTION 10.7  DISCLOSURE OF PROVISIONS OF AGREEMENT........................35

                                     - iii -
<Page>

   SECTION 10.8  INDEPENDENT CONTRACTORS......................................36

   SECTION 10.9  NO STRICT CONSTRUCTION.......................................36

   SECTION 10.10  HEADINGS....................................................36

   SECTION 10.11  NO IMPLIED WAIVERS; RIGHTS CUMULATIVE.......................36

   SECTION 10.12  SEVERABILITY................................................37

   SECTION 10.13  EXECUTION IN COUNTERPARTS...................................37

   SECTION 10.14  NO CONSEQUENTIAL DAMAGES....................................37

   SECTION 10.15  PATENT VALIDITY.............................................37
</Table>

<Table>
<Caption>

EXHIBITS:
---------

Exhibit A through Exhibit G    - Omitted
<S>                <C>
Exhibit H-1   -    Third Party License Agreements
Exhibit H-2   -    Other License Agreements
Exhibit I     -    Tullis Patents
Exhibit J     -    UMass Agreement
Exhibit K     -    Excluded Hybridon Intellectual Property
Exhibit L     -    UMass Patent Rights
Exhibit M     -    Drug Potentiation Patent Rights
Exhibit N     -    Tullis Agreement
</Table>

                                     - iv -
<Page>

                       COLLABORATION AND LICENSE AGREEMENT

      This Collaboration and License Agreement (the "Agreement") is entered into
as of the 24th day of May, 2001 (the "Effective Date") by and between Isis
Pharmaceuticals, Inc., a corporation organized and existing under the laws of
the State of Delaware ("Isis"), and Hybridon, Inc., a corporation organized and
existing under the laws of the State of Delaware ("Hybridon").

                                  INTRODUCTION

      1. Hybridon is the owner or has the right to use under license certain
patents and patent applications relating to the practice of Antisense Technology
(as defined below).

      2. Isis is the owner or has the right to use under license certain patents
and patent applications relating to the practice of Antisense Technology.

      3. Hybridon and Isis are interested in licensing or sublicensing to the
other party these patents and patent applications and in collaborating from time
to time on the further research and development of Antisense Products.

      4. Hybridon and Isis have entered into a Master Agreement dated as of the
date hereof (the "Master Agreement").

5. Isis and Hybridon each recognizes that the other Party has expended
significant efforts and resources in the research and development of Antisense
Technology and the payments to be made under the Master Agreement to each Party
for the patent licenses and sublicenses granted hereunder will allow each Party
to recoup such expenditures.

      NOW, THEREFORE, Hybridon and Isis agree as follows:

                                   ARTICLE I
                                   DEFINITIONS

When used in this Agreement, each of the following terms shall have the meanings
set forth in this Article I:

      Section 1.1 "AFFILIATE". Affiliate shall mean, with respect to a person or
entity, any corporation, company, partnership, joint venture or other entity
which controls, is controlled by, or is under common control with such person or
entity. For purposes of this Section 1.1 and Section 1.21, "control" shall mean
(a) in the case of corporate entities, direct or indirect ownership of fifty
percent (50%) or more of the stock or shares having the right to vote for the
election of directors, and (b) in the case of non-corporate entities, direct or
indirect ownership of fifty percent (50%) or more of the equity interest with
the

<Page>

power to direct the management and policies of such non-corporate entities,
provided that in either such case such person or entity has the power to direct
the management and policies of such entities, whether by contract or through
representation on the board of directors or other governing body of such
entities.

      Section 1.2 "AMINO PATENT RIGHTS". Amino Patent Rights shall mean the
claims of all patents and patent applications set forth on EXHIBIT A hereto and
any continuations or divisions thereof, any patent issued with respect to any
such patent applications, any reissue, reexamination, renewal or extension
(including any supplemental patent certificate) of any such patent, any
confirmation patent or registration patent or patent of addition based on any
such patent, and all foreign counterparts of any of the foregoing.

      Section 1.3 "ANTISENSE PRODUCTS". Antisense Products shall mean
oligonucleotides or oligonucleotide analogs or mimics thereof targeted to a
specific sequence of RNA that hybridize to such sequence and through such
hybridization modulate the production of the targeted gene product. The term
Antisense Products shall not include Ribozymes.

      Section 1.4 "ANTISENSE TECHNOLOGY". Antisense Technology shall mean the
use of any oligonucleotide or oligonucleotide analog or mimic thereof targeted
to a specific sequence of RNA that hybridizes to such sequence and through such
hybridization modulates the production of the targeted gene product. The term
Antisense Technology shall not include Ribozyme Technology.

      Section 1.5 "CONFIDENTIAL INFORMATION". Confidential Information shall
mean all information, including, without limitation, proprietary information and
materials (whether or not patentable) regarding a Party's technology, products,
business information or objectives, which is designated as confidential in
writing by the disclosing Party, whether by letter or by the use of an
appropriate stamp or legend, prior to or at the time any such information is
disclosed by the disclosing Party to the other Party. Notwithstanding the
foregoing, all information which is orally, electronically or visually disclosed
by a Party, or is disclosed in writing without an appropriate letter, stamp or
legend, shall constitute Confidential Information of a Party if the disclosing
Party, within thirty (30) days after such disclosure, delivers to the other
Party a written document or documents describing the information and referencing
the place and date of such oral, visual, electronic or written disclosure and
the names of the persons to whom such disclosure was made.

      Section 1.6 "DOCKET 104". Docket 104 shall mean all patents and patent
applications set forth on EXHIBIT B-1 hereto and any continuations or divisions
thereof, any patent issued with respect to any such patent applications, any
reissue, reexamination, renewal or extension (including any

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supplemental patent certificate) of any such patent, any confirmation patent or
registration patent or patent of addition based on any such patent, and all
foreign counterparts of any of the foregoing.

      Section 1.7 "DOCKET 105". Docket 105 shall mean all patents and patent
applications set forth on EXHIBIT B-2 hereto and any continuations or divisions
thereof, any patent issued with respect to any such patent applications, any
reissue, reexamination, renewal or extension (including any supplemental patent
certificate) of any such patent, any confirmation patent or registration patent
or patent of addition based on any such patent, and all foreign counterparts of
any of the foregoing.

      Section 1.8 "DRUG POTENTIATION PATENT RIGHTS". Drug Potentiation Patent
Rights shall mean the claims of all patents and patent applications set forth on
EXHIBIT M hereto and any continuations or divisions thereof, any patent issued
with respect to any such patent applications, any reissue, reexamination,
renewal or extension (including any supplemental patent certificate) of any such
patent, any confirmation patent or registration patent or patent of addition
based on any such patent, and all foreign counterparts of any of the foregoing.

      Section 1.9 "EXHIBIT K PATENTS". Exhibit K Patents shall mean the claims
of all patents and patent applications set forth on EXHIBIT K hereto and any
continuations or divisions thereof, any patent issued with respect to any such
patent applications, any reissue, reexamination, renewal or extension (including
any supplemental patent certificate) of any such patent, any confirmation patent
or registration patent or patent of addition based on any such patent, and all
foreign counterparts of any of the foregoing.

      Section 1.10 "FACILITATOR PATENT RIGHTS". Facilitator Patent Rights shall
mean the claims of all patents and patent applications set forth on EXHIBIT C
hereto and any continuations or divisions thereof, any patent issued with
respect to any such patent applications, any reissue, reexamination, renewal or
extension (including any supplemental patent certificate) of any such patent,
any confirmation patent or registration patent or patent of addition based on
any such patent, and all foreign counterparts of any of the foregoing.

      Section 1.11 "FINDERON PATENT RIGHTS". Finderon Patent Rights shall mean
the claims of all patents and patent applications set forth on EXHIBIT D hereto
and any continuations or divisions thereof, any patent issued with respect to
any such patent applications, any reissue, reexamination, renewal or extension
(including any supplemental patent certificate) of any such patent, any
confirmation patent or registration patent or patent of addition based on any
such patent, and all foreign counterparts of any of the foregoing.

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      Section 1.12 "HYBRIDON ANTISENSE DRUG". Hybridon Antisense Drug shall mean
an Antisense Product which is a therapeutic or prophylactic product for the
treatment or prevention of disease in a human or an animal that is discovered,

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developed and/or Optimized either by Hybridon or a Subsidiary alone or as
part of a "bona fide drug discovery collaboration".

      For purposes of this Section 1.12 only, a "bona fide drug discovery
collaboration" is an arrangement between Hybridon or a Subsidiary and a third
party (i) in which the intent of the collaborators in engaging in discovery,
development and/or Optimization activities is to discover, develop, Optimize and
commercialize an Antisense Product. [*] Initiation of IND supporting
toxicology is the initiation of animal toxicity studies in support of the filing
of an Investigational New Drug application with the U.S. Food and Drug
Administration or a similar regulatory filing with a similar regulatory
authority in another jurisdiction. If a contractor (which is not the third party
collaborator) in the business of performing preclinical studies provides such
services through the performance of IN VIVO animal studies under the supervision
of Hybridon or a Subsidiary, the services so provided shall be treated as work
performed directly by Hybridon or a Subsidiary for purposes of this definition.
Work performed by a contractor of, and paid for by, Hybridon or a Subsidiary
under the supervision of Hybridon or a Subsidiary shall be treated as work
performed directly by Hybridon or a Subsidiary for purposes of this definition.
The Parties acknowledge that a part of the discovery, development and
Optimization of an Hybridon Antisense Drug may involve the validation and
prioritization of gene targets to form the basis for antisense drug discovery
activities.

      In the event of a sale or other transfer of the assets of Hybridon, no
Antisense Product developed by the acquiring company prior to the acquisition
will be deemed to be a Hybridon Antisense Drug unless (i) such acquiring company
acquires all or substantially all of the assets of the antisense business of
Hybridon, and (ii) such Antisense Product [*]by the acquiring company prior to
the acquisition; provided, however, that an Antisense Product that would qualify
as a Hybridon Antisense Drug irrespective of the acquisition will not lose its
status as such as a result of such acquisition.

      Section 1.13 "HYBRIDON ANTISENSE PATENT RIGHTS". Hybridon Antisense Patent
Rights shall mean the claims of all patents and patent applications and any
continuations or divisions thereof, whether now existing, now filed or later
filed on inventions invented, licensed or sublicensed by Hybridon prior to April
26, 2001, any patent issued with respect to any such patent applications, any
reissue, reexamination, renewal or extension (including any supplemental patent
certificate) of any such patent, any confirmation patent or registration patent
or patent of addition based on any such patent, and all foreign counterparts of
any of the foregoing, which Hybridon owned or had the right to sublicense as of
April 26, 2001 and which are necessary or useful to practice Antisense
Technology, including without limitation the patents and patent applications set
forth on EXHIBIT E, but not including the Hybridon Excluded Patent Rights and
the patents and patent

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applications licensed to Hybridon (the "Hybridon IDT Patent Rights") pursuant
to the Non-Exclusive License Agreement dated as of March 12, 1999 between
Integrated DNA Technologies, Inc. ("IDT") and Hybridon.

      Section 1.14 "HYBRIDON EXCLUDED PATENT RIGHTS". Hybridon Excluded Patent
Rights shall mean the Amino Patent Rights, Docket 104, Docket 105, Facilitator
Patent Rights, Finderon Patent Rights, Immune Stimulation Patent Rights, Drug
Potentiation Patent Rights and the Exhibit K Patents.

      Section 1.15 "HYBRIDON INTELLECTUAL PROPERTY". Hybridon Intellectual
Property shall mean collectively the Hybridon Antisense Patent Rights and the
Hybridon Excluded Patent Rights (all solely to the extent licensed to Isis under
Section 2.1), but shall exclude the Hybridon IDT Patent Rights.

      Section 1.16 "IMMUNE STIMULATION PATENT RIGHTS". Immune Stimulation Patent
Rights shall mean the claims of all patents and patent applications set forth on
EXHIBIT F hereto and any continuations or divisions thereof, any patent issued
with respect to any such patent applications, any reissue, reexamination,
renewal or extension (including any supplemental patent certificate) of any such
patent, any confirmation patent or registration patent or patent of addition
based on any such patent, and all foreign counterparts of any of the foregoing.

