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                                                                     EXHIBIT 4.1

                       AMENDMENT NO. 1 TO RIGHTS AGREEMENT

         Amendment No. 1 to Rights Agreement (the "Amendment"), made as of
August 16, 2004, by and among Vion Pharmaceuticals, Inc. a Delaware corporation
(the "Company"), and American Stock Transfer & Trust Company (the "Rights
Agent"). Reference is made herein to that certain Rights Agreement, dated as of
October 26, 1998, by and between the Company and the Rights Agent (the "Rights
Agreement"). Capitalized terms not herein defined shall have the meaning
ascribed thereto in the Rights Agreement.

         WHEREAS, the Rights Agreement may be amended by the parties pursuant to
Section 27; and

         WHEREAS, the Company and the Rights Agent wish to amend the Rights
Agreement;

         NOW, THEREFORE, in consideration of the premises and other good and
valuable consideration, the parties hereby agree as follows:

         1. Amendment to Section 11(a)(iii). Section 11(a)(iii) of the Rights
Agreement is hereby amended and restated in its entirety to read as follows:

              (iii) In the event that the number of shares of Common Stock
         which are authorized by the Company's certificate of incorporation but
         not outstanding or reserved for issuance for purposes other than upon
         exercise of the Rights are not sufficient to permit the exercise in
         full of the Rights in accordance with the foregoing subparagraph (ii),
         the Company shall: (A) determine the excess of (1) the value of the
         shares of Common Stock issuable upon the exercise of a Right (the
         "Current Value") over (2) the Purchase Price (such excess, the
         "Spread"), and (B) with respect to each Right, make adequate provision
         to substitute for the shares of Common Stock so issuable, upon payment
         of the applicable Purchase Price, (1) cash, (2) a reduction in the
         Purchase Price, (3) other equity securities of the Company (including,
         without limitation, shares, or units of shares, of preferred stock)
         which the Board of Directors of the Company has deemed to have the
         same economic value as shares of Common Stock (such shares of
         preferred stock, "common stock equivalents"), (4) debt securities of
         the Company, (5) other assets, or (6) any combination of the
         foregoing, having an aggregate value equal to the Current Value, where
         such aggregate value has been determined by the Board of Directors of
         the Company based upon the advice of a nationally recognized
         investment banking firm selected by the Board of Directors of the
         Company; provided, however, if the Company shall not have made
         adequate provision to deliver value pursuant to clause (B) above
         within 30 days following the later of (x) the first occurrence of an
         event described in Section 11(a)(ii) and (y) the date on which the
         Company's right of redemption pursuant to Section 23 expires, then the
         Company shall be obligated to deliver, upon the surrender for exercise
         of a Right and without requiring payment of the Purchase Price, shares
         of Common Stock (to the extent available) and then, if necessary,

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         cash, which in the aggregate are equal to the Spread. If the Board of
         Directors of the Company shall determine in good faith that it is
         likely that sufficient additional shares of Common Stock could be
         authorized for issuance upon exercise in full of the Rights, the 30
         day period set forth above may be extended to the extent necessary,
         but not more than 120 days following the first occurrence of an event
         described in Section 11(a)(ii), in order that the Company may seek
         stockholder approval for the authorization of such additional shares
         (such period as it may be extended, the "Substitution Period"). To the
         extent that the Company determines that some action need be taken
         pursuant to the first and/or second sentences of this Section
         11(a)(iii), the Company (x) shall provide, that such action shall
         apply uniformly to all outstanding Rights, and (y) may suspend the
         exercisability of the Rights until the expiration of the Substitution
         Period in order to seek any authorization of additional shares and/or
         to decide the appropriate form of distribution to be made pursuant to
         such first sentence and to determine the value thereof. In the event
         of any such suspension, the Company shall issue a public announcement
         stating that the exercisability of the Rights has been temporarily
         suspended, as well as a public announcement at such time as the
         suspension is no longer in effect. For purposes of this Section
         11(a)(iii), the value of the Common Stock shall be the current market
         price (as determined pursuant to Section 11(d)) per share of the
         Common Stock on the date of the first occurrence of an event referred
         to in Section 11(a)(ii) and the value of any "common stock equivalent"
         shall be deemed to have the same value as the Common Stock on such
         date.

         2. Rights Agreement Otherwise Unamended. The terms of the Rights
Agreement not amended hereby shall, except as the context unambiguously
requires, remain in full force and effect.

         3. Entire Agreement. This Amendment, together with the provisions of
the Rights Agreement not amended hereby, constitute the entire agreement between
the parties hereto with respect to the subject matter hereof and supersede all
other prior agreements, whether written or oral, between the parties hereto.

         4. Counterparts. This Amendment may be executed in one or more
counterparts, each of which shall be deemed an original and all of which
together shall constitute one and the same document.



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         IN WITNESS WHEREOF, each of the parties hereto has caused this
Amendment to be executed in its respective corporate name by one of its duly
authorized officers, all as of the date first above written.

                                   VION PHARMACEUTICALS, INC.


                                   By: /s/ Howard B. Johnson
                                       ------------------------------------
                                   Name: Howard B. Johnson
                                   Title: President and Chief Financial Officer

                                   AMERICAN STOCK TRANSFER
                                   TRUST COMPANY


                                   By: /s/ Herbert J. Lemmer
                                       ------------------------------------
                                   Name: Herbert J. Lemmer
                                   Title: Vice President