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                                                                   EXHIBIT 10.22

                            STOCK PURCHASE AGREEMENT

                             DATED NOVEMBER 1, 1999

                                     BETWEEN

                           EPOCH PHARMACEUTICALS, INC.

                                       AND

                             THE INVESTORS LISTED ON

                                SCHEDULE A HERETO




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                           EPOCH PHARMACEUTICALS, INC.

                            STOCK PURCHASE AGREEMENT


        THIS STOCK PURCHASE AGREEMENT (this "Agreement") is made as of the 1st
day of November, 1999, by and between Epoch Pharmaceuticals, Inc., a Delaware
corporation (the "Company"), and the persons or entities listed on Schedule A
attached hereto (individually, an "Investor" and collectively, the "Investors").

        WHEREAS, the Company and Investors wish to enter into this Agreement to
set forth the terms of Investors' purchase of Common Stock from the Company.

        NOW THEREFORE, BE IT RESOLVED, that the parties hereto, intending to be
legally bound, hereby agree as follows:

        1. PURCHASE AND SALE OF COMMON STOCK.

               1.1 SALE AND ISSUANCE OF COMMON STOCK. Subject to the terms and
conditions of this Agreement, each Investor agrees to purchase, and the Company
agrees to sell and issue to each Investor, at the Initial Closing and the Second
Closing (collectively, the "Closings," defined in Section 1.2(a) below), that
number of shares of the Company's Common Stock set forth opposite such
Investor's name on Schedule A (the "Shares") for the purchase price set forth
thereon, which shall not be less than $2.50 per share.

               1.2 CLOSINGS.

                    (a) Initial Closing. Subject to the satisfaction or waiver
of the conditions set forth in Sections 4 and 5 hereof, the purchase and sale of
2,080,000 of the Shares to the Investors shall take place at the offices of
Stradling Yocca Carlson & Rauth, a Professional Corporation, 660 Newport Center
Drive, Suite 1600, Newport Beach, California, at 10:00 a.m., on November 1,
1999, or at such other time and place as the Company and Investors mutually
agree upon, either orally or in writing (which time and place is designated as
the "Initial Closing").

                    (b) Second Closing. Subject to the satisfaction or waiver of
the conditions set forth in Sections 4 and 5 hereof, the purchase and sale of up
to 1,320,000 of the Shares to the Investors shall take place at the offices of
Stradling Yocca Carlson & Rauth, a Professional Corporation, 660 Newport Center
Drive, Suite 1600, Newport Beach, California, at 10:00 a.m., on November 15,
1999, or at such other time and place as the Company and Investors mutually
agree upon, either orally or in writing (which time and place is designated as
the "Second Closing"), but in no event later than forty-five (45) days after the
date of the Initial Closing.

                    (c) Subject to the terms of this Agreement, at the Closings,
the Company shall deliver to each Investor a certificate representing that
number of Shares set forth opposite such Investor's name on Schedule A, against
payment of the purchase price therefor by check, wire transfer, evidence of the
cancellation of debt, or evidence of the cancellation of certain prepayments, as
set forth on Schedule A.




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        2. REPRESENTATIONS AND WARRANTIES OF THE COMPANY.

        Except as disclosed in the Schedules attached hereto by reference to the
specific Section or Sections hereof to which the disclosure pertains, the
Company represents and warrants to the Investors as follows:

               2.1 ORGANIZATION, GOOD STANDING AND QUALIFICATION. The Company is
a corporation duly organized, validly existing and in good standing under the
laws of the State of Delaware and has all requisite corporate power and
authority to own and operate its properties and assets and to carry on its
business as presently conducted. The Company is duly qualified and authorized to
transact business and is in good standing as a foreign corporation in each
jurisdiction where the nature of its activities and of its properties makes such
qualification necessary, except where failure to so qualify would not have a
material adverse effect upon the Company.

               2.2 CAPITALIZATION. The authorized capital stock of the Company
consists of 50,000,000 shares of Common Stock, $.01 par value, and 10,000,000
shares of Preferred Stock, $.01 par value. As of October 22, 1999, there were
issued and outstanding 15,132,669 shares of Common Stock and no shares of
Preferred Stock. Immediately following the Closings all issued and outstanding
shares of the Company's capital stock will have been duly authorized, validly
issued, fully paid and non-assessable and issued in compliance with federal and
state securities laws. The Company has reserved (a) an aggregate of 1,301,812
shares of Common Stock for issuance upon the exercise of certain warrants at an
exercise price of $2.50 per share (the "Exchange Warrants"), (b) an aggregate of
2,500,000 shares of Common Stock for issuance upon the exercise of certain other
warrants at an exercise price of $2.50 per share (the "Private Placement
Warrants"), (c) an aggregate of 3,796,963 shares of Common Stock for issuance
upon the exercise of certain other warrants at an exercise price ranging from
$.30 to $9.21 per share (the "Other Warrants"), and (d) an aggregate of
1,936,470 shares of Common Stock for issuance pursuant to the Company's
Incentive Stock Option, Nonqualified Stock Option and Restricted Stock Purchase
Plans, of which 1,623,269 shares are subject to currently outstanding options.
Except as set forth in the immediately preceding sentence, none of the Common
Stock is subject to any preemptive or subscription right, any voting trust
agreement or other contract, agreement, arrangement, option, warrant, call,
commitment or other right of any character obligating or entitling the Company
to issue, sell, redeem or repurchase any of its securities, and there is no
outstanding security of any kind convertible into or exercisable or exchangeable
for Common Stock. Except as set forth on Schedule 2.2 attached hereto, there are
no agreements or arrangements pursuant to which the Company is or could be
required to register shares of the Company's capital stock or other securities
under the Securities Act of 1933, as amended (the "Securities Act"), or other
agreements or arrangements (including voting agreements) with or, to the
knowledge of the Company, among any security holders of the Company with respect
to any securities of the Company.

