Document:

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                                                                     Exhibit 4.5
                          REGISTRATION RIGHTS AGREEMENT

                  This Registration Rights Agreement (the "Agreement") is made
and entered as of this 16th day of December, 1999 by and between Avi BioPharma,
Inc., a corporation organized under the laws of Oregon (the "Company"), and the
persons identified as Investors pursuant to the Purchase Agreement of even date
herewith by and between the Company and such persons (the "Purchase Agreement").

                  The parties hereby agree as follows:

                  1. CERTAIN DEFINITIONS

                     As used in this Agreement, the following terms shall have
the following meanings:

                     "ADDITIONAL REGISTRABLE SECURITIES" shall mean the shares
of Common Stock, if any, issued to the Investors pursuant to Section 7.1 of the
Purchase Agreement.

                     "COMMON STOCK" shall mean the Company's shares of Common
Stock, par value $.0001 per

share.

                     "INVESTOR" shall mean each person so identified in the
Purchase Agreement, and andsubsequent holder of any Common Stock, Warrant or
Registrable Securities.

                     "PROSPECTUS" shall mean the prospectus included in any
Registration Statement, as amended or supplemented by any prospectus supplement,
with respect to the terms of the offering of any portion of the Registrable
Securities and Additional Registrable Securities covered by such Registration
Statement and by all other amendments and supplements to the prospectus,
including post-effective amendments and all material incorporated by reference
in such prospectus.

                     "REGISTER," "REGISTERED" and "REGISTRATION" refer to a
registration made by preparing and filing a registration statement or similar
document in compliance with the 1933 Act (as defined below), and the declaration
or ordering of effectiveness of such registration statement or document.

                     "REGISTRABLE SECURITIES" shall mean the shares of Common
Stock issued and issuable to the Investors pursuant to the Purchase Agreement
(other than additional shares of Common Stock issuable pursuant to Section 7.1
of the Purchase Agreement) and issuable upon the exercise of the Warrants, and
any securities issued with respect to, or in exchange for, such securities

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                     "REGISTRATION STATEMENT" shall mean any registration
statement filed under the 1933 Act of the Company that covers the resale of any
of the Registrable Securities or Additional Registrable Securities pursuant to
the provisions of this Agreement, amendments and supplements to such
Registration Statement, including post-effective amendments, all exhibits and
all material incorporated by reference in such Registration Statement.

                     "SEC" means the U.S. Securities and Exchange Commission.

                     "1933 ACT" means the Securities Act of 1933, as amended,
and the rules and regulations promulgated thereunder.

                     "1934 ACT" means the Securities Exchange Act of 1934, as
amended, and the rules and regulations promulgated thereunder.

                     "WARRANTS" mean the warrants to purchase shares of Common
Stock issued to the Investor pursuant to the Purchase Agreement.

                     Other capitalized terms used herein but not defined herein
shall have the meaning provided therefor in the Purchase Agreement.

                  2. REGISTRATION.

                     (a) REGISTRATION STATEMENT. Promptly following the closing
of the transactions contemplated by the Purchase Agreement (the "Closing Date")
(but no later than 45 days after the Closing Date), the Company shall prepare
and file with the SEC one Registration Statement on Form S-3 (or, if Form S-3 is
not then available to the Company, on such form of registration statement as is
then available to effect a registration for resale of the Registrable
Securities, subject to the Investor's consent) covering the resale of the
Registrable Securities. Such Registration Statement shall cover, to the extent
allowable under the 1933 Act and the Rules promulgated thereunder (including
Rule 416), such indeterminate number of additional shares of Common Stock
resulting from stock splits, stock dividends or similar transactions with
respect to the Registrable Securities. No securities shall be included in the
Registration Statement without the consent of the Investors other than the
Registrable Securities. The Registration Statement (and each amendment or
supplement thereto, and each request for acceleration of effectiveness thereof)
shall be provided in accordance with Section 3(c) to (and subject to the
approval of) the Investors and their counsel prior to its filing or other
submission, which approval shall not be unreasonably withheld or delayed.

                     (b) EXPENSES. The Company will pay all expenses associated
with the registration and in addition shall pay the reasonable fees of single
counsel to the Investors relating thereto in an amount of $5,000, excluding
discounts, commissions, fees of underwriters, selling brokers, dealer managers
or similar securities industry professionals.

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                  (c) EFFECTIVENESS.

                         (i) The Company shall use its best efforts to have the
Registration Statement declared effective as soon as practicable. If (A) the
Registration Statement is not declared effective by the SEC within 90 days
following the Closing Date (the "Registration Date"), or (B) after the
Registration Statement has been declared effective by the SEC, sales cannot be
made pursuant to the Registration Statement for any reason but except as excused
pursuant to subparagraph (ii) below, then the Company will make payments to each
Investor, as damages and not as a penalty, for any 30 day period or portion
thereof following the Registration Date during which any of the events described
in (A) or (B) above occurs and is continuing (the "Blackout Period") in an
amount equal to 2% of the aggregate Purchase Price paid by such Investor to the
Company on the Closing Date. The amounts payable as damages pursuant to this
paragraph shall be payable in lawful money of the United States and shall be
paid on demand from time to time following the commencement of the Blackout
Period until the termination of the Blackout Period. The same remedy shall be
available in the case of any failure to timely issue Warrant Shares upon
exercise of the Warrant, or in the case of any suspension from trading or
delisting from the Nasdaq Stock Market. If at any time a payment due hereunder
remains unpaid for more than sixty (60) days after demand, the rate of damage
payments shall thereafter be increased for all purposes to a rate equal to 3%
per 30 day period. The remedies set forth in this section are not intended to be
exclusive, and shall be in addition to any other remedies available at law or in
equity. Amounts payable as damages hereunder to an Investor shall cease when the
Investor no longer holds Warrants or Registrable Securities, or Additional
Registrable Securities, as applicable.

