Document:

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                                                                   EXHIBIT 4.2.1

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

               SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      This Second Amended and Restated Stockholders Agreement (this "Agreement")
is made as of this 21st day of January, 2005, by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation (the "Company"), the
holders of the Company's Common Stock (as defined below) set forth on Schedule A
attached hereto (the "Common Stockholders"), the holders of the Company's
Preferred Stock (as defined below) set forth on Schedule B attached hereto (each
individually, a "Preferred Stockholder", and together, the "Preferred
Stockholders", and together with the Common Stockholders and such other
individuals or entities who may become a party hereto from time to time upon
execution of a joinder agreement in a form satisfactory to the Company, referred
to collectively herein as the "Stockholders" and individually as a
"Stockholder").

                                   WITNESSETH:

      WHEREAS, the Company has sold shares of Series C Preferred Stock (the
"Series C Financing") pursuant to that certain Securities Purchase and Exchange
Agreement, dated as of August 9, 2004 by and among the Company and certain
Purchasers (as defined therein) (the "Securities Purchase Agreement");

      WHEREAS, pursuant to the initial closing of the Series C Financing, the
Company and certain of its stockholders entered into that certain Amended and
Restated Stockholders Agreement, dated as of August 9, 2004, by and among the
Company and certain holders of Capital Stock (as defined below) of the Company
(the "Amended and Restated Stockholders Agreement");

      WHEREAS, in connection with the sale of up to an additional 86,244,688
shares of Series C Preferred Stock pursuant to the terms of the Securities
Purchase Agreement, the Company and certain holders of the Company's Capital
Stock now desire to amend and restate the Amended and Restated Stockholders
Agreement;

      WHEREAS, the Amended and Restated Stockholders Agreement may be amended by
the agreement of the Company and the holders of not less than 60% in interest of
Capital Stock of the Company held by the stockholders which are a party to the
Amended and Restated Stockholders Agreement;

      WHEREAS, the Board of Directors of the Company (the "Board of Directors")
has determined that it is in the best interests of the Company that the Company
further amend and restate the Amended and Restated Stockholders Agreement and
enter into this Agreement;

      WHEREAS, pursuant to that certain Co-Sale Agreement (the "Co-Sale
Agreement") dated October 12, 1995, by and among the Company and the
stockholders named therein, as

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amended on each of October 31, 1997, May 13, 1999 and May 16, 2000, certain
provisions herein shall be subject to the terms of the Co-Sale Agreement until
such time as the Co-Sale Agreement is duly terminated.

      NOW, THEREFORE, in consideration of the covenants and agreements set forth
herein and for other good and valuable consideration, the receipt and
sufficiency of which are hereby mutually acknowledged, the parties hereto
covenant and agree as follows:

      SECTION 1. Certain Definitions.

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

      "Capital Stock" means the Preferred Stock and Common Stock.

      "Commission" means the Securities and Exchange Commission, or any other
federal agency at the time administering the Securities Act.

      "Common Stock" means the Company's common stock, par value $.01 per share.

      "Derivative Securities" shall mean any shares of stock and other
securities that are convertible into or exchangeable for shares of Common Stock
and any options, warrants, and other rights to acquire shares of Common Stock or
securities convertible into or exchangeable for shares of Common Stock.

      "Exchange Act" means the Securities Exchange Act of 1934, as amended, or
any successor federal statute, and the rules and regulations of the Commission
issued under such Act, as they each may, from time to time, be in effect.

      "Funding Warrants" means those certain warrants to purchase shares of the
Company's capital stock, dated on or about August 8, 2003, issued by the Company
to certain holders of the Company's Capital Stock.

      "Indemnified Party" means a party entitled to indemnification pursuant to
Section 2(e).

      "Indemnifying Party" means a party obligated to provide indemnification
pursuant to Section 2(e).

      "Initiating Holders" means the Series C Preferred Stockholders initiating
a request for registration pursuant to Section 2(a)(i) or (ii), as the case may
be.

      "Initial Public Offering" means the initial underwritten public offering
of shares of Common Stock pursuant to an effective Registration Statement under
the Securities Act resulting in gross proceeds to the Company of at least $40
million (prior to the deduction of underwriters' commissions, discounts and
expenses) and at a pre-money valuation of the Company of no less than $135
million.

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      "Other Holders" means holders of securities of the Company (other than the
Preferred Stockholders) who are entitled, by contract with the Company, to have
securities included in a Registration Statement.

      "Preferred Stock" means the Series AB Preferred Stock and the Series C
Preferred Stock.

      "Prospectus" means the prospectus included in any Registration Statement,
as amended or supplemented by an amendment or prospectus supplement, including
post-effective amendments, and all material incorporated by reference or deemed
to be incorporated by reference in such Prospectus.

      "Registrable Shares" means (a) the shares of Common Stock issued or
issuable upon conversion of the Preferred Stock, (b) any other shares of Common
Stock, and any shares of Common Stock issued or issuable upon the conversion or
exercise of any other securities, including the Funding Warrants and Series AB
Warrants, acquired by the Preferred Stockholders, and (c) any other shares of
Common Stock issued in respect of such shares (because of stock splits, stock
dividends, reclassifications, recapitalizations or similar events); provided,
however, that, shares of Common Stock which are Registrable Shares shall cease
to be Registrable Shares (i) upon any sale pursuant to a Registration Statement,
or (ii) upon the occurrence of the events set forth in Section 2(l). Wherever
reference is made in this Agreement to a request or consent of holders of a
certain percentage of Registrable Shares, the determination of such percentage
shall only include shares of Common Stock issued or issuable upon conversion of
the Series C Preferred Stock (even if such conversion has not been effected).

      "Registration Expenses" means all expenses incurred by the Company in
complying with the provisions of Section 2, including, without limitation, all
registration and filing fees, exchange listing fees, printing expenses, fees and
expenses of counsel for the Company and the reasonable fees and expenses of one
counsel selected by the Selling Stockholders to represent the Selling
Stockholders, which expenses shall not exceed $25,000, state Blue Sky fees and
expenses, and the expense of any special audits incident to or required by any
such registration, but excluding underwriting discounts, selling commissions and
the fees and expenses of Selling Stockholders' own counsel (other than the
counsel selected to represent all Selling Stockholders).

      "Registration Statement" means a registration statement filed by the
Company with the Commission for a public offering and sale of securities of the
Company (other than a registration statement on Form S-8 or Form S-4, or their
successors, or any other form for a similar limited purpose, or any registration
statement covering only securities proposed to be issued in exchange for
securities or assets of another corporation).

      "Securities" means the Preferred Stock, Funding Warrants, Common Stock,
the Series AB Warrants and any shares of the Company's Capital Stock issuable
upon the conversion or exercise thereof

      "Securities Act" means the Securities Act of 1933, as amended, or any
successor federal statute, and the rules and regulations of the Commission
issued under such Act, as they each may, from time to time, be in effect.

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      "Selling Stockholder" means any Preferred Stockholder owning Registrable
Shares included in a Registration Statement.

      "Series AB Preferred Stock" means the Company's Series AB Convertible
Preferred Stock, par value $.01 per share.

      "Series AB Warrants" means those warrants to purchase shares of Series AB
Preferred Stock, dated on or about August 9, 2004, issued pursuant to the
Securities Purchase Agreement.

      "Series C Preferred Stock" means the Company's Series C Convertible
Preferred Stock, par value $.01 per share.

      "Shares" means the shares of Capital Stock of the Company now held or
hereafter acquired by a Stockholder.

      SECTION 2. Registration Rights.

         (a) Required Registrations.

                  (i) At any time after the earlier to occur of (A) six months
            after the closing of the Initial Public Offering and (B) January 21,
            2008, a Series C Preferred Stockholder or Series C Preferred
            Stockholders holding in the aggregate at least 40% of the
            Registrable Shares then outstanding may request, in writing, that
            the Company effect the registration on Form S-1 or Form S-2 (or any
            successor form) of Registrable Shares owned by such Series C
            Preferred Stockholder or Series C Preferred Stockholders having an
            aggregate value of at least $5,000,000 (based on the market price or
            fair value on the date of such request).

                  (ii) At any time after the Company becomes eligible to file a
            Registration Statement on Form S-3 (or any successor form relating
            to secondary offerings), a Series C Preferred Stockholder or Series
            C Preferred Stockholders holding Registrable Shares may request, in
            writing, that the Company effect the registration on Form S-3 (or
            such successor form), of Registrable Shares having an aggregate
            value of at least $2,000,000 (based on the public market price on
            the date of such request).

                  (iii) Upon receipt of any request for registration pursuant to
            this Section 2, the Company shall promptly give written notice of
            such proposed registration to all other Preferred Stockholders. Such
            Preferred Stockholders shall have the right, by giving written
            notice to the Company within 30 days after the Company provides its
            notice, to elect to have included in such registration such number
            of their Registrable Shares as such Preferred Stockholders may
            request in such notice of election, subject in the case of an
            underwritten offering to the terms of Section 2(a)(iv) below.
            Thereupon, the Company shall, as expeditiously as possible, use its
            best efforts to effect the registration on an appropriate
            registration form of all Registrable Shares which the Company has
            been requested to so register; provided, however, that in the case
            of a registration

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            requested under Section 2(a)(ii), the Company will only be obligated
            to effect such registration on Form S-3 (or any successor form).

                  (iv) If the Initiating Holders intend to distribute the
            Registrable Shares covered by their request by means of an
            underwriting, they shall so advise the Company as a part of their
            request made pursuant to Section 2(a)(i) or (ii), as the case may
            be, and the Company shall include such information in its written
            notice referred to in Section 2(a)(iii). In such event, (i) the
            right of any other Preferred Stockholder to include its Registrable
            Shares in such registration pursuant to Section 2(a)(i) or (ii), as
            the case may be, shall be conditioned upon such other Preferred
            Stockholders' participation in such underwriting on the terms set
            forth herein, and (ii) all Preferred Stockholders including
            Registrable Shares in such registration shall enter into an
            underwriting agreement upon customary terms with the underwriter or
            underwriters managing the offering; provided that such underwriting
            agreement shall not provide for indemnification or contribution
            obligations on the part of the Preferred Stockholders materially
            greater than the obligations of the Preferred Stockholders pursuant
            to Section 2(e) herein. The Initiating Holders shall have the right
            to select the managing underwriter(s) for any underwritten offering
            requested pursuant to Section 2(a)(i) or (ii), subject to the
            approval of the Company, which approval will not be unreasonably
            withheld, conditioned or delayed. If any Preferred Stockholder who
            has requested inclusion of its Registrable Shares in such
            registration as provided above disapproves of the terms of the
            underwriting, such person may elect, by written notice to the
            Company, to withdraw its Registrable Shares from such Registration
            Statement and underwriting. If the managing underwriter advises the
            Company in writing that marketing factors require a limitation on
            the number of shares to be underwritten, the number of Registrable
            Shares to be included in the Registration Statement and underwriting
            shall be allocated among all Preferred Stockholders requesting
            registration in proportion, as nearly as practicable, to the
            respective number of Registrable Shares held by them on the date of
            the request for registration made by the Initiating Holders pursuant
            to Section 2(a)(i) or (ii), as the case may be. If any Preferred
            Stockholder would thus be entitled to include more Registrable
            Shares than such Preferred Stockholder requested to be registered,
            the excess shall be allocated among other requesting Preferred
            Stockholders pro rata in the manner described in the preceding
            sentence.

                  (v) The Company shall not be required to effect more than two
            registrations in the aggregate pursuant to Section 2(a)(i) or more
            than two registrations in any twelve month period pursuant to
            Section 2(a)(ii). In addition, the Company shall not be required to
            effect any registration pursuant to Section 2(a)(i): (A) within six
            months after the closing of the Initial Public Offering or (B) if
            the Company delivers notice to the holders of Registrable Shares
            within 30 days of any registration request of its intent to file a
            registration statement for a public offering within 90 days,
            provided that the Company, shall, in good faith, use its best
            efforts to cause such registration statement to become effective.
            For purposes of this Section 2(a)(v), a Registration Statement shall
            not be counted as

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            having been effected until such time as such Registration Statement
            has been declared effective by the Commission (unless the Initiating
            Holders withdraw their request for such registration (other than as
            a result of information concerning the business or financial
            condition of the Company which is made known to the Preferred
            Stockholders after the date on which such registration was
            requested) and elect not to pay the Registration Expenses therefor
            pursuant to Section 2(d)). For purposes of this Section 2(a)(v), a
            Registration Statement shall not be counted as having been effected
            if, as a result of an exercise of the underwriter's cut-back
            provisions, less than 50% of the total number of Registrable Shares
            that Preferred Stockholders have requested to be included in such
            Registration Statement are so included.

                  (vi) If at the time of any request to register Registrable
            Shares by Initiating Holders pursuant to this Section 2(a), the
            Company is engaged or has plans to engage in a registered public
            offering or is engaged in any other activity which, in the good
            faith determination of the Company's board of directors, would be
            adversely affected by the requested registration, then the Company
            may at its option direct that such request be delayed for a period
            not in excess of 90 days from the date of such request, such right
            to delay a request to be exercised by the Company not more than once
            in any 12-month period.

         (b) Incidental Registration.

                  (i) Whenever the Company proposes to file a Registration
            Statement covering shares of Common Stock (other than a Registration
            Statement filed pursuant to Section 2(a) or on Form S-4 or Form S-8
            or similar or successor forms) at any time and from time to time, it
            will, prior to such filing, give written notice to all Preferred
            Stockholders of its intention to do so; provided, that no such
            notice need be given if no Registrable Shares are to be included in
            the Company's initial public offering as a result of a written
            notice from the managing underwriter pursuant to Section 2(b)(ii)
            below. Upon the written request of a Preferred Stockholder or
            Preferred Stockholders given within 20 days after the Company
            provides such notice (which request shall state the intended method
            of disposition of such Registrable Shares), the Company shall use
            its best efforts to cause all Registrable Shares which the Company
            has been requested by such Preferred Stockholder or Preferred
            Stockholders to register to be registered under the Securities Act
            to the extent necessary to permit their sale or other disposition in
            accordance with the intended methods of distribution specified in
            the request of such Preferred Stockholder or Preferred Stockholders;
            provided that the Company shall have the right to postpone or
            withdraw any registration effected pursuant to this Section 2(b)
            without obligation to any Preferred Stockholder.