               2.3 AUTHORIZATION. All corporate action on the part of the
Company, its officers, directors and stockholders necessary for the
authorization, execution and delivery of this Agreement, the performance of the
Company's obligations hereunder and the authorization, issuance, sale and
delivery of the Shares has been taken or will be taken prior to the Closings.
This Agreement when executed and delivered by the Company, shall constitute a
valid and legally binding obligation of the Company, enforceable against the
Company in accordance with its terms except (a) as limited by applicable
bankruptcy, insolvency, reorganization, moratorium, and other laws of general
application affecting enforcement of creditors' rights generally, (b) as limited
by laws relating to the availability of specific performance, injunctive relief
or other equitable remedies, or (c) to the extent the



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indemnification provisions in Section 6.5 below may be limited by applicable
federal or state securities law.

               2.4 VALID ISSUANCE OF THE SHARES; COMPLIANCE WITH SECURITIES
LAWS. When issued, sold and delivered in compliance with the provisions of this
Agreement and the Company's certificate of incorporation, the Shares will be
duly and validly issued, fully paid and nonassessable and will be free of any
liens, encumbrances, and restrictions on transfer other than restrictions on
transfer under this Agreement and applicable state and federal securities laws.
Assuming the accuracy of the representations and warranties of the Investors set
forth in this Agreement, the offer, sale and issuance of the Shares as
contemplated by this Agreement are exempt from the registration requirements of
the Securities Act, and have been registered or qualified (or are exempt from
registration or qualification) under the registration, permit, or qualification
requirements under all applicable state securities laws.

               2.5 GOVERNMENTAL CONSENTS. All consents, approvals, orders, or
authorizations of, or registrations, qualifications, designations, declarations,
or filings with, any governmental authority, required on the part of the Company
in connection with the valid execution and delivery of this Agreement, the
offer, sale or issuance of the Shares, or the consummation of any other
transaction contemplated hereby have been obtained, or will be effective at the
Closings, except for notices required or permitted to be filed with certain
state and federal securities commissions after the Closings, which notices will
be filed by the Company on a timely basis.

               2.6 SEC FILINGS. The Company has filed with the Securities and
Exchange Commission (the "SEC") all reports, schedules, forms, statements and
other documents required pursuant to the Securities Act and the Securities
Exchange Act of 1934, as amended (the "Exchange Act"), since January 1, 1998
(collectively, and in each case including all exhibits and schedules thereto and
documents incorporated by reference therein, the "SEC Documents"). As of their
respective dates, the SEC Documents complied as to form in all material respects
with the requirements of the Securities Act or the Exchange Act, as the case may
be, and the rules and regulations of the SEC promulgated thereunder applicable
to such SEC Documents. As of their respective dates, (i) none of the SEC
Documents (including any and all financial statements included therein) filed
pursuant to the Securities Act or any rule or regulation thereunder contained
any untrue statement of a material fact or omitted to state a material fact
required to be stated therein or necessary in order to make the statements
therein not misleading, and (ii) none of the SEC Documents (including any and
all financial statements included therein) filed pursuant to the Exchange Act or
any rule or regulation thereunder contained any untrue statement of a material
fact or omitted to state a material fact required to be stated therein or
necessary in order to make the statements therein, in the light of the
circumstances under which they were made, not misleading. Except to the extent
that information contained in any SEC Document has been revised or superseded by
a later filed SEC Document, none of the SEC Documents (including any and all
financial statements included therein) contains any untrue statement of a
material fact or omits to state a material fact required to be stated therein or
necessary in order to make the statements therein, in the light of the
circumstances under which they were made, not misleading. The consolidated
financial statements of the Company included in all SEC Documents filed since
January 1, 1998 (the "SEC Financial Statements") comply as to form in all
material respects with applicable accounting requirements and the published
rules and regulations of the SEC with respect thereto, have been prepared in
accordance with generally accepted accounting principles (except, in the case of
unaudited consolidated quarterly statements, as permitted by Form 10-Q of the
SEC), applied on a consistent basis during the periods involved (except as may
be indicated in the notes thereto). The



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SEC Financial Statements fairly present the consolidated financial position of
the Company as of the dates thereof and the consolidated results of its
operations and cash flows for the periods then ended (subject, in the case of
unaudited quarterly statements, to normal recurring audit adjustments). The
Company does not have any liabilities or obligations of any nature (whether
accrued, absolute, contingent or otherwise) required by generally accepted
accounting principles to be recognized or disclosed on a consolidated balance
sheet of the Company or in the notes thereto, except (i) liabilities reflected
in the consolidated unaudited balance sheet of the Company as of December 31,
1998 or the notes thereto (subject to ordinary year-end adjustments), (ii)
liabilities disclosed in any SEC Documents filed by the Company prior to the
date of this Agreement with respect to any period ending, or date occurring,
after December 31, 1998, and (iii) liabilities incurred since December 31, 1998
in the ordinary course of business consistent with past practice.

               2.7 FULL DISCLOSURE. The Company has provided Investors with all
the information that Investors have requested for deciding whether to purchase
the Shares. Neither this Agreement nor the representations and warranties
contained herein, nor any other written statements or certificates made or
delivered in connection herewith, when read together, contains any untrue
statement of a material fact or omits to state a material fact necessary to make
the statements herein or therein not misleading.