                         (ii) The Company may suspend the use of a prospectus
under the Registration Statement contemplated by this Section for up to two (2)
periods of not more than twenty (20) days in the aggregate in any consecutive 12
months, if the Company shall deliver to the Investor 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 (A) be seriously detrimental to the
business of the Company for such registration to be effected or remain effective
at such time, (B) interfere with any proposed or pending material corporate
transaction involving the Company or any of its subsidiaries, or (C) result in
any premature disclosure thereof. In such a case, the Company shall not disclose
to the Investor any facts or circumstances constituting material non-public
information, without the prior written consent of Investor. The duration of the
MFN Period provided for in the Purchase Agreement will be extended by the number
of days of any termination or suspension of the effectiveness of any
registration or suspension of the use of any prospectus contemplated by this
Section 2.

                     (d) UNDERWRITTEN OFFERING. If any offering pursuant to a
Registration Statement pursuant to Section 2(a) hereof involves an underwritten
offering, the Investor shall have the right to select an investment banker and
manager to administer the offering, which investment banker or manager shall be
reasonably satisfactory to the Company. An underwritten offering will not be
conducted without the consent of all Investors.

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                     (e) Promptly following the issuance of any Additional
Registrable Securities, the Company shall file a Registration Statement and use
its best efforts to have such Registration Statement covering the Additional
Registrable Securities declared effective as soon as possible. All time periods,
provisions and remedies covering the registration of Registrable Securities
shall apply, MUTATIS MUTANDIS, to the registration of the Additional Registrable
Securities.

                  3. COMPANY OBLIGATIONS. The Company will use its best efforts
to effect the registration of the Registrable Securities and Additional
Registrable Securities in accordance with the terms hereof, and pursuant thereto
the Company will, as expeditiously as possible:

                     (a) use its best efforts to cause such Registration
Statement to become effective and to remain continuously effective for a period
that will terminate upon the earlier of the date on which all Registrable
Securities or Additional Registrable Securities, as the case may be, covered by
such Registration Statement, as amended from time to time, have been sold or
until such time as they become eligible for distribution pursuant to Rule
144(k), or any successor provision thereof, under the 1933 Act (the
"Registration Period") (however, the Registration Statement shall be continued
effective for so long on the as the Warrants remain outstanding);

                     (b) prepare and file with the SEC such amendments and
post-effective amendments to the Registration Statement and the Prospectus as
may be necessary to keep the Registration Statement effective for the period
specified in Section 3(a) and to comply with the provisions of the 1933 Act and
the 1934 Act with respect to the distribution of all Registrable Securities and
Additional Registrable Securities; provided that, at a time reasonably prior to
the filing of a Registration Statement or Prospectus, or any amendments or
supplements thereto, the Company will furnish to the Investor copies of all
documents proposed to be filed, which documents will be subject to the comments
of the Investor;

                     (c) permit a single firm of counsel designated by the
Investors to review the Registration Statement and all amendments and
supplements thereto no fewer than ten (10) days prior to their filing with the
SEC, and not file any document in a form to which such counsel reasonably
objects;

                     (d) furnish to all of the Investors and their legal counsel
(i) promptly after the same is prepared and publicly distributed, filed with the
SEC, or received by the Company, one copy of the Registration Statement and any
amendment thereto, each preliminary prospectus and Prospectus and each amendment
or supplement thereto, and each letter written by or on behalf of the Company to
the SEC or the staff of the SEC, and each item of correspondence from the SEC or
the staff of the SEC, in each case relating to such Registration Statement
(other than any portion of any thereof which contains information for which the
Company has sought confidential treatment), and (ii) such number of copies of a
Prospectus, including a preliminary prospectus, and all amendments and
supplements thereto and such other documents as such Investor may reasonably
request in order to facilitate the disposition of the Registrable Securities and
Additional Registrable Securities owned by such Investor;

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                     (e) in the event the Investors select underwriters for the
offering, the Company shall enter into and perform its reasonable obligations
under an underwriting agreement, in usual and customary form, including, without
limitation, customary indemnification and contribution obligations, with the
underwriters of such offering;

                     (f) at the request of the Investor, the Company shall
furnish, on the date that Registrable Securities or Additional Registrable
Securities, as applicable, are delivered to an underwriter, if any, for sale in
connection with the Registration Statement (i) an opinion, dated as of such
date, from counsel representing the Company for purposes of such Registration
Statement, in form, scope and substance as is customarily given in an
underwritten public offering, addressed to the underwriter and the Investor and
(ii) a letter, dated such date, from the Company's independent certified public
accountants in form and substance as is customarily given by independent
certified public accountants to underwriters in an underwritten public offering,
addressed to the underwriters and the Investors;

                     (g) make reasonable effort to prevent the issuance of any
stop order or other suspension of effectiveness and, if such order is issued,
obtain the withdrawal of any such order at the earliest possible moment;