                  (ii) If the registration for which the Company gives notice
            pursuant to Section 2(b)(i) is a registered public offering
            involving an underwriting, the Company shall so advise the Preferred
            Stockholders as a part of the written notice given pursuant to
            Section 2(b)(i). In such event, (i) the right of any Preferred

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            Stockholder to include its Registrable Shares in such registration
            pursuant to this Section 2(b) shall be conditioned upon such
            Preferred Stockholder's participation in such underwriting on the
            terms set forth herein and (ii) all Preferred Stockholders including
            Registrable Shares in such registration shall enter into an
            underwriting agreement upon customary terms with the underwriter or
            underwriters selected for the underwriting by the Company. If any
            Preferred Stockholder who has requested inclusion of its Registrable
            Shares in such registration as provided above disapproves of the
            terms of the underwriting, such person may elect, by written notice
            to the Company, to withdraw its shares from such Registration
            Statement and underwriting. If the managing underwriter advises the
            Company in writing that marketing factors require a limitation on
            the number of shares to be underwritten, the shares held by holders
            other than Preferred Stockholders and Other Holders shall be
            excluded from such Registration Statement and underwriting to the
            extent deemed advisable by the managing underwriter, and, if a
            further reduction of the number of shares is required, the number of
            shares that may be included in such Registration Statement and
            underwriting shall be allocated among all Preferred Stockholders and
            Other Holders requesting registration in proportion, as nearly as
            practicable, to the respective number of shares of Common Stock (on
            an as-converted basis) held by them on the date the Company gives
            the notice specified in Section 2(b)(i) above; provided that, except
            where such proposed underwritten public offering is the Company's
            initial public offering, in each of the foregoing cases, holders of
            Registrable Shares shall be entitled to include, on a pro rata
            basis, an aggregate of such Registrable Shares equal to 30% of the
            total number of securities registered in such proposed underwritten
            public offering. If any Preferred Stockholder or Other Holder would
            thus be entitled to include more shares than such holder requested
            to be registered, the excess shall be allocated among other
            requesting Preferred Stockholders and Other Holders pro rata in the
            manner described in the preceding sentence. Unless the registration
            is with respect to the Company's initial public offering, in no
            event shall the shares to be sold pursuant to this Section 2(b) by
            the Preferred Stockholders be reduced below 30% of the total amount
            of securities included in such registration.

         (c) Registration Procedures.

                  (i) If and whenever the Company is required by the provisions
            of this Agreement to use its best efforts to effect the registration
            of any Registrable Shares under the Securities Act, the Company
            shall:

                        (1)   file with the Commission a Registration Statement
                              with respect to such Registrable Shares and use
                              its best efforts to cause that Registration
                              Statement to become effective as soon as possible;

                        (2)   as expeditiously as possible prepare and file with
                              the Commission any amendments and supplements to
                              the Registration Statement and the prospectus
                              included in the

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                              Registration Statement as may be necessary to
                              comply with the provisions of the Securities Act
                              (including the anti-fraud provisions thereof) and
                              to keep the Registration Statement effective for
                              12 months from the effective date or such lesser
                              period until all such Registrable Shares are sold;
                              provided, however, that (A) such 12 month period
                              shall be extended for a period of time equal to
                              the period the Selling Stockholder refrains from
                              selling any securities included in such
                              registration at the request of any underwriter of
                              Common Stock (or other securities) of the Company;
                              and (B) in the case of any registration of
                              Registrable Shares on Form S-3 which are intended
                              to be offered on a continuous or delayed basis,
                              such 12 month period shall be extended, if
                              necessary, to keep the Registration Statement
                              effective until all such Registrable Shares are
                              sold, provided that Rule 415, or any successor
                              rule under the Securities Act, permits an offering
                              on a continuous or delayed basis, and provided
                              further that applicable rules under the Securities
                              Act governing the obligation to file a
                              post-effective amendment permit, in lieu of filing
                              a post-effective amendment which (I) includes any
                              prospectus required by Section 10(a)(3) of the
                              Securities Act or (II) reflects facts or events
                              representing a material or fundamental change in
                              the information set forth in the Registration
                              Statement, the incorporation by reference of
                              information required to be included in (I) and
                              (II) above to be contained in periodic reports
                              filed pursuant to Section 13 or 15(d) of the
                              Exchange Act in the registration statement;

                        (3)   as expeditiously as possible furnish to each
                              Selling Stockholder such reasonable numbers of
                              copies of the Prospectus, including any
                              preliminary Prospectus, in conformity with the
                              requirements of the Securities Act, and such other
                              documents as such Selling Stockholder may
                              reasonably request in order to facilitate the
                              public sale or other disposition of the
                              Registrable Shares owned by such Selling
                              Stockholder;

                        (4)   as expeditiously as possible use its best efforts
                              to register or qualify the Registrable Shares
                              covered by the Registration Statement under the
                              securities or Blue Sky laws of such states as the
                              Selling Stockholders shall reasonably request, and
                              do any and all other acts and things that may be
                              necessary or desirable to enable the Selling
                              Stockholders to consummate the public sale or
                              other disposition in such states of the
                              Registrable Shares owned by the Selling
                              Stockholders; provided, however, that the Company
                              shall

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                              not be required in connection with this paragraph
                              (4) to qualify as a foreign corporation or execute
                              a general consent to service of process in any
                              jurisdiction;

                        (5)   as expeditiously as possible, cause all such
                              Registrable Shares to be listed on each securities
                              exchange or automated quotation system on which
                              similar securities issued by the Company are then
                              listed;

                        (6)   promptly provide a transfer agent and registrar
                              for all such Registrable Shares and a CUSIP number
                              for all such Registrable Shares not later than the
                              effective date of such Registration Statement;

                        (7)   promptly make available for inspection by the
                              Selling Stockholders, any managing underwriter
                              participating in any disposition pursuant to such
                              Registration Statement, and any attorney or
                              accountant or other agent retained by any such
                              underwriter or selected by the Selling
                              Stockholders, all financial and other records,
                              pertinent corporate documents and properties of
                              the Company and cause the Company's officers,
                              directors, employees and independent accountants
                              to supply all information reasonably requested by
                              any such seller, underwriter, attorney, accountant
                              or agent in connection with such Registration
                              Statement;

                        (8)   as expeditiously as possible, notify each Selling
                              Stockholder, promptly after it shall receive
                              notice thereof, of the time when such Registration
                              Statement has become effective or a supplement to
                              any Prospectus forming a part of such Registration
                              Statement has been filed; and

                        (9)   as expeditiously as possible following the
                              effectiveness of such Registration Statement,
                              notify each Selling Stockholder covered by such
                              Registration Statement, at any time when a
                              Prospectus relating thereto is required to be
                              delivered under the Securities Act, of (i) any
                              request by the Commission for the amending or
                              supplementing of such Registration Statement or
                              Prospectus or the issuance of any stop order by
                              the Commission in respect of such Registration
                              Statement, or (ii) the happening of any event as a
                              result of which the Prospectus, as then in effect,
                              includes an untrue statement of a material fact or
                              omits 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.

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                  (ii) If the Company has delivered a Prospectus to the Selling
            Stockholders and after having done so the Prospectus is amended to
            comply with the requirements of the Securities Act, the Company
            shall promptly notify the Selling Stockholders and, if requested,
            the Selling Stockholders shall immediately cease making offers of
            Registrable Shares and return all Prospectuses to the Company. The
            Company shall promptly provide the Selling Stockholders with revised
            Prospectuses and, following receipt of the revised Prospectuses, the
            Selling Stockholders shall be free to resume making offers of the
            Registrable Shares.

                  (iii) In the event that, in the judgment of the Company, it is
            advisable to suspend use of a Prospectus included in a Registration
            Statement due to pending material developments or other events that
            have not yet been publicly disclosed and as to which the Company
            believes public disclosure would be detrimental to the Company, the
            Company shall notify all Selling Stockholders to such effect, and,
            upon receipt of such notice, each such Selling Stockholder shall
            immediately discontinue any sales of Registrable Shares pursuant to
            such Registration Statement until such Selling Stockholder has
            received copies of a supplemented or amended Prospectus or until
            such Selling Stockholder is advised in writing by the Company that
            the then current Prospectus may be used and has received copies of
            any additional or supplemental filings that are incorporated or
            deemed incorporated by reference in such Prospectus. Notwithstanding
            anything to the contrary herein, the Company shall not exercise its
            rights under this Section 2(c)(iii) to suspend sales of Registrable
            Shares for a period in excess of 30 days consecutively or 60 days in
            any 365-day period.

         (d) Allocation of Expenses. The Company will pay all Registration
   Expenses for all registrations under this Agreement; provided, however, that
   if a registration under Section 2(a) is withdrawn at the request of the
   Initiating Holders (other than as a result of information concerning the
   business or financial condition of the Company which is made known to the
   Selling Stockholders after the date on which such registration was requested)
   and if the Initiating Holders elect not to have such registration counted as
   a registration requested under Section 2(a), the Selling Stockholders shall
   pay the Registration Expenses of such registration pro rata in accordance
   with the number of their Registrable Shares included in such registration.

         (e) Indemnification and Contribution.

                  (i) In the event of any registration of any of the Registrable
            Shares under the Securities Act pursuant to this Agreement, the
            Company will indemnify and hold harmless each Selling Stockholder,
            each underwriter of such Registrable Shares, and each other person,
            if any, who controls such Selling Stockholder or underwriter within
            the meaning of the Securities Act or the Exchange Act against any
            losses, claims, damages or liabilities, joint or several, to which
            such Selling Stockholder, underwriter or controlling person may
            become subject under the Securities Act, the Exchange Act, state
            securities or Blue Sky laws or otherwise, insofar as such losses,
            claims, damages or liabilities (or actions in respect thereof)

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            arise out of or are based upon (a) any untrue statement or alleged
            untrue statement of any material fact contained in any Registration
            Statement under which such Registrable Shares were registered under
            the Securities Act, any preliminary prospectus or final prospectus
            contained in the Registration Statement, or any amendment or
            supplement to such Registration Statement, (b) the omission or
            alleged omission to state a material fact required to be stated
            therein or necessary to make the statements therein not misleading,
            or (c) any violation or alleged violation by the Company of the
            Securities Act, the Exchange Act, any state securities law or any
            rule or regulation promulgated under the Securities Act, the
            Exchange Act or any state securities law in connection with the
            Registration Statement or the offering contemplated thereby; and the
            Company will reimburse such Selling Stockholder, underwriter and
            each such controlling person for any legal or any other expenses
            reasonably incurred by such Selling Stockholder, underwriter or
            controlling person in connection with investigating or defending any
            such loss, claim, damage, liability or action; provided, however,
            that the Company will not be liable in any such case to the extent
            that any such loss, claim, damage or liability arises out of or is
            based upon any untrue statement or omission made in such
            Registration Statement, preliminary prospectus or prospectus, or any
            such amendment or supplement, in reliance upon and in conformity
            with information furnished to the Company, in writing, by or on
            behalf of such Selling Stockholder, underwriter or controlling
            person specifically for use in the preparation thereof.

                  (ii) In the event of any registration of any of the
            Registrable Shares under the Securities Act pursuant to this
            Agreement, each Selling Stockholder, severally and not jointly, will
            indemnify and hold harmless the Company, each of its directors and
            officers and each underwriter (if any) and each person, if any, who
            controls the Company or any such underwriter within the meaning of
            the Securities Act or the Exchange Act, against any losses, claims,
            damages or liabilities, joint or several, to which the Company, such
            directors and officers, underwriter or controlling person may become
            subject under the Securities Act, Exchange Act, state securities or
            Blue Sky laws or otherwise, insofar as such losses, claims, damages
            or liabilities (or actions in respect thereof) arise out of or are
            based upon (a) any untrue statement or alleged untrue statement of a
            material fact contained in any Registration Statement under which
            such Registrable Shares were registered under the Securities Act,
            any preliminary prospectus or final prospectus contained in the
            Registration Statement, or any amendment or supplement to the
            Registration Statement, or (b) any omission or alleged omission to
            state a material fact required to be stated therein or necessary to
            make the statements therein not misleading, if and to the extent
            (and only to the extent) that the statement or omission (referenced
            in "(a)" or "(b)" above) was made in reliance upon and in conformity
            with information relating to such Selling Stockholder furnished in
            writing to the Company by such Selling Stockholder specifically for
            use in connection with the preparation of such Registration
            Statement, prospectus, amendment or supplement; provided, however,
            that the obligations of a Selling Stockholder hereunder shall be
            limited to an amount

                                      11

<PAGE>

            equal to the net proceeds to such Selling Stockholder of Registrable
            Shares sold in connection with such registration.

                  (iii) Each Indemnified Party shall give notice to the
            Indemnifying Party promptly after such Indemnified Party has actual
            knowledge of any claim as to which indemnity may be sought, and
            shall permit the Indemnifying Party to assume the defense of any
            such claim or any litigation resulting therefrom; provided, that
            counsel for the Indemnifying Party, who shall conduct the defense of
            such claim or litigation, shall be approved by the Indemnified Party
            (whose approval shall not be unreasonably withheld, conditioned or
            delayed); 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 under this Section
            2(e) except to the extent that the Indemnifying Party is adversely
            affected by such failure. The Indemnified Party may participate in
            such defense and retain its own counsel at such party's expense;
            provided, however, that the Indemnifying Party shall pay such
            reasonable fees and expenses if, in the reasonable opinion of
            counsel to the Indemnified Party, either (x) one or more defenses
            are available to the Indemnified Party that are not available to the
            Indemnifying Party, or (y) a conflict or potential conflict exists
            between the Indemnified Party, on the one hand, and the Indemnifying
            Party, on the other hand, that would make separate representation
            advisable; and provided, further, that in no event shall the
            Indemnifying Party be required to pay the expenses of more than one
            law firm as counsel for the Indemnified Party. The Indemnifying
            Party also shall be responsible for the expenses of such defense if
            the Indemnifying Party does not elect to assume such defense. No
            Indemnifying Party, in the defense of any such claim or litigation
            shall, except with the consent of each Indemnified Party, consent to
            entry of any judgment or enter into any settlement which 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 of such claim or litigation, and no Indemnified
            Party shall consent to entry of any judgment or settle such claim or
            litigation without the prior written consent of the Indemnifying
            Party, which consent shall not be unreasonably withheld, conditioned
            or delayed.

