<PAGE>
 
                                                                   EXHIBIT 10.23
                                    OMNIBUS AMENDMENT AGREEMENT

       This Omnibus Amendment Agreement (the "Amendment") is entered into this
   18th day of December, 1996, by and between ChemGenics Pharmaceuticals Inc.
   (formerly known as Myco Pharmaceuticals Inc.), a Delaware corporation
   ("ChemGenics") and PerSeptive Biosystems, Inc., a Delaware corporation
   ("PerSeptive" or "PBIO").

       WHEREAS, ChemGenics and PerSeptive are parties to a Master Agreement
   dated May 7, 1996 (the "Master Agreement");

       WHEREAS, at the Closing under the Master Agreement, the parties executed
   and delivered among other documents the various documents listed in Section
   1.03 of the Master Agreement (the "Ancillary Agreements"), including without
   limitation the Consulting and Interim Services Agreement, the Standstill and
   Registration Rights Agreement and the Warrant (as such terms are defined in
   the Master Agreement) and stock certificates for the Shares (as defined in
   the Master Agreement); and

       WHEREAS, ChemGenics and PerSeptive have agreed upon modifications to the
   terms of the transaction reflected in the Master Agreement and the Ancillary
   Agreements, and wish to set forth such modifications herein, to be effective
   retroactively to the Closing Date (as defined in the Master Agreement), as if
   initially set forth in the Master Agreement and the Ancillary Agreements.

       NOW THEREFORE, in consideration of the premises and the mutual covenants
   contained in the Master Agreement, the Ancillary Agreements and this
   Amendment, and for other good and valuable consideration, the receipt and
   sufficiency of which is hereby acknowledged, the parties, intending to be
   legally bound, agree as follows:

   1.  Definitions.
       ----------- 

       1.1  Terms which are defined in the Master Agreement and the Ancillary
            Agreements are used herein as so defined.

   2.  Amendments to the Master Agreement.
       ---------------------------------- 
       The Master Agreement is hereby amended as follows:

       2.01 The first seven lines of Section 1.01.B are deleted from the Master
            Agreement, and the following is inserted in lieu thereof:

                  "In consideration for the License Agreement and the transfer
                  of the Transferred Assets, upon the terms and subject to the
                  conditions set forth in this Agreement, on the Closing Date,
                  ChemGenics shall issue to PerSeptive an aggregate of 6,792,679
                  shares (the "Shares") of ChemGenics' Common Stock, $.001 par
                  value per share (the 
<PAGE>
 
                  "Common Stock") and shall deliver to PerSeptive a Promissory
                  Note in the principal amount of $3,000,000, such Note to be in
                  the form of Exhibit 1.03(B). Of such shares, 662,500"

             Section 1.01(B) is further amended by deleting the numbers
             "979,268, 652,844 and 326,422" from the chart on page 3, and
             inserting, in lieu thereof, the numbers "662,500, 441,667 and
             220,833".

       2.02  Section 8.04 is amended by deleting clause (ii) thereof, and
             inserting in lieu thereof the following:

                  "(ii)  PerSeptive will agree to restrictions on its sale or
                  transfer of Capital Stock of ChemGenics,"

       2.03  Section 8.06 is amended by deleting the text thereof in its
             entirety, and replacing it with the following:

                  "ChemGenics will use commercially reasonable efforts to
                  accomplish an underwritten registered initial public offering
                  of its Common Stock (a "Public Offering"), in which ChemGenics
                  will seek to raise at least $15,000,000 in gross proceeds on
                  or before June 30, 1997.  If a Public Offering is not
                  consummated by June 30, 1997, then PerSeptive will deliver to
                  ChemGenics a certificate for 2,000,000 of the Shares delivered
                  to PerSeptive hereunder, leaving PerSeptive with an aggregate
                  of 4,792,679 Shares, and ChemGenics will deliver to PerSeptive
                  a Promissory Note in the principal amount of $2,000,000 in the
                  form of Exhibit 8.06.  PerSeptive shall at its own cost,
                  assist and cooperate with ChemGenics as ChemGenics may
                  reasonably request in effecting the Public Offering in a
                  timely manner."

       2.04  Section 8.07 is deleted from the Master Agreement.

       2.05  It is understood and agreed that the terms of Exhibits 1.03(C)(i),
             1.03(C)(ii), 1.03(C)(iii), 1.03(C)(iv) and Exhibit 1.03(C)(v) are
             superseded in their entirety by the agreements executed at the
             Closing as amended by this Agreement.