                     (h) furnish to the Investors at least five copies of the
Registration Statement and any post-effective amendment thereto, including
financial statements and schedules by courier pursuant to the notice
requirements of Section 10.4 of the Purchase Agreement;

                     (i) prior to any public offering of Registrable Securities
or Additional Registrable Securities, use its best efforts to register or
qualify or cooperate with the Investors and its counsel in connection with the
registration or qualification of such Registrable Securities or Additional
Registrable Securities, as applicable, for offer and sale under the securities
or blue sky laws of all U.S. jurisdictions and do any and all other reasonable
acts or things necessary or advisable to enable the distribution in such
jurisdictions of the Registrable Securities or Additional Registrable Securities
covered by the Registration Statement;

                     (j) cause all Registrable Securities or Additional
Registrable Securities covered by the Registration Statement to be listed on
each securities exchange, interdealer quotation system or other market on which
similar securities issued by the Company are then listed;

                     (k) immediately notify the Investors, at any time when a
Prospectus relating to the Registrable Securities or Additional Registrable
Securities is required to be delivered under the Securities Act, upon discovery
that, or upon the happening of any event as a result of which, the Prospectus
included in such Registration Statement, as then in effect, includes an untrue
statement of a material fact or omits to state any material fact required to be
stated therein or necessary to make the statements therein not misleading in the
light of the circumstances then existing, and at the request of any such holder,
promptly prepare and furnish to such holder a reasonable number of copies of a
supplement to or an amendment of such Prospectus as may be necessary so that, as
thereafter delivered to the purchasers of such

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Registrable Securities or Additional Registrable Securities, as applicable, such
Prospectus shall not include an untrue statement of a material fact or omit to
state a material fact required to be stated therein or necessary to make the
statements therein not misleading in the light of the circumstances then
existing; and

                     (l) otherwise use its best efforts to comply with all
applicable rules and regulations of the SEC under the 1933 Act and the 1934 Act,
take such other actions as may be reasonably necessary to facilitate the
registration of the Registrable Securities and Additional Registrable Securities
hereunder.

                  4. OBLIGATIONS OF THE INVESTORS.

                     (a) It shall be a condition precedent to the obligations of
the Company to complete the registration pursuant to this Agreement with respect
to the Registrable Securities or Additional Registrable Securities of an
Investor, if applicable, that such Investor shall furnish in writing to the
Company such information regarding itself, the Registrable Securities or
Additional Registrable Securities, as applicable, held by it and the intended
method of disposition of the Registrable Securities or Additional Registrable
Securities, as applicable, held by it as shall be reasonably required to effect
the registration of such Registrable Securities or Additional Registrable
Securities, as applicable, and shall execute such documents in connection with
such registration as the Company may reasonably request. At least ten (10)
business days prior to the first anticipated filing date of the Registration
Statement, the Company shall notify the Investors of the information the Company
requires from the Investors if the Investors elect to have any of the
Registrable Securities or Additional Registrable Securities included in the
Registration Statement.

                     (b) Each Investor, by its acceptance of the Registrable
Securities and Additional Registrable Securities, if any, agrees to cooperate
with the Company as reasonably requested by the Company in connection with the
preparation and filing of the Registration Statement hereunder, unless such
Investor has notified the Company in writing of its election to exclude all of
its Registrable Securities or Additional Registrable Securities, as applicable,
from the Registration Statement.

                     (c) In the event the Investors determine to engage the
services of an underwriter, the Investors agree to enter into and perform their
obligations under an underwriting agreement, in usual and customary form,
including, without limitation, customary indemnification and contribution
obligations, with the managing underwriter of such offering and take such other
actions as are reasonably required in order to expedite or facilitate the
dispositions of the Registrable Securities or Additional Registrable Securities,
as applicable.

                     (d) Each Investor agrees that, upon receipt of any notice
from the Company of the happening of any event rendering the Registration
Statement no longer effective, the Investor will immediately discontinue
disposition of Registrable Securities or Additional Registrable Securities
pursuant to the Registration Statement covering such Registrable Securities or
Additional Registrable Securities until the Investor's receipt of the copies of
the supplemented or amended prospectus filed with the SEC and declared effective
and, if so

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directed by the Company, the Investor shall deliver to the Company (at the
expense of the Company) or destroy (and deliver to the Company a certificate of
destruction) all copies in the Investor's possession of the prospectus covering
the Registrable Securities or Additional Registrable Securities, as applicable,
current at the time of receipt of such notice.

                     (e) No Investors may participate in any underwritten
registration hereunder unless it (i) agrees to sell the Registrable Securities
or Additional Registrable Securities, as applicable, on the basis provided in
any underwriting arrangements in usual and customary form entered into by the
Company, (ii) completes and executes all questionnaires, powers of attorney,
indemnities, underwriting agreements and other documents reasonably required
under the terms of such underwriting arrangements, and (iii) agrees to pay its
pro rata share of all underwriting discounts and commissions and any expenses in
excess of those payable by the Company pursuant to the terms of this Agreement.