      Section 1.17 "ISIS INTELLECTUAL PROPERTY RIGHTS". Isis Intellectual
Property Rights shall mean the claims that cover Motifs or RNaseH Dependent
Mechanisms of Action of all patents and patent applications and any
continuations or divisions thereof, whether now existing, now filed or later
filed on inventions invented, licensed or sublicensed by Isis prior to April 26,
2001, any patent issued with respect to any such patent applications, any
reissue, reexamination, renewal or extension (including any supplemental patent
certificate) of any such patent, any confirmation patent or registration patent
or patent of addition based on any such patent, and all foreign counterparts of
any of the foregoing, which Isis owned or had the right to sublicense as of
April 26, 2001, including without limitation the patents and patent applications
set forth on EXHIBIT G hereto; provided, however, that Isis Intellectual
Property Rights shall not include manufacturing methods, including without
limitation reagents, synthons and processes used in manufacturing and analyzing
oligonucleotides; chemistries, including without limitation modifications made
to the backbone, sugar or base of an oligonucleotide and oligonucleotide
conjugates (including the chemistries of the conjugate and the conjugation
methods); formulations, including without limitation methods and reagents for
delivery and uptake of oligonucleotides; gene-related patents, including without
limitation patents to specific gene structures, gene targets and treatments
based upon a genetic target; and patents and patent applications licensed to

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Isis pursuant to the Non-Exclusive License Agreement dated March 19, 1999
between IDT and Isis.

      Section 1.18 [*]

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      Section 1.19 "MOTIFS". Motifs shall mean hybrid oligonucleotide structures
that have at least two regions within the oligonucleotide that have different
chemistries, one of which will support cleavage via RNaseH Dependent Mechanisms
of Action. Motifs do not include specific chemistries necessary or useful to
create or Optimize such structures, whether or not such chemistries are also
disclosed by or claimed in the same patent or patent application.

      Section 1.20 "NAKED SUBLICENSE". Naked Sublicense shall mean any license
or sublicense of intellectual property granted by a Party or a Subsidiary to a
third party other than a license or sublicense which is granted as part of a
bona fide research, development, manufacturing or commercialization
collaboration between the Party or a Subsidiary and the third party (it being
agreed by the Parties that the definition of the term "collaboration" in this
Section 1.20 shall not be interpreted by reference to the definition of
collaboration used in Section 1.12). For purposes of this definition, a bona
fide research, development, manufacturing or commercialization collaboration may
include collaborative research and discovery, including without limitation gene
functionalization and target validation.

      Section 1.21 "NON-PARENT AFFILIATE". Non-Parent Affiliate shall mean, with
respect to a person or entity, any Affiliate of such person or entity other than
any corporation, company, partnership, joint venture or other entity which
controls (as defined in Section 1.1) such person or entity.

      Section 1.22 "OPTIMIZATION". Optimization shall mean the process by which
the properties of an Antisense Product are improved by making chemical
modifications to such Antisense Product or by selecting a different sequence of
RNA for such Antisense Product.

      Section 1.23 "PARTY". Party shall mean Isis or Hybridon; "Parties" shall
mean Isis and Hybridon. As used in this Agreement, references to "third parties"
do not include a Party or its Subsidiaries.

      Section 1.24 "RIBOZYMES". Ribozymes shall mean oligonucleotides or
oligonucleotide analogs or mimics containing a catalytic core having a bulge or
stem loop and regions flanking the catalytic core that hybridize to a targeted
RNA and modulate the targeted RNA by cleavage at a site next to a specific
ribonucleotide triplet by an oligonucleotide catalyzed transesterification
reaction.

      Section 1.25 "RIBOZYME TECHNOLOGY". Ribozyme Technology shall mean the use
of any oligonucleotides or oligonucleotide analogs or mimics thereof containing
a catalytic core having a bulge or stem loop and regions flanking the catalytic
core that hybridize to a targeted RNA and modulate the

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targeted RNA by cleavage at a site next to a specific ribonucleotide triplet
by an oligonucleotide catalyzed transesterification reaction.

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      Section 1.26 "RNASEH DEPENDENT MECHANISMS OF ACTION". RNaseH Dependent
Mechanisms of Action shall mean methods of using RNaseH enzymes to cleave a
targeted RNA in vitro or in vivo. RNaseH Dependent Mechanisms of Action do not
include chemistries necessary or useful to facilitate or Optimize such cleavage,
whether or not such chemistries are also disclosed by or claimed in the same
patent or patent application.

      Section 1.27 "SUBLICENSE INCOME". Sublicense Income shall mean all
consideration received from Sublicensees by Isis or a Subsidiary pursuant to a
Naked Sublicense by Isis or a Subsidiary which covers, in whole or in part,
Hybridon Intellectual Property and all consideration received from Sublicensees
by Isis or an Affiliate pursuant to a Naked Sublicense not involving Hybridon
Intellectual Property if such Naked Sublicense arose out of the same transaction
as, or was otherwise related to, a Naked Sublicense which covers, in whole or in
part, Hybridon Intellectual Property. Sublicense Income does not include (i)
payments made by a Sublicensee in consideration for the issuance of equity or
debt securities of Isis to the extent such payments do not exceed the fair
market value of the securities being issued. [*] If non-monetary consideration
is received from Sublicensees by Isis or its Subsidiaries, then a commercially
reasonable monetary value will be assigned for purposes of calculating
Sublicense Income.

      Section 1.28 "SUBLICENSEE". Sublicensee shall mean any third party granted
the right hereunder by a Party, its Subsidiaries or a Sublicensee having the
right to grant further sublicenses, to discover, develop, make, have made, use,
sell, have sold, offer to sell, import or have imported products covered by the
Hybridon Intellectual Property (in the case of a Sublicensee of Isis, its
Subsidiaries or a Sublicensee having the right to grant further sublicenses) or
Isis Intellectual Property or Tullis Patents (in the case of a Sublicensee of
Hybridon, its Subsidiaries or a Sublicensee having the right to grant further
sublicenses).

      Section 1.29 "SUBSIDIARY". Subsidiary shall mean with respect to a Party,
any corporation, company, partnership, joint venture or other entity, 100% of
the equity securities of which are directly or indirectly owned by such Party;
provided, however, that if such Party does not directly or indirectly own 100%
of the equity securities of the entity, such entity shall nevertheless be deemed
a Subsidiary for purposes of this definition if the equity securities not owned
directly or indirectly by such Party consist solely of: (a) director qualifying
shares, (b) equity securities of the entity owned by employees, directors or
officers of the Party or the entity so long as such ownership by employees,
directors and officers does not exceed 10% of the equity securities of the
entity and/or (c) in the case of entities, the operations of which are
substantially conducted outside the United States, equity securities of the
entity owned by financial investors so long as such ownership by financial
investors does not exceed 20% of the equity securities of the entity. For

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purposes of this Section 1.29, indirect ownership shall mean ownership through
an entity or a chain

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of entities as to each member of which the Party or another entity in the
chain owns 100% of the equity securities (other than director qualifying
shares).

      Section 1.30 "THIRD PARTY LICENSE AGREEMENTS". Third Party License
Agreements shall mean those agreements set forth on EXHIBIT H-1 attached hereto
pursuant to which Hybridon has licensed Hybridon Intellectual Property to third
parties.

      Section 1.31 "TULLIS NET SALES". Tullis Net Sales shall mean the gross
sales revenues received by Hybridon, its Subsidiaries or Sublicensees from the
sale of Tullis Products, minus (a) all sales, use, and excise taxes, and customs
duties or other charges; (b) transportation and handling charges (including
transport insurance) actually incurred and paid by the buyer as part of the
purchase price; and (c) amounts repaid or credited by reason of rejections or
returns. Sales of a Tullis Product by Hybridon to a Subsidiary of Hybridon for
sale by the Subsidiary shall not be considered a sale of Tullis Products
hereunder.

      Section 1.32 "TULLIS PATENTS". Tullis Patents shall mean the Technology
Rights (as defined in the Non-Exclusive Patent License Agreement dated September
14, 1992 (the "Tullis Agreement") between Isis and Molecular Biosystems, Inc.
("MBI")) licensed by Isis from MBI under the Tullis Agreement, including without
limitation the patents and patent applications set forth on EXHIBIT I hereto.

      Section 1.33 "TULLIS PRODUCT". Tullis Product shall mean any product whose
use, manufacture or sale by Hybridon, its Subsidiaries or Sublicensees, in any
jurisdiction in which a patent which is a Tullis Patent has been allowed, would
but for the provisions of Section 3.3 constitute an infringement of such patent.

      Section 1.34 "UMASS PATENT RIGHTS". UMass Patent Rights shall mean the
Patent Rights (as defined in the UMass Agreement (as defined below)) licensed by
Hybridon from UMass under the UMass Agreement, including without limitation the
patents and patent applications set forth on EXHIBIT L hereto.

      Section 1.35 "VALID CLAIM". Valid Claim shall mean a claim which (i) in
the case of any unexpired United States or foreign patent, shall not have been
donated to the public, disclaimed or held invalid or unenforceable by a court of
competent jurisdiction in an unappealed or unappealable decision, or (ii) in the
case of any United States or foreign patent application, shall not have been
permanently cancelled, withdrawn, abandoned or been pending for more than seven
(7) years.

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                                   ARTICLE II
                           GRANT OF RIGHTS BY HYBRIDON

Section 2.1 LICENSE GRANT.

            (a) License Grant to Hybridon Antisense Patent Rights. Subject to
the terms and conditions of this Agreement, including without limitation
Hybridon's retained rights under Section 2.3 and Section 2.5(a) of this
Agreement, Hybridon hereby grants to Isis and its Subsidiaries an exclusive
worldwide license or sublicense, as applicable, under the Hybridon Antisense
Patent Rights, to practice Antisense Technology and to discover, develop, make,
have made, use, sell, have sold, offer to sell, import and have imported
Antisense Products. These rights shall only be sublicensable as explicitly
provided in Section 2.2.

            (b) Limited License Grant to Hybridon Excluded Patent Rights.
Subject to the terms and conditions of this Agreement, including without
limitation Hybridon's retained rights under Section 2.3 and Section 2.5(a) of
this Agreement, Hybridon hereby grants to Isis and its Subsidiaries the limited
worldwide licenses or sublicenses, as applicable, under the Hybridon Excluded
Patent Rights to practice Antisense Technology and to discover, develop, make,
have made, use, sell, have sold, offer to sell, import and have imported
Antisense Products, in each case solely to the extent specifically described
below. These rights shall only be sublicensable as explicitly provided in
Section 2.2.

                     (i)   [*]

                     (ii)  [*]

            (iii)    under the Immune Stimulation Patent Rights (A) to discover,
                     develop, make, have made, use, sell, have sold, offer to
                     sell, import and have imported Antisense Products which
                     contain modifications which have neutralized the immune
                     stimulation caused by an immunostimulatory CpG dinucleotide
                     in such Antisense Products, (B) to practice Antisense
                     Technology using oligonucleotides which contain
                     modifications which have neutralized the immune stimulation
                     caused by an immunostimulatory CpG dinucleotide in such
                     oligonucleotides, and (C) to discover, develop, make, have
                     made, use, sell, have sold, offer to sell, import and have
                     imported Antisense Products which target genes involved in
                     immunity modulation;

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            (iv)     under the Facilitator Patent Rights to discover, develop,
                     make, have made, use, sell, have sold, offer to sell,
                     import and have imported Antisense Products and practice
                     Antisense Technology, provided that neither such Antisense
                     Products nor such Antisense Technology use, or are used
                     with, a Ribozyme or Ribozyme Technology;

            (v)      under the Finderon Patent Rights to discover, develop,
                     make, have made, use, sell, have sold, offer to sell,
                     import and have imported Antisense Products and practice
                     Antisense Technology, provided that neither such Antisense
                     Products nor such Antisense Technology use, or are used
                     with, a Ribozyme or Ribozyme Technology;

            (vi)     under the Amino Patent Rights to discover, develop, make,
                     have made, use, sell, have sold, offer to sell, import and
                     have imported Antisense Products and practice Antisense
                     Technology, provided that such Antisense Products and
                     Antisense Technology use, or are used with, the technology
                     covered by the claims of the Amino Patent Rights solely for
                     the conjugation of functional groups for therapeutic or
                     prophylactic purposes only;

            (vii)    under the Drug Potentiation Patent Rights to discover,
                     develop, make, have made, use, sell, have sold, offer to
                     sell, import and have imported Antisense Products and
                     practice Antisense Technology, which Antisense Products and
                     Antisense Technology primarily act against a gene target
                     implicated in cancer through an antisense mechanism, but
                     which may incidentally potentiate an anti-cancer prodrug;
                     and

            (viii)   under the Exhibit K Patents to discover, develop, make,
                     have made, use, sell, have sold, offer to sell, import and
                     have imported Antisense Products and practice Antisense
                     Technology; provided, however, that the license
                     contemplated by this clause (viii) shall not extend to
                     Antisense Products or Antisense Technology related to
                     specific claimed gene targets or pseudo-cyclic
                     oligonucleotide structures and applications.

