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                                                                    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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                  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

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                       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.

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         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