                  5. INDEMNIFICATION.

                     (a) INDEMNIFICATION BY COMPANY. The Company agrees to
indemnify and hold harmless, to the fullest extent permitted by law each
Investor, its officers, directors, partners and employees and each person who
controls the Investor (within the meaning of the 1933 Act) against all losses,
claims, damages, liabilities, costs (including, without limitation, reasonable
attorney's fees) and expenses caused by (i) any untrue or alleged untrue
statement of a material fact contained in any Registration Statement, Prospectus
or any preliminary prospectus or any amendment or supplement thereto 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,
except insofar as the same are based upon any information furnished in writing
to the Company by such Investor, expressly for use therein, or (ii) any
violation by the Company of any federal, state or common law, rule or regulation
applicable to the Company in connection with any Registration Statement,
Prospectus or any preliminary prospectus, or any amendment or supplement
thereto, and shall reimburse in accordance with subparagraph (c) below, each of
the foregoing persons for any legal and any other expenses reasonably incurred
in connection with investigating or defending any such claims. The foregoing is
subject to the condition that, insofar as the foregoing indemnities relate to
any untrue statement, alleged untrue statement, omission or alleged omission
made in any preliminary prospectus or Prospectus that is eliminated or remedied
in any Prospectus or amendment or supplement thereto, the above indemnity
obligations of the Company shall not inure to the benefit of any indemnified
party if a copy of such corrected Prospectus or amendment or supplement thereto
had been made available to such indemnified party and was not sent or given by
such indemnified party at or prior to the time such action was required of such
indemnified party by the 1933 Act and if delivery of such Prospectus or
amendment or supplement thereto would have eliminated (or been a sufficient
defense to) any liability of such indemnified party with respect to such
statement or omission. Indemnity under this Section 5(a) shall remain in full
force and effect regardless of any investigation made by or on behalf of any
indemnified party and shall survive the permitted transfer of the Registrable
Securities and Additional Registrable Securities.

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                     (b) INDEMNIFICATION BY HOLDER OF REGISTRABLE SECURITIES. In
connection with any registration pursuant to the terms of this Agreement, each
Investor severally will furnish to the Company in writing such information as
the Company reasonably requests concerning the holders of Registrable Securities
and Additional Registrable Securities or the proposed manner of distribution for
use in connection with any Registration Statement or Prospectus and severally
agrees to indemnify and hold harmless, to the fullest extent permitted by law,
the Company, its directors, officers, employees, stockholders and each person
who controls the Company (within the meaning of the 1933 Act) against any
losses, claims, damages, liabilities and expense (including reasonable
attorney's fees) resulting from any untrue statement of a material fact or any
omission of a material fact required to be stated in the Registration Statement
or Prospectus or preliminary prospectus or amendment or supplement thereto or
necessary to make the statements therein not misleading, to the extent, but only
to the extent that such untrue statement or omission is contained in any
information furnished in writing by such holder of Registrable Securities or
Additional Registrable Securities to the Company specifically for inclusion in
such Registration Statement or Prospectus or amendment or supplement thereto and
that such information was substantially relied upon by the Company in
preparation of the Registration Statement or Prospectus or any amendment or
supplement thereto. In no event shall the liability of a holder of Registrable
Securities or Additional Registrable Securities be greater in amount than the
dollar amount of the proceeds (net of all expense paid by such holder and the
amount of any damages such holder has otherwise been required to pay by reason
of such untrue statement or omission) received by such holder upon the sale of
the Registrable Securities or Additional Registrable Securities included in the
Registration Statement giving rise to such indemnification obligation.

                     (c) CONDUCT OF INDEMNIFICATION PROCEEDINGS. Any person
entitled to indemnification hereunder shall (i) give prompt notice to the
indemnifying party of any claim with respect to which it seeks indemnification
and (ii) permit such indemnifying party to assume the defense of such claim with
counsel reasonably satisfactory to the indemnified party; PROVIDED that any
person entitled to indemnification hereunder shall have the right to employ
separate counsel and to participate in the defense of such claim, but the fees
and expenses of such counsel shall be at the expense of such person unless (a)
the indemnifying party has agreed to pay such fees or expenses, or (b) the
indemnifying party shall have failed to assume the defense of such claim and
employ counsel reasonably satisfactory to such person or (c) in the reasonable
judgment of any such person, based upon written advice of its counsel, a
conflict of interest exists between such person and the indemnifying party with
respect to such claims (in which case, if the person notifies the indemnifying
party in writing that such person elects to employ separate counsel at the
expense of the indemnifying party, the indemnifying party shall not have the
right to assume the defense of such claim on behalf of such person); 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
hereunder, except to the extent that such failure to give notice shall
materially adversely affect the indemnifying party in the defense of any such
claim or litigation. It is understood that the indemnifying party shall not, in
connection with any proceeding in the same jurisdiction, be liable for fees or
expenses of more than one separate firm of attorneys at any time for all such
indemnified parties. No indemnifying party will, except with the consent of the
indemnified party, consent to entry of any judgment or enter into any

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settlement that 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 to such claim or litigation.

                     (d) CONTRIBUTION. If for any reason the indemnification
provided for in the preceding paragraphs (a) and (b) is unavailable to an
indemnified party or insufficient to hold it harmless, other than as expressly
specified therein, then the indemnifying party shall contribute to the amount
paid or payable by the indemnified party as a result of such loss, claim, damage
or liability in such proportion as is appropriate to reflect the relative fault
of the indemnified party and the indemnifying party, as well as any other
relevant equitable considerations. No person guilty of fraudulent
misrepresentation within the meaning of Section 11(f) of the 1933 Act shall be
entitled to contribution from any person not guilty of such fraudulent
misrepresentation. In no event shall the contribution obligation of a holder of
Registrable Securities or Additional Registrable Securities be greater in amount
than the dollar amount of the proceeds (net of all expenses paid by such holder
and the amount of any damages such holder has otherwise been required to pay by
reason of such untrue or alleged untrue statement or omission or alleged
omission) received by it upon the sale of the Registrable Securities or
Additional Registrable Securities giving rise to such contribution obligation.