               2.8 ABSENCE OF CERTAIN CHANGES OR EVENTS. Except as disclosed on
Schedule 2.8 attached hereto, since December 31, 1998, the Company has conducted
its business only in the ordinary course consistent with past practice, and
there is not and has not been: (i) since December 31, 1998, any condition, event
or occurrence which has had a material adverse effect on the business,
properties, financial condition or results of operations of the Company (a
"Material Adverse Effect"); (ii) since December 31, 1998, any condition, event
or occurrence which as of the date of this Agreement, individually or in the
aggregate, could reasonably be expected to have a Material Adverse Effect with
respect to the Company; or (iii) since December 31, 1998, any condition, event
or occurrence which, individually or in the aggregate, could reasonably be
expected to prevent or materially delay the ability of the Company to consummate
the transactions contemplated by this Agreement or perform its obligations
hereunder.

               2.9 LITIGATION. Except as disclosed on Schedule 2.9 attached
hereto, there is (a) no suit, action, arbitration or proceeding pending, and (b)
to the knowledge of the Company, no suit, action, arbitration or proceeding
threatened against or investigation pending with respect to the Company that,
individually or in the aggregate, could reasonably be expected to have a
Material Adverse Effect with respect to the Company or prevent or materially
delay the ability of the Company to consummate the transactions contemplated by
this Agreement or to perform its obligations hereunder, nor is there any
judgment, decree, citation, injunction, rule or order of any court or
administrative or governmental body or agency (a "Governmental Entity") or
arbitrator outstanding against the Company which, individually or in the
aggregate, has or could reasonably be expected to have, any such effect.

               2.10 NO CONFLICTS OR DEFAULTS. The execution and delivery of this
Agreement by the Company and the consummation of the transactions contemplated
hereby do not and will not (a) contravene the certificate of incorporation or
by-laws of the Company or (b) with or without the giving of notice or the
passage of time, (i) violate, conflict with, or result in a breach of, or a
default or loss of rights under, any material covenant, agreement, mortgage,
indenture, lease, instrument, permit or license to which the Company is a party
or by which the Company or any of its assets is bound, or any judgment, order or
decree, or any law, rule or regulation to which the Company or any



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of its assets is subject, or (ii) result in the creation of, or give any party
the right to create, any lien, charge, security interest, encumbrance or any
other right or adverse interest upon any of the capital stock or assets of the
Company.

               2.11 COMPLIANCE WITH LAWS. The Company holds all permits,
licenses, variances, exemptions, orders and approvals of all Governmental
entities which are material to the operation of the businesses of the Company
(the "Company Permits"). The Company is in compliance with the terms of the
Company Permits, except where the failure so to comply, individually or in the
aggregate, would not have a Material Adverse Effect with respect to the Company.
The businesses of the Company are not being conducted in violation of any law
(domestic or foreign), ordinance or regulation of any Governmental Entity,
except for possible violations which, individually or in the aggregate, do not
and could not reasonably be expected to have a Material Adverse Effect with
respect to the Company.

        3. REPRESENTATIONS AND WARRANTIES OF INVESTORS.

        Each Investor, severally and not jointly, hereby represents and warrants
to the Company as follows:

               3.1 LEGAL POWER. Investor has the power and authority to enter
into this Agreement, to purchase the Shares hereunder and to carry out and
perform its obligations under the terms of this Agreement.

               3.2 DUE EXECUTION. This Agreement has been duly authorized,
executed and delivered by Investor, and, upon due execution and delivery by the
Company, this Agreement will be a valid and binding obligation of Investor,
enforceable in accordance with its terms, except (a) as limited by applicable
bankruptcy, insolvency, reorganization, moratorium, and other laws of general
application affecting enforcement of creditors' rights generally, (b) as limited
by laws relating to the availability of specific performance, injunctive relief
or other equitable remedies, or (c) to the extent the indemnification provisions
in Section 6.5 below may be limited by applicable federal or state securities
law.

               3.3 INFORMATION. Investor believes that it, or its
representatives, have received all information Investor considers necessary for
evaluating the risks and merits of acquiring the Shares. Investor further
represents that Investor has had the opportunity to ask questions and receive
answers from the Company regarding the terms and conditions of the Shares and
the business, properties, prospects and financial condition of the Company. The
foregoing, however, does not limit or modify the representations and warranties
of the Company in Section 2 of this Agreement or the right of Investor to rely
thereon.

               3.4 INVESTMENT REPRESENTATIONS.

                    (a) Investor is acquiring the Shares for its own account,
not as nominee or agent, for investment and not with a view to, or for resale in
connection with, any distribution or public offering thereof within the meaning
of the Securities Act .

                    (b) Investor understands that (i) the Shares have not been
registered under the Securities Act by reason of a specific exemption therefrom,
that the securities are "restricted securities" and the Investor must hold the
Shares indefinitely, and that it must, therefore, bear the



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economic risk of such investment indefinitely, unless a subsequent disposition
thereof is registered under the Securities Act or is exempt from such
registration; (ii) each certificate representing the Shares will be endorsed
with the following legend:

               "THE SECURITIES EVIDENCED BY THIS CERTIFICATE HAVE NOT BEEN
               REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED, (THE
               "1933 ACT") AND MAY NOT BE SOLD, TRANSFERRED, ASSIGNED OR
               HYPOTHECATED EXCEPT PURSUANT TO AN EFFECTIVE REGISTRATION
               STATEMENT UNDER THE 1933 ACT COVERING SUCH SECURITIES OR IF THE
               COMPANY RECEIVES AN OPINION OF COUNSEL FOR THE HOLDER OF THESE
               SECURITIES REASONABLY SATISFACTORY TO THE COMPANY, STATING THAT
               SUCH SALE, TRANSFER, ASSIGNMENT OR HYPOTHECATION IS EXEMPT FROM
               THE REGISTRATION AND PROSPECTUS DELIVERY REQUIREMENTS OF THE 1933
               ACT."

and (iii) the Company will instruct any transfer agent not to register the
transfer of any of the Shares unless the conditions specified in the foregoing
legend are satisfied; provided, however, that no such opinion of counsel shall
be necessary if the sale, transfer or assignment is made pursuant to SEC Rule
144 and the Investor provides the Company with evidence reasonably satisfactory
to the Company and its counsel that the proposed transaction satisfies the
requirements of Rule 144. The Company agrees to remove the foregoing legend from
any securities if the requirements of SEC Rule 144(k) (or any successor rule or
regulation) apply with respect to such securities and the Company and its
counsel are provided with reasonably satisfactory evidence that the requirements
of Rule 144(k) apply.