       2.06  The last sentence of Section 8.03 and clause (i) of Section 10.15
             of the Master Agreement are hereby deleted from the Master
             Agreement.

   3.  Amendment of Consulting and Interim Services Agreement.  The Consulting
       ------------------------------------------------------                 
       and Interim Services Agreement is hereby amended as follows:

       3.01 Section 3 is amended by adding the following sentence immediately
            after the first sentence thereof:
<PAGE>
 
                  "The Supplies will be provided free of charge until the later
                  of (i) March 31, 1997 or (ii) the closing of the first Public
                  Offering (as defined in the Master Agreement), and thereafter
                  will be supplied for the balance of the three-year period at a
                  price equal to (a) fully-burdened manufacturing cost for
                  Supplies manufactured by PBIO, and (b) and the actual cost of
                  acquisition for Supplies distributed by PBIO."

       3.02  Section 4.A is amended by deleting the words "During the three year
             period commencing on the date hereof, PBIO shall loan to
             ChemGenics" at the beginning thereof, and replacing them with the
             words:

                  "Until the earlier of (i) June 30, 1997 or (ii) the closing of
                  the first Public Offering (as defined in the Master
                  Agreement), PBIO shall loan to ChemGenics, and thereafter
                  through June 27, 1999, shall sell to ChemGenics at fully-
                  burdened manufacturing cost for Equipment manufactured by PBIO
                  and the actual cost of acquisition for Equipment distributed
                  by PBIO"

             Section 4.A is further amended by adding the phrase "or sold as
             provided above" following the word "loaned" in the twelfth line on
             page 4.

       3.03  Section 5 is amended by deleting the numbers "979,268, 652,844 and
             326,422" from the chart on page 7, and inserting, in lieu thereof,
             the numbers "662,500, 441,667 and 220,833".

       3.04  Section 9 is amended by deleting the third sentence thereof and
             inserting the following:

                  "PBIO will on demand pay or reimburse ChemGenics for the
                  payment of all Severance Pay and other severance related costs
                  in excess of the Space Value for Drug Discovery Program
                  Employees terminated on or before the earlier of the closing
                  of the Public Offering or March 31, 1997."

             and by adding the following to the last sentence of the first
             paragraph thereof:

                  ", provided the employment of such employee is terminated on
                  or before the earlier of the closing of the Public Offering or
                  March 31, 1997."

   4.   Amendment of Standstill and Registration Rights Agreement.  The
        ---------------------------------------------------------      
        Standstill and Registration Rights Agreement is hereby amended as
        follows:
<PAGE>
 
        4.01 The number 9,792,679 in the first "whereas" clause is replaced with
             the number 6,792,679.

        4.02 Section 2.02 is amended by deleting the first paragraph thereof,
             but not subparagraphs (a), (b), (c) and (d), and replacing it with
             the following:

                  "A.  PBIO agrees that until the Initial Release Date (which
                  shall be the earlier of (i) twelve months following the
                  Closing of the Company's first Public Offering ("IPO") or (ii)
                  December 30, 1998), it will not, nor will it permit any of its
                  affiliates or associates, to (x) distribute to its
                  shareholders, or (y) sell, solicit an offer to sell, agree to
                  sell, offer or propose to sell (collectively, "Sell") any
                  Voting Securities of the Company or derivative securities
                  relating thereto ("Company Securities").  After such period:

                  (1) (a) during the period from the Initial Release Date until
                  six (6) months thereafter, PBIO may distribute to the
                  shareholders of PBIO (i) up to one-third of the number of
                  shares of ChemGenics Common Stock held by PBIO as of the
                  earlier of the closing of the IPO or December 30, 1998,
                  excluding for this purpose any shares of ChemGenics Common
                  Stock issued upon exercise of the Warrant (the "Non-Warrant
                  Shares") and/or (ii) up to one-third of the number of shares
                  of Common Stock originally issuable to PBIO upon exercise of
                  the Warrant ("Warrant Shares"), but only to the extent PBIO
                  has exercised the Warrant and acquired Warrant Shares
                  ("Exercised Warrant Shares"), (b) in the next two succeeding
                  six-month periods thereafter, PBIO may distribute to its
                  shareholders (i) up to one-third of the Non-Warrant Shares
                  and/or (ii) Exercised Warrant Shares up to one-third of the
                  Warrant Shares and/or (iii) the Non-Warrant Shares and the
                  Exercised Warrant Shares permitted to be but not distributed
                  by PBIO in the prior six-month period and (c) thereafter,
                  subject to the following clause 3 of this paragraph, Section
                  3.09 and applicable securities laws, PBIO shall be permitted
                  to distribute any or all of its Non-Warrant Shares and
                  Exercised Warrant Shares to its shareholders; (2) (a) during
                  the six-month period beginning on the earlier of (i) 18 months
                  from the closing of the Company's IPO or (ii) December 30,
                  1998, PBIO may Sell up to one-third of PBIO's
<PAGE>
 