                  6. MISCELLANEOUS.

                     (a) AMENDMENTS AND WAIVERS. This Agreement may be amended
only by a writing signed by the parties hereto. The Company may take any action
herein prohibited, or omit to perform any act herein required to be performed by
it, only if the Company shall have obtained the written consent to such
amendment, action or omission to act, of the Investor.

                     (b) NOTICES. All notices and other communications provided
for or permitted hereunder shall be made as set forth in Section 10.4 of the
Purchase Agreement.

                     (c) ASSIGNMENTS AND TRANSFERS BY INVESTOR. This Agreement
and all the rights and obligations of the Investors hereunder may not be
assigned or transferred to any transferee or assignee except as set forth
herein. An Investor may make such assignment or transfer to any transferee or
assignee of any Common Stock, Warrant or Registrable Securities, or Additional
Registrable Securities, PROVIDED, that (i) such transfer is made expressly
subject to this Agreement and the transferee agrees in writing to be bound by
the terms and conditions hereof, and (ii) the Company is provided with written
notice of such assignment.

                     (d) ASSIGNMENTS AND TRANSFERS BY THE COMPANY. This
Agreement may not be assigned by the Company without the prior written consent
of Investor, except that without the prior written consent of the Investor, but
after notice duly given, the Company shall assign its rights and delegate its
duties hereunder to any successor-in-interest corporation, and such
successor-in-interest shall assume such rights and duties, in the event of a
merger or consolidation of the Company with or into another corporation or the
sale of all or substantially all of the Company's assets.

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                     (e) BENEFITS OF THE AGREEMENT. The terms and conditions of
this Agreement shall inure to the benefit of and be binding upon the respective
permitted successors and assigns of the parties. 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.

                     (f) COUNTERPARTS. This Agreement may be executed in two or
more counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same instrument.

                     (g) 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.

                     (h) 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 this Agreement shall be
interpreted as if such provision were so excluded and shall be enforceable in
accordance with its terms to the fullest extent permitted by law.

                     (i) FURTHER ASSURANCES. The parties shall execute and
deliver all such further instruments and documents and take all such other
actions as may reasonably be required to carry out the transactions contemplated
hereby and to evidence the fulfillment of the agreements herein contained.

                     (j) ENTIRE AGREEMENT. This Agreement is intended by the
parties as a final expression of their agreement and intended to be a complete
and exclusive statement of the agreement and understanding of the parties hereto
in respect of the subject matter contained herein. This Agreement supersedes all
prior agreements and understandings between the parties with respect to such
subject matter.

                     (k) APPLICABLE LAW. This Agreement shall be governed by,
and construed in accordance with, the laws of the State of New York without
regard to principles of conflicts of law.

[REMAINDER OF PAGE INTENTIONALLY BLANK]

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     IN WITNESS WHEREOF, the parties have executed this Agreement as of the date
first written above.

The Company:                 AVI BIOPHARMA, INC.

                             By:_________________________
                             Name:
                             Title:

The Investor:                THE TAIL WIND FUND, LTD.

                             By:_________________________
                             Name:
                             Title:

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     IN WITNESS WHEREOF, the parties have executed this Agreement as of the date
first written above.

The Company:                  AVI BIOPHARMA, INC.

                              By:_________________________
                              Name:
                              Title:

The Investor:                 RESONANCE LTD.

                              By:_________________________
                              Name:  Mo Bodner
                              Title:<PAGE>

                                                                    Exhibit 4.6

                             SUBSCRIPTION AGREEMENT

         This Subscription Agreement is made this 1st day of December, 1999,
by and between SUPERGEN, INC., a Delaware corporation ("SuperGen"), and AVI
BIOPHARMA, INC., an Oregon corporation ("AVI"), in connection with the
subscription by SuperGen for 1,000,000 shares of the common stock of AVI (the
"AVI Securities"), par value .0001, for a price of Five Dollars ($5.00) per
share.

         1.       SUBSCRIPTION.  SuperGen subscribes for the AVI Securities.

                  1.1 CASH CONSIDERATION. At closing, SuperGen shall pay to
AVI the amount of Two Million Five Hundred Dollars ($2,500,000) in
immediately available funds.

                  1.2 STOCK CONSIDERATION. At closing, SuperGen shall deliver
to AVI 100,000 shares of the common stock of SuperGen, .001 par value,
registered in the name of AVI (the "SuperGen Securities"), which shares shall
be deemed to have a value of Two Million Five Hundred Thousand Dollars
($2,500,000).

         2.       REPRESENTATIONS OF SUPERGEN.

                  2.1 INVESTMENT INTENT. SuperGen represents and warrants to AVI
that SuperGen is purchasing the AVI Securities for SuperGen's own account and
investment and not with a view to, or for sale in connection with, any
distribution, and that SuperGen can withstand the loss of SuperGen's entire
investment and has no need for liquidity in the investment the Securities
represent.