                    (c) Investor has not been offered the Shares by any form of
advertisement, article, notice or other communication published in any
newspaper, magazine or similar media or broadcast over television or radio, or
any seminar or meeting whose attendees have been invited by such media.

                    (d) Investor acknowledges that it is able to fend for
itself, can bear the economic risk of its investment and has such knowledge and
experience in financial and business matters that it is capable of evaluating
the merits and risks of acquisition of the Shares and of making an informed
investment decision with respect thereto.

                    (e) Investor's principal place of business or address is as
set forth on the signature page hereto, and, if it is an individual, it does not
reside in any state of the United States other than the state, if any, specified
in its address on the signature page.

                    (f) Investor acknowledges that an investment in the Shares
is speculative and involves a high degree of risk of loss of all or part of
Investor's investment therein.

                    (g) Investor understands that the foregoing representations
and warranties are to be relied upon by the Company as a basis for exemption of
the sale of the Shares under the Securities Act, under the securities laws of
all applicable states and for other purposes. In the event



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any of such representations and warranties become inaccurate or untrue prior to
the Closings, the Investor will promptly notify the Company.

                    (h) Investor was not formed for the specific purpose of
acquiring the Shares.

               3.5 FURTHER REPRESENTATIONS BY FOREIGN INVESTORS. If Investor is
not a U.S. person or entity such Investor hereby represents that it is satisfied
as to the full observance of the laws of such Investor's jurisdiction in
connection with the purchase of the Shares or any use of this Agreement,
including (i) the legal requirements with such Investor's jurisdiction for the
purchase of the Shares, (ii) any foreign exchange restrictions applicable to
such purchase, (iii) any governmental or other consents that may need to be
obtained, and (iv) the income tax and other tax consequences, if any, which may
be relevant to the purchase, holding, redemption, sale, or transfer of the
Shares. Such Investor's purchase of and payment for, and such Investor's
continued beneficial ownership of, the Shares will not violate any applicable
securities or other laws of such Investor's jurisdiction.

        4. CONDITIONS OF THE INVESTORS' OBLIGATIONS AT CLOSINGS.

        The obligations of Investors under subsection 1.1 of this Agreement are
subject to the fulfillment on or before the Closings of each of the following
conditions, the waiver of which shall not be effective against Investors unless
consented to by Investors in writing thereto:

               4.1 REPRESENTATIONS AND WARRANTIES. The representations and
warranties of the Company contained in Section 2 shall be true and correct in
all material respects on and as of the Closings, except those representations
and warranties qualified by materiality, which shall be true and correct in all
respects, with the same force and effect as though such representations and
warranties had been made on and as of the Closings.

               4.2 PERFORMANCE OF OBLIGATIONS. The Company shall have performed
and complied in all material respects with all agreements, obligations and
conditions contained herein that are required to be performed or complied with
by it on or prior to the Closings.

               4.3 COMPLIANCE CERTIFICATE. The Company shall deliver to
Investors at the Closings a Certificate, executed by the President of the
Company, certifying that the conditions specified in subsections 4.1 and 4.2
have been fulfilled.

               4.4 QUALIFICATIONS. All authorizations, approvals, or permits, if
any, of any governmental authority or regulatory body of the United States, of
any state or any foreign country that are required in connection with the lawful
sale and issuance of the Shares pursuant to this Agreement shall have been duly
obtained and shall be effective on and as of the Closings. No stop order or
other order enjoining the sale of the Shares shall have been issued and no
proceedings for such purpose shall be pending or, to the knowledge of the
Company, threatened by the SEC, the California Commissioner of Corporations, or
any commissioner of corporations or similar officer of any other state or
foreign country having jurisdiction over this transaction. At the time of the
Closings, the sale and issuance of the Shares shall be legally permitted by all
laws and regulations to which Investor and the Company are subject.

               4.5 PROCEEDINGS AND DOCUMENTS. All corporate and other
proceedings in connection with the transactions contemplated at the Closings and
all documents and instruments



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incident thereto shall be reasonably satisfactory in form and substance to
Investor, which shall have received all such counterpart original and certified
or other copies of such documents as it may reasonably request.

        5. CONDITIONS OF THE COMPANY'S OBLIGATIONS AT CLOSINGS.

        The obligations of the Company to Investors under this Agreement are
subject to the fulfillment, on or before the Closings, of each of the following
conditions by Investor:

               5.1 REPRESENTATIONS AND WARRANTIES. The representations and
warranties of Investors contained in Section 3 hereof shall be true and correct
in all material respects on and as of the Closings, except those representations
and warranties qualified by materiality, which shall be true and correct in all
respects, with the same force and effect as though such representations and
warranties had been made on and as of the Closings.