      The Parties agree that if, during the term of the license and sublicense
granted by Hybridon to Isis and its Subsidiaries in this Section 2.1(b), a claim

                                     - 10 -
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issues from any patent application included in Hybridon Excluded Patent Rights
that is necessary or useful for the practice of Antisense Technology, Hybridon
shall not use such claim to preclude or otherwise interfere with the ability of
Isis or its Subsidiaries to discover, develop, make, have made, use, sell, have
sold, offer to sell, import and have imported Antisense Products and practice
Antisense Technology; provided, however, that to the extent that the license or
sublicense grant set forth above in this Section 2.1(b) is limited in scope as
to its application to Antisense Products or Antisense Technology, such
limitation shall also be applicable to the restrictions on Hybridon's rights to
preclude or otherwise interfere with Isis and its Subsidiaries set forth in this
paragraph (i.e., if the license or sublicense grant is not applicable, Hybridon
shall not be restricted from precluding or interfering).

                  (c) The licenses and sublicenses granted by Hybridon to Isis
      and its Subsidiaries in Sections 2.1(a) and (b) to the extent such
      licenses or sublicenses cover UMass Patent Rights are subject to, without
      limitation Sections 2.2(a), 2.2(b), 2.2(d), 2.6, 2.7, 4.3(a), 4.3(d), 7.1,
      10.4 and 12.4(a) of the License Agreement dated as of February 21, 1990
      and restated as of September 8, 1993 by and between Hybridon and
      University of Massachusetts Medical Center (formerly the Worcester
      Foundation for Biomedical Research, Inc. and referred to herein as
      "UMass") (the "UMass Agreement"). A copy of the UMass Agreement is
      attached to this Agreement as EXHIBIT J. Hybridon hereby represents and
      warrants as of the date hereof: (i) that Exhibit J is a true, correct and
      complete copy of the UMass Agreement and all amendments and/or other
      changes thereto, (ii) that the UMass Agreement is in full force and
      effect, (iii) that Hybridon is not in default thereunder and (iv) that
      there has been no waiver of rights by Hybridon thereunder. Hybridon
      further represents and warrants as of the date hereof that Isis shall have
      no payment obligation to UMass arising out of the execution and delivery
      of this Agreement or the sublicensing by Hybridon of the UMass Patent
      Rights hereby and that any payment obligations that do arise under the
      UMass Agreement shall be the sole responsibility of Hybridon; provided
      that Isis may have payment obligations to UMass directly in the case of a
      termination of the UMass Agreement pursuant to the last paragraph of
      Section 2.2(c) of the UMass Agreement.

      Section 2.2 SUBLICENSING RIGHT.

                  (a) Isis and its Subsidiaries shall have the right to grant
      sublicenses under the licenses and sublicenses from Hybridon set forth in
      Section 2.1 above to third parties. Each such sublicense shall be subject
      and subordinate to, and consistent with, the terms and conditions of this
      Agreement, and shall provide that any Sublicensee shall have no right to
      grant further sublicenses except on terms consistent with this Section
      2.2. In the event of a material default by any

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      Sublicensee under a sublicense agreement, Isis will inform Hybridon and
      take commercially reasonable efforts to cause the Sublicensee to cure
      the default or will terminate the sublicense or, if Isis is not the
      sublicensor under such sublicense, Isis will cause the sublicensor under
      such sublicense to take commercially reasonable efforts to cause the
      Sublicensee to cure the default or to terminate such sublicense; provided,
      however that none of Isis, its Subsidiaries or the sublicensor under such
      sublicense shall be responsible to Hybridon for the default by the
      Sublicensee under the sublicense agreement.

                  (b) (i) Isis shall provide UMass with a copy of any sublicense
      granted pursuant to this Section 2.2 by Isis or its Subsidiaries or
      Sublicensees which includes a sublicense of UMass Patent Rights, within
      thirty (30) days after the grant of such sublicense. Hybridon shall use
      its reasonable best efforts to cause UMass to enter into a confidentiality
      agreement with Isis with respect to sublicenses provided to UMass under
      this clause (i) (it being understood that Hybridon shall not be obligated
      to make any payment or to provide any other consideration to UMass for
      such confidentiality agreement by UMass).

                      (ii) Isis shall provide Hybridon with written notice of
any sublicense (an "Isis Sublicense") granted pursuant to this Section 2.2 by
Isis or its Subsidiaries or Sublicensees within thirty (30) days after the grant
of such sublicense, such written notice specifying the name of the Sublicensee,
the date of the sublicense and whether such Isis Sublicense includes UMass
Patent Rights or is a Naked Sublicense. Hybridon shall have the right, not more
than twice during any calendar year, to have any Isis Sublicense reviewed by an
independent third party chosen by Hybridon to ascertain whether such Isis
Sublicense includes UMass Patent Rights or is a Naked Sublicense. Isis shall
cooperate in all reasonable respects with the review of such Isis Sublicense by
the independent third party under this Section 2.2(b)(ii), including without
limitation responding to questions directed at determining whether such Isis
Sublicense includes UMass Patent Rights or is a Naked Sublicense. Hybridon shall
pay all costs of such review; provided, however, that if, contrary to the
information provided by Isis in the written notice provided to Hybridon in
connection with the grant of such Isis Sublicense, such Isis Sublicense does in
fact include UMass Patent Rights or is a Naked Sublicense, Isis shall reimburse
Hybridon for the costs of such review. If the independent third party determines
that such Isis Sublicense includes UMass Patent Rights or is a Naked Sublicense,
such independent third party shall notify Isis and Hybridon. If Isis disagrees
with the determination of the independent third party, the third party shall be
permitted hereunder to provide Hybridon with a copy of the Isis Sublicense.

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                  (c) Any Naked Sublicense of Hybridon Intellectual Property by
      Isis or its Subsidiaries to (i) third parties which are parties to license
      or sublicense agreements with Isis or its Affiliates or Subsidiaries not
      involving Hybridon Intellectual Property and (ii) Affiliates of Isis or
      its Subsidiaries shall be made by Isis or its Subsidiaries on commercially
      reasonable terms. Isis and its Subsidiaries shall not sublicense Hybridon
      Intellectual Property separately from any intellectual property of Isis or
      its Affiliates or Subsidiaries, including without limitation the Isis
      Intellectual Property, for the purpose of reducing the amount of
      Sublicense Income payable by Isis or its Subsidiaries to Hybridon under
      Section 4.3.

      Section 2.3 NO IMPLIED LICENSES; RETAINED RIGHTS. Other than those rights
and licenses explicitly granted herein, no right or license under the Hybridon
Intellectual Property is granted to Isis or its Subsidiaries or Sublicensees.
Notwithstanding the rights and licenses granted herein, Hybridon shall retain
its rights under the Hybridon Intellectual Property for all purposes, including
without limitation its rights to discover, develop, make, have made, use, sell,
have sold, offer to sell, import and have imported Antisense Products, to
practice Antisense Technology and to license or sublicense Hybridon Intellectual
Property; provided, that, except for licenses and sublicenses provided under the
Third Party License Agreements, Hybridon and its Subsidiaries shall not grant
any Naked Sublicenses of the Hybridon Antisense Patent Rights to any third
parties (other than Subsidiaries).

      Section 2.4 COMMERCIALIZATION EFFORTS. Isis hereby agrees to undertake
reasonable efforts to bring one or more products covered by a claim of the UMass
Patent Rights into commercial use as quickly as is reasonably possible.

      Section 2.5 LICENSE AGREEMENTS TO WHICH HYBRIDON IS A PARTY.

                  (a) Notwithstanding Section 2.1 of this Agreement, Hybridon
      shall not and is not licensing or sublicensing to Isis or its Subsidiaries
      any rights under the Hybridon Intellectual Property to the extent that
      such Hybridon Intellectual Property has been licensed or sublicensed by
      Hybridon under the Third Party License Agreements.

                  (b) Hybridon hereby represents and warrants as of the date
      hereof that, except for the agreements set forth on EXHIBIT H-2 attached
      hereto: (i) Hybridon has not entered into any agreement under which it has
      licensed from another party any of the Hybridon Intellectual Property and
      (ii) Hybridon has not entered into any agreement under which it has
      licensed to another party any of the Hybridon Intellectual Property other
      than the Third Party License Agreements.

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                  (c) Hybridon agrees that it shall not amend or expand any
      Third Party License Agreement in a manner that is inconsistent with this
      Agreement, including without limitation amending any Third Party License
      Agreement to grant any new exclusive license under the Hybridon Antisense
      Patent Rights, without the prior written consent of Isis, which consent
      shall not be unreasonably withheld or delayed.

                  (d) Hybridon hereby represents and warrants as of the date
      hereof as to the Third Party License Agreements: (i) that it has provided
      true

                                     - 14 -
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      and correct copies of all such agreements to Isis, (ii) that all such
      agreements are in full force and effect, (iii) that Hybridon is not in
      default under any such agreement and (iv) that there has been no waiver of
      rights by Hybridon thereunder.

      Section 2.6 METHYLGENE LICENSE AGREEMENT. If Methylgene Inc.
("Methylgene") designates a target which Methylgene desires to select as a
Second Molecular Target or a Third Molecular Target (as such terms are defined
in the Amended and Restated License Agreement made effective as of January 4,
1996, as amended and restated on September 21, 2000 (the "Methylgene License
Agreement")) pursuant to the terms of the Methylgene License Agreement [*].

      Section 2.7 ORIGENIX LICENSE AGREEMENT. Hybridon shall [*] License
Agreement dated as of January 22, 1999 (the "OriGenix License Agreement")
between Hybridon and OriGenix Technologies Inc. ("OriGenix")) and shall [*]

      Section 2.8 AFFILIATES. Hybridon hereby represents and warrants as of the
date hereof that no Affiliate of Hybridon owns or controls any patents, patent
applications or inventions invented, licensed or sublicensed by such Affiliate
prior to April 26, 2001 which are necessary or useful to practice Antisense
Technology.

                                  ARTICLE III
                             GRANT OF RIGHTS BY ISIS

      Section 3.1 LICENSE GRANT. Subject to the terms and conditions of this
Agreement, Isis hereby grants to Hybridon and its Subsidiaries a worldwide
non-exclusive license or sublicense, as applicable under the Isis Intellectual
Property Rights to discover, develop, make, have made, use, sell, have sold,
offer to sell, import and have imported Hybridon Antisense Drugs. These rights
shall only be sublicensable as explicitly provided in Section 3.2.

      Section 3.2 SUBLICENSING RIGHT. Hybridon and its Subsidiaries shall have
the right to grant sublicenses under the license from Isis set forth in Section
3.1 above to third parties only to discover, develop, make, have made, use,
sell, have sold, offer to sell, import and have imported Hybridon Antisense
Drugs. Each such sublicense shall be subject and subordinate to, and consistent
with, the terms and conditions of this Agreement, and shall provide that any
Sublicensee shall have no right to grant further sublicenses except on

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terms consistent with this Section 3.2. In the event of a material default by
any Sublicensee under a sublicense agreement, Hybridon will inform Isis and
take commercially reasonable efforts to cause the Sublicensee to cure the
default or will terminate the sublicense or, if Hybridon is not the sublicensor
under such sublicense, Hybridon will cause the sublicensor under such
sublicense to take commercially reasonable efforts to cause the Sublicensee
to cure the default or to terminate such sublicense; provided however that none
of Hybridon, its Subsidiaries or the sublicensor under such sublicense shall
be responsible to Isis for the default by the Sublicensee under the sublicense
agreement. Notwithstanding the rights granted under this Section 3.2, Hybridon
and its Subsidiaries shall [*]

      Section 3.3 TULLIS PATENTS.