                  2.2 QUALIFIED INVESTOR. SuperGen warrants and represents to
AVI that SuperGen is an accredited investor within the meaning of Regulation
501, as promulgated under the Securities Act of 1933, as amended, and warrants
that all information there presented is materially accurate.

                  2.3 INVESTMENT EXPERIENCE. SuperGen is experienced in
evaluating and investing in companies in the development stage, and has such
knowledge and experience in financial or business matters that it is capable of
evaluating the merits and risks of the investment in the AVI Securities.

                  2.4 AUTHORIZATION. The execution, delivery and performance of
this Agreement by SuperGen does not (i) require the consent, approval or
authorization of any governmental or regulatory authority having jurisdiction
and (ii) will not violate any applicable law, judgment, order, injunction,
decree, rule, regulation or ruling of any governmental authority applicable to
SuperGen.

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PAGE 1 - SUBSCRIPTION AGREEMENT

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                  2.5 AUTHORITY TO EXECUTE AGREEMENT. SuperGen has full power
and authority and legal right to make this Agreement and to incur and perform
its obligations hereunder and the performance by SuperGen of this Agreement has
been duly authorized by all necessary action of SuperGen.

                  2.6 ACCESS TO INFORMATION. SuperGen represents and warrants
that SuperGen and its Board of Directors has received copies of AVI's filings
under the Securities and Exchange Act of 1934, as amended, including, without
limitation, the risk factors they contain; SuperGen further understands that
forward-looking statements in such filings are not warranted and must be
regarded as highly speculative and uncertain. SuperGen has had such opportunity
to ask questions and to examine the operations of AVI as SuperGen wishes, and
has availed themselves of such opportunity as SuperGen deems appropriate.

                  2.7 RESTRICTED SECURITIES, LEGEND. SuperGen understands that
the AVI Securities have not been registered under the Securities Act of 1933, as
amended, in reliance upon an exemption from registration. Such exemption depends
upon, among other things, the bona fide nature of SuperGen's investment intent
stated in this Subscription Agreement. SuperGen understands that the AVI
Securities must be held indefinitely, unless the Securities subsequently are
registered under the Securities Act of 1933 or unless an exemption from
registration is otherwise available. SuperGen understands that AVI is not
obligated to register the Securities, except as hereafter provided. SuperGen
agrees that the AVI Securities may not be offered, sold, transferred, pledged,
or otherwise disposed of in the absence of an effective registration statement
under the Securities Act of 1933 and applicable state securities laws or an
opinion of counsel acceptable to AVI that such registration is not required.
SuperGen understands that the documentation representing the Securities will be
imprinted with substantially the following legend:

         THE SHARES REPRESENTED BY THIS CERTIFICATE HAVE NOT BEEN REGISTERED
         UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE "ACT"), OR APPLICABLE
         STATE SECURITIES LAWS. THE SHARES HAVE BEEN ACQUIRED WITHOUT A VIEW TO
         DISTRIBUTION AND MAY NOT BE OFFERED, SOLD, TRANSFERRED, PLEDGED OR
         HYPOTHECATED IN THE ABSENCE OF AN EFFECTIVE REGISTRATION STATEMENT FOR
         THE SHARES UNDER THE ACT AND UNDER ANY APPLICABLE SECURITIES LAWS, OR
         AN OPINION OF COUNSEL FOR THE HOLDER (CONCURRED IN BY LEGAL COUNSEL FOR
         THE CORPORATION) THAT SUCH REGISTRATION IS NOT REQUIRED AS TO SUCH
         OFFER OR SALE. THE STOCK TRANSFER AGENT HAS BEEN ORDERED TO EFFECTUATE
         TRANSFERS OF THIS CERTIFICATE ONLY IN ACCORDANCE WITH THE ABOVE
         INSTRUCTION.

         3.       REPRESENTATIONS OF AVI.

                  3.1 INVESTMENT INTENT. AVI represents and warrants to SuperGen
that AVI is purchasing the SuperGen Securities for AVI's own account and
investment and not with a view

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to, or for sale in connection with, any distribution, and that AVI can withstand
the loss of AVI's entire investment and has no need for liquidity in the
investment the Securities represent.

                  3.2 QUALIFIED INVESTOR. AVI warrants and represents to
SuperGen that AVI is an accredited investor within the meaning of Regulation
501, as promulgated under the Securities Act of 1933, as amended, and warrants
that all information there presented is materially accurate.

                  3.3 INVESTMENT EXPERIENCE. AVI is experienced in evaluating
and investing in companies in the development stage, and has such knowledge and
experience in financial or business matters that it is capable of evaluating the
merits and risks of the investment in the SuperGen Securities.

                  3.4 AUTHORIZATION. The execution, delivery and performance of
this Agreement by AVI does not (i) require the consent, approval or
authorization of any governmental or regulatory authority having jurisdiction
and (ii) will not violate any applicable law, judgment, order, injunction,
decree, rule, regulation or ruling of any governmental authority applicable to
AVI.

                  3.5 AUTHORITY TO EXECUTE AGREEMENT. AVI has full power and
authority and legal right to make this Agreement and to incur and perform its
obligations hereunder and the performance by AVI of this Agreement has been duly
authorized by all necessary action of AVI.