               5.2 QUALIFICATIONS. All authorizations, approvals, or permits, if
any, of any governmental authority or regulatory body of the United States, of
any state or any foreign country that are required in connection with the lawful
sale and issuance of the Shares pursuant to this Agreement shall have been duly
obtained and shall be effective on and as of the Closings. No stop order or
other order enjoining the sale of the Shares shall have been issued and no
proceedings for such purpose shall be pending or, to the knowledge of the
Company, threatened by the SEC, the California Commissioner of Corporations, or
any commissioner of corporations or similar officer of any other state or
foreign country having jurisdiction over this transaction. At the time of the
Closings, the sale and issuance of the Shares shall be legally permitted by all
laws and regulations to which Investor and the Company are subject.

               5.3 CANCELLATION OF PROMISSORY NOTE. The Company shall have
received from Bay City Fund I, LLP ("Bay City") (one of the Investors hereunder)
satisfactory evidence of the cancellation of that certain $3,000,000 promissory
note from the Company in favor of Bay City, dated February, 1998 (the "Note"),
as referenced in Schedule A.

               5.4 CANCELLATION OF PRE-PAYMENT. The Company shall have received
from PE Corporation (formerly known as The Perkin-Elmer Corporation) ("PE") (one
of the Investors hereunder) satisfactory evidence acknowledging the cancellation
of $1,000,000 in pre-payments made by PE for future purchases of MGB
Oligonucleotides and MGB Intermediates, pursuant to Section 5.11 of that certain
License and Supply agreement by and between the Company and PE dated as of the
January 11, 1999 (the "License Agreement"), as referenced in Schedule A.

               5.5 PERFORMANCE. All covenants, agreements and conditions
contained in this Agreement to be performed by Investors on or prior to the
Closings shall have been performed or complied with in all material respects.



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        6. REGISTRATION OF SHARES.

        The Company hereby grants to each of the Investors the registration
rights set forth in this Section 6 with respect to the Registrable Securities
(as hereinafter defined) owned by such Investors. The Company and the Investors
agree that the registration rights provided herein set forth the sole and entire
agreement on the subject matter between the Company and the Investors.

               6.1 DEFINITIONS.

                    (a) The terms "register," "registered," and "registration"
refer to a registration effected by filing with SEC a registration statement
(the "Registration Statement") in compliance with the Securities Act, and the
declaration or ordering by the SEC of the effectiveness of such Registration
Statement.

                    (b) The term "Registrable Shares" means the Shares issued to
the Investors pursuant to this Agreement, as well as the Warrant Shares to be
issued to Bay City (as set forth in Schedule A) and any Common Stock of the
Company issued as (or issuable upon the conversion or exercise of any warrant,
right, or other security that is issued as) a dividend or other distribution
with respect to, or in exchange or in replacement of, such Registrable Shares.
In the event of any recapitalization by the Company, whether by stock split,
reverse stock split, stock dividend or the like, the number of shares of
Registrable Shares used throughout this Agreement for various purposes shall be
proportionately increased or decreased, provided, however, that any such
security shall cease to be a Registrable Share at such time as it is publicly
saleable without restriction, pursuant to Rule 144(k) of the SEC, or otherwise.

                    (c) The term "Initiating Investors" means any Investor or
Investors of not less than fifty percent (50%) of the Registrable Shares held by
all of the Investors then outstanding and not registered pursuant to paragraph
6.2 of this Agreement.

               6.2 DEMAND REGISTRATION. If the Company shall receive from the
Initiating Investors a written demand (a "Demand Registration") that the Company
effect any registration under the Securities Act with respect to all or a part
of the Registrable Shares held by the Initiating Investors the Company will (i)
as soon as reasonably practicable, give written notice of such request to all
Investors; (ii) use its best efforts to effect such registration as soon as
practicable and as will permit or facilitate the sale and distribution of all or
such portion of the Initiating Investors' Registrable Shares as are specified in
such demand (including any Registrable Shares which are held by Investors, which
such Investors request to include in such registration within twenty (20) days
after the receipt of the notice given pursuant to (i) above), and (iii) use its
best efforts to cause such registration to remain effective until the earlier to
occur of the date (A) the Registrable Shares covered thereby have been sold, or
(B) the Investors are able to use Rule 144 of the Securities Act to sell the
Shares without restriction, provided that the Company shall not be obligated to
take any action to effect any such registration, pursuant to this Section 6.2:

                    (a) At any time prior to six (6) months following the
Closings;

                    (b) After the Company has effected one registration pursuant
to this Section 6.2; or




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                    (c) If the Company shall furnish to the Initiating Investors
a certificate signed by the President of the Company, stating that in the good
faith judgment of the Board of Directors of the Company it would be seriously
detrimental to the Company and its shareholders for such Registration Statement
to be filed at the date filing would be required, in which case the Company
shall have an additional period of not more than 180 days within which to file
such Registration Statement.

               6.3 REGISTRATION PROCEDURES. When the Company effects the
registration of the Registrable Shares under the Securities Act pursuant to
Section 6.2 hereof, the Company will, at its expense, as expeditiously and as
reasonably possible, use its reasonable best efforts, to:

                    (a) In accordance with the Securities Act and the rules and
regulations of the SEC, prepare and file with the SEC a Registration Statement
with respect to such securities and use its best efforts to cause such
Registration Statement to become and remain effective for the period described
in Section 6.2, and prepare and file with the SEC such amendments to such
Registration Statement and supplements to the prospectus contained therein as
may be necessary to keep such Registration Statement effective for such period
and such Registration Statement and prospectus accurate and complete for such
period;

                    (b) Furnish to Investors such reasonable number of copies of
the Registration Statement, preliminary prospectus, final prospectus and such
other documents as Investor may reasonably request in order to facilitate the
public offering of such securities;

                    (c) Use its best efforts to register or qualify the
securities covered by such Registration Statement under such state securities or
blue sky laws of such jurisdictions as Investor may reasonably request within
twenty (20) days following the original filing of such Registration Statement,
except that the Company shall not for any purpose be required to execute a
general consent to service of process or to qualify to do business as a foreign
corporation in any jurisdiction where it is not so qualified;