                  (a) Subject to the terms and conditions of this Agreement,
      Isis hereby grants to Hybridon and its Subsidiaries a worldwide
      non-exclusive sublicense, with the right to grant sublicenses as provided
      in Section 3.3(b), under the Tullis Patents to discover, develop, make,
      have made, use, sell, have sold, offer to sell, import and have imported
      Hybridon Antisense Drugs, provided that such Hybridon Antisense Drugs
      employ technology covered by the Isis Intellectual Property as a material
      element thereof.

                  (b) (i) Hybridon and its Subsidiaries shall have the right to
      grant sublicenses under the license from Isis set forth in Section 3.3(a)
      to third parties (x) provided that such sublicense may only be granted to
      third parties in connection with the grant of a sublicense to such third
      parties of Isis Intellectual Property under Section 3.2, and (y) solely to
      discover, develop, make, have made, use, sell, have sold, offer to sell,
      import and have imported Hybridon Antisense Drugs that employ technology
      covered by the Isis Intellectual Property as a material element thereof.
      Each such sublicense shall be subject and subordinate to, and consistent
      with, the terms and conditions of this Agreement, and shall provide that
      any such Sublicensee shall have no right to grant further sublicenses
      except on terms consistent with this Section 3.3(b).

                      (ii) Hybridon shall provide MBI with a copy of any
sublicense granted by Hybridon or its Subsidiaries or Sublicensees pursuant to
this Section 3.3(b) within thirty (30) days after the grant of such sublicense.
Isis shall use its reasonable best efforts to cause MBI to enter into a
confidentiality agreement with Hybridon with respect to sublicenses provided to
MBI under this Section 3.3(b) (it being understood that Isis shall not be
obligated to make any payment or to provide any other consideration to MBI for
such confidentiality agreement by MBI). In the event that MBI does not sign such
a confidentiality agreement with Hybridon, Isis shall enforce against MBI, for
and on behalf of Hybridon, the confidentiality provisions of the Tullis

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Agreement with respect to the sublicenses provided by Hybridon, its Subsidiaries
or Sublicensees to MBI and with respect to any other confidential information
of Hybridon or a Subsidiary or Sublicensee of Hybridon that MBI receives.

                      (iii)  In the event of a material default by any
Sublicensee under a sublicense agreement pursuant to this Section 3.3(b),
Hybridon will inform Isis and take commercially reasonable efforts to cause the
Sublicensee to cure the default or will terminate the sublicense, or if Hybridon
is not the sublicensor under such sublicense, Hybridon will cause the
sublicensor under such sublicense to take commercially reasonable efforts to
cause the Sublicensee to cure the default or to terminate such sublicense;
provided however that none of Hybridon, its Subsidiaries or the sublicensor
under such sublicense shall be responsible to Isis for the default by the
Sublicensee under the sublicense agreement. Notwithstanding the rights granted
under this Section 3.3(b), Hybridon shall [*]

                  (c) A copy of the Tullis Agreement is attached to this
      Agreement as EXHIBIT N. Isis hereby represents and warrants as of the date
      hereof: (i) that Exhibit N is a true, correct and complete copy of the
      Tullis Agreement and all amendments and/or other changes thereto that
      affect the rights of Hybridon as a sublicensee thereunder, (ii) that the
      Tullis Agreement is in full force and effect, (iii) that Isis is not in
      default thereunder and (iv) that there has been no waiver of rights by
      Isis thereunder. Isis further represents and warrants as of the date
      hereof that Hybridon shall have no payment obligation to MBI arising out
      of the execution and delivery of this Agreement or the sublicensing by
      Isis of the Tullis Patents hereby and that any payment obligations that do
      arise shall be the sole responsibility of Isis.

      Section 3.4 SCOPE OF LICENSE. Hybridon acknowledges that Isis claims
intellectual property covering numerous chemical modifications to
oligonucleotides including without limitation modifications to backbone
linkages, sugars, heterocyclic bases and conjugates and to methods of making the
same, including methods of making various oligonucleotide intermediates (the
"Isis Chemistry Intellectual Property"). Hybridon acknowledges and agrees that
no Isis Chemistry Intellectual Property is included in the Isis Intellectual
Property being licensed or sublicensed to Hybridon and its Subsidiaries pursuant
to Section 3.1 of this Agreement, except as expressly set forth below in this
Section 3.4. [*] Isis hereby agrees that any patents owned or controlled by
Isis or an Affiliate as of the date hereof or any patents that may issue in the
future to Isis or an Affiliate from or in respect of any patent applications
which Isis or an Affiliate owned or had the right to sublicense as of April 26,
2001, which would otherwise be infringed by the practice of the Hybridon 2'-O
Methyl Chemistry, shall constitute Isis Intellectual Property for all purposes
of this Agreement, including without limitation the license grant provided in
Section

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3.1; provided, however, that the license grant with respect to such patents
shall only provide Hybridon and its Subsidiaries with the right to discover,
develop, make, have made, use, sell, have sold, offer to sell, import and have
imported Hybridon Antisense Drugs which incorporate the Hybridon 2'-O

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Methyl Chemistry. If any patent of Isis or an Affiliate includes claims to a
combination of modifications to both substitution with 2'-O-methyl and Isis
Chemistry Intellectual Property in addition to 2'-O-methyl substituents, nothing
in this Section 3.4 shall be deemed to be a grant of rights to Hybridon or its
Subsidiaries to practice the Isis Chemistry Intellectual Property other than
2'-O-methyl substituents.

      Section 3.5 NO IMPLIED LICENSES. Other than those rights and licenses
explicitly granted herein, no right or license under the Isis Intellectual
Property or the Tullis Patents is granted to Hybridon or its Subsidiaries or
Sublicensees.

      Section 3.6 LIMITATION ON LICENSE GRANT WITH RESPECT TO TARGET VALIDATION
AND GENE FUNCTIONALIZATION ACTIVITIES. Notwithstanding anything to the contrary
in Sections 3.1 and 3.3(a), the licenses set forth in Sections 3.1 and 3.3(a)
above do not grant Hybridon and its Subsidiaries the right:

                  (a) to use the Isis Intellectual Property and the Tullis
      Patents for target validation and gene functionalization activities,
      except when, and only to the extent that, (i) such activities are directed
      to the discovery, development, Optimization and commercialization of a
      Hybridon Antisense Drug and (ii) such activities are performed only by
      Hybridon or a Subsidiary and not by a contractor or a collaborator, or

                  (b) to use, or enable any third party to use, any information
      that is developed during such target validation and gene functionalization
      activities in the development of a drug other than a Hybridon Antisense
      Drug, including without limitation, small molecules, ribozymes, proteins
      and pseudocyclic oligonucleotide structures.

      Section 3.7 NOTICE OF HYBRIDON ANTISENSE DRUGS. Hybridon shall provide
Isis with written notice of any Hybridon Antisense Drugs developed under a
sublicense granted by Hybridon or its Subsidiaries under Section 3.2 (a
"Hybridon Antisense Drug Sublicense") promptly after such Hybridon Antisense
Drug is developed. Isis shall have the right, not more than twice during any
calendar year, to have any Hybridon Antisense Drug Sublicense reviewed by an
independent third party chosen by Isis to confirm whether such Hybridon
Antisense Drug qualifies as a Hybridon Antisense Drug as defined under this
Agreement. Hybridon shall cooperate in all reasonable respects with the review
of such Hybridon Antisense Drug Sublicense by the independent third party under
this Section 3.6, including without limitation responding to questions directed
at determining whether such Hybridon Antisense Drug qualifies as a Hybridon
Antisense Drug. Isis shall pay all costs of such review; provided, however, that
if such Hybridon Antisense Drug does not qualify as a Hybridon Antisense Drug as
defined under this Agreement, Hybridon shall reimburse Isis for the costs of
such review. If the independent third party determines that such Hybridon
Antisense Drug does not qualify as

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a Hybridon Antisense Drug as defined under this Agreement, such independent
third

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party shall notify Hybridon and Isis. If Hybridon disagrees with the
determination of the independent third party, the third party shall be permitted
to provide Isis with a copy of the Hybridon Antisense Drug Sublicense.

      Section 3.8 AFFILIATES. Isis hereby represents and warrants as of the date
hereof that no Affiliate of Isis owns or controls any patents, patent
applications or inventions invented, licensed or sublicensed by such Affiliate
prior to April 26, 2001 which cover or claim Motifs or RNaseH Dependent
Mechanisms of Action.

                                   ARTICLE IV
                               PAYMENT OBLIGATIONS

      Section 4.1 CONSIDERATION FOR LICENSES OF HYBRIDON INTELLECTUAL PROPERTY
AND ISIS INTELLECTUAL PROPERTY. In consideration of the licenses and sublicenses
granted under Sections 2.1 and 3.1 of this Agreement and the restrictions on use
agreed to by Hybridon under this Agreement, Hybridon and Isis each shall pay to
the other the consideration set forth in the Master Agreement and Section 4.2
and Section 4.3 of this Agreement. Isis and Hybridon each recognizes that the
other Party has expended significant efforts and resources in the research and
development of Antisense Technology and the payments to be made under the Master
Agreement to each Party for the patent licenses and sublicenses granted
hereunder will allow each Party to recoup such expenditures.

      Section 4.2 CONSIDERATION FOR SUBLICENSE OF TULLIS PATENTS. In
consideration of the sublicense granted by Isis to Hybridon under Section 3.3 of
this Agreement, Hybridon shall pay to Isis the annual maintenance fee and
royalties provided below:

                  (a) On the date hereof and each anniversary of such date
      thereafter (until the earlier of the termination of the sublicense grant
      under Section 3.3 or the date on which there ceases to be any Valid Claims
      included in the Tullis Patents), an annual maintenance fee of [*]

                  (b) Hybridon shall pay to Isis earned royalties at the rate of
      [*] of Tullis Net Sales of Tullis Products. Hybridon shall be obligated
      to pay such royalties on a country-by-country basis, so long as there
      continues to be a Valid Claim included in the Tullis Patents which covers
      the manufacture, use or sale of the applicable Tullis Product in such
      country. During the term of the sublicense under Section 3.3 and for so
      long thereafter as Hybridon is required to report royalties payable under
      this Section 4.2, Hybridon shall deliver to Isis within thirty (30) days
      after March 31, June 30, September 30 and December 31 of each year a
      report indicating (i) Tullis Net Sales for each Tullis Product, on a
      Tullis

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      Product-by-Tullis Product and country-by-country basis, including an
      accounting of the deductions from Tullis Net Sales permitted by the
      definition thereof and (ii) total royalties owed. Simultaneously with the
      delivery of each such report, Hybridon shall pay to Isis the royalty
      payments due under this Agreement for the period covered by such report.
      If no royalties are due, it shall be so reported.

      Section 4.3 ISIS SUBLICENSE INCOME. Isis shall pay to Hybridon [*] of all
Sublicense Income, [*] in respect of Sublicense Income received in connection
with a Naked Sublicense [*]. Such payment by Isis shall be paid to Hybridon
within 30 days after the calendar quarter in which the Sublicense Income was
received by Isis or a Subsidiary. Isis shall deliver to Hybridon with such
payment a report describing such Sublicense Income and how such Sublicense
Income was calculated, all on a country-by-country and product-by-product basis.