                  (iv) In order to provide for just and equitable contribution
            in circumstances in which the indemnification provided for in this
            Section 2(e) is due in accordance with its terms but for any reason
            is held to be unavailable to an Indemnified Party in respect to any
            losses, claims, damages and liabilities referred to herein, then the
            Indemnifying Party shall, in lieu of indemnifying such Indemnified
            Party, contribute to the amount paid or payable by such Indemnified
            Party as a result of such losses, claims, damages or liabilities to
            which such party may be subject in such proportion as is appropriate
            to reflect the relative fault of the Company on the one hand and the
            Selling Stockholders on the other in connection with the statements
            or omissions which resulted in such losses, claims, damages or
            liabilities, as well as any other relevant equitable considerations.
            The relative fault of the Company and the Selling Stockholders shall
            be determined by reference to, among other things, whether the
            untrue or

                                      12

<PAGE>

            alleged untrue statement of material fact related to information
            supplied by the Company or the Selling Stockholders and the parties'
            relative intent, knowledge, access to information and opportunity to
            correct or prevent such statement or omission. The Company and the
            Selling Stockholders agree that it would not be just and equitable
            if contribution pursuant to this Section 2(e)(iv) were determined by
            pro rata allocation or by any other method of allocation which does
            not take account of the equitable considerations referred to above.
            Notwithstanding the provisions of this Section 2(e)(iv), (a) in no
            case shall any one Selling Stockholder be liable or responsible for
            any amount in excess of the net proceeds received by such Selling
            Stockholder from the offering of Registrable Shares and (b) the
            Company shall be liable and responsible for any amount in excess of
            such proceeds; provided, however, that no person guilty of
            fraudulent misrepresentation (within the meaning of Section 11(f) of
            the Securities Act) shall be entitled to contribution from any
            person who was not guilty of such fraudulent misrepresentation. Any
            party entitled to contribution will, promptly after receipt of
            notice of commencement of any action, suit or proceeding against
            such party in respect of which a claim for contribution may be made
            against another party or parties under this Section 2(e)(iv), notify
            such party or parties from whom contribution may be sought, but the
            omission so to notify such party or parties from whom contribution
            may be sought shall not relieve such party from any other obligation
            it or they may have thereunder or otherwise under this Section
            2(e)(iv). No party shall be liable for contribution with respect to
            any action, suit, proceeding or claim settled without its prior
            written consent, which consent shall not be unreasonably withheld,
            conditioned or delayed.

                  (v) The rights and obligations of the Company and the Selling
            Stockholders under this Section 2(e) shall survive the termination
            of this Agreement.

         (f) Other Matters with Respect to Underwritten Offerings. In the event
   that Registrable Shares are sold pursuant to a Registration Statement in an
   underwritten offering pursuant to Section 2(a), the Company agrees to (a)
   enter into an underwriting agreement containing customary representations and
   warranties with respect to the business and operations of the Company and
   customary covenants and agreements to be performed by the Company, including
   without limitation customary provisions with respect to indemnification by
   the Company of the underwriters of such offering; (b) use its best efforts to
   cause its legal counsel to render customary opinions to the underwriters with
   respect to the Registration Statement; and (c) use its best efforts to cause
   its independent public accounting firm to issue customary "cold comfort
   letters" to the underwriters with respect to the Registration Statement.

         (g) Information by Holder. Each holder of Registrable Shares included
   in any registration shall furnish to the Company such information regarding
   such holder and the distribution proposed by such holder as the Company may
   reasonably request in writing and as shall be required in connection with any
   registration, qualification or compliance referred to in this Agreement.

                                      13

<PAGE>

         (h) Transfer of Registration Rights. Each holder of Registrable Shares
   may transfer his, her or its Registration Rights to (i) an Affiliate (as
   defined in Section 3(c)); (ii) a member of the Family (as defined in Section
   3(c)) or to trusts or limited or general partnerships established for the
   benefit of such holder or members of such holder's Family or (iii) any
   transferee who acquires at least 200,000 shares of Preferred Stock or the
   number of Common Stock issuable upon conversion thereof (as adjusted for
   stock splits, combinations and the like); provided, however, that the Company
   be given written notice thereof in accordance with Section 18 at least 10
   days in advance of such transfer.

         (i) "Lock-Up" Agreement: Confidentiality of Notices. Each Preferred
   Stockholder and any transferee thereof, if requested by the Company and the
   managing underwriter of the Initial Public Offering, shall not sell or
   otherwise transfer or dispose of any Shares (excluding securities acquired in
   the Initial Public Offering or in the public market after such offering) held
   by such Preferred Stockholder or such transferee for a period of 180 days
   following the effective date of the Registration Statement for the Initial
   Public Offering; provided, that all stockholders of the Company then holding
   at least 1% of the outstanding Common Stock (on an as-converted basis) and
   all executive officers and directors of the Company enter into similar
   agreements; and provided further, that to the extent that any such officer,
   director, or stockholder of the Company is released (in whole or in part)
   from such lock-up agreement prior to its scheduled termination date, each
   Preferred Stockholder executing such a lock-up agreement will have the
   proportionate percentage of its securities released from such lock-up
   agreement. Notwithstanding the foregoing, nothing in this Section 2(i) shall
   prevent a Preferred Stockholder from making a transfer of any Common Stock
   that was listed on a national stock exchange actively traded over-the-counter
   or traded on the Nasdaq National Market at the time it was acquired by the
   Preferred Stockholder or was acquired by such Preferred Stockholder pursuant
   to Rule 144A of the Securities Act, including any shares acquired in the
   Initial Public Offering of the Company.

            The Company may impose stop-transfer instructions with respect to
   the Shares subject to the foregoing restriction until the end of such 180-day
   period.

            Any Preferred Stockholder and any transferee thereof receiving any
   written notice from the Company regarding the Company's plans to file a
   Registration Statement shall treat such notice confidentially and shall not
   disclose such information to any person other than as necessary to exercise
   its rights under this Agreement.

         (j) Limitations on Subsequent Registration Rights. The Company shall
   not, without the prior written consent of holders of Series C Preferred Stock
   holding at least 66 2/3% of the Registrable Shares then held by all holders
   of Series C Preferred Stock, enter into any agreement (other than this
   Agreement) with any holder or prospective holder of any securities of the
   Company which grant such holder or prospective holder rights to include
   securities of the Company in any Registration Statement, unless such
   registration rights, including, without limitation, the related lock-up
   provisions, are on a subordinated basis to the registration rights granted
   herein.

         (k) Rule 144 Requirements. After the earliest of (i) the closing of the
   sale of securities of the Company pursuant to a Registration Statement, (ii)
   the registration by the

                                      14

<PAGE>

   Company of a class of securities under Section 12 of the Exchange Act, or
   (iii) the issuance by the Company of an offering circular pursuant to
   Regulation A under the Securities Act, the Company agrees to:

                  (i) make and keep current public information about the Company
            available, as those terms are understood and defined in Rule 144;

                  (ii) file with the Commission in a timely manner all reports
            and other documents required of the Company under the Securities Act
            and the Exchange Act (at any time after it has become subject to
            such reporting requirements); and

                  (iii) furnish to any holder of Registrable Shares upon request
            (i) a written statement by the Company as to its compliance with the
            reporting requirements of Rule 144 and of the Securities Act and the
            Exchange Act (at any time after it has become subject to such
            reporting requirements), (ii) a copy of the most recent annual or
            quarterly report of the Company, and (iii) such other reports and
            documents of the Company as such holder may reasonably request to
            avail itself of any similar rule or regulation of the Commission
            allowing it to sell any such securities without registration.

         (l) Termination. All of the Company's obligations to register the
   Registrable Shares pursuant to this Section 2 shall terminate upon the
   earlier of (i) five years after the closing of the Initial Public Offering,
   (ii) the date on which no Preferred Stockholder holds any Registrable Shares
   or (iii) as to any Preferred Stockholder, such earlier time at which all
   Registrable Shares held by such Preferred Stockholder (and any Affiliate if
   the Preferred Stockholder must aggregate its sales under Rule 144) can be
   sold in any single ninety (90) day period without registration in compliance
   with Rule 144 of the Securities Act (without reliance on Rule 144(k)
   thereunder).

      SECTION 3. General Restrictions on Transfer of Securities.

         (a) During the term of this Agreement, none of the Securities owned on
   the date hereof or hereafter acquired by any Stockholder may be transferred,
   assigned, pledged, encumbered or otherwise hypothecated except in accordance
   with the provisions of this Agreement.

         (b) Any attempted transfer of Securities other than in accordance with
   this Agreement (other than an involuntary transfer by operation of law) shall
   be null and void and the Company shall refuse to recognize any such transfer
   and shall not reflect on its records any change in record ownership of
   Securities pursuant to any such transfer.

         (c) Notwithstanding anything contained herein to the contrary, it is
   understood and agreed that: (i) each of the Stockholders who is an individual
   may transfer any or all of the shares of Capital Stock of the Company
   beneficially owned by such Stockholder to such Stockholder's spouse, lineal
   ascendants or descendants, brothers or sisters ("Family"), or to trusts or
   limited or general partnerships established for the benefit of such
   Stockholder or such Stockholder's Family members; provided, however, that in
   connection with such transfer, the transferee executes a counterpart
   signature page to this Agreement and

                                      15

<PAGE>

   agrees to be bound by all of the provisions hereof as if it were the
   transferor hereunder; (ii) each of the Stockholders which is a trust may
   transfer any or all of the shares of Capital Stock owned by it to the
   beneficiaries thereof provided, however, that in connection with such
   transfer, the transferee executes a counterpart signature page to this
   Agreement and agrees to be bound by all the provisions hereof as if it were
   the transferor hereunder; (iii) each of the Stockholders that is a
   corporation, partnership, limited liability company or other business entity
   may transfer any shares of Capital Stock owned by it to Affiliate(s) (as
   hereinafter defined) of such Stockholder; provided, however, that in
   connection with such transfer, each transferee executes a counterpart
   signature page to this Agreement and agrees to be bound by all of the
   provisions hereof as if it were the transferor hereunder; and (iv) each of
   the Stockholders may transfer the Funding Warrants in accordance with the
   terms thereof and hereof. For purposes hereof, "Affiliate" shall mean with
   respect to any Stockholder that is a corporation, partnership, limited
   liability company or other business entity, any of the stockholders,
   subsidiaries, officers, directors, current or former members or current or
   former partners of such Stockholder, and any other corporation, partnership
   or other business entity which directly or indirectly controls, is controlled
   by or is under common control with such Stockholder.

         (d) Notwithstanding the foregoing, no Stockholder shall be permitted to
   transfer any shares of Capital Stock, without the approval of the Board of
   Directors, to a transferee that is a competitor of the Company, as determined
   by the Board of Directors of the Company in its sole discretion; provided
   however, that none of Yamanouchi Pharmaceutical Co., Ltd., Yamanouchi Group
   Holding, Inc. or Yamanouchi Pharma America, Inc. shall be deemed a competitor
   of the Company. For purposes of this Agreement, the transferor shall
   cooperate with the Company and provide all necessary information about such
   transferee when deemed necessary and appropriate by the Board of Directors of
   the Company to determine whether a potential transferee is a competitor of
   the Company.

      SECTION 4. Offer of Sale: Notice of Proposed Sale.

      If any Stockholder desires to transfer any of the Shares held by such
Stockholder to a third party pursuant to a bona fide offer, or any interest in
such Shares, in any transaction other than pursuant to Sections 3(c) and (d) of
this Agreement, such Stockholder (the "Selling Holder") shall deliver written
notice of his, her or its desire to do so (the "Notice") to the Company, in the
manner prescribed in Section 18 of this Agreement. The Notice must specify: (i)
the name and address of the party to which the Selling Holder proposes to sell
or otherwise dispose of the Shares or an interest in the Shares (the "Offeror"),
(ii) the number of Shares the Selling Holder proposes to sell or otherwise
dispose of (the "Offered Shares"), (iii) the consideration per Share to be
delivered to the Selling Holder for the proposed sale, transfer or disposition,
and (iv) all other material terms and conditions of the proposed transaction
(the "Proposed Transaction"). If such Stockholder is also a party to the Co-Sale
Agreement, then such Stockholder shall first comply with the provisions of the
Co-Sale Agreement. If all or any portion of such Shares are not transferred
pursuant to the terms of the Co-Sale Agreement, then such Stockholder shall next
comply with the provisions of this Agreement as set forth below.

                                      16

<PAGE>

      SECTION 5. Company's Option to Purchase.

         (a) The Company shall have the first option to purchase all or any part
   of the Offered Shares for the consideration per share and on the terms and
   conditions specified in the Notice. The Company must exercise such option, no
   later than 15 days after such Notice is deemed under Section 18 hereof to
   have been delivered to it, by written notice to the Selling Holder.

         (b) In the event the Company does not exercise its option in writing
   within such 15-day period with respect to all of the Offered Shares, the
   Company shall, by the last day of such period, give written notice of that
   fact to the Selling Holder (the "Company Notice"). The Company Notice shall
   specify the number of Offered Shares not purchased by the Company (the
   "Remaining Shares").