                    (d) Notify Investors, promptly after it shall receive notice
thereof, of the date and time when such Registration Statement and each
post-effective amendment thereto has become effective or a supplement to any
prospectus forming a part of such Registration Statement has been filed;

                    (e) Notify Investors promptly of any request by the SEC for
the amending or supplementing of such Registration Statement or prospectus or
for additional information;

                    (f) Notify Investors promptly if, at the time when a
prospectus relating to such securities is required to be delivered under the
Securities Act, any event has occurred as the result of which any such
prospectus or any other prospectus as then in effect would include an untrue
statement of a material fact or omit to state any material fact required to be
stated therein or necessary to make the statements therein not misleading and
prepare and promptly file with the SEC, and promptly notify Investors of the
filing of, such amendments or supplements to such Registration Statement or
prospectus as may be necessary to correct such statements or omissions;

                    (g) In case any Investor is required to deliver a prospectus
at a time when the prospectus then in circulation is not in compliance with the
Securities Act or the rules and



                                       10
<PAGE>   12

regulations of the SEC, prepare promptly upon request such amendments or
supplements to such Registration Statement and such prospectus as may be
necessary in order for such prospectus to comply with the requirements of the
Securities Act and such rules and regulations;

                    (h) Advise Investors, promptly after it shall receive notice
or obtain knowledge thereof, of the issuance of any stop order by the SEC
suspending the effectiveness of such Registration Statement or the initiation or
threatening of any proceeding for that purpose and promptly use its best efforts
to prevent the issuance of any stop order or to obtain its withdrawal if such
stop order should be issued;

                    (i) Use its best efforts to obtain a comfort letter from the
Company's independent public accountants in customary form and covering such
matters of the type customarily covered by comfort letters with respect to
offerings of such type as the Investors may reasonably request; and

                    (j) Cause all such securities to be listed on each
securities exchange on which similar securities issued by the Company are then
listed, provided that the applicable listing requirements are satisfied.

               6.4 EXPENSES. With respect to any registration effected pursuant
to Section 6.2 hereof, the Company agrees to bear all fees, costs and expenses
of and incidental to such registration and the public offering in connection
therewith, provided however, that Investors shall bear all underwriting
discounts and commissions, state transfer taxes and brokerage commissions. The
fees, costs and expenses of registration to be borne by the Company as provided
in this Section 6.4 shall include, without limitation, all registration, filing
and NASD fees, printing expenses, fees and disbursements of counsel and
accountants for the Company, and all legal fees and disbursements and other
expenses of complying with state securities or blue sky laws of any
jurisdictions in which the securities to be offered are to be registered or
qualified.

               6.5 INDEMNIFICATION.

                    (a) The Company will, and does hereby undertake to,
indemnify and hold harmless each Investor, each of such Investor's officers,
directors, partners and agents, and each person controlling such Investor, with
respect to any registration, qualification, or compliance effected pursuant to
this Section 6, and each underwriter, if any, and each person who controls
within the meaning of Section 15 of the Securities Act any underwriter, of the
Registrable Shares held by or issuable to such Investor, against all claims,
losses, damages, and liabilities (or actions in respect thereto) to which they
may become subject under the Securities Act, the Exchange Act, or other federal
or state law arising out of or based on (i) any untrue statement (or alleged
untrue statement) of a material fact contained in any prospectus, offering
circular, or other similar document (including any related Registration
Statement, notification, or the like) incident to any such registration,
qualification, or compliance, or based on any omission (or alleged omission) to
state therein a material fact required to be stated therein or necessary to make
the statements therein not misleading, or (ii) any violation or alleged
violation by the Company of any federal, state or common law rule or regulation
applicable to the Company in connection with any such registration,
qualification, or compliance, and will reimburse, as incurred, each Investor,
each underwriter, and each director, officer, partner, agent and controlling
person, for any legal and any other expenses reasonably incurred in connection
with investigating or defending any such claim, loss, damage, liability, or
action; provided that the Company will not be liable in any such case to the
extent that any such



                                       11
<PAGE>   13

claim, loss, damage, liability or expense, arises out of or is based on any
untrue statement or omission based upon written information furnished to the
Company by an instrument duly executed by any of the Investors or underwriter
and stated to be specifically for use therein.

                    (b) Each Investor will, if Registrable Securities held by or
issuable to such Investor are included in such registration, qualification, or
compliance, severally and not jointly, indemnify the Company, each of its
directors, officers, legal counsel and accountants and each underwriter, if any,
of the Company's securities covered by such Registration Statement, each person
controlling the Company or such underwriter, within the meaning of Section 15 of
the Securities Act, against 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 a material fact contained in any such Registration
Statement, prospectus, offering circular, or other document, or any omission (or
alleged omission) to state therein a material fact required to be stated therein
or necessary to make the statements therein not misleading, and will reimburse,
as incurred, the Company, and each such underwriter or other person, for any
legal or any other expenses reasonably incurred in connection with investigating
or defending any such claim, loss, damage, liability, or action, in each case to
the extent, but only to the extent, that such untrue statement (or alleged
untrue statement) or omission (or alleged omission) was made in such
Registration Statement, prospectus, offering circular, or other document, in
reliance upon and in conformity with written information furnished to the
Company by an instrument duly executed by such Investor and stated to be
specifically for use therein; provided, however, that the liability of each such
Investor hereunder shall be limited to the gross proceeds received by such
Investor from the sale of securities under such Registration Statement. In no
event will any Investor be required to enter into any agreement or undertaking
in connection with any registration under this Section 6 providing for any
indemnification or contribution obligations on the part of such Investor greater
than such Investor's obligations under this Section 6.