                  3.6 ACCESS TO INFORMATION. AVI represents and warrants that
AVI and its Board of Directors has received copies of SuperGen's filings under
the Securities and Exchange Act of 1934, as amended, including, without
limitation, the risk factors they contain; AVI further understands that
forward-looking statements in such filings are not warranted and must be
regarded as highly speculative and uncertain. AVI has had such opportunity to
ask questions and to examine the operations of SuperGen as AVI wishes, and has
availed themselves of such opportunity as AVI deems appropriate.

                  3.7 RESTRICTED SECURITIES, LEGEND. AVI understands that the
SuperGen Securities have not been registered under the Securities Act of 1933,
as amended, in reliance upon an exemption from registration. Such exemption
depends upon, among other things, the bona fide nature of AVI's investment
intent stated in this Subscription Agreement. AVI understands that the SuperGen
Securities must be held indefinitely, unless the Securities subsequently are
registered under the Securities Act of 1933 or unless an exemption from
registration is otherwise available. AVI understands that SuperGen is not
obligated to register the Securities, except as hereafter provided. AVI agrees
that the SuperGen Securities may not be offered, sold, transferred, pledged, or
otherwise disposed of in the absence of an effective registration statement
under the Securities Act of 1933 and applicable state securities laws or an
opinion of counsel acceptable to SuperGen that such registration is not
required. SuperGen understands that the documentation representing the
Securities will be imprinted with substantially the following legend:

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         THE SHARES REPRESENTED BY THIS CERTIFICATE HAVE NOT BEEN REGISTERED
         UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE "ACT"), OR APPLICABLE
         STATE SECURITIES LAWS. THE SHARES HAVE BEEN ACQUIRED WITHOUT A VIEW TO
         DISTRIBUTION AND MAY NOT BE OFFERED, SOLD, TRANSFERRED, PLEDGED OR
         HYPOTHECATED IN THE ABSENCE OF AN EFFECTIVE REGISTRATION STATEMENT FOR
         THE SHARES UNDER THE ACT AND UNDER ANY APPLICABLE SECURITIES LAWS, OR
         AN OPINION OF COUNSEL FOR THE HOLDER (CONCURRED IN BY LEGAL COUNSEL FOR
         THE CORPORATION) THAT SUCH REGISTRATION IS NOT REQUIRED AS TO SUCH
         OFFER OR SALE. THE STOCK TRANSFER AGENT HAS BEEN ORDERED TO EFFECTUATE
         TRANSFERS OF THIS CERTIFICATE ONLY IN ACCORDANCE WITH THE ABOVE
         INSTRUCTION.

         4. CLOSING. The closing of the transaction contemplated hereunder shall
take place at a place and time mutually agreed by SuperGen and AVI not more than
fifteen (15) days after the date hereof.

         5. EXCLUSIVE RIGHT TO NEGOTIATE. SuperGen and AVI presently are
negotiating the terms and conditions of a definitive agreement wherein SuperGen
shall enjoy the rights to market and sell AVICINE, AVI's anti-cancer therapeutic
vaccine. For and in consideration of this Subscription, SuperGen and AVI agree
that between the date of this Subscription Agreement and the earlier of (a)
termination of negotiations with respect to the Definitive Agreement by mutual
agreement of SuperGen and AVI, or (b) February 28, 2000, AVI shall not, and
shall use its best efforts to insure that its directors, officers and advisors
do not, directly or indirectly, institute, pursue or enter into any discussions,
negotiations, or agreements (whether preliminary or definitive) with any person
or entity other than SuperGen contemplating or providing for the marketing and
sale of AVICINE by any party other than SuperGen. In addition, AVI shall suspend
and not resume during such time period any discussions or negotiations described
above which were initiated prior to the execution of this Subscription
Agreement. AVI further agrees that any definitive agreement entered into between
SuperGen and AVI to market and sell AVICINE, contemplated by this section, shall
include provisions, mutually agreed by the parties, whereby SuperGen shall enjoy
a first option on AVI's portfolio of anti-cancer therapeutic products.

         6.       REGISTRATION RIGHTS.

                  6.1 REGISTRATION OF AVI SECURITIES. At the closing, AVI shall
enter into a Registration Rights Agreement with SuperGen providing Super Gen
"piggyback" registration rights with respect to the AVI Securities but providing
further for the registration of the AVI Securities not later than ninety (90)
days after the closing date hereof.

                  6.2 REGISTRATION OF SUPERGEN. At the closing, SuperGen shall
enter into a Registration Rights agreement with AVI providing AVI "piggyback"
registration rights with

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respect to the SuperGen Securities but providing further for the registration of
the SuperGen Securities not later than ninety (90) days after the closing date
hereof.

      7.       OTHER MATTERS.

                  7.1 SEVERABILITY. Each clause of this agreement is severable.
If any clause is ruled void or unenforceable, the balance of the agreement shall
nonetheless remain in effect.

                  7.2 NON-WAIVER. A waiver of one or more breaches of any clause
of this agreement shall not act to waive any other breach, whether of the same
or different clauses.

                  7.3 GOVERNING LAW, JURISDICTION. This agreement is governed by
the laws of the state of Oregon, and is enforceable only in the state or federal
courts located in Oregon, in which both parties consent to jurisdiction.

                  7.4 ATTORNEYS' FEES. The prevailing party in any suit, action,
arbitration, or appeal filed or held concerning this agreement shall be entitled
to reasonable attorneys' fees.