      Section 4.4 RECORDS; AUDITS. For a period not less than three (3) years
after the relevant period, each Party shall keep full, true and accurate books
of account sufficient to determine the amounts payable pursuant to Section
4.2(b) or 4.3, as the case may be. Each Party shall have the right, not more
than once during any calendar year, to have the books and records of the other
Party audited by a qualified independent accounting firm of its choosing, under
appropriate confidentiality provisions, to ascertain the accuracy of the reports
and payments hereunder and compliance by the other Party and its Subsidiaries
and Sublicensees with their obligations under Section 4.2(b) or 4.3, as the case
may be. Such audit shall be conducted upon at least ten (10) days' advance
notice during normal business hours and in a manner that does not interfere
unreasonably with the business of the audited entity. Any underpayment or
overpayment determined by such audit shall promptly be paid or refunded by
Hybridon or Isis, as the case may be. If a Party has underpaid an amount due
under Section 4.2(b) or 4.3, as the case may be, by more than five percent (5%),
such Party shall also reimburse the other Party for the cost of such audit (with
the cost of the audit to be paid by the other Party in all other cases).

      Section 4.5 PAYMENT CURRENCY. All amounts due under this Agreement shall
be paid to the designated Party in United States currency by wire transfer to an
account in a United States bank specified by such Party or in such other form
and/or manner as such Party may reasonably request. The payments due on sales in
currencies other than United States dollars shall be calculated using the
appropriate exchange rate of such currency quoted in the Wall Street Journal on
the close of business on the last business day prior to which such payment is
made.

      Section 4.6 LATE PAYMENTS; COLLECTIONS. Any amount not paid when due under
this Agreement or the Master Agreement shall bear interest at the lesser

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of (i) one and one-half percent (1.5%) per month, compounded monthly, or (ii)
the highest rate permitted by law. Each Party agrees to pay all costs of
collection, including reasonable attorneys' fees, incurred by the other Party in
enforcing the payment obligations of the first Party under this Agreement and
the Master Agreement.

                                    ARTICLE V
                                 COLLABORATION

      In addition to the collaboration between the Parties with respect to
intellectual property protection under Article VI, the Parties shall further
collaborate hereunder through a committee (the "Collaboration Committee")
consisting of two representatives of each Party. The Parties shall establish the
Collaboration Committee within thirty (30) days after the Effective Date. The
Collaboration Committee shall meet at least twice each calendar year in person
or by video conference during the term of this Agreement to review the progress
of Isis' development efforts with respect to Isis' Antisense Products that are
covered by Hybridon Intellectual Property. The Parties intend that the
Collaboration Committee shall act as a forum for the Parties to work
cooperatively [*] The Parties also anticipate that the Collaboration Committee
may recommend to the Parties from time to time that certain aspects of the drug
development process be performed by Hybridon for Isis or that the Parties
consider entering into further collaborations. Neither Party shall be bound by
any recommendation of the Collaboration Committee but shall consider its
recommendations in good faith. In addition, neither Party shall be obligated to
disclose any Confidential Information to the Collaboration Committee.

                                   ARTICLE VI
                        INTELLECTUAL PROPERTY PROTECTION

      Section 6.1 Patent Prosecution and Cooperation.

                  (a) PROSECUTION AND MAINTENANCE OF HYBRIDON ANTISENSE PATENT
      RIGHTS.

                      (i) Hybridon will be responsible for prosecuting and
maintaining the Hybridon Antisense Patent Rights. Hybridon shall promptly
forward to Isis' patent counsel any substantive actions prepared for or received
from the U.S. Patent and Trademark Office or any foreign patent office which may
materially affect patent rights, e.g., claim scope or patent term. Isis' patent
counsel shall provide any comments to Hybridon in sufficient time for Hybridon
to reflect such comments in any response. Any comments made by Isis shall be
made in good faith and shall be directed to maximizing the claims covered by the
Hybridon Antisense Patent Rights.

                      (ii)  If Hybridon agrees with the comments of Isis' patent
counsel, it shall reflect such comments in its response. If Hybridon

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disagrees with such comments, it shall notify Isis, and either Party may then
submit such dispute (a "Patent Comment Dispute") for resolution by an
intellectual property lawyer (the "Neutral Lawyer") with at least five years of
experience and a background in biotechnology or pharmaceutical patent matters.
The Neutral Lawyer shall be selected by mutual agreement of the Parties;
provided, however, that if the Parties

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cannot agree on a Neutral Lawyer within five days of a Party's request for a
Neutral Lawyer under this provision, the Neutral Lawyer shall be selected by the
American Arbitration Association in Washington, D.C. Each Party shall submit its
position as to the Patent Comment Dispute to the Neutral Lawyer, who shall
resolve the dispute by agreeing to one of the submitted positions of the Parties
without any changes to such position. The Parties agree that the position agreed
to by the Neutral Lawyer shall be reflected in the action or response being
prepared and that the costs of the Neutral Lawyer shall be paid by the Party
whose position is not agreed to by the Neutral Lawyer. The decision of the
Neutral Lawyer shall be final and binding on the Parties. In light of the
foregoing dispute resolution mechanism, neither Party shall submit a Patent
Comment Dispute to binding arbitration in accordance with the provisions of
Article VIII. The Parties shall cooperate in all respects to resolve any Patent
Comment Dispute in sufficient time to avoid any loss of rights, including
without limitation jointly instructing the Neutral Lawyer to make a decision in
sufficient time to avoid any loss of rights.

                      (iii)  Isis will be responsible for and pay fifty percent
(50%) of Hybridon's costs incurred in prosecuting and maintaining the Hybridon
Antisense Patent Rights, net of amounts paid to Hybridon for such costs by other
licensees and not including any costs of Hybridon incurred in connection with a
Patent Comment Dispute (except as otherwise specified in the foregoing Section
6.1(a)(ii)). Hybridon shall direct its counsel to invoice Isis directly for
Isis' share of such costs as such costs are incurred.

                  (b) JOINT PATENT COMMITTEE. Hybridon and Isis will, within
      sixty (60) days after the execution of this Agreement, establish a
      committee (the "Joint Patent Committee") consisting of three
      representatives of each Party. The Joint Patent Committee shall confer
      twice each calendar year or as necessary to support timely decision making
      during the term of this Agreement to discuss patent prosecution issues,
      budgets and strategies relating to the Hybridon Antisense Patent Rights.
      The Joint Patent Committee shall also, as set forth in Section 5.2(b),
      determine which Party faces the greatest competitive threat in the event
      of infringement by a third party of any of the Hybridon Antisense Patent
      Rights. In the event that the Joint Patent Committee is unable to resolve
      any matter presented for resolution,. either Party shall have the right to
      submit such matter to binding arbitration in accordance with the
      provisions of Article VIII.

                  (c) INTERFERENCE BETWEEN ISIS INTELLECTUAL PROPERTY AND
      HYBRIDON ANTISENSE PATENT RIGHTS. If an interference is declared between
      any of the Isis Intellectual Property and any of the Hybridon Antisense
      Patent Rights (other than the UMass Patent Rights), each Party shall be
      represented by its own counsel in the interference proceedings; provided,
      however, that Hybridon's counsel shall be jointly selected by Isis and

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      Hybridon; and provided further that if Hybridon and Isis can not agree on
      counsel for Hybridon, a patent lawyer with at least five years of
      experience in interference practice and a background in biotechnology or
      pharmaceutical patent matters shall be selected to represent Hybridon by
      the American Arbitration Association in Washington, D.C. Each Party shall
      seek to resolve the interference in a manner that maximizes the value to
      both parties of the combined portfolio of the Hybridon Antisense Patent
      Rights and the Isis Intellectual Property. If an interference is declared
      between any UMass Patent Rights and any Isis Intellectual Property,
      Hybridon will cooperate with Isis in the resolution thereof to the extent
      permitted under the UMass Agreement or, if Hybridon cannot so cooperate
      due to obligations to UMass, Isis will not be obligated to reimburse
      Hybridon for any expenses related to the interference proceedings. If an
      interference is declared between any of the Hybridon Antisense Patent
      Rights and the intellectual property of a third party or between any of
      the Isis Intellectual Property and the intellectual property of a third
      party, then Hybridon or Isis, as the case may be, shall have sole control
      of prosecuting the interference.

                  (d) PATENT COOPERATION. Isis hereby represents and warrants as
      of the date hereof that since April 26, 2001, neither Isis nor any of its
      Affiliates has challenged, opposed or taken any action to provoke any
      interference with any Hybridon Intellectual Property, and Isis agrees that
      from and after the date of this Agreement Isis shall not, and shall cause
      its Non-Parent Affiliates to not, challenge, oppose or take any action to
      provoke any interference with, or maintain any current challenge or
      opposition to, any Hybridon Intellectual Property. Hybridon hereby
      represents and warrants as of the date hereof that since April 26, 2001,
      neither Hybridon nor any of its Affiliates has challenged, opposed or
      taken any action to provoke any interference with any Isis Intellectual
      Property, and Hybridon agrees that from and after the date of this
      Agreement Hybridon shall not, and shall cause its Non-Parent Affiliates to
      not, challenge, oppose or take any action to provoke any interference
      with, or maintain any current challenge or opposition to, any Isis
      Intellectual Property. Hybridon further agrees that it will not use any
      Hybridon Antisense Patent Rights to challenge or interfere with any
      patents owned by Isis arising out of inventions invented, licensed or
      sublicensed by Isis prior to April 26, 2001, including those included in
      the Isis Intellectual Property, and that Hybridon will not oppose any
      patents claiming inventions invented, licensed or sublicensed by Isis
      prior to April 26, 2001, including those included in the Isis Intellectual
      Property, that cover chemical modifications to antisense oligonucleotides.
      The foregoing obligations not to challenge, oppose or interfere include,
      without limitation obligations not to directly or indirectly provoke an
      interference, participate in an opposition or make any claims of
      invalidity; PROVIDED THAT either Party and its Affiliates may raise a
      claim

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      of invalidity as a defense in a lawsuit filed by the other Party or its
      Affiliates. In addition, in the context of any interference between any of
      the Isis Intellectual Property and any of the Hybridon Antisense Patent
      Rights provoked by the U.S. Patent and Trademark Office, the Parties shall
      use commercially reasonable efforts to reach a settlement that maximizes
      the value to both Parties of the combined portfolio of the Hybridon
      Antisense Patent Rights and the Isis Intellectual Property.

                  (e) Notwithstanding any provision of this Section 6.1 to the
      contrary, nothing in this Section 6.1 shall (x) prevent Hybridon from
      complying with its obligations with respect to the Hybridon Intellectual
      Property under the UMass Agreement or the Third Party License Agreements,
      as applicable, or (y) limit the rights of the third parties under such
      agreements with respect to the Hybridon Intellectual Property, including
      as to clauses (x) and (y):

      (i)   UMass' right to prepare, file, prosecute and maintain certain
            patents and patent applications in the name of UMass pursuant to
            Section 8.1 of the UMass Agreement;

            (ii)  Hybridon's obligation to use counsel acceptable to UMass
            and to consult with UMass regarding the preparation, filing,
            prosecution or maintenance of certain patents and patent
            applications pursuant to Section 8.1 of the UMass Agreement;

            (iii) Hybridon's obligation pursuant to Section 8.2 of the
            UMass Agreement (A) to provide notice to UMass prior to abandoning,
            or failing to make payment or take other necessary actions to
            maintain, certain patents and patent applications and (B) to
            continue the prosecution or maintenance of such patents after notice
            has been provided and before UMass has had sufficient time to assume
            the prosecution or maintenance of such patent;

            (iv) Methylgene's right under Section 5.5 of the Methylgene License
            Agreement to take measures to ensure the registration and
            maintenance of certain patents and patent applications if Hybridon
            fails to register and maintain such patents and patent applications;

            (v) Methylgene's right under Section 5.5 of the Methylgene License
            Agreement to (A) approve the patent agent selected to prosecute
            certain patents and patent applications, (B) be kept informed
            regarding progress or problems related to certain patents and patent
            applications and (C) have its comments on such progress or problems
            be considered;

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            (vi) OriGenix's right under Section 5.5 of the OriGenix License
            Agreement to take measures to ensure the registration and
            maintenance of certain patents and patent applications if Hybridon
            fails to register and maintain such patents and patent applications;