                    (c) Promptly after receipt by a party indemnified pursuant
to the provisions of paragraph (a) or (b) of this Section 6.5 of notice of the
commencement of any action involving the subject matter of the foregoing
indemnity provisions, such indemnified party shall, if a claim thereof is to be
made against the indemnifying party pursuant to the provisions of such Sections
6.5(a) or 6.5(b), notify the indemnifying party of the commencement thereof;
provided, however, that the failure to so notify the indemnifying party shall
not relieve the indemnifying party from any liability which it may have to the
indemnified party otherwise than hereunder unless the failure to give such
notice is materially prejudicial to the indemnifying party's ability to defend
such action. In case such action is brought against any indemnified party and it
notifies the indemnifying party of the commencement thereof, the indemnifying
party shall have the right to participate in, and to the extent that it may
wish, jointly assume the defense thereof, with counsel reasonably satisfactory
to such indemnified party, and after notice from the indemnifying party to such
indemnified party of its election to so assume the defense thereof, the
indemnifying party shall not be liable to such indemnified party pursuant to the
provisions of Section 6.5(a) or 6.5(b) for any legal or other expenses
subsequently incurred by such indemnified party in connection with the defense
thereof other than reasonable costs of investigation (except if representation
of such indemnified party by counsel to 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). No
indemnifying party shall be liable to an indemnified party for any settlement of
any action or claim without the consent of the indemnifying party.




                                       12
<PAGE>   14

               6.6 REPORTING REQUIREMENTS UNDER THE EXCHANGE ACT. The Company
shall timely file such information, documents and reports as the SEC may require
or prescribe under Section 13 or 15(d) of the Exchange Act. The Company
acknowledges and agrees that the purposes of the requirements contained in this
Section 6.6 are to enable Investors to comply with the current public
information requirement contained in paragraph (c) of Rule 144 should any
Investor ever wish to dispose of any of the Registrable Shares without
registration under the Securities Act in reliance upon Rule 144 (or any other
similar exemptive provision).

               6.7 INVESTOR INFORMATION. The Company may require Investors to
furnish the Company such information with respect to Investors and the
distribution of the Registrable Shares as the Company may from time to time
reasonably request in writing as shall be required by law or by the SEC in
connection therewith.

               6.8 TRANSFER OF REGISTRATION RIGHTS. The registration rights of
the Investors under this Agreement may be transferred (i) in the case of an
individual, to any member of the immediate family of such individual or to any
trust for the benefit of the individual or any such family member or members,
(ii) to any partner or affiliate of such Investor, (iii) to any transferee
provided (1) that the transferee receives the lesser of (A) at least 800,000
Registrable Shares (as constituted on the date hereof) or (B) all of the
Registrable Shares held by such Investor; (2) the transferee is bound by the
terms of this Agreement; and (3) the Company is given written notice prior to
such transfer. Notwithstanding the foregoing, the registration rights of
Investors under this Agreement may not be transferred to an entity, or a person
controlled by, under common control with or controlling such entity, which is a
direct competitor of the Company.

        7. AFFIRMATIVE COVENANTS OF COMPANY

               7.1 ATTENDANCE AT BOARD MEETINGS. So long as PE (or an affiliate
of PE) continues to hold at least fifty percent (50%) of the total number of
shares of Common Stock originally purchased by PE pursuant to this Agreement, PE
will be entitled to appoint a representative (the "PE Representative") to attend
all meetings of the Board of Directors of the Company, and the Company will
provide the PE Representative with copies of all notices of such meetings and
all other written materials provided to the Directors of the Company at the same
time as such notices and written materials are provided to the Directors of the
Company. PE acknowledges and agrees that the Company's management will have the
right to exclude the PE Representative from all or portions of meetings of the
Board of Directors, or omit to provide the PE Representative with certain
information, if the Company's management believes it is necessary in order to
preserve the attorney-client privilege, or fulfill the Company's obligations
with respect to confidential or proprietary information of third parties, or if
such meeting or information involves matters concerning the Company's
relationship or prospective relationship with PE or its affiliates or
competitors of PE or its affiliates, or other situations where a director would
customarily not participate in a meeting or be provided such information. In
addition, PE and the PE Representative will maintain the confidentiality of all
information obtained through the PE Representative's position, except to the
extent that (i) such information is already in PE's position, (ii) such
information becomes public knowledge other than as a result of PE's actions or
inactions, (iii) PE rightfully obtains such information subsequently from a
third party, (iv) PE develops such information independently and without use of
the information provided by the Company or (v) such information is approved in
writing for release by the Company.




                                       13
<PAGE>   15

        8. MISCELLANEOUS.

               8.1 ENTIRE AGREEMENT. This Agreement, the Schedules hereto, and
the documents referred to herein constitute the full and entire understanding
and agreement between the parties and no party shall be liable or bound to any
to any other party in any manner by any warranties, representations or covenants
except as specifically set forth herein or therein.

               8.2 SURVIVAL OF WARRANTIES. Unless otherwise set forth in this
Agreement, the warranties, representations and agreements of the Company and
Investors contained herein shall survive the execution and delivery of this
Agreement and the Closings and shall in no way be affected by any investigation
of the subject matter thereof made by or on behalf of Investors or the Company.

               8.3 SUCCESSORS AND ASSIGNS. Except as otherwise expressly
provided herein, the terms and conditions of this Agreement shall inure to the
benefit of and be binding upon the respective successors and assigns of the
parties (including permitted transferees of any Shares sold hereunder). Nothing
in this Agreement, express or implied, is intended to confer upon any party
other than the parties hereto or their respective successors and assigns any
rights, remedies, obligations or liabilities under or by reason of this
Agreement, except as expressly provided in this Agreement.