         (c) In the event the Company duly exercises its option to purchase all
   or part of the Offered Shares, the closing of such purchase shall take place
   at the offices of the Company on the later of (i) the date five days after
   the expiration of such 15-day period or (ii) the date that the Stockholders
   consummate their purchase of Remaining Shares under Section 6 hereof.

         (d) To the extent that the consideration proposed to be paid by the
   Offeror for the Offered Shares consists of property other than cash or a
   promissory note, the consideration required to be paid by the Company and/or
   the Stockholders exercising their options under Sections 5 and 6 hereof may
   consist of cash equal to the value of such property, as determined in good
   faith by agreement of the Selling Holder and the Company and/or the
   Stockholders acquiring such Offered Shares.

      SECTION 6. Stockholders' Option to Purchase.

         (a) In the event the Company elects to purchase less than all of the
   Offered Shares pursuant to Section 5 above, then the Selling Holder shall
   deliver a notice (the "Stockholder Notice") to the Company and to each other
   Stockholder who, together with its Affiliates, then holds at least 2% of the
   then outstanding Capital Stock of the Company, on an as converted to Common
   Stock basis (each a "Qualified Stockholder"), which Stockholder Notice shall
   be in the form and substance satisfactory to the Company, granting each
   Qualified Stockholder an option, exercisable for a period of 15 days from the
   date of delivery of the Stockholder Notice, to purchase any or all of the
   Remaining Shares for the consideration per share and on the terms and
   conditions set forth in the Notice, subject to a pro-rata reduction, if
   necessary, as provided by Section 6(b) below. Such option shall be exercised
   by delivery by such Qualified Stockholder of written notice to the Selling
   Holder, Secretary of the Company and to the other Qualified Stockholders.

         (b) In the event two or more such Qualified Stockholders exercise their
   option in Section 6(a) above, for a total number of Remaining Shares in
   excess of the number available, then the Remaining Shares available for each
   such Qualified Stockholder's option shall be allocated to such Qualified
   Stockholder pro rata based on the number of Shares held

                                      17

<PAGE>

   by such Qualified Stockholder divided by the total number of Shares held by
   all of the Qualified Stockholders so electing.

         (c) If the options to purchase the Remaining Shares are exercised in
   full by the Qualified Stockholders, the Company shall immediately notify all
   of the exercising Qualified Stockholders of that fact. The closing of the
   purchase of the Remaining Shares shall take place at the offices of the
   Company no later than five days after the date of such notice to the
   Qualified Stockholders.

         (d) If the Company or the Qualified Stockholders shall not have
   purchased all of the Offered Shares, subject to the provisions of Section 7
   below, then the Selling Holder may sell such Remaining Shares to the Offeror
   on terms no more favorable to the Offeror than as set forth in the Notice
   within 90 days of the date of the Notice. Otherwise, such Shares must then
   again comply with the terms of this Agreement. Notwithstanding the foregoing,
   any Selling Holder may not transfer such Offered Shares to a competitor of
   the Company, unless otherwise agreed to by the Board of Directors of the
   Company. The definition of a competitor shall be determined by the Board of
   Directors of the Company, in its sole discretion. For purposes hereof, the
   Selling Holder shall cooperate with the Company and provide all necessary
   information about such Offeror when deemed necessary and appropriate by the
   Board of Directors of the Company to determine whether a potential Offeror is
   a competitor of the Company.

         (e) Any Qualified Stockholder may allow an Affiliate thereof to
   exercise the rights of such Qualified Stockholder to purchase Shares under
   this Section 6, and such Affiliate shall be deemed to be a Qualified
   Stockholder for purposes hereof; provided, however, that neither the Company
   nor the Selling Holder shall be responsible for providing notice to any such
   Affiliate, and provided further that such Affiliate shall be required to
   comply with all applicable notice periods and other requirements under this
   Agreement.

      SECTION 7. Failure to Fully Exercise Options; Co-Sale.

         (a) If any of Michael Kauffman, Chen Schor, Oren Becker or Silvia
   Noiman (each a "Co-Sale Offeror") desires to transfer any of the Shares held
   by such individual to a third party pursuant to a bona fide offer, or any
   interest in such Shares, in any transaction other than pursuant to Section
   3(c) of this Agreement, after meeting the requirements of Sections 4, 5, and
   6 herein, such Co-Sale Offeror shall only be able to transfer any Remaining
   Shares after meeting the requirements of this Section 7 which entitles each
   holder of shares of Preferred Stock to transfer its Shares in such Proposed
   Transaction pursuant to this Section 7(a) (each such holder of Preferred
   Stock who so elects to transfer, a "Participating Stockholder"). As soon as
   practicable following the expiration of the 15-day period set forth in
   Section 6(a), and in no event later than five days thereafter, the Co-Sale
   Offeror shall provide notice to each holder of Preferred Stock (the "Co-Sale
   Notice") of its right to participate in the Proposed Transaction on a pro
   rata basis with the Co-Sale Offeror (the "Co-Sale Option"). Each of the
   holders of Preferred Stock shall have the right to exercise its Co-Sale
   Option by giving written notice of such intent to participate (the "Co-Sale
   Acceptance Notice") to the Co-Sale Offeror within ten days after receipt of
   the Co-Sale Notice (the "Co-Sale Election Period"). Each such acceptance
   notice shall indicate the

                                      18

<PAGE>

   maximum number of Shares which the Participating Stockholder wishes to
   transfer. Any Participating Stockholder shall be permitted to transfer to the
   relevant Offeror in connection with any exercise of the Co-Sale Option, at
   its option, (i) shares of Common Stock acquired upon conversion of such
   Preferred Stock, (ii) an option to acquire Common Stock when such
   Participating Stockholder receives the same upon conversion of such Preferred
   Stock, with the same effect as if Common Stock were being conveyed, or (iii)
   shares of Preferred Stock. The Co-Sale Offeror shall use his best efforts to
   interest the Offeror in purchasing, in addition to the Remaining Shares, the
   Shares the Participating Stockholders wish to transfer. If the Offeror does
   not wish to purchase all of the Shares made available by the Co-Sale Offeror
   and the Participating Stockholders, then each Participating Stockholder and
   the Co-Sale Offeror shall be entitled to sell, at the price and on the terms
   and conditions set forth in the Notice (provided that the price set forth in
   the Offer with respect to shares of Common Stock shall be appropriately
   adjusted, if necessary, based on the conversion ratio of any Preferred Stock
   to be sold), a portion of the Shares being sold to the Offeror, in the same
   proportion as such Co-Sale Offeror's or Participating Stockholder's ownership
   of Shares (on an as-converted to Common Stock basis) bears to the aggregate
   number of Shares (on an as-converted to Common Stock basis) owned by the
   Co-Sale Offeror and the Participating Stockholders. The transaction
   contemplated by the Notice, as adjusted pursuant to this Section 7(a), shall
   be consummated not later than 60 days after the expiration of the Option
   Period.

         (b) If the Participating Stockholders do not elect to sell the full
   number of Shares which they are entitled to sell pursuant to Section 7(a),
   the Co-Sale Offeror shall be entitled to sell to the Offeror, according to
   the terms set forth in the Notice, that number of his own Remaining Shares
   which equals the difference between the number of Shares desired to be
   purchased by the Offeror and the number of Shares the Participating
   Stockholders are entitled to sell pursuant to Section 7(a). If the Co-Sale
   Offeror wishes to sell any such Shares at a price per Share which differs
   from that set forth in the Notice, upon terms different from those previously
   offered to the Company and the Qualified Stockholders, or more than 60 days
   after the expiration of the Option Period, then, as a condition precedent to
   such transaction, such Shares must first be offered to the Company and the
   Qualified Stockholders on the same terms and conditions as given the Offeror,
   and in accordance with the procedures and time periods set forth above.

         (c) Within ten calendar days after the end of the Co-Sale Election
   Period, the Co-Sale Offeror shall promptly notify each Participating
   Stockholder of the number of Shares held by such Participating Stockholder
   that will be included in the sale in connection with the Proposed Transaction
   and the date on which the Proposed Transaction will be consummated, which
   shall be no later than the later of (i) 30 calendar days after the end of the
   Co-Sale Election Period and (ii) the satisfaction of any governmental
   approval or filing requirements, if any. Each Participating Stockholder may
   effect its participation in any Proposed Transaction hereunder by delivery to
   the Offeror, or to the Co-Sale Offeror for delivery to the Offeror, of one or
   more instruments or certificates, properly endorsed for transfer,
   representing the Shares it elects to sell pursuant thereto. At the time of
   consummation of the Proposed Transaction, the Offeror shall remit directly to
   each Participating Stockholders that portion of the sale proceeds to which
   the Participating Stockholder is entitled by reason of its participation with
   respect thereto. No Shares may be purchased by the Offeror from the Co-Sale
   Offeror unless the Offeror simultaneously

                                      19

<PAGE>

   purchases from the Participating Stockholders all of the Shares that they
   have elected to sell pursuant to this Section 7.

         (d) Prior to the effectiveness of any sale to an Offeror hereunder,
   such Offeror shall have executed and delivered a counterpart signature page
   hereto, and such Offeror shall have all the rights and obligations under
   Sections 4, 5, 6 and 7 as if such Offeror were a Co-Sale Offeror.

         (e) Notwithstanding anything to the contrary herein, the rights
   provided to the holders of Preferred Stock in this Section 7 will terminate
   upon the closing of (i) an Initial Public Offering or (ii) a Sale (as
   hereinafter defined) of the Company in consideration for cash proceeds or to
   any entity required to file periodic reports pursuant to the Exchange Act
   (such transaction, a "Public Sale").

      SECTION 8. Purchasers or Transferees of Securities. Any person or entity
who shall acquire (either voluntarily or involuntarily, by operation of law or
otherwise) any Securities from a Stockholder or any permitted transferee, shall
be bound by the provisions of this Agreement relating to the transfer and sale
of such Securities to the same extent as the parties hereto and, prior to the
registration of the transfer of any such Securities on the books of the Company,
any purchaser or other transferee shall execute a counterpart to this Agreement
agreeing to be bound by such provisions.

      SECTION 9. Sale of Shares Upon Death. In the event of the death of a
Stockholder, all Securities owned by such Stockholder at the date of death shall
be subject to the restrictions contained in this Agreement and shall not
thereafter be sold, pledged, transferred or otherwise disposed of in any manner,
except in compliance with the applicable provisions of this Agreement.

      SECTION 10. Voting and Required Sale. If: (i) any person or entity offers
to acquire all or substantially all of the assets, stock or business of the
Company by consolidation, merger or reorganization of the Corporation with or
into any other person(s) or entity(-ies) or a sale, lease, exclusive license or
other disposition (whether in a single transaction or a series of related
transactions) of all or substantially all of the assets or outstanding capital
stock of the Corporation or other similar transaction (other than a sale of
equity securities for the primary purpose of raising capital) (a "Sale"); (ii)
such transaction is approved by the Board of Directors; and (iii) the holders of
at least 66 2/3% of the voting power of the Series C Preferred Stock consent in
writing to such Sale (including by means of a proxy or stockholder consent
voting in favor of such transaction), then the Stockholders shall be obligated
to (a) vote all of his, her or its Shares in favor of such transaction, to the
extent any such vote is required for the consummation of such transaction, (b)
sell, transfer or exchange all of his, her or its Shares in connection with such
transaction on the same terms as those consented to by such Stockholders, and
(c) execute and deliver such instruments of conveyance and transfer and take
such other action, including executing any purchase agreement, merger agreement,
indemnity agreement, escrow agreement or related documents, as may be reasonably
required by the Company in order to carry out the terms and provisions of this
Section 10. If a party to this Agreement fails or refuses to vote or sell his,
her or its Shares as required by, or votes his, her or its Shares in
contravention of this Section 10, then such party hereby grants to the President
and Treasurer of the Company an

                                      20

<PAGE>

irrevocable proxy, coupled with an interest, to vote such Shares in accordance
with this Section 10, and hereby appoints the President and Treasurer of the
Company and each of them acting singly, his, her or its attorney-in-fact, to
sell such Shares in accordance with the terms of this Section 10. At the closing
of such transaction, each of the parties to this Agreement shall deliver,
against receipt of the consideration payable in such transaction, certificates
representing the Shares which such party holds of record or beneficially, with
all endorsements necessary for transfer. In the event that any party fails or
refuses to comply with the provisions of this Section 10, the Company, the
Stockholders and the purchaser in such transaction, at their option, may elect
to proceed with such transaction notwithstanding such failure or refusal and, in
such event and upon tender of the specified consideration to any such party, the
rights of any such party with respect to the Shares of such party of such party
shall cease.

      SECTION 11. Legend on Stock Certificates. Each of the presently
outstanding certificates, and each of the certificates issued after the date
hereof representing Shares shall conspicuously bear a legend, in substantially
the following form, until such time as the Shares represented thereby are no
longer subject to the provisions hereof:

      "THE SECURITIES REPRESENTED BY THIS CERTIFICATE OR AGREEMENT ARE SUBJECT
      TO THE TERMS AND CONDITIONS OF THE AMENDED AND RESTATED STOCKHOLDERS
      AGREEMENT, AS MAY BE AMENDED FROM TIME TO TIME, BY AND AMONG PREDIX
      PHARMACEUTICALS HOLDINGS, INC. (THE "COMPANY") AND CERTAIN OF THE
      STOCKHOLDERS OF THE COMPANY. COPIES OF SUCH AGREEMENT MAY BE OBTAINED AT
      NO COST BY WRITTEN REQUEST MADE BY THE HOLDER OF THIS CERTIFICATE TO THE
      COMPANY."

      The Company covenants that it shall keep a copy of this Agreement on file
at the address listed in Section 18 for the purpose of furnishing copies to the
holders of record of shares of Capital Stock.

      SECTION 12. Financial Statements and Other Information.