            (vii) OriGenix's right under Section 5.5 of the OriGenix License
            Agreement to (A) approve the patent agent selected to prosecute
            certain patents and patent applications, (B) be kept informed
            regarding progress or problems related to certain patents and patent
            applications and (C) have its comments on such progress or problems
            be considered;

            (viii) EpiGenesis' right pursuant to Section 6.2.2 of the
            Development and License Agreement between EpiGenesis
            Pharmaceuticals, Inc. and Hybridon, dated as August 9, 2000 (the
            "EpiGenesis License Agreement") to file, prosecute and maintain
            certain patents and patent applications if Hybridon elects not to
            continue to seek or maintain patent protection on such patents or
            patent applications;

            (ix) EpiGenesis' right pursuant to Section 6.2.2 of the EpiGenesis
            License Agreement to (A) have Hybridon consult with EpiGenesis
            regarding the prosecution of certain patents and patent
            applications, (B) have a reasonable amount of time to consider and
            comment on any document to be filed in connection with the
            prosecution of such patents and patent applications and (c) have its
            comments on such comments be seriously considered;

            (x) Hybridon's obligation pursuant to Section 6.2.3 of the
            EpiGenesis License Agreement (A) to provide notice to EpiGenesis
            prior to abandoning, or failing to make payment or take other
            necessary actions to maintain certain patents and patent
            applications and (B) to continue the prosecution or maintenance of
            such patents and patent applications after notice has been provided
            and before EpiGenesis has had sufficient time to assume the
            prosecution or maintenance of such patents and patent applications;
            and

            (xi) Boston Biosystems, Inc.'s (BBI) right and Avecia Holdings plc's
            right to prosecute or maintain certain patents and patent
            applications if Hybridon declines to prosecute or maintain such
            patents or patent applications pursuant to (A) Section 4.03 of the
            PNT Monomer Patent License and Option Agreement dated as of
            September 20, 2000 by and between Hybridon and BBI, (B) Section 4.03
            of the Oligonucleotide Purification Patent License Agreement

                                     - 24 -
<Page>

            dated as of September 20, 2000 by and between Hybridon and BBI, and
            (C) Section 5.03 of the Interference Patent Sublicense Option
            Agreement dated as of September 20, 2000 by and between Hybridon and
            BBI.

      Section 6.2 ENFORCEMENT OF HYBRIDON ANTISENSE PATENT RIGHTS

              (a) NOTICE. If Hybridon or Isis becomes aware that any of the
      Hybridon Antisense Patent Rights is infringed by a third party or is
      subject to a declaratory judgment action relating to infringement or
      invalidity, Hybridon or Isis, as the case may be, shall promptly notify
      the other Party.

              (b) FIRST RIGHT OF ENFORCEMENT. In the event of infringement of
      the Hybridon Antisense Patent Rights by a third party, the Party facing
      the greatest competitive threat from the infringement shall have the first
      right (but not the obligation), at its sole expense, to undertake such
      action as it shall determine, in its discretion, appropriate to enforce
      the Hybridon Antisense Patent Rights; provided, however, that such Party
      shall not admit the invalidity or unenforceability of any Hybridon
      Antisense Patent Rights, grant a license to the allegedly infringing third
      party or enter into any settlement agreement without the other Party's
      prior written consent. The determination of which Party faces the greatest
      competitive threat from the infringement shall be made by the Joint Patent
      Committee. If the Joint Patent Committee determines that neither Party
      faces a greater competitive threat than the other Party, then Hybridon
      shall have the first right to enforce the Hybridon Antisense Patent
      Rights. The Party enforcing the Hybridon Antisense Patent Rights shall
      keep the other Party reasonably informed on a quarterly basis, in person
      or by telephone, prior to and during any such enforcement. The other Party
      shall assist the Party enforcing the Hybridon Antisense Patent Rights,
      upon the enforcing Party's request and at the enforcing Party's sole
      expense, in taking any action to enforce the Hybridon Antisense Patent
      Rights and shall join in any such action if deemed by a court of competent
      jurisdiction to be a necessary party. Neither Party shall incur liability
      to the other Party as a consequence of such litigation or any unfavorable
      decision resulting therefrom, including any decision holding any of the
      Hybridon Antisense Patent Rights invalid, not infringed or unenforceable.
      Notwithstanding the foregoing, if Isis is the Party enforcing the Hybridon
      Antisense Patent Rights under this Section 6.2(b) and such Hybridon
      Antisense Patent Rights are included in the claims that are the subject
      matter of the UMass Agreement or are licensed by Hybridon under the Third
      Party License Agreements, Isis' rights to enforce such Hybridon Antisense
      Patent Rights shall be limited to the rights of Hybridon to enforce such
      Hybridon Antisense Patent Rights, and subject to and limited by the rights
      of the other parties to the

                                     - 25 -
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      UMass Agreement and the Third Party License Agreements, as set forth in
      the UMass Agreement or the Third Party License Agreements, as applicable,
      including:

      (i)   UMass's right pursuant to Section 9.2 of the UMass Agreement to
            prosecute any infringements of certain patents and patent
            applications licensed to Hybridon pursuant to the UMass Agreement;

            (ii) Hybridon's obligation pursuant to Section 9.3 of the UMass
            Agreement to seek the consent of UMass to any settlement, consent
            judgement or other voluntary final disposition of a suit involving
            certain patents and patent applications licensed to Hybridon
            pursuant to the UMass License;

            (iii) UMass' right to intervene and take over the sole defense of a
            declaratory judgment action pursuant to Section 9.6 of the UMass
            Agreement;

            (iv) Methylgene's right pursuant to Section 5.1(b) of the Methylgene
            License Agreement to initiate infringement actions related to
            certain patents and patent applications as it may in its discretion
            deem necessary or desirable;

            (v) OriGenix's right pursuant to Section 5.1(v) of the OriGenix
            License Agreement to initiate infringement actions related to
            certain patents and patent applications as it may in its discretion
            deem necessary or desirable; and

            (vi) EpiGensesis' right pursuant to Section 6.6 of the EpiGenesis
            License Agreement to initiate infringement actions related to
            certain patents and patent applications and to consent to any
            settlement of infringement litigation that would materially diminish
            the rights of EpiGenesis in certain patents and patent applications.

Items (i) through (vi) of this Section 6.2(b) are collectively referred to as
the "Other Enforcement Rights".

                  (c) ENFORCEMENT BY OTHER PARTY. If the Party having the first
      right to enforce the Hybridon Antisense Patent Rights pursuant to Section
      5.2(b) above fails to file an action to abate an infringement of the
      Hybridon Antisense Patent Rights, within six (6) months after a written
      request from the other Party to do so, or if such Party fails to
      diligently prosecute or discontinues the prosecution of any such action,
      the other Party at its sole expense may, in its discretion, undertake such
      action as it determines appropriate (other than the grant of a license to
      the allegedly infringing third party) to enforce such Hybridon Antisense

                                     - 26 -
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      Patent Rights. Such other Party shall keep the Party that had the first
      right to enforce the Hybridon Antisense Patent Rights reasonably informed
      on a quarterly basis, in person or by telephone, prior to and during any
      such enforcement. In such case, the Party that had the first right to
      enforce the Hybridon Antisense Patent Rights shall assist such other
      Party, upon such other Party's request and at such other Party's sole
      expense, in taking any action to enforce the Hybridon Antisense Patent
      Rights and shall join in any such action if deemed by a
      court of competent jurisdiction to be a necessary party. Neither Party
      shall incur liability to the other Party as a consequence of such
      litigation or any unfavorable decision resulting therefrom, including any
      decision holding any of the Hybridon Antisense Patent Rights invalid, not
      infringed or unenforceable. Notwithstanding the foregoing, if Isis is the
      Party enforcing the Hybridon Antisense Patent Rights under this Section
      6.2(c) and such Hybridon Antisense Patent Rights are included in the
      claims that are the subject matter of the UMass Agreement or are licensed
      by Hybridon under the Third Party License Agreements, Isis' rights to
      enforce such Hybridon Antisense Patent Rights shall be limited to the
      rights of Hybridon to enforce such Hybridon Antisense Patent Rights, and
      subject to and limited by the rights of the other parties to the UMass
      Agreement and the Third Party License Agreements, as set forth in the
      UMass Agreement or the Third Party License Agreements, as applicable,
      including the Other Enforcement Rights.

                  (d) RECOVERIES. All monies recovered upon the final judgment
or settlement of any action involving the enforcement of Hybridon Antisense
Patent Rights as contemplated by this Section 6.2 shall be allocated in the
following order of priority: (i) first to reimburse the costs and expenses
(including reasonable attorney fees and costs) incurred by the Parties in
prosecuting such action, and (ii) any remaining portion of the recovery shall be
divided between the Parties in proportion to the respective total losses,
determined by aggregating both past and prospective losses, each Party would
have been reasonably likely to have suffered had such infringement continued
unabated. Notwithstanding the foregoing, if the Hybridon Antisense Patent Rights
that were the subject of the action are included in the claims that are the
subject matter of the UMass Agreement or are licensed by Hybridon under the
Third Party License Agreements, the provisions of this Section 6.2(d) shall only
apply to such monies recovered upon the final judgment or settlement of such
action as remain following payment of monies to third parties as required under
the UMass Agreement and the Third Party License Agreements.

                                   ARTICLE VII
                                 CONFIDENTIALITY

      Section 7.1 CONFIDENTIAL INFORMATION. Each Party agrees that all
Confidential Information of a Party that is disclosed by a Party to the other

                                     - 27 -
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Party (a) shall be maintained in confidence by the receiving Party and shall not
be used by the receiving Party for any purpose other than as permitted under
this Agreement, and (b) shall not be disclosed by the receiving Party to any
third party who is not a Subsidiary of the receiving Party, or a consultant or
an advisor to the receiving Party or a Subsidiary of the receiving Party,
without the prior written consent of the disclosing Party; provided, however,
that Confidential Information may only be disclosed by the receiving Party to
Subsidiaries or consultants or advisors to the receiving Party or its
Subsidiaries if such Subsidiaries, consultants or advisors, as the case may be,
have agreed in writing to be bound by the obligations of the
receiving Party under this Section 7.1. Notwithstanding the foregoing, the
receiving Party shall be entitled to use and disclose Confidential Information
that:

                  (a) was known or used by the receiving Party or its
      Subsidiaries prior to its date of disclosure to the receiving Party as
      demonstrated by legally admissible evidence available to the receiving
      Party or its Subsidiaries; or

                  (b) either before or after the date of the disclosure to the
      receiving Party is lawfully disclosed to the receiving Party or its
      Subsidiaries by sources other than the disclosing Party rightfully in
      possession of the Confidential Information and not bound by
      confidentiality obligations to the disclosing Party or its Subsidiaries;
      or

                  (c) either before or after the date of the disclosure to the
      receiving Party is or becomes published or otherwise is or becomes part of
      the public domain through no breach hereof on the part of the receiving
      Party or its Subsidiaries; or

                  (d) is independently developed by or for the receiving Party
      or its Subsidiaries without reference to or reliance upon the Confidential
      Information as demonstrated by competent written records; or

                  (e) is reasonably necessary to conduct clinical trials or for
      regulatory approval of products or for the filing, prosecution and
      maintenance of patents and patent applications, PROVIDED THAT the
      receiving Party provides prior written notice of such disclosure to the
      disclosing Party and takes reasonable and lawful actions to avoid and/or
      minimize the degree of such disclosure; or

                  (f) is required to be disclosed by the receiving Party to
      comply with applicable laws, to defend or prosecute litigation or to
      comply with governmental regulations, PROVIDED THAT the receiving Party
      provides prior written notice of such disclosure to the disclosing Party

                                     - 28 -
<Page>

      and takes reasonable and lawful actions to avoid and/or minimize the
      degree of such disclosure.

                                  ARTICLE VIII
                               DISPUTE RESOLUTION

Section 8.1 Except as set forth in Section 6.1(a)(ii), each Party must submit
any dispute under this Agreement or the Master Agreement to arbitration by
notifying the other Party, in writing, of such dispute. Within 30 days after
receipt of such notice, the Parties shall designate in writing one arbitrator to
resolve the dispute; PROVIDED, that if the Parties cannot agree on an arbitrator
within such 30 days period, the arbitrator shall be selected by the office of
the American
Arbitration Association in the city where arbitration will take place. The
arbitrator shall not be an employee, consultant, officer, director or
stockholder of any Party or its Affiliates. If neither the Parties nor the
applicable office of the American Arbitration Association is able to identify an
individual to serve as the arbitrator, the American Arbitration Association
shall select an arbitrator from the CPC Panel of Distinguished Neutrals of the
CPR Institute for Dispute Resolution.