               8.4 GOVERNING LAW; JURISDICTION AND VENUE; ATTORNEY'S FEES. This
Agreement and all acts and transactions pursuant hereto and the rights and
obligations of the parties hereto shall be governed by and construed under the
laws of the State of Washington without reference to principles of conflicts of
laws. The parties hereby consent and agree that the United States District Court
for the Western District of Washington will have exclusive jurisdiction over any
legal action or proceeding arising out of or relating to this Agreement, and
each party consents to the in personam jurisdiction of such courts for the
purpose of any such action or proceeding and agrees that venue is proper in such
courts. If any action at law or in equity is necessary to enforce or interpret
the terms of this Agreement, the prevailing party shall be entitled to
reasonable attorney's and expert witness fees, costs and necessary disbursements
in addition to any other relief to which such party may be entitled.

               8.5 COUNTERPARTS. This Agreement may be executed in any number of
counterparts, each of which shall be deemed an original and all of which
together shall constitute one and the same instrument.

               8.6 TITLES AND SUBTITLES. The titles and subtitles used in this
Agreement are used for convenience only and are not to be considered in
construing or interpreting this Agreement.

               8.7 NOTICES. Unless otherwise provided, any notice required or
permitted under this Agreement shall be given in writing and shall be deemed
effectively given upon personal delivery, delivery by nationally recognized
overnight courier or five days after deposit with the United States Post Office,
by registered or certified mail, postage prepaid and addressed to the party to
be notified at the address indicated for such party on the signature page
hereto, or at such address as such party may designate by ten days advance
written notice to the other party.

               8.8 FINDERS' FEES. Each Investor agrees to indemnify and to hold
harmless the Company from any liability for any commission or compensation in
the nature of a finders' fee to



                                       14
<PAGE>   16

any broker or other person or firm (and the costs and expenses of defending
against such liability or asserted liability) for which such Investor or any of
its officers, partners, employees or representatives is responsible. The Company
agrees to indemnify and hold harmless Investors from any liability for any
commission or compensation in the nature of a finders' fee to any broker or
other person or firm (and the costs and expenses of defending against such
liability or asserted liability) for which the Company or any of its officers,
employees or representatives is responsible.

               8.9 EXPENSES. Irrespective of whether the Closings are effected,
the Company and each Investor shall each pay all costs and expenses that it
incurs with respect to the negotiation, execution, delivery and performance of
this Agreement.

               8.10 AMENDMENTS AND WAIVERS. Any term of this Agreement may be
amended and the observance of any term of this Agreement may be waived (either
generally or in a particular instance and either retroactively or
prospectively), only with the written consent of the Company and Investors
holding a majority of the Shares purchased hereunder. Any amendment or waiver
effected in accordance with this paragraph shall be binding upon all the
Investors and the securities purchased under this Agreement at the time
outstanding (including securities into which such securities have been
converted), each future holder of all such securities and the Company.
Notwithstanding the foregoing, Section 7.1 of this Agreement shall only be
amended or waived by the written consent of PE and the Company.

               8.11 SEVERABILITY. If one or more provisions of this Agreement
are held to be unenforceable under applicable law, such provision shall be
excluded from this Agreement and the balance of the Agreement shall be
interpreted as if such provision were so excluded and the balance of the
Agreement shall be enforceable in accordance with its terms.

               8.12 INFORMATION CONFIDENTIAL. Each Investor acknowledges that
the information received by it pursuant hereto is confidential and for such
Investor's use only, and it will refrain from using such information or
reproducing, disclosing, or disseminating such information to any other person
(other than its employees, affiliates, agents, or partners having a need to know
the contents of such information and its attorneys), except in connection with
the exercise of rights under this Agreement, unless the Company has made such
information available to the public generally or it is required by a
governmental body to disclose such information.



                                       15
<PAGE>   17

        IN WITNESS WHEREOF, the parties hereto have caused this Stock Purchase
Agreement to be executed by their respective officers thereunto duly authorized,
as of the date first above written.



Address:                               EPOCH PHARMACEUTICALS, INC.

12277 134th Court NE, #110             By: /s/ William G. Gerber
Redmond, Washington 98052                  William G. Gerber,
                                           Chief Executive Officer


Address:                               BAY CITY FUND I, LLP

750 Battery Street, Suite 600          By: /s/ Fred Craves
San Francisco, California 94111            Fred Craves



                    (Additional signatures on following page)


<PAGE>   18

Address:                               GRACE BROTHERS LTD.

1560 Sherman Avenue                    By: /s/ Bradford T. Whitmore
Evanston, Illinois 60201                   Bradford T. Whitmore
                                           General Partner


Address:                               PE CORPORATION

761 Main Avenue                        By: /s/ Michael Hunkapiller
Norwalk, Connecticut 06859                 Michael W. Hunkapiller
                                           Senior Vice President


Address:                               HILSPEN CAPITAL MANAGEMENT

330 Primrose Road, Suite 312           By: /s/ Robert Duich
Burlingame, California 941010              Robert Duich
                                           Chief Operating Officer



                    (Additional signatures on following page)



<PAGE>   19

Address:                                     Grace Brothers, Ltd.

1560 Sherman Avenue                          By: /s/ Bradford T. Whitmore
Evanston, Illinois 60201                         Bradford T. Whitmore
                                                 General Partner

Address:                                     PE Corporation

761 Main Avenue                              By: /s/ Michael Hunkapiller
Norwalk, Connecticut 06859                       Michael Hunkapiller
                                                 Senior Vice President

Address:                                     Hilspen Capital Management

330 Primrose Rd., Suite 312                  By: /s/ Joseph Craves
Burlingame, California 94101                     Joseph Craves