         (a) The Company shall deliver to each holder of at least 3,000,000
   shares of Preferred Stock and/or Common Stock issued on conversion thereof
   (as adjusted for any stock splits, stock dividends, recapitalizations or
   similar events):

                  (i) within 120 days after the end of each fiscal year of the
            Company, an audited balance sheet of the Company as at the end of
            such year and audited statements of income and of cash flows of the
            Company for such year, certified by certified public accountants of
            established national reputation selected by the Company, and
            prepared in accordance with generally accepted accounting principles
            consistently applied;

                  (ii) within 45 days after the end of each fiscal quarter of
            the Company (other than the fourth quarter), an unaudited balance
            sheet of the Company as at the end of such quarter, and unaudited
            statements of income and of cash flows of

                                      21

<PAGE>

            the Company for such fiscal quarter and for the current fiscal year
            to the end of such fiscal quarter, compared against the annual
            budget and business plan set forth in paragraph (iii) below; and

                  (iii) as soon as available, but in any event prior to the
            commencement of each new fiscal year, an annual budget and business
            plan (which shall include projected financial statements) for such
            fiscal year.

         (b) The foregoing financial statements shall be prepared on a
   consolidated basis if the Company then has any subsidiaries. The financial
   statements delivered pursuant to clause (ii) above shall be accompanied by a
   certificate of the chief financial officer of the Company stating that such
   statements have been prepared in accordance with generally accepted
   accounting principles consistently applied (except as noted) and fairly
   present the financial condition and results of operations of the Company at
   the date thereof and for the periods covered thereby.

         (c) The Company shall permit each holder of at least 3,000,000 shares
   of Preferred Stock and/or Common Stock issued upon conversion thereof (as
   adjusted for any stock splits, stock dividends, recapitalizations or similar
   events) to visit and inspect the properties of the Company, including its
   corporate and financial records, and to discuss its business and finances
   with officers, advisors and representatives of the Company, during normal
   business hours following reasonable notice and as often as may be reasonably
   requested.

         (d) Notwithstanding anything to the contrary herein, the rights
   provided in this Section 12 will terminate upon the closing of an Initial
   Public Offering or the Public Sale of the Company.

      SECTION 13. Insurance. The Company will maintain key-man life insurance
with respect to the life of Michael Kauffman, having a death benefit of at least
$2,000,000, payable to the Company. The Company will maintain this key-man life
insurance with respect to Michael Kauffman for so long as each he continues to
be employed by the Company; and the Company will maintain with financially sound
and reputable insurance companies, funds, or underwriters insurance of the
kinds, covering the risks and in the relative proportionate amounts usually
carried by reasonable and prudent companies conducting businesses similar to
that of the Company. Key man insurance shall be obtained for other senior
executives of the Company as may be determined from time to time by the
Company's Board of Directors.

      SECTION 14. Representations and Warranties.

      The Company (with respect to each of clauses (i) and (ii) below) and each
Stockholder (with respect to clause (ii) below) represents and warrants,
severally and not jointly, to the Company and the other Stockholders as follows:

                  (i) The execution, delivery and performance of this Agreement
            by the Company will not violate any provision of law, any order of
            any court or other agency of government, or any provision of any
            material indenture, agreement or other instrument to which the
            Company or any of its properties or assets is bound,

                                      22

<PAGE>

            or conflict with, result in a breach of or constitute (with due
            notice or lapse of time or both) a default under any such indenture,
            agreement or other instrument, or result in the creation or
            imposition of any lien, charge or encumbrance of any nature
            whatsoever upon any of the properties or assets of the Company
            (other than those arising hereunder).

                  (ii) This Agreement has been duly executed and delivered by
            the Company or such Stockholder, as the case may be, and constitutes
            the legal, valid and binding obligation of the Company or such
            Stockholder, enforceable against the Company or such Stockholder in
            accordance with its terms, except as enforcement may be limited by
            applicable bankruptcy, insolvency, reorganization, moratorium or
            other laws of general application affecting the enforcement of
            creditors' rights, and except that the availability of the equitable
            remedies of specific performance and injunctive relief may be
            subject to the discretion of the court before which any proceeding
            may be brought.

      SECTION 15. Duration of Agreement. Other than Section 2, which shall
terminate pursuant to the provisions set forth in Section 2(l) and as otherwise
specifically set forth herein, all other terms and provisions of this Agreement
shall terminate upon the consummation of the Company's Initial Public Offering
and shall not apply to such offering; provided, however, Sections 16 through 23
shall survive so long as Section 2 shall survive. Additionally, this Agreement
shall terminate as to each Stockholder upon the transfer of all Securities owned
by such Stockholder and such Stockholder will thereafter no longer be deemed to
be a Stockholder for purposes of this Agreement. Further, except as specifically
set forth in Section 10 hereof and otherwise specifically set forth therein, the
provisions of this Agreement shall terminate upon the consummation of the Public
Sale of the Company.

      SECTION 16. Governing Law. This Agreement shall be governed by, and
construed in accordance with, the laws of the State of Delaware.

      SECTION 17. Benefits of Agreement. This Agreement shall be binding upon
and inure to the benefit of the parties hereto and their respective successors
and assigns, legal representatives and heirs; provided, however, that the
Agreement may only be assigned in connection with an estate transfer or a
transfer permitted under the terms hereof.

      SECTION 18. Notices. Any notice, demand or request required or permitted
to be given under the provisions of this Agreement: (a) shall be in writing; (b)
shall be delivered personally, including by means of telecopy or courier, or
mailed by registered or certified mail, postage prepaid and return receipt
requested; (c) shall be deemed given on the date of personal delivery or on the
date set forth on the return receipt; and (d) shall be delivered or mailed as
follows or to such other address as any party may from time to time direct the
Company in writing:

                  (i) if to the Company, at Predix Pharmaceuticals Holdings,
            Inc., 10K Gill Street, Woburn, MA, 01801, Attention: Chief Executive
            Officer; and

                  (ii) if to any Stockholder, at its respective address set
            forth on Schedule A or Schedule B attached hereto.

                                      23

<PAGE>

      SECTION 19. Modification. Except as otherwise provided herein, neither
this Agreement nor any provision hereof may be modified, changed, discharged or
terminated except by the agreement of holders of not less than 66 2/3% in
interest of Series C Preferred Stock held by the Series C Preferred
Stockholders, and all Stockholders shall be bound by such modification, change,
discharge or termination with the same force and effect as if all such
Stockholders agreed thereto. Notwithstanding the foregoing, (i) any adverse
modification, change, discharge or termination to or of the rights, privileges
or obligations of holders of a specific class or series of Capital Stock
(different than that made to or affecting all classes of Capital Stock generally
herein) shall require the agreement of a majority of such affected class or
series or Capital Stock; (ii) the right of any Nominator to elect a Series C
Director or Series AB Director pursuant to Section 24(b) herein may not be
modified, changed, discharged or terminated except by the agreement of such
Nominator; (iii) Schedules A & B may be amended from time to time to add
additional holders of Common Stock or Preferred Stock, as the case may be, who
may acquire such Capital Stock of the Company from time to time and who agree to
become a party to this Agreement; (iv) the penultimate sentence of subsection
(d) of Section 3 may not be amended, modified, changed, discharged or terminated
without the consent of Yamanouchi Venture Capital LLC so long as Yamanouchi
Venture Capital LLC owns at least 1,588,238 shares of Series C Preferred Stock
and (v) Section 7 shall not be amended without the consent of not less than a
majority of the voting power of the outstanding shares held by the Co-Sale
Offerors (including any options or warrants held by such Co-Sale Offerors)
calculated on a fully-diluted basis.

      SECTION 20. Severability. In the event that any one or more of the
provisions contained in this Agreement or in any other instrument referred to
herein shall, for any reason, be held to be invalid, illegal or unenforceable,
such illegality, invalidity or unenforceability shall not affect any other
provisions of this Agreement.

      SECTION 21. Counterparts. This Agreement may be executed in one or more
counterparts, each of which shall be deemed to be an original, but all of which
taken together shall constitute one and the same instrument.

      SECTION 22. Pronouns. Whenever the context may require, any pronouns used
in this Agreement shall include the corresponding masculine, feminine or neuter
forms, and the singular form of nouns and pronouns shall include the plural, and
vice versa.

      SECTION 23. Entire Agreement. This Agreement and the Schedules attached
hereto constitute the entire agreement of the parties with respect to the
subject matter hereof, and, except with respect to the Co-Sale Agreement,
supersedes and replaces all previous agreements, including all stockholders
agreements signed by the Company prior to the date hereof, relating to the
subject matter hereof. In the event of any conflict between this Agreement and
any other agreement or instrument with respect to the subject matter hereof, the
provisions of this Agreement shall control.

      SECTION 24. Board of Directors.

         (a) For so long as this Agreement remains in effect, each Stockholder
   will vote (or consent pursuant to an action by written consent of
   stockholders) any and all Shares,

                                      24

<PAGE>

   and will use his, her or its best efforts to cause the several members of the
   Company's Board of Directors to vote, so as to elect members of the Board of
   Directors, to maintain the membership of the Board of Directors, and to cause
   the Company to act or abstain from acting, in accordance with all of the
   provisions of this Agreement. The Company will not recognize or give effect
   to any vote or consent of any Stockholder in violation of this Agreement to
   the extent permitted by Delaware law.

         (b) The Stockholders agree to vote (or consent pursuant to an action by
   written consent of stockholders) all Shares now or hereafter owned or
   controlled by them, and otherwise to use their respective best efforts as
   stockholders of the Company, to fix the number of directors constituting the
   whole Board of Directors at ten (10), and to elect as directors of the
   Company on the date hereof and in any subsequent election of directors the
   following persons: (i) the Chief Executive Officer of the Company (so long as
   he is employed by the Company) as the representative of the holders of Common
   Stock, who shall initially be Michael Kauffman; (ii) one person nominated by
   Orbimed Advisors LLC for so long as Orbimed Advisors LLC (or its Affiliates)
   holds shares of Series C Preferred Stock (who shall initially be Jonathan
   Silverstein); (iii) one person nominated by Forward Ventures V, L.P. for so
   long as Forward Ventures V, L.P. (or its Affiliates) holds shares of Series C
   Preferred Stock (who shall initially be Joel Martin); (iv) one person
   nominated by Boston Millennia Partners for so long as Boston Millenia
   Partners II Limited Partnership (or its Affiliates) holds shares of Series C
   Preferred Stock (who shall initially be Patrick Fortune); (v) one person
   nominated by S.R. One Limited for so long as S.R. One Limited (or its
   Affiliates) holds shares of Series C Preferred Stock (who shall initially be
   Maxine Gowen); (vi) one person nominated by CMEA Ventures VI, L.P. for so
   long as CMEA Ventures VI, L.P. (or its Affiliates) holds shares of Series C
   Preferred Stock (who shall initially be David Collier); (vii) one person
   nominated by Yozma II Israel L.P. for so long as Yozma II Israel L.P. (or its
   Affiliates) holds shares of Series AB Preferred Stock (who shall initially be
   Yigal Erlich); and (viii) three independent directors mutually acceptable to
   all of the remaining members of the Board of Directors, who initially shall
   be Julian Adams, Frederick Frank and Ted Love.

         The power to nominate a director pursuant to this Section 24(b)
   includes the exclusive power to remove such director. If any person or entity
   or group of persons or entities specified in this Section 24(b) as having the
   right to nominate a director (a "Nominator") gives written notice to the
   other Stockholders of a desire to remove a director nominated by the
   Nominator, the other Stockholders will vote all of their Shares in favor of
   removing that director. If for any reason any director nominated by a
   Nominator ceases to hold office, the Nominator will have the exclusive right
   to nominate another individual to fill the vacancy so created for the
   unexpired term of office of such former director, and the other Stockholders
   will vote all of their Shares in favor of electing the individual so
   nominated to fill such vacancy.

         In the event that any Nominator set forth in Sections 24(b)(ii), (iii),
   (iv), (v) and (vi) (each, a "Series C Director") is no longer entitled to
   nominate a Series C Director pursuant to the terms of Sections 24(b)(ii),
   (iii), (iv), (v) and (vi), the Series C Director previously nominated by such
   Nominator shall be replaced with a member of the Board of Directors nominated
   by the holders of a majority of the shares of Series C Preferred Stock.

                                      25

<PAGE>

         In the event that the Nominator set forth in Section 24(b)(vii) (the
   "Series AB Director") is no longer entitled to nominate the Series AB
   Director pursuant to the terms of Section 24(b)(vii), the Series AB Director
   previously nominated by such Nominator shall be replaced with a member of the
   Board of Directors nominated by the holders of a majority of the shares of
   Series AB Preferred Stock.

         (c) The Company agrees to use its best efforts to ensure that the
   rights granted hereunder are effective and that the parties hereto enjoy the
   benefits thereof. Such actions include, without limitations, the use of the
   Company's best efforts to cause the nomination and election of the directors
   as provided above, by causing a meeting of stockholders to be held or by
   causing a written consent of stockholders to be circulated. The Company will
   not, by any voluntary action, avoid or seek to avoid the observance or
   performance of any of the terms to be performed hereunder by the Company, but
   will at all times in good faith assist in the carrying out of all of the
   provisions of this Agreement and in the taking of all such actions as may be
   necessary, appropriate or reasonably requested by the holders of a majority
   of the outstanding voting securities held by the parties hereto (assuming
   conversion of all outstanding securities) in order to protect the rights of
   the parties hereunder against impairment.

         (d) From and after the date hereof, one representative of Yamanouchi
   Venture Capital LLC (for so long as Yamanouchi Venture Capital LLC holds an
   amount of shares of Preferred Stock representing at least 5% of the Capital
   Stock of the Company, calculated on a fully-diluted basis) (the "Observer"),
   shall be entitled to (a) be present at all meetings of the Board of
   Directors, and (b) notification of any such meetings, including such
   meetings' time and place, in the same manner as the directors thereof. The
   Observer shall have the same access to information concerning the business
   and operations of the Company and at the same time as the directors of the
   Company and shall be entitled to participate in discussions, consult with,
   and furnish advice to, the Board of Directors. Notwithstanding the above, the
   Observer shall not be a director. As such, the Observer shall not have the
   right to vote at any meetings and shall not be entitled to any
   indemnification or any insurance coverage provided by the Company. The
   Company, in its sole discretion, reserves the right to exclude any Observer
   from all or part of any meeting of the Board of Directors to extent
   reasonably necessary to protect confidential information of the Company or
   maintain a legal privilege with respect to information of the Company, or to
   conduct business without the presence of non-director employees of the
   Company. Notwithstanding anything to the contrary herein, the prohibitions
   and rights provided in this subsection (d) of Section 23 will terminate upon
   the closing of an Initial Public Offering or the Public Sale of the Company.