      Section 8.2 Within 30 days after the designation of the arbitrator, the
arbitrator and the Parties shall meet, at which time the Parties shall be
required to set forth in writing all disputed issues and a proposed ruling on
the merits of each such issue.

      Section 8.3 The arbitrator shall set a date for a hearing, which shall be
no later than 45 days after the submission of written proposals to discuss each
of the issues identified by the Parties. Each Party shall have the right to be
represented by counsel. Except as provided herein, the arbitration shall be
governed by the Commercial Arbitration Rules of the American Arbitration
Association; PROVIDED, HOWEVER, that the Federal Rules of Evidence shall apply
with regard to the admissibility of evidence and the arbitration shall be
conducted by a single arbitrator.

      Section 8.4 The arbitrator shall use his or her best efforts to rule on
each disputed issue within 30 days after the completion of the hearings. The
determination of the arbitrator as to the resolution of any dispute shall be
final and binding and conclusive upon all parties hereto. All determinations of
the arbitrator shall be in writing and shall be delivered to the Parties. The
determinations of the arbitrator may be entered in any court of competent
jurisdiction.

      Section 8.5 The attorneys' fees of the Parties in any arbitration, the
fees of the arbitrator, and the costs and expenses of the arbitration
(collectively, the "Arbitration Costs") shall be borne by the Parties as
determined by the arbitrator.

                                     - 29 -
<Page>

      Section 8.6 The arbitration shall take place in Boston, Massachusetts if
brought by Isis and in San Diego, California if brought by Hybridon.

      Section 8.7 Nothing in this Article VIII shall prevent either Party from
seeking a preliminary injunction, temporary restraining order or similar relief
in order to prevent or limit and irreparable harm that might occur in the
absence thereof from a court of competent jurisdiction.

                                   ARTICLE IX
                              TERM AND TERMINATION

      Section 9.1 TERM. This Agreement shall commence as of the date hereof and
shall continue until the last of the patents and patent applications included in
the Hybridon Intellectual Property, the Isis Intellectual Property and the
Tullis Patents has expired, subject to earlier termination of this Agreement in
accordance with this Article IX. Notwithstanding the foregoing, the licenses or
sublicenses granted hereunder shall terminate on a country-by-country basis
concurrently with the expiration or termination of the applicable Valid Claim
under the Hybridon Intellectual Property, the Isis Intellectual Property or the
Tullis Patents, as the case may be, in the applicable country.

      Section 9.2 TERMINATION OF LICENSES AND SUBLICENSES FOR BREACH.

                  (a) Except as set forth in Section 9.2(b), (i) if an
      arbitrator has rendered a ruling pursuant to Article VIII that a Party or
      a Subsidiary has materially breached this Agreement or the Master
      Agreement, which ruling specified the remedies imposed on such breaching
      party for such breach, including without limitation a ruling on a dispute
      as to breach of a Party's obligation to issue stock or pay cash in lieu of
      stock as required under the Master Agreement (the "ADVERSE RULING"), and
      (ii) the breaching Party has failed to comply with the terms of the
      Adverse Ruling within the time period specified therein for compliance, or
      if such compliance cannot be fully achieved by such date, the breaching
      Party has failed to commence compliance and to use diligent efforts to
      achieve full compliance as soon thereafter as is reasonably possible, then
      the non-breaching Party shall be entitled to terminate the licenses and
      sublicenses granted to the breaching Party and its Subsidiaries by such
      non-breaching Party under this Agreement (without prejudice to any of the
      other rights of the non-breaching Party under this Agreement or the Master
      Agreement) upon written notice to the breaching Party.

                  (b) (i) If a Party breaches an obligation to issue stock or
      pay cash in lieu of stock as required under the Master Agreement, then the
      non-breaching Party may terminate the licenses and sublicenses granted to
      the breaching Party and its Subsidiaries by such

                                     - 30 -
<Page>

      non-breaching Party under this Agreement immediately upon written notice
      to the breaching Party if the breaching Party fails to cure such breach
      within ten (10) business days of written notice of such breach from the
      non-breaching Party; provided, however, that if the breaching Party
      believes that a bona fide dispute exists as to the amount of any payment,
      then the breaching Party may, not later than five business days following
      the notice of the breach, (i) provide the non-breaching Party with a
      written notice setting forth the nature of the dispute and the amount in
      dispute, (ii) at the same time, pay to the non-breaching Party the amount
      of the payment which is not in dispute and (iii) promptly submit the
      dispute to binding arbitration pursuant to Article VIII, in which case the
      non-payment of the disputed portion shall not be deemed a breach during
      the pendency of the arbitration.

                                     - 31 -
<Page>

                      (ii) If the final arbitration order or ruling issued
in the arbitration proceeding resolves the dispute against the breaching Party
and orders the breaching Party to pay all or part of the disputed portion to the
non-breaching Party, then the arbitrator shall include in its award, in addition
to such other remedies as it deems appropriate, the following against the
breaching Party: (A) the Arbitration Costs, (B) [*] and (C) if the arbitrator
finds that a cash payment was due, an amount equal to interest at the rate equal
to the lower of 1.5% per month, compounded monthly, or the highest rate
permitted by law on the amount of cash determined to have been due commencing on
the due date determined by the arbitrator through the date of actual payment.

                  (c) The right of either Party to terminate the licenses and
      sublicenses granted by such Party under this Agreement pursuant to this
      Section 9.2 shall not be affected in any way by its waiver of, or failure
      to take action with respect to any previous default.

                  (d) If the licenses and sublicenses granted by Hybridon to
      Isis and its Subsidiaries under this Agreement are terminated by Hybridon
      pursuant to this Section 9.2, (i) Hybridon shall be entitled to retain the
      licenses granted to it and its Subsidiaries pursuant to Article III,
      subject to the payment obligations of Hybridon specified in the Master
      Agreement and in Article IV, and to continue to receive the stock of Isis
      issuable to it pursuant to Section 2.3 of the Master Agreement, and (ii)
      the provisions of Articles V and VI shall terminate in their entirety. If
      the licenses and sublicenses granted by Isis to Hybridon and its
      Subsidiaries under this Agreement are terminated by Isis pursuant to this
      Section 9.2, Isis shall be entitled to retain the licenses granted to it
      and its Subsidiaries pursuant to Article II, subject to the payment
      obligations of Isis specified in the Master Agreement and in Article IV,
      and to continue to receive the stock of Hybridon issuable to it pursuant
      to Section 2.2 of the Master Agreement.

      Section 9.3 TERMINATION OF SUBLICENSE OF TULLIS PATENTS. Hybridon shall
have the right to terminate the sublicense granted to it and its Subsidiaries
pursuant to Section 3.3 (and the related payment obligations under Section 4.2)
for any reason or no reason at any time upon fifteen (15) days prior written
notice to Isis.

      Section 9.4 SURVIVAL. The expiration or termination of this Agreement for
any reason shall not relieve the Parties of any obligation due and accruing, or
for any liability as to any breach occurring, prior to such expiration or
termination. In addition, the provisions of Section 4.4, Article VII, Article
VIII, Section 9.4, Section 9.5, and Article X shall survive the expiration or
termination of this Agreement.

*Confidential Treatment Requested    - 31 -
<Page>

      Section 9.5 SUBLICENSE SURVIVAL.

                  (a) Notwithstanding the termination of this Agreement or any
      of the licenses or sublicenses granted hereunder pursuant to this Article
      IX, any sublicenses to Isis Intellectual Property and the Tullis Patents
      granted by Hybridon or its Subsidiaries pursuant to Section 3.2 or 3.3(b)
      hereof prior to such termination shall survive such termination. In such
      event, Isis shall have the right to receive directly from the Sublicensee
      any payments or other consideration otherwise payable to Hybridon or its
      Subsidiaries as the sublicensor under such sublicense, and to otherwise
      exercise all of the rights of Hybridon or its Subsidiaries as the
      sublicensor under such sublicense; provided however that Isis shall not
      assume, and shall not be responsible for, any representations, warranties
      or obligations of Hybridon or its Subsidiaries as the sublicensor to any
      Sublicensees other than the licenses under such sublicenses.

                  (b) Notwithstanding the termination of this Agreement or any
      of the licenses or sublicenses granted hereunder pursuant to this Article
      IX, any sublicenses of Hybridon Intellectual Property granted by Isis or
      its Subsidiaries pursuant to Section 2.2 hereof prior to such termination
      shall survive such termination. In such event, Hybridon shall have the
      right to receive directly from the Sublicensee any payments or other
      consideration otherwise payable to Isis or its Subsidiaries as the
      sublicensor, under such sublicense and to otherwise exercise all of the
      rights of Isis or its Subsidiaries as the sublicensor under such
      sublicense; provided however that Hybridon shall not assume, and shall not
      be responsible for, any representations, warranties or obligations of Isis
      or its Subsidiaries as the sublicensor to any Sublicensees other than the
      licenses under such sublicenses.

      Section 9.6 FAILURE TO MAKE MASTER AGREEMENT DELIVERIES. Notwithstanding
any provision in this Agreement to the contrary, including without limitation
Article VIII, [*] Hybridon shall have the right, at its sole election, effective
immediately upon written notice to Isis, [*]

                                   ARTICLE X
                            MISCELLANEOUS PROVISIONS

      Section 10.1 INDEMNIFICATION. Each Party (the "Indemnifying Party") agrees
to defend the other Party and such other Party's Subsidiaries and their
respective directors, officers, employees and agents (the "Indemnified Parties")
at the Indemnifying Party's cost and expense, and shall indemnify and hold the
Indemnified Parties harmless from and against any losses, costs, damages, fees
or expenses arising out of any third party claim relating to (i) any breach by
the Indemnifying Party of any of its representations, warranties or obligations

*Confidential Treatment Requested    - 32 -
<Page>

pursuant to this Agreement, (ii) provided that the third party is not an
Affiliate of the Indemnified Parties, infringement of such third party's patents
resulting from the exercise by the Indemnifying Party or a Subsidiary or a
Sublicensee of the

*Confidential Treatment Requested    - 33 -
<Page>

rights granted by the Indemnified Parties to the Indemnifying Party hereunder or
(iii) product liability resulting from use of a product made, sold or imported
by or for the Indemnifying Party or by or for a Subsidiary or a Sublicensee
under the rights granted by the Indemnified Parties hereunder. In the event of
any claim against the Indemnified Parties by any third party for which
indemnification may be sought pursuant to this Agreement, the Indemnified
Parties shall promptly notify the Indemnifying Party in writing of the claim;
provided that the failure to promptly notify the Indemnifying Party of such
claim shall not result in the loss of rights of indemnification hereunder except
to the extent that the Indemnifying Party was materially prejudiced by such
failure. The Indemnifying Party shall assume, at its sole expense, the defense
of the claim and its settlement. The Indemnified Parties shall cooperate with
the Indemnifying Party and may, at their option and expense, be represented in
any such action or proceeding. The Indemnifying Party shall not be liable for
any litigation costs or expenses incurred by the Indemnified Parties. In
addition, the Indemnifying Party shall not be responsible for the
indemnification of any Indemnified Party arising from any negligent or wrongful
acts by such Indemnified Party, or as the result of any settlement or compromise
by the Indemnified Parties without the Indemnifying Party's prior written
consent. The Indemnifying Party may not settle or compromise any matter without
the consent of the Indemnified Parties unless such settlement or compromise
imposes no obligations on the Indemnified Parties and does not restrict the
rights of the Indemnified Parties.

      Section 10.2 GOVERNING LAW. This Agreement shall be construed and the
respective rights of the Parties determined according to the laws of the State
of Delaware (without regard to the conflict of law rules of any jurisdiction),
except matters of the intellectual property law, which shall be determined in
accordance with the national intellectual property laws relevant of the
intellectual property in question.