                  7.5 AMENDMENTS. This agreement may be modified only in writing
signed by the original parties hereto, their successors, or by their authorized
representatives.

         IN WITNESS WHEREOF, the parties have heretofore signed this
Subscription Agreement.

SUPERGEN, INC., a Delaware corporation            AVI BIOPHARMA, INC. an Oregon
                                                  corporation

By: /s/ Joseph Rubinfeld                          By: /s/ Alan Timmins
    --------------------                              ----------------

Title: Chief Executive Officer & President        Title: Chief Operating Officer
                                                  & Chief Financial Officer

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                      AMENDMENT 1 TO SUBSCRIPTION AGREEMENT

This amendment to Section 1 of the Subscription agreement is an addition to the
terms previously agreed to.

1.3      RE-EXCHANGE OF CASH CONSIDERATION. SuperGen and AVI each have the
         right, but not the obligation, to demand a re-exchange of AVI's 500,000
         shares and SuperGen's $2.5 million in cash if an arrangement, under the
         general terms of the Letter of Intent between the two companies, is not
         agreed to by the date contemplated therein. This right shall last for
         30 days from the termination date of the Letter of Intent and will be
         completed within 180 days of such date.

IN WITNESS WHEREOF, the parties have heretofore signed this Amendment.

AVI BIOPHARMA, INC., an Oregon corporation

By:      /s/ Alan Timmins
         ----------------

Title:   Chief Operating Officer & Chief Financial Officer

SUPERGEN, INC., a Delaware corporation

By:      /s/ Joseph Rubinfeld
         --------------------

Title:   Chief Executive Officer & President

<PAGE>

                       AMENDMENT TO SUBSCRIPTION AGREEMENT
         This Amendment (the "AMENDMENT") is made as of December 15, 1999 by and
between SuperGen, Inc., a Delaware corporation ("SUPERGEN") and AVI BioPharma,
Inc., an Oregon corporation ("AVI").

                                   BACKGROUND
         A. SuperGen and AVI entered into a Subscription Agreement dated as of
December 1, 1999 (the "SUBSCRIPTION AGREEMENT") providing for SuperGen to pay
AVI $2.5 million in cash (the "CASH CONSIDERATION") and issue to AVI 100,000
shares of SuperGen common stock in exchange for 1,000,000 shares of AVI common
stock and the exclusive right from the date of the Subscription Agreement until
February 28, 2000 to negotiate an agreement for SuperGen to market and sell
Avicine and have a right of first option with respect to AVI's portfolio of
anti-cancer therapeutic compounds.
         B. Pursuant to Section 7.5 of the Subscription Agreement, SuperGen and
AVI previously amended the Subscription Agreement and desire to further amend
the Subscription Agreement to clarify the conditions under which there may be a
redemption of 500,000 shares of AVI common stock. Unless defined in this
Amendment, all capitalized terms shall have the meanings set forth in the
Subscription Agreement.
         NOW, THEREFORE, SuperGen and AVI agree as follows:
         Section 1.3 of the Agreement shall be deleted and replaced in its
entirety by the following:
         1.3 REDEMPTION. In the event that by February 28, 2000 (the "EXPIRATION
DATE") SuperGen and AVI have not entered into a definitive agreement for
SuperGen to market and sell Avicine and for SuperGen to have a right of first
option with respect to AVI's portfolio of anti-cancer therapeutic compounds, all
on substantially the terms as set forth in the letter of intent attached to this
Amendment, SuperGen and AVI shall each have the right, but not the obligation,
to request in writing a redemption of 500,000 shares of AVI common stock in
exchange for return to SuperGen of the Cash Consideration (the "REDEMPTION").
                  (a) NOTICE PERIOD. For a period of 30 calendar days following
the Expiration Date (the "NOTICE PERIOD"), SuperGen and AVI may each deliver
written notice to the other of their desire to cause the Redemption.
                  (b) EXCHANGE DATE. The Redemption shall occur on a date (the
"REDEMPTION DATE") no later than 180 calendar days after the Expiration Date.
                  (c) DELIVERY. AVI shall deliver to SuperGen the full amount of
the Cash Consideration, along with any interest earned thereon, and SuperGen
shall deliver 500,000 shares of AVI common stock on the Redemption Date.
                  (d) SECURITY. To ensure AVI's obligations under this Section
1.3, AVI shall establish an account for the receipt of the Cash Consideration.
The account will be owned by AVI and will require the signature of an officer of
AVI and an officer of SuperGen before any funds can be disbursed from this
account. Once established, there will be no changes of any nature whatsoever to
the account without the written consent of an officer from both SuperGen and
AVI. SuperGen agrees to terminate this security arrangement promptly after the
earlier of (i) the expiration of the Notice Period (if a Redemption was not
requested) or (ii) AVI's full performance of its obligations under the
Redemption provisions of Section 1.3.

<PAGE>

         IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be
executed as of the day and year first above written.

                                    SUPERGEN, INC.

                                    By: /s/ Joseph Rubinfeld
                                        --------------------
                                         Joseph Rubinfeld
                                         Chief Executive Officer and President

                                    AVI BIOPHARMA, INC.

                                    By: /s/ Alan P. Timmins
                                        -------------------
                                         Alan P. Timmins
                                         Chief Operating Officer and
                                         Chief Financial Officer

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