      SECTION 25. Preemptive Rights.

         (a) The Company hereby grants to each Stockholder who holds at least
   3,000,000 shares of Preferred Stock and/or Common Stock issued upon
   conversion thereof (each a "Right Holder") the right to purchase, pro rata,
   all (or any part) of any New Securities (as defined in Section 25(b) hereof)
   that the Company may, from time to time, propose to sell or issue. Each such
   Right Holder's pro rata share of the New Securities (its "Basic Amount") for
   purposes of this Section 25, is equal to the ratio of (i) the number of
   shares of Common Stock then held of record by, plus the total number of
   shares of Common Stock issuable upon

                                      26

<PAGE>

   conversion of any other shares of Capital Stock and Derivative Securities of
   the Company convertible into shares of Common Stock then held of record by,
   such Right Holder to (ii) the sum of the total number of shares of the Common
   Stock issued and outstanding as of the date of such determination plus the
   total number of shares of Common Stock issuable upon exercise, conversion, or
   exchange of the shares of Capital Stock and Derivative Securities of the
   Company or exercisable, convertible, or exchangeable into shares of Common
   Stock outstanding at such time.

         (b) "New Securities" shall mean any equity securities of the Company,
   whether now authorized or not, and rights, options, or warrants to purchase
   said equity securities, and securities of any type whatsoever that are, or
   may become, convertible into said equity securities; provided that "New
   Securities" does not include the issuances of the following types of
   securities: (i) shares of Common Stock issued by the Company pursuant to
   stock dividends, stock splits, recapitalizations, and similar transactions;
   (ii) shares of Common Stock issued upon conversion of shares of Series C
   Preferred Stock or Series AB Preferred Stock; (iii) shares of Common Stock
   issued upon exercise, conversion, or exchange of any Derivative Securities
   that are outstanding as of the date hereof or that are issued after the date
   hereof so long as the Rights Holder was offered the right to purchase such
   Derivative Securities when first issued pursuant to this Section 25(a); (iv)
   shares of Common Stock issuable or issued to employees, consultants, officers
   or directors of the Company either directly or pursuant to a stock option
   plan or other incentive plan approved by the Board of Directors of the
   Company (including at least three Series C Directors), where such issuance is
   approved by the Board of Directors of the Company or a committee designated
   by the Board of Directors; (v) shares of the Company's capital stock
   including options, warrants or other similar securities issued in
   consideration of or in connection with the grant by or to the Company of
   marketing rights, license rights or similar rights or in consideration of or
   in connection with the exchange of proprietary technology, in each such case
   with the prior approval of the Board of Directors (including at least three
   Series C Directors); (vi) shares of the Company's capital stock including
   options, warrants or other similar securities issued to landlords, lenders,
   commercial financing, leasing companies or other service providers of the
   Company, in each such case with the prior approval of the Board of Directors
   (including at least three Series C Directors); (vii) shares of the Company's
   capital stock including options, warrants or other similar rights issued in
   connection with acquisitions or strategic alliances in each such case with
   the prior approval of the Board of Directors (including at least three Series
   C Directors); (viii) shares of the Company's capital stock issued in
   connection with a public offering in which all outstanding shares of
   Preferred Stock convert to Common Stock; (ix) shares of the Company's Capital
   Stock issued pursuant to the Funding Warrants; (x) up to 61,093,320 shares of
   Series AB Preferred Stock (as adjusted for stock splits, combinations and the
   like of the Series AB Preferred Stock) issued pursuant to the Series AB
   Warrants; and (xi) shares of Series C Preferred Stock issued pursuant to the
   Securities Purchase Agreement (including, without limitation, such shares
   issued under any "Securities Purchase Agreement" referenced in Section 2(c)
   of the Second Amendment to the Securities Purchase and Exchange Agreement
   dated the date hereof).

         (c) The Company shall not issue, sell or exchange, agree to issue, sell
   or exchange, or reserve or set aside for issuance, sale or exchange any New
   Securities unless the Company shall deliver to each Right Holder a written
   notice of any proposed or intended

                                      27

<PAGE>

   issuance, sale or exchange of New Securities (the "Offer"), which Offer shall
   (i) identify and describe the New Securities, (ii) describe the price and
   other terms upon which they are to be issued, sold or exchanged, and the
   number or amount of the New Securities to be issued, sold or exchanged, (iii)
   identify the persons or entities, if known, to which or with which the New
   Securities are to be offered, issued, sold or exchanged and (iv) offer to
   issue and sell to or exchange with such Right Holder (A) such Right Holder's
   Basic Amount, and (B) any additional portion of the New Securities required
   to be offered to Right Holders hereunder as such Right Holder shall indicate
   it will purchase or acquire should the other Right Holders subscribe for less
   than their respective Basic Amounts (the "Undersubscription Amount"). Each
   Right Holder shall have the right, for a period of 15 days following delivery
   of the Offer, to purchase or acquire, at the price and upon the other terms
   specified in the Offer, the number or amount of New Securities described
   above. The Offer by its terms shall remain open and irrevocable for such
   15-day period.

         (d) To accept an Offer, in whole or in part, a Right Holder must
   deliver a written notice to the Company prior to the end of the 15-day period
   of the Offer, setting forth the portion of the Right Holder's Basic Amount
   that such Right Holder elects to purchase and, if such Right Holder shall
   elect to purchase all of its Basic Amount, the Undersubscription Amount (if
   any) that such Right Holder elects to purchase (the "Notice of Acceptance").
   If the Basic Amounts subscribed for by all Right Holders are less than the
   Basic Amounts to which all Right Holders are entitled, then each Right Holder
   who has set forth an Undersubscription Amount in its Notice of Acceptance
   shall be entitled to purchase, in addition to the Basic Amount subscribed
   for, the Undersubscription Amount it has subscribed for; provided that should
   the Undersubscription Amounts subscribed for exceed the difference between
   the Basic Amounts to which all Right Holders are entitled and the Basic
   Amounts subscribed for (the "Available Undersubscription Amount"), each Right
   Holder who has subscribed for any Undersubscription Amount shall be entitled
   to purchase only that portion of the Available Undersubscription Amount as
   the Undersubscription Amount subscribed for by such Right Holder bears to the
   total Undersubscription Amounts subscribed for by all Right Holders, subject
   to rounding by the Board of Directors to the extent it reasonably deems
   necessary. (e) The Company shall have 180 days from the expiration of the
   period set forth in Section 25(c) above to issue, sell or exchange all or any
   part of such New Securities as to which a Notice of Acceptance has not been
   given by the Right Holders (the "Refused Securities"), but only upon terms
   and conditions which are not more favorable in any material respect to the
   acquiring party or parties or less favorable in any material respect to the
   Company than those described in the Offer.

         (f) Upon the closing of the issuance, sale or exchange of all or less
   than all the Refused Securities, the Right Holders shall acquire from the
   Company, and the Company shall issue to the Right Holders, the number or
   amount of New Securities specified in the Notices of Acceptance upon the
   terms and conditions specified in the Offer.

         (g) Pursuant to the terms of the Amended and Restated Stockholders
   Agreement, each of Eaton Vance Worldwide Health Sciences Portfolio, Hare and
   Co. FAO: Finsbury Worldwide Pharmaceutical Trust, Orbimed Associates LLC,
   Caduceus Private Investment, L.P., PW Juniper Crossover Fund, LLP, Yozma II
   (Israel) LP, Yozma Venture Capital Ltd., YVC-Yozma Management & Investments
   Ltd., as trustee for Yozma II (B.V.I)

                                      28

<PAGE>

   LP, PCM Venture Capital LP, International Life Science Partners L.P., S.R.
   One Limited and Foulon Limited agrees and acknowledges that each Funding
   Warrant held by such entity was terminated and of no further force and
   effect. Further, in consideration for receipt of the rights set forth in this
   Section 25, each other Rights Holder who holds a Funding Warrant agrees and
   acknowledges that the Funding Warrant held by each such Rights Holder is
   hereby terminated and of no further force and effect. Furthermore, PA
   International Limited acknowledges that it is considered a Rights Holder and
   its Funding Warrant is hereby terminated and of no further force and effect.
   For purposes of clarity, PA International Limited acknowledges that it shall
   have no rights to purchase shares of Series C Preferred Stock in accordance
   with the terms of its Funding Warrant following the sale of shares of Series
   C Preferred Stock pursuant to that certain Securities Purchase Agreement
   dated as of the date hereof by and among the Company and the Purchasers (as
   defined therein).

         (h) Notwithstanding anything to the contrary herein, the prohibitions
   and rights provided in this Section 25 will terminate upon the closing of an
   Initial Public Offering or the Public Sale of the Company.

         (i) Any Stockholder may, but shall not be required to, consider the
   number of shares of Preferred Stock owned by an Affiliate as being owned by
   such Stockholder solely for the purpose of determining whether such
   Stockholder shall be deemed a Rights Holder and be permitted to exercise the
   right to purchase shares under this Section 25.

      SECTION 26. Arbitration. Any controversy or claim arising out of or in
conjunction with this Agreement (other than an action for injunctive relief)
shall be settled by arbitration in accordance with the rules of the American
Arbitration Association then in effect in the State of Delaware and judgment
upon such award rendered by the arbitrator shall be final and binding upon the
parties and may be entered and enforced in any court having jurisdiction
thereof. The arbitration shall be held in the State of Delaware. The arbitration
award shall include attorneys' fees and costs to the prevailing party, as of the
day and year first above written.

      SECTION 27. Affirmative Covenants.

         (a) The Company shall cause each person who is presently an employee of
   or a consultant or independent contractor to the Company or who becomes an
   employee of or a consultant to the Company subsequent to the date hereof and
   who shall have or be proposed to have access to confidential or proprietary
   information of the Company to execute a confidentiality and assignment of
   inventions agreement, in a form approved by the Board of Directors, prior to
   the commencement of such person's employment or engagement by the Company in
   such capacity.

         (b) Any stock options granted after the date hereof by the Company
   shall provide that such options shall vest 25% one year following the date of
   such issuance or grant with the balance to vest in a series of 36 successive
   equal monthly installments, unless such stock option is granted with the
   prior approval of at least three of the Series C Directors.

         (c) Such stock options shall provide the Company with a right of first
   refusal on all transfers on Common Stock by employees and other persons
   pursuant to the Company's

                                      29

<PAGE>

   stock option/stock issuance plans, subject to customary exceptions and
   terminations. The Company shall assign its right of first refusal contained
   in any such options agreements (including Section 4 of each option agreement
   issued pursuant to the Company's 2003 Equity Incentive Plan) to the holders
   of outstanding Preferred Stock, on a pro rata basis, if the Company chooses
   not to exercise such right of first refusal.

         (d) The Company will indemnify board members to the broadest extent
   permitted by applicable law as currently provided in the Company's Amended
   and Restated Certificate of Incorporation pursuant to indemnification
   agreements. In addition, the Company shall implement and secure a policy of
   directors' and officers' liability insurance that is reasonably acceptable to
   Forward Ventures V, L.P.

         (e) The Company will reimburse each non-employee board member for any
   reasonable expenses incurred in connection with his or her attendance at the
   board meetings of the Company.

         (f) With the exception of the Chairman of the Board of Directors, each
   non-employee board member shall be compensated in an equal manner.

         (g) Notwithstanding anything to the contrary herein, the prohibitions
   and rights provided in this Section 27 will terminate upon the closing of an
   Initial Public Offering or the Public Sale of the Company.

      SECTION 28. Amended and Restated Stockholders' Agreement. By execution of
this Agreement, each Stockholder, holding in the aggregate a sufficient number
of shares of stock to amend the Amended and Restated Stockholders' Agreement in
accordance with the provisions of Section 18 thereof, hereby agrees, for and on
behalf of all parties to the Amended and Restated Stockholders' Agreement, that
the Amended and Restated Stockholders' Agreement is hereby terminated and
replaced in its entirety by this Agreement. Any signatory to the Amended and
Restated Stockholders' Agreement who does not sign this Agreement shall be bound
by the terms and conditions of this Agreement, pursuant to the provisions of
Section 18 of the Amended and Restated Stockholders' Agreement, as if the
signatory to the Amended and Restated Stockholders' Agreement had signed this
Agreement.

                                    * * * * *

                                      30

<PAGE>

Executed and delivered as an agreement under seal as of the date first above
written.

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By:   /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

<PAGE>

PREDIX PHARMACEUTICALS HOLDINGS, INC.

INSTRUMENT OF ADHERENCE
TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                                Signature: /s/ OREN BECKER
                                                           _____________________

                                                Print Name: Oren M. Becker
                                                            ____________________

                                                         Title: CSO
                                                                ________________

                                                         Address: ______________

                                                                  ______________

                                                         Telephone: ____________

                                                         Fax: __________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By:  /s/ MICHAEL KAUFFMAN
     _______________________________________
     Michael Kauffman
     Chief Executive Officer
<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                              CMEA Ventures Life Sciences 2000, L.P.