                  Non-Warrant Shares and/or Exercised Warrant Shares up to one-
                  third of the Warrant Shares and (b) in the next two succeeding
                  six-month periods thereafter, PBIO may Sell (i) an additional
                  one-third of PBIO's Non-Warrant Shares and/or (ii) Exercised
                  Warrant Shares up to one-third of the Warrant Shares and/or
                  (iii) the Non-Warrant Shares and the Exercised Warrant Shares
                  permitted to be but not sold by PBIO in the prior six-month
                  period and (c) thereafter, subject to the following clause 3
                  of this paragraph, Section 3.09 and applicable securities
                  laws, PBIO shall be permitted to Sell any or all of its Non-
                  Warrant Shares and Exercised Warrant Shares; and

                  (3)  In addition to the restrictions and limitations set forth
                  in the preceding clauses, in any six (6) month period ending
                  on or before (i) twenty four (24) months after the closing of
                  the IPO, if the IPO closes on or before June 30, 1997 or (ii)
                  the later of twelve months after the closing of the IPO or
                  June 30, 1999 if the IPO closes after June 30, 1997, PBIO
                  shall not distribute or Sell more than a total of one-third of
                  the Non-Warrant Shares and Exercised Warrant Shares up to one-
                  third of the Warrant Shares.  As used herein, "Public
                  Offering" shall mean an underwritten public offering of
                  ChemGenics Common Stock registered with the SEC.
                  Notwithstanding the foregoing:"

       4.03  Section 3.01 is amended by deleting the words commencing
             immediately following the words "provided, however," where
                                              --------  -------
             appearing in the first sentence thereof and ending with the word
             "Shares" at the beginning of the fifth line on page 6 and inserting
             the following words: "that the Company shall not be required to
             include in any such registration statement any Registrable Shares
             which PBIO is not permitted to Sell pursuant to the initial
             paragraph of Section 2.02 and provided further that as a condition
             to including any shares issued or issuable upon exercise of the
             Warrant ("Warrant Shares")

       4.04  Sections 3.01 and 3.02 are amended by deleting the words "at any
             time after the third anniversary of this Agreement" from the first
             sentence thereof and replacing them with the words "at any time
             when PBIO is permitted to Sell Company Securities pursuant to the
             initial paragraph of Section 2.02,".
<PAGE>
 
       4.05  Section 3.09 is amended by inserting after the words "held by it"
             where appearing in the first sentence thereof, the following words:
             "for such period of time, and on such other terms, as shall be
             agreed to among the Company, the underwriters and a majority of the
             venture capital partnerships that hold Company Securities as of the
             IPO, nor will PBIO permit any of its affiliates to do any of the
             foregoing" and deleting the remainder of the first sentence.
             Section 3.09 is further amended by deleting the words "180-day"
             where appearing in the last sentence thereof and inserting the
             words "agreed-upon."

   5.   Exchange of Warrants.
        -------------------- 

        5.01 Contemporaneously with the execution hereof, PerSeptive will
             deliver to ChemGenics the Warrant as delivered at the Closing, and
             ChemGenics shall deliver to PerSeptive a new Warrant in the form
             attached hereto. The new Warrant shall, for all purposes, be deemed
             to be the "Warrant" under the Master Agreement and the Ancillary
             Agreements.

   6.   Exchange of Stock Certificates.  Contemporaneously with the execution
        ------------------------------                                       
        hereof, PerSeptive shall deliver to ChemGenics certificates numbered
        C0028-31 for 8,813,411, 326,423, 326,423 and 326,422 shares of Common
        Stock of ChemGenics and ChemGenics shall deliver to PerSeptive
        certificates for 4,130,179, 2,000,000, 220,833, 220,833 and 220,834
        shares of Common Stock of ChemGenics.