      Section 10.3 ASSIGNMENT. Neither Hybridon nor Isis may assign this
Agreement in whole or in part without the consent of the other Party, except if
such assignment occurs in connection with the sale or transfer of all or
substantially all of the business or assets of the assigning Party to which the
subject matters of this Agreement pertains.

      Section 10.4 ENTIRE AGREEMENT; AMENDMENTS. This Agreement, together with
the Master Agreement, constitutes the entire agreement between the Parties with
respect to the subject matter hereof, and supersedes all previous arrangements
with respect to the subject matter hereof, whether written or oral. Any
amendment or modification to this Agreement shall be made in writing signed by
both Parties.

      Section 10.5 NOTICES.

                                     - 33 -
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      Notices to Hybridon shall be addressed to:
               Hybridon, Inc.
               345 Vassar Street
               Cambridge, Massachusetts 02139
               Attention: Chief Executive Officer

      with a copy to:

               Holland and Knight, LLP
               10 St. James Avenue
               Boston, Massachusetts 02116
               Attention: James Pollock, Esq.

               And

               Hale and Dorr LLP
               60 State Street
               Boston, MA  02109
               Attention: David E. Redlick, Esq.

                                     - 34 -
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      Notices to Isis shall be addressed to:

               Isis Pharmaceuticals, Inc.
               2292 Faraday Avenue
               Carlsbad, California 92008
               Attention:  Chief Executive Officer
               Copy to: Executive Vice President

      Any Party may change its address by giving notice to the other Party in
the manner herein provided. Any notice required or provided for by the terms of
this Agreement shall be in writing and shall be (a) delivered personally, (b)
sent by registered or certified mail, return receipt requested, postage prepaid,
(c) sent via a reputable overnight courier service, or (d) sent by facsimile
transmission with an original to be followed the same day via a reputable
overnight courier service, in each case properly addressed in accordance with
the paragraph above. The effective date of notice shall be the actual date of
receipt by the Party receiving the same.

      Section 10.6 FORCE MAJEURE. No failure or omission by a Party in the
performance of any of its obligations of this Agreement shall be deemed a breach
of this Agreement or create any liability if the same shall arise from any cause
or causes beyond the control of such Party, including, but not limited to, the
following: acts of God; acts or omissions of any government; any rules,
regulations or orders issued by any governmental authority or by any officer,
department, agency or instrumentality thereof; fire; storm; flood; earthquake;
accident; war; rebellion; insurrection; riot; and invasion and provided that
such failure or omission resulting from one of the above causes is cured as soon
as is practicable after the occurrence of one or more of the above-mentioned
causes.

      Section 10.7 DISCLOSURE OF PROVISIONS OF AGREEMENT.

                  (a) Each Party agrees to hold as confidential the terms of
      this Agreement, except that (i) Hybridon may furnish a copy of this
      Agreement to UMass, Isis may furnish a copy of this Agreement to MBI
      (other than Exhibits containing information relating to patent
      applications of Hybridon) and each Party shall have the right to disclose
      the terms of this Agreement (other than the information on the Exhibits
      hereto relating to patent applications of Isis or Hybridon) to potential
      investors and other third parties in connection with financing activities
      and to potential collaborators, provided that any such third party has
      entered into a written obligation with the disclosing Party to treat such
      information and materials as confidential and to not use the information
      and materials for any purposes other than the evaluation of the potential

                                     - 35 -
<Page>

      investment or collaboration and that the disclosing Party shall enforce
      against the third party recipient of such information and materials, for
      and on behalf of the other Party, such written obligation, and (ii) each
      Party may furnish a copy of this Agreement or disclose the terms of this
      Agreement if such is required to be disclosed by the receiving Party to
      comply with applicable laws, to defend or prosecute litigation or to
      comply with governmental regulations, PROVIDED THAT the receiving Party
      provides prior written notice of such disclosure to the disclosing Party
      and takes reasonable and lawful actions to avoid and/or minimize the
      degree of such disclosure. At the request of the other Party, the
      disclosing Party shall use commercially reasonable efforts to enforce such
      obligations against such third parties.

                  (b) Notwithstanding Section 10.7(a) to the contrary, either
      Party may include this Agreement, in any report, statement or other
      document filed by such Party with the United States Securities and
      Exchange Commission (the "SEC"). In such event, the disclosing Party shall
      use reasonable efforts to obtain, to the extent permitted by law,
      confidential treatment from the SEC of any trade secrets and commercial or
      financial information of a privileged or confidential nature, including
      without limitation all information on the Exhibits hereto relating to
      patent applications of Isis or Hybridon, and shall notify the other Party
      as to such efforts and all related communications with the SEC; provided
      that notwithstanding the foregoing no Party shall submit a confidentiality
      request or include this Agreement without the prior review and approval of
      the confidentiality request by the other Party, which review and approval
      shall not be unreasonably withheld or delayed.

      Section 10.8 INDEPENDENT CONTRACTORS. It is understood and agreed that the
relationship between the Parties hereunder is that of independent contractors
and that nothing in this Agreement shall be construed as authorization for
either Party to act as agent for the other.

      Section 10.9 NO STRICT CONSTRUCTION. This Agreement has been prepared
jointly and shall not be strictly construed against any Party.

      Section 10.10 HEADINGS. The captions or headings of the Sections or other
subdivisions hereof are inserted only as a matter of convenience or for
reference and shall have no effect on the meaning of the provisions hereof.

      Section 10.11 NO IMPLIED WAIVERS; RIGHTS CUMULATIVE. No failure on the
part of either Party to exercise, and no delay in exercising, any right, power,
remedy or privilege under this Agreement, or provided by statute or at law or in
equity or otherwise, shall impair, prejudice or constitute a waiver of any such
right, power, remedy or privilege or be construed as a waiver of any breach of
this Agreement or as an acquiescence therein, nor shall any single or partial

                                     - 36 -
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exercise of any such right, power, remedy or privilege preclude any other or
further exercise thereof or the exercise of any other right, power, remedy or
privilege. In particular, the Parties hereby agree that termination of the
licenses or sublicenses granted under this Agreement as provided in Article IX
shall not be the exclusive remedy of a Party in the event of a breach of this
Agreement or the Master Agreement by the other Party and that the non-breaching
Party shall be entitled to seek any and all other remedies to which the
non-breaching Party may be entitled at law or in equity.

      Section 10.12 SEVERABILITY. If any provision hereof should be held
invalid, illegal or unenforceable in any respect in any jurisdiction, then, to
the fullest extent permitted by law, (a) all other provisions hereof shall
remain in full force and effect in such jurisdiction and shall be liberally
construed in order to carry out the intentions of the Parties as nearly as may
be possible and (b) such invalidity, illegality or unenforceability shall not
affect the validity, legality or enforceability of such provision in any other
jurisdiction.

      Section 10.13 EXECUTION IN COUNTERPARTS. This Agreement may be executed in
counterparts, each of which counterparts, when so executed and delivered, shall
be deemed to be an original, and all of which counterparts, taken together,
shall constitute one and the same instrument.

      Section 10.14 NO CONSEQUENTIAL DAMAGES. NEITHER PARTY HERETO WILL BE
LIABLE FOR SPECIAL, INCIDENTAL OR CONSEQUENTIAL DAMAGES ARISING OUT OF THIS
AGREEMENT OR THE EXERCISE OF ITS RIGHTS HEREUNDER, REGARDLESS OF ANY NOTICE OF
SUCH DAMAGES.

      Section 10.15 PATENT VALIDITY. Notwithstanding anything in this Agreement
to the contrary, neither Party represents and warrants or shall be deemed to
have represented and warranted to the other Party that the Hybridon Intellectual
Property (in the case of Hybridon) and the Isis Intellectual Property and the
Tullis Patents (in the case of Isis) are valid or otherwise enforceable.

                    [Remainder of page intentionally omitted]

                                     - 37 -
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         IN WITNESS WHEREOF, the Parties have executed this License Agreement as
of the Effective Date.

                                            ISIS PHARMACEUTICALS, INC.

                                            By: /s/ B. Lynne Parshall
                                                --------------------------------
                                            Name: B. Lynne Parshall
                                                  ------------------------------
                                            Title: Executive Vice President
                                                   -----------------------------

                                            HYBRIDON, INC.

                                            By: /s/ Sudhir Agrawal
                                                --------------------------------
                                            Name: Sudhir Agrawal
                                                  ------------------------------
                                            Title: President and CSO
                                                   -----------------------------
                                                   /s/ Robert Andersen, CFO

                                     - 38 -

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                                    EXHIBIT A

                                      [ * ]

*Confidential Treatment Requested

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                                   EXHIBIT B1

                                      [ * ]

*Confidential Treatment Requested

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                                   EXHIBIT B2

                                      [ * ]

*Confidential Treatment Requested

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                                    EXHIBIT C

                                      [ * ]

*Confidential Treatment Requested

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                                    EXHIBIT D

                                      [ * ]

*Confidential Treatment Requested

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                                    EXHIBIT E

                                       [*]

*Confidential Treatment Requested

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                                    EXHIBIT F

                                      [ * ]

*Confidential Treatment Requested

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                                    EXHIBIT G

                                      [ * ]

*Confidential Treatment Requested

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                                   EXHIBIT H-1

                         THIRD PARTY LICENSE AGREEMENTS

Methylgene

AMENDED AND RESTATED LICENSE AGREEMENT MADE EFFECTIVE AS OF JANUARY 4, 1996, AS
AMENDED AND RESTATED ON SEPTEMBER 21, 2000.

Origenix

LICENSE AGREEMENT DATED AS OF JANUARY 22, 1999 BETWEEN HYBRIDON AND ORIGENIX.

Epigenesis

DEVELOPMENT AND LICENSE AGREEMENT BETWEEN EPIGENESIS PHARMACEUTICALS, INC. AND
HYBRIDON, INC., DATED AS OF AUGUST 9, 2000.

Boston Biosystems, Inc. (BBI)

PNT MONOMER PATENT LICENSE AND OPTION AGREEMENT DATED AS OF SEPTEMBER 20, 2000
BY AND BETWEEN HYBRIDON AND BBI.

OLIGONUCLEOTIDE PURIFICATION PATENT LICENSE AGREEMENT DATED AS OF SEPTEMBER 20,
2000 BY AND BETWEEN HYBRIDON AND BBI.

INTERFERENCE PATENT SUBLICENSE OPTION AGREEMENT DATED AS OF SEPTEMBER 20, 2000
BY AND BETWEEN HYBRIDON AND BBI.

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                                   EXHIBIT H-2

                            OTHER LICENSE AGREEMENTS

UMass Agreement

LICENSE AGREEMENT DATED AS OF FEBRUARY 21, 1990 AND RESTATED AS OF SEPTEMBER 8,
1993 BY AND BETWEEN HYBRIDON AND UNIVERSITY OF MASSACHUSETTS MEDICAL CENTER
(FORMERLY THE WORCESTER FOUNDATION FOR BIOMEDICAL RESEARCH, INC.)

IDT Agreement

Non-Exclusive License Agreement dated as of March 12, 1999 between Integrated
DNA Technologies, Inc. and Hybridon

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                                    EXHIBIT I

                                      [ * ]

*Confidential Treatment Requested

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                                    EXHIBIT J

                                 UMASS AGREEMENT

Incorporated by reference to Exhibit 10.1 to Hybridon's Registration Statement
on Form S-1 (File No. 33-99024)

*Confidential Treatment Requested

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                                    EXHIBIT K

                                      [ * ]

*Confidential Treatment Requested

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                                    EXHIBIT L

                                      [ * ]

*Confidential Treatment Requested

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                                    EXHIBIT M

                                      [ * ]

*Confidential Treatment Requested

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                                    EXHIBIT N

                                TULLIS AGREEMENT

Incorporated by reference to Exhibit 10.1 to Isis's Quarterly Report Pursuant to
Section 13 or 15(d) of the Securities Exchange Act of 1934 for the quarterly
period ended September 30, 1992, on Form 10-Q (File No. 0-19125).

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00028-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00028-of-00352.parquet"}]]