                              Signature:  /s/ DAVID COLLIER
                                          --------------------------------------

                              Print Name: DAVID COLLIER

                                   Title: ______________________________________

                                   Address: ____________________________________

                                            ____________________________________

                                   Telephone: __________________________________

                                   Fax: ________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ---------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                         CMEA Ventures Life Sciences 2000, Civil Law Partnership

                         Signature:  /s/ DAVID COLLIER
                                     --------------------------------------

                         Print Name: DAVID COLLIER

                              Title: ______________________________________

                              Address: ____________________________________

                                       ____________________________________

                              Telephone: __________________________________

                              Fax: ________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ---------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                              CMEA Ventures VI, LP

                              Signature:  /s/ DAVID COLLIER
                                          --------------------------------------

                              Print Name: DAVID COLLIER

                                   Title: ______________________________________

                                   Address: ____________________________________

                                            ____________________________________

                                   Telephone: __________________________________

                                   Fax: ________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ---------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                              CMEA Ventures VI, GmbH & Co, K.G.

                              Signature:  /s/ DAVID COLLIER
                                          --------------------------------------

                              Print Name: DAVID COLLIER

                                   Title: ______________________________________

                                   Address: ____________________________________

                                            ____________________________________

                                   Telephone: __________________________________

                                   Fax: ________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ---------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                              Signature: /s/ SIDNEY DILGREN
                                         --------------------------------------

                              Print Name: SIDNEY DILGREN

                                   Title:  Vice President

                                   Address: ____________________________________

                                            ____________________________________

                                   Telephone: __________________________________

                                   Fax: ________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ---------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                              YOZMA VENTURE CAPITAL LTD.

                              By: /s/ YOAV DOPPELT
                                  ----------------------------------------------
                                  Name:  Yoav Doppelt
                                  Title: CEO

                                   Address: ____________________________________

                                            ____________________________________

                                   Telephone: __________________________________

                                   Fax: ________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ---------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                              Signature: /s/ MAXINE DRABBLE
                                         ---------------------------------------

                              Print Name: Maxine Drabble

                                    Title:  Director - PA International Limited

                                   Address: ____________________________________

                                            ____________________________________

                                   Telephone: __________________________________

                                   Fax: ________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ---------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                              YOZMA II (ISRAEL), L.P.

                              By: /s/ YIGAL ERLICH
                                  ---------------------------------------------
                                  Name: Yigal Erlich
                                  Title:

                              Address: ____________________________________

                                       ____________________________________

                              Telephone: __________________________________

                              Fax: ________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ---------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                              YVC-YOZMA MANAGEMENT & INVESTMENTS LTD.,
                              AS TRUSTEE FOR YOZMA II (B.V.I.) L.P.

                              By: /s/ YIGAL ERLICH
                                  ----------------------------------------------
                                  Name:  Yigal Erlich
                                  Title:

                              Address: ____________________________________

                                       ____________________________________

                              Telephone: __________________________________

                              Fax: ________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ---------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                              PCM VENTURE CAPITAL L.P.

                              By: /s/ YIGAL ERLICH
                                  -----------------------------------------
                                  Name: Yigal Erlich
                                  Title:

                              Address: ____________________________________

                                       ____________________________________

                              Telephone: __________________________________

                              Fax: ________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ---------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                              Signature: /s/ FREDERICK FRANK
                                         ---------------------------------------

                              Print Name: FREDERICK FRANK

                                   Title: ______________________________________

                                   Address: ____________________________________

                                   Telephone: __________________________________

                                   Fax: ________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ----------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                              BOSTON MILLENNIA PARTNERS II-A
                              LIMITED PARTNERSHIP

                              By: Glen Partners II Limited Partnership

                              By: /s/ MARTIN J. HERNON
                                  ---------------------------------------------
                                  Martin J. Hernon, General Partner

                              Address: ________________________________________

                                       ________________________________________

                              Telephone: ______________________________________

                              Fax: ____________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ----------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                             BOSTON MILLENNIA PARTNERS GMBH & CO. KG

                             By: Boston Millennia Verwaltungs GmbH

                             By: /s/ MARTIN J. HERNON
                                 ---------------------------------------------
                                 Martin J. Hernon, Managing Director

                              Address: ________________________________________

                                       ________________________________________

                              Telephone: ______________________________________

                              Fax: ____________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ----------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                              BOSTON MILLENNIA PARTNERS II LIMITED PARTNERSHIP

                              By: Glen Partners II Limited Partnership

                              By: /s/ MARTIN J. HERNON
                                  ----------------------------------------------
                                  Martin J. Hernon, General Partner

                              Address: ________________________________________

                                       ________________________________________

                              Telephone: ______________________________________

                              Fax: ____________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ----------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                              BOSTON MILLENNIA ASSOCIATES II LIMITED PARTNERSHIP

                              By: /s/ MARTIN J. HERNON
                                  --------------------------------------------
                                  Martin J. Hernon, General Partner

                              Address: ________________________________________

                                       ________________________________________

                              Telephone: ______________________________________

                              Fax: ____________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ----------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                              STRATEGIC ADVISORS FUND LIMITED PARTNERSHIP

                              By: Glen Partners II Limited Partnership,
                                  its General Partner

                              By: /s/ MARTIN J. HERNON
                                  --------------------------------------------
                                  Martin J. Hernon, General Partner

                              Address: ________________________________________

                                       ________________________________________

                              Telephone: ______________________________________

                              Fax: ____________________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ----------------------------------
    Michael Kauffman
    Chief Executive Officer
<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
                                       TO
               SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                    Signature: /s/ MICHAEL G. KAUFFMAN
                                               ---------------------------------

                                    Print Name: Michael G. Kauffman

                                           Title: CEO

                                           Address: ____________________________

                                                    ____________________________

                                           Telephone: __________________________

                                           Fax: ________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    -----------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                    Signature: /s/ TOMIO KEZUKA
                                               ---------------------------------

                                    Print Name: Tomio Kezuka

                                           Title: Executive Vice President
                                                  JAFCO Co., Ltd.
                                                  Its General Partner

                                           Address: ____________________________

                                                    ____________________________

                                           Telephone: __________________________

                                           Fax: ________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                    Signature: /s/ CHARLENE LEDBETTER
                                               ---------------------------------

                                    Print Name: Charlene Ledbetter
                                                Ledbetter Stevens, Inc.

                                           Title: Chairman

                                           Address: ____________________________

                                                    ____________________________

                                           Telephone: _________________________

                                           Fax: _______________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ---------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                    Signature: /s/ JEAN-MARC LESIEUR
                                               ---------------------------------

                                    Print Name: JEAN-MARC LESIEUR - DIRECTOR
                                                HBM BioPartners Ltd.
                                                General partner of International
                                                Life Science Managers, L.P.,
                                         Title: General Partner of International
                                                Life Science Partners, L.P.

                                         Address: ______________________________

                                                  ______________________________

                                         Telephone: __________________________

                                         Fax: ________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    --------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                   The Yasuda Enterprise Development II, Limited
                                   Partnership

                                   Signature: /s/ MINORU OKA
                                              ----------------------------------

                                   Print Name: Minoru Oka
                                                President and Representative
                                                Director
                                         Title: Yasuda Enterprise Development
                                                Co., Ltd.

                                         Address: ______________________________

                                                  ______________________________

                                         Telephone: ________________________

                                         Fax: ______________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                    Signature: /s/ H.H. MUNCHMEYER
                                               ---------------------------------

                                    Print Name: H.H. MUNCHMEYER

                                           Title: M.D.

                                           Address: ____________________________

                                                    ____________________________

                                           Telephone: __________________________

                                           Fax: ________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ----------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                    Signature: /s/ IVOR ROYSTON
                                               ---------------------------------

                                    Print Name: IVOR ROYSTON

                                                 Managing Member
                                          Title: Forward Associates V, LLC

                                          Address: _____________________________

                                                   _____________________________

                                          Telephone: __________________________

                                          Fax: ________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    --------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
                                       TO
               SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                    Signature: /s/ CHEN SCHOR
                                               ---------------------------------

                                    Print Name: Chen Schor

                                           Title: CBO, SVP

                                           Address: ____________________________

                                                    ____________________________

                                           Telephone: _________________________

                                           Fax: _______________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    --------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                 Signature: /s/ PHILIP L. SMITH /s/ MAXINE GOWEN
                                            ------------------------------------

                                 Print Name: PHILIP L. SMITH    MAXINE GOWEN

                                        Title: General Partner  President

                                        Address: _______________________________

                                                 _______________________________

                                        Telephone: ____________________________

                                        Fax: __________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    --------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                           NOVEL BIOVENTURES, LLC
                                           By: NOVEL BIOVENTURES, INC., its sole
                                               member

                                    Signature: /s/ YI-CHUNG YANG
                                               ---------------------------------

                                    Print Name: Yi-Chung Yang

                                           Title: Managing Director

                                           Address: ____________________________

                                                    ____________________________

                                           Telephone: _________________________

                                           Fax: _______________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    -------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                               Signature: /s/ YOSHITAKA YONEYAMA
                                          ---------------------------------

                               Print Name: YONEYAMA, YOSHITAKA

                                      Title: PRESIDENT & CHIEF EXECUTIVE OFFICER

                                      Address: _________________________________

                                               _________________________________

                                      Telephone: ____________________________

                                      Fax: __________________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ---------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                                  Trefoil, S.A.

                                    Signature: /s/ JEFFERSON R. VOSS
                                               ---------------------------------

                                    Print Name: Jefferson R. Voss

                                           Title: Director

                                           Address: ____________________________

                                                    ____________________________

                                           Telephone: ________________________

                                           Fax: ______________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
                                       TO
               SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                    Signature: /s/ SILVIA NOIMAN
                                               ---------------------------------

                                    Print Name: SILVIA NOIMAN

                                           Title: SVP Pipeline Management

                                           Address: ____________________________

                                                    ____________________________

                                           Telephone: _________________________

                                           Fax: _______________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    --------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                    Signature: /s/ ERIC BITTELMAN
                                               ---------------------------------

                                    Print Name: CADUCEUS PRIVATE INVESTMENTS LP

                                           Title: CFO

                                           Address: ____________________________

                                                    ____________________________

                                           Telephone: _________________________

                                           Fax: _______________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                    Signature: /s/ ERIC BITTELMAN
                                               ---------------------------------

                                    Print Name: ORBIMED ASSOCIATES LLC

                                           Title: CFO

                                           Address: ____________________________

                                                    ____________________________

                                           Telephone: _________________________

                                           Fax: _______________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    -------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                    Signature: /s/ ERIC BITTELMAN
                                               ---------------------------------

                                    Print Name: UBS JUNIPER CROSSOVER FUND LLC

                                           Title: CFO

                                           Address: ____________________________

                                                    ____________________________

                                           Telephone: ______________________

                                           Fax: ____________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    --------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                   Signature: /s/ ERIC BITTELMAN
                                              ---------------------------------

                                               HARE + CO. FAO FINSBURY WORLDWIDE
                                   Print Name: HEALTH SCIENCES PORTFOLIO

                                          Title: CFO

                                          Address: _____________________________

                                                   _____________________________

                                          Telephone: _________________________

                                          Fax: _______________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    -------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                    Signature: /s/ ERIC BITTELMAN
                                               ---------------------------------

                                                EATON VANCE WORLDWIDE
                                    Print Name: HEALTH SCIENCES PORTFOLIO

                                           Title: CFO

                                           Address: ____________________________

                                                    ____________________________

                                           Telephone: ________________________

                                           Fax: ______________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ----------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                 Signature: /s/ LISA CRAWFORD /s/ MARC HOLLANDER
                                            ----------------------------------
                                              LISA CRAWFORD    Marc Hollander
                                              `A' DIRECTOR     B-Director

                                  Print Name: Investor Group L.P.

                                         By: Investor Group G.P. Limited

                                         Address: _____________________________

                                                  _____________________________

                                         Telephone: _________________________

                                         Fax: _______________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    -------------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                    Signature: /s/ ROBERT SHAPIRO
                                               ---------------------------------

                                                DELAWARE CHARTER GUARANTEE TRUST
                                    Print Name: C/F ROBERT F. SHAPIRO, IRA

                                           Title: ______________________________

                                           Address: ____________________________

                                                    ____________________________

                                           Telephone: _________________________

                                           Fax: _______________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ----------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                             INSTRUMENT OF ADHERENCE
              TO SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      By execution and delivery of this signature page, the undersigned hereby
agrees to become a party to that certain Second Amended and Restated
Stockholders Agreement (the "Stockholders Agreement") by and among Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation, and the Stockholders (as
defined in the Stockholders Agreement), dated as of January 21, 2005 (which
amends and restates that certain Amended and Restated Stockholders Agreement
dated as of August 9, 2004) and is entitled to all of the benefits under and
subject to all of the obligations, restrictions and limitations set forth in the
Stockholders Agreement that are applicable to the Stockholders. This Counterpart
Signature Page shall take effect and shall become a part of said Stockholders
Agreement immediately upon execution.

      Executed, in counterpart, as of the date set forth below.

                                    Signature: /s/ ROBERT SHAPIRO
                                               ---------------------------------

                                    Print Name: NORTH FORK ASSOCIATES, L.P.

                                           Title: MANAGING PARTNER

                                           Address: ____________________________

                                                    ____________________________

                                           Telephone: ________________________

                                           Fax: ______________________________

Accepted:

PREDIX PHARMACEUTICALS HOLDINGS, INC.