   7.   No Other Changes.  In all other respects, the Master Agreement and the
        ----------------                                                      
        Ancillary Agreements shall not be affected hereby, and shall remain in
        force and effect as initially executed and delivered.

       IN WITNESS WHEREOF, ChemGenics and PerSeptive have executed this
   Amendment as of the day and year first above written.

   CHEMGENICS PHARMACEUTICALS INC.



   By:  /s/ Barry Berkowitz
       -----------------------------------
            Barry Berkowitz
            President
<PAGE>
 
   PERSEPTIVE BIOSYSTEMS, INC.



   By:  /s/ Noubar B. Afeyan
      ------------------------------------
            Noubar B. Afeyan
            Chief Executive Officer
<PAGE>
 
                                                                 EXHIBIT 1.03(B)


                                    PROMISSORY NOTE

   $3,000,000                              December 18, 1996


       For value received, ChemGenics Pharmaceuticals Inc. ("ChemGenics")
promises to pay to PerSeptive Biosystems, Inc. ("PerSeptive") in lawful money of
the United States of America the sum of $3,000,000 with interest at the lowest
applicable federal rate which would avoid imputed interest under the Internal
Revenue Code of 1986, as amended and regulations thereunder, in the manner and
at the time set forth below.

1.      In the event (a) the closing of a Public Offering (as defined in Section
        8.06 of the Master Agreement dated May 7, 1996 between ChemGenics and
        PerSeptive, as amended, (the "Master Agreement")) takes place prior to
        December 31, 1998 with gross proceeds of $15,000,000 or more, or (b)
        ChemGenics shall, prior to December 31, 1998, consolidate or merge with
        another party (other than a merger or consolidation with another party
        where the stockholders of ChemGenics before such transaction directly or
        indirectly own at least a majority of the voting stock of the combined
        or acquired entity after such transaction) or convey, sell or lease to
        another entity all or substantially all of the stock, assets or business
        of ChemGenics and its subsidiaries, taken as a whole (an "Acquisition"),
        then at the closing of such Public Offering or Acquisition, this Note
        shall be payable in full.

2.      In the event of the closing of a Public Offering prior to December 31,
        1998 in which the gross proceeds to ChemGenics are less than
        $15,000,000, then ten percent (10%) of the gross proceeds to ChemGenics
        of such Public Offering shall be paid to PerSeptive at the closing of
        such Public Offering, and the remainder of this Note shall be due in two
        equal installments six months after said closing and twelve months after
        said closing, each such payment to be made, at ChemGenics' option,
        either in cash or in shares of Common Stock of ChemGenics valued at 75%
        of the Market Value thereof at the time the payment is due or a
        combination thereof.  Either the issuance of such shares or the resale
        thereof by PerSeptive shall to the extent permitted by the rules and
        regulations of the Securities Exchange Commission be registered under
        the Securities Act of 1933.  As used herein, Market Value shall mean the
        average of the closing prices on the NASDAQ National Market (or, if the
        Common Stock of ChemGenics is not listed 


<PAGE>
 
        on the NASDAQ National Market, the principal stock exchange or
        interdealer quotation system on which the ChemGenics Common Stock is
        listed) for the five trading days preceding the date as of which Market
        Value is determined, or if there is then no public market for the Common
        Stock of ChemGenics, as reasonably determined by ChemGenics Board of
        Directors.

3.      In the event that there is no Closing of a Public Offering and no
        closing of an Acquisition prior to December 31, 1998, this Note shall be
        paid in full on December 31, 2002 by payment at ChemGenics' option
        either in cash or in shares of Common Stock of ChemGenics valued at the
        Market Value thereof at the time the payment is due or a combination
        thereof.

4.      Acceptance by PerSeptive of any partial payment shall not be deemed to
        constitute a waiver by PerSeptive of the right to require prompt payment
        of all sums when due.  No delay or omission on the part of PerSeptive in
        exercising any right hereunder shall operate as a waiver of such right
        or of any other right under this Note.  No waiver of any right shall be
        effective unless in writing and signed by PerSeptive, nor shall a waiver
        on any one occasion by construed as a bar to or waiver of any such right
        on any future occasion.

5.      ChemGenics waives presentment, demand, notice, protest and all other
        notices (except for notice of default) in connection with the delivery,
        acceptance, performance, default or enforcement of this Note and assents
        to any extension or postponement of the time of payment or any other
        indulgence under this Note.

6.      ChemGenics agrees to pay costs of collection (including reasonable
        counsel fees) if default is made in the payment hereof on this Note.

7.      This Note shall be governed by and construed in accordance with the laws
        of the Commonwealth of Massachusetts.

8.      This Note is delivered pursuant to the Master Agreement.

        IN WITNESS WHEREOF, ChemGenics has caused this Note to executed under
seal by its duly authorized officer as of the date written above.


CHEMGENICS PHARMACEUTICALS INC.


By: /s/ Barry Berkowitz
   ----------------------------
        Barry Berkowitz
        President
                                           [CORPORATE SEAL]
<PAGE>
                                                                    EXHIBIT 8.06

                                PROMISSORY NOTE

$2,000,000                                                  July 1, 1997

      For value received, ChemGenics Pharmaceuticals Inc. ("ChemGenics") 
promises to pay to PerSeptive Biosystems, Inc. ("PerSeptive") in lawful money of
the United States of America the sum of $2,000,000 plus interest at the lowest 
applicable federal rate which would avoid imputed interest under the Internal 
Revenue Code of 1986, as amended and regulations thereunder, in the manner and 
at the time set forth below.

1.   In the event (a) the closing of a Public Offering (as defined in Section
     8.06 of the Master Agreement dated May 7, 1996 between ChemGenics and
     PerSeptive, as amended, (the "Master Agreement") takes place prior to
     December 31, 1998 with gross proceeds of $25,000,000 or more, or
     (b) ChemGenics shall, prior to December 31, 1998, consolidate or merge with
     another party (other than a merger or consolidation with another party
     where the stockholders of ChemGenics before such transaction directly or
     indirectly own at least a majority of the voting stock of the combined or
     acquired entity after such transaction) or convey, sell or lease to another
     entity all or substantially all of the stock, assets or business of
     ChemGenics and its subsidiaries, taken as a whole (an "Acquisition"), then
     at the closing of such Public Offering or Acquisition, this Note shall be
     payable in full. 

2.   In the event of the closing of a Public Offering prior to December 31, 1998
     in which the gross proceeds to ChemGenics are less than $25,000,000, then
     twenty percent (20%) of the gross proceeds to ChemGenics of such Public
     Offering in excess of $15,000,000 shall be paid to PerSeptive at the
     closing of such Public Offering, and the remainder of this Note shall be
     due and payable twelve months after said closing.

3.   In the event that there is no Closing of a Public Offering and no closing
     of an Acquisition prior to December 31, 1998, this Note shall be paid in
     full on December 31, 2002 by payment at ChemGenics' option either in cash
     or in shares of Common Stock of ChemGenics valued at the Market Value
     thereof at the time the payment is due or a combination thereof. As used
     herein, Market Value shall mean the average of the closing prices on the
     NASDAQ National Market (or, if


<PAGE>

      the Common Stock of ChemGenics is not listed on the NASDAQ National
      Market, the principal stock exchange or interdealer quotation system on
      which the ChemGenics Common Stock is listed) for the five trading days
      preceding the date as of which Market Value is determined, or if there is
      then no public market for the Common Stock of ChemGenics, as reasonably
      determined by ChemGenics Board of Directors.

4.    Acceptance by PerSeptive of any partial payment shall not be deemed to
      constitute a waiver by PerSeptive of the right to require prompt payment
      of all sums when due. No delay or omission on the part of PerSeptive in
      exercising any right hereunder shall operate as a waiver of such right or
      of any other right under this note. No waiver of any right shall be
      effective unless in writing and signed by PerSeptive, nor shall a waiver
      on any one occasion by construed as a bar to or waiver of any such right
      on any future occasion.

5.    ChemGenics waives presentment, demand, notice, protest and all other
      notices (except for notice of default) in connection with the delivery,
      acceptance, performance, default or enforcement of this Note and assents
      to any extension or postponement of the time of payment or any other
      indulgence under this Note.

6.    ChemGenics agrees to pay costs of collection (including reasonable counsel
      fees) if default is made in the payment hereof on this Note.

7.    This Note shall be governed by and construed in accordance with the laws 
      of the Commonwealth of Massachusetts.

8.    This Note is delivered pursuant to the Master Agreement.

      IN WITNESS WHEREOF, ChemGenics has caused this Note to executed under seal
by its duly authorized officer as of the date written above. 

CHEMGENICS PHARMACEUTICALS INC.

By:________________________
     Barry Berkowitz
     President 

                                                          [CORPORATE SEAL]