By: /s/ MICHAEL KAUFFMAN
    ----------------------------
    Michael Kauffman
    Chief Executive Officer

<PAGE>

SCHEDULE A

LIST OF HOLDERS OF COMMON STOCK

Denis Noble
[ADDRESS]

The Chancellor, Masters & Scholars of the University of Oxford
[ADDRESS]

Penelope Noble
[ADDRESS]

Auckland UniServices Limited
c/o University of Auckland
[ADDRESS]

Jerry Balter
[ADDRESS]

The Jerry Balter Irrevocable Trust
[ADDRESS]

Punk Ziegel & Company
[ADDRESS]

The Johns Hopkins University
Licencing Johns Hopkins University
[ADDRESS]

Jane Maida
[ADDRESS]

Sherry Reynolds
[ADDRESS]

Gary Pestano
[ADDRESS]

Jian Li
[ADDRESS]

John Jeremy Rice
[ADDRESS]

<PAGE>

Peter Kohl
[ADDRESS]

Peter Mark Grehlinger
[ADDRESS]

William Gibb
[ADDRESS]

Melanie Nelson
[ADDRESS]

Roberta Susnow
[ADDRESS]

John Doherty
[ADDRESS]

Charles DeLisi
Boston University
[ADDRESS]

Emilie Eng
[ADDRESS]

Thomas J. Colatsky
Paradigm Genetics
[ADDRESS]

Colin Bridgeman
[ADDRESS]

Svetlana Romanovic
[ADDRESS]

Oren Becker
[ADDRESS]

Silvia Noiman
[ADDRESS]

Zvi Naor
[ADDRESS]

Ramot At Tel Aviv University Ltd.
Univ Authority for Applied Research

<PAGE>

Attn: Mr. Isaac Kohlberg, CEO
[ADDRESS]

Frederick S. Livingston III
[ADDRESS]

Nicholas John Gardner Hayes
[ADDRESS]

Ned Haubein
[ADDRESS]

Colette Manhire
[ADDRESS]

Raphael Nudelman
[ADDRESS]

Nicholas Aschenbach
[ADDRESS]

Robert Shapiro
[ADDRESS]

W. Elliott Walden
Joels S. Marcus Trustee of the Joel & Barbara Marcus Family Trust

Investor Growth Capital Limited
[ADDRESS]

Investor Group LP
[ADDRESS]

Lombard Odier & Cle
c/o Ultreia Capital
[ADDRESS]

Motorola, Inc.
[ADDRESS]

Viator One Limited -- c/o M.A.L.J. Group
[ADDRESS]

Biocentive Limited
c/o Mesco II Ltd.
[ADDRESS]

<PAGE>

Oxford Bioscience Partners II L.P.
[ADDRESS]

Oxford Bioscience Partners (Bermuda) II L.P.
[ADDRESS]

Oxford Bioscience Partners (Adjunct) II L.P.
[ADDRESS]

Ariane Health Limited, LDC
c/o Muzinich & Co., Inc.
[ADDRESS]

New England Partners Capital, L.P.
[ADDRESS]

Hans-Detlef Boesel
M.M. Warburg & CO
[ADDRESS]

Dieter Pfundt
[ADDRESS]

Lee F. Meier
[ADDRESS]

James V. Mitchell
[ADDRESS]

Patricia W. Leicher
[ADDRESS]

GSI Global Shipping, Inc.
Att: Joseph Elmaleh, Ph.D.
[ADDRESS]

PA International Limited
[ADDRESS]

Ernst Equities
[ADDRESS]

CIP Capital L.P.
c/o SCP Private Equity Partners
[ADDRESS]

<PAGE>

Peggy Danziger
[ADDRESS]

TLF Limited Partnership
[ADDRESS]

Leah S. Levin
[ADDRESS]

Steven Elms
[ADDRESS]

Larry Abrams
[ADDRESS]

PM Fallon Life Interest Trust
AIB Trust Company (Jersey Ltd.)
[ADDRESS]

Matthew Morahan
[ADDRESS]

William R. Miller
[ADDRESS]

TBA Acquisition Corp.
c/o Gerald E. Morris
Morris Asset Management Inc.
[ADDRESS]

Toni L. Katz
[ADDRESS]

Marc Kozin
[ADDRESS]

Robert J. Kheel
[ADDRESS]

Haulbowline II
Brean Murray & Co., Inc.
[ADDRESS]

George Gould
[ADDRESS]

<PAGE>

SCHEDULE B

                       LIST OF HOLDERS OF PREFERRED STOCK

S.R. One Limited
[ADDRESS]

Steven Elms
[ADDRESS]

Foulon Limited
[ADDRESS]

Michael Gaito
[ADDRESS]

Neil Borg
[ADDRESS]

Haim Aviv
[ADDRESS]

Tzvi Aviv
[ADDRESS]

Ayelet Aviv
[ADDRESS]

ODIE Partnership
[ADDRESS]

Michael  G. Kauffman, MD, PhD
[ADDRESS]

Frederick Frank
[ADDRESS]

Eaton Vance Worldwide Health Sciences Portfolio
c/o OrbiMed Advisors LLC
[ADDRESS]

<PAGE>

Hare and Co. FAO: Finsbury Worldwide Pharmaceutical Trust
c/o OrbiMed Advisors LLC
[ADDRESS]

Orbimed Associates LLC
Attn: Jonathan Silverstein
[ADDRESS]

Caduceus Private Investments LP
c/o OrbiMed Advisors LLC
[ADDRESS]

PW Juniper Crossover Fund LLC
c/o OrbiMed Advisors LLC
[ADDRESS]

Stelios Papadopoulos
[ADDRESS]

Yozma II (Israel) LP
c/o YVC - Yozma Mgt & Investments Ltd
[ADDRESS]

YVC Yozma Management and Investment Ltd., as trustees for Yozma II (BVI) LP
c/o YVC - Yozma Mgt & Investments Ltd
[ADDRESS]

Yozma Venture Capital Ltd.
c/o YVC - Yozma Management & Investments Ltd.
 [ADDRESS]

PCM Venture Capital L.P.
c/o YVC - Yozma Management & Investments Ltd.
[ADDRESS]

Shelly D. Guyer
[ADDRESS]

<PAGE>

Danziger Capital Partners
[ADDRESS]

SLRB-1
The Ayco Company, L.P.
[ADDRESS]

Geese Capital Partners
[ADDRESS]

Richard M. Danziger
[ADDRESS]

SK&CS Capital Partners
[ADDRESS]

INVESCO Global Health Sciences Fund
Aim Investment Services, Inc.
[ADDRESS]

Whitehall Financial  Group, Inc.
[ADDRESS]

Trefoil S.A.
[ADDRESS]

Detlef Bierbaum
[ADDRESS]

Eli W. Kaufman
[ADDRESS]

North Fork Associates L.P.
Klingenstein Fields & Co.,L.L.C.
[ADDRESS]

Delaware Charter Guarantee Trust,
C/F Robert Shapiro IRA
Attn: Robert Shapiro, Esq.
Klingenstein Fields & Co., LLC
[ADDRESS]

<PAGE>

Joseph H. Flom
Skadden Arps Slate Meagher & Flom
[ADDRESS]

Walter W. Hess, Jr.
[ADDRESS]

Mulligan Beteligungs GmbH
Attn: Jens Klein
[ADDRESS]

Nelson Long, Jr. & Theresa G. Long
[ADDRESS]

International Life Science Partners L.P.
c/o DJG Advisors LLP
[ADDRESS]

Daniel Green
[ADDRESS]

Vivek Jain
JP Morgan
[ADDRESS]

Novel BioVentures, LLC
C/o Novel BioVentures Inc.
[ADDRESS]

Yamanouchi Venture Capital, LLC
[ADDRESS]

JAFCO Life Science No.1 Investment Enterprise Partnership
[ADDRESS]

Boston Millenia Partners GmbH
[ADDRESS]

Boston Millenia Partners II-A Limited Partnership
[ADDRESS]

Strategic Advisors Fund Limited Partnership
[ADDRESS]

<PAGE>

Boston Millenia Associates II Partnership
[ADDRESS]

Boston Millenia Partners II Limited Partnership
[ADDRESS]

Forward Ventures V, L.P.
[ADDRESS]

Ledbetter Stevens, Inc.
[ADDRESS]

CMEA Ventures Life Sciences 2000, L.P.
[ADDRESS]

CMEA Ventures Life Sciences 2000, Civil Law Partnership
[ADDRESS]

CMEA Ventures VI, L.P.
[ADDRESS]

CMEA Ventures VI, GmbH & Co. K.G.
[ADDRESS]

The Yasuda Enterprise Development II, Limited Partnership
[ADDRESS]

AEOW 96, LLC
[ADDRESS]

Dickon & Lisa Pownell-Grey
[ADDRESS]

PA International Limited
[ADDRESS]

New England Partners Capital, L.P.
[ADDRESS]

TLF Limited Partnership
[ADDRESS]

George Gould
[ADDRESS]

<PAGE>

Robert Shapiro
[ADDRESS]<PAGE>

                                                                   EXHIBIT 4.2.2

                      PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                 FIRST AMENDMENT
                                       TO
               SECOND AMENDED AND RESTATED STOCKHOLDERS AGREEMENT

      This First Amendment (the "Amendment") to the Second Amended and Restated
Stockholders Agreement, dated January 21, 2005, by and between Predix
Pharmaceuticals Holdings, Inc., a Delaware corporation (the "Company"), and
certain Stockholders (the "Stockholders Agreement"), is made as of August 1,
2005, by and among the Company and the signatories hereto. Capitalized terms
used herein but not defined shall have the meanings ascribed to such terms in
the Stockholders Agreement.

      WHEREAS, the Company is contemplating an initial public offering of shares
of its Common Stock;

      WHEREAS, Section 2(b) of the Stockholders Agreement provides certain
Stockholders incidental registration rights (the "piggyback rights");

      WHEREAS, the Stockholders Agreement may be modified, changed, discharged
or terminated by the agreement of the Company and not less than 66 2/3% in
interest of Series C Preferred Stock held by the Series C Preferred
Stockholders; and

      WHEREAS, the Company and the signatories hereto (comprising not less than
66 2/3% in interest of Series C Preferred Stock held by the Series C Preferred
Stockholders) believe that it is in the best interests of the Company and the
Stockholders to amend Section 2(b)(i) of the Stockholders Agreement such that
the piggyback rights of Section 2(b) do not apply to an Initial Public Offering.

      NOW THEREFORE, the Company and the signatories hereto, hereby agree to
amend the Stockholders Agreement as follows:

1.    AMENDMENT TO AGREEMENT.

      a.    SECTION 2(b)(i)

      Section 2(b)(i) of the Stockholders Agreement is hereby amended by
deleting the first sentence of such Section 2(b)(i) in its entirety and
inserting in lieu thereof the following sentence:

      "If at any time subsequent to the expiration of any lock-up agreement that
      the Company's stockholders have entered into with the underwriters in
      connection with an Initial Public Offering the Company proposes to file a
      Registration Statement covering shares of Common Stock (other than a
      Registration Statement

<PAGE>

      filed pursuant to Section 2(a) or on a Form S-4 or Form S-8 or similar or
      successor forms), the Company will, prior to such filing, give written
      notice to all Preferred Stockholders of its intention to do so."

      b.    NO OTHER AMENDMENT

      Except as otherwise expressly set forth herein, all terms and conditions
of the Stockholders Agreement shall remain in full force and effect. Except as
expressly set forth herein, nothing herein shall be construed to be an amendment
or a waiver of any requirements of the Stockholders Agreement.

2.    MISCELLANEOUS.

      a.    MODIFICATION AND AMENDMENT.

      This Amendment shall not be modified or amended except by an instrument in
writing signed by or on behalf of the parties hereto.

      b.    COUNTERPARTS.

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

                            [Signature Pages Follow]

<PAGE>

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

                           THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                           THE STOCKHOLDERS:

                                ________________________________________
                                By its duly authorized officer:

                                ________________________________________
                                Name:
                                Title:

                                New England Partners Capital, L.P.
                                By: NEP Capital, LLC
                                Its: General Partner
                                By: /s/ Illegible
                                    ------------------------------------
                                Its: President

<PAGE>

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

                           THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                           THE STOCKHOLDERS:

                                /s/ SHELLY D. GUYER
                                ----------------------------------------
                                By its duly authorized officer:

                                ________________________________________
                                Name: Shelly D. Guyer
                                Title:

<PAGE>

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

                           THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                           THE STOCKHOLDERS:

                                /s/ FREDERICK FRANK
                                ----------------------------------------
                                By its duly authorized officer:

                                ________________________________________
                                Name: Frederick Frank
                                Title:

<PAGE>

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

                           THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                ------------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                           THE STOCKHOLDERS:

                                AIM COUNSELOR SERIES TRUST, on behalf of its
                                portfolio, AIM ADVANTAGE HEALTH SCIENCES FUND
                                ---------------------------------------------

                                By its duly authorized officer:

                                /s/ J. PHILIP FERGUSON
                                ---------------------------------------------
                                Name: J. Philip Ferguson
                                Title: Chief Investment Officer
                                       AIM Capital Management

<PAGE>

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

                           THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                           THE STOCKHOLDERS:

                                /s/ ELI W. KAUFMAN
                                ----------------------------------------
                                By its duly authorized officer:

                                ________________________________________
                                Name:
                                Title:

<PAGE>

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

                           THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                           THE STOCKHOLDERS:

                                The Yasuda Enterprise Development II, Limited
                                Partnership
                                ---------------------------------------------
                                By its duly authorized officer:

                                /s/ MINORU OKA
                                ---------------------------------------------
                                Name: Minoru Oka
                                Title: President & Representative Director
                                       Yasuda Enterprise Development Co., Ltd.

<PAGE>

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

                           THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                           THE STOCKHOLDERS:

                                ________________________________________
                                By its duly authorized officer:

                                /s/ JEAN-MARC LESIEUR
                                ----------------------------------------
                                Name: JEAN-MARC LESIEUR
                                Title: HBM BioPartners Ltd.
                                       General partner of International Life
                                       Science Managers, L.P.,
                                       General Partner of International Life
                                       Science Partners, L.P.

<PAGE>

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

                           THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                           THE STOCKHOLDERS:

                                ASTELLAS VENTURE CAPITAL LLC
                                ----------------------------------------
                                By its duly authorized officer:

                                /s/ YOSHITAKA YONEYAMA
                                ----------------------------------------
                                Name: YOSHITAKA YONEYAMA
                                Title: PRESIDENT & CHIEF EXECUTIVE OFFICER

<PAGE>

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

                           THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                           THE STOCKHOLDERS:

                                ________________________________________
                                By its duly authorized officer:

                                /s/ C. NELSON LONG JR. and TERESA G. LONG
                                -----------------------------------------
                                Name: C. NELSON LONG, JR. + TERESA G. LONG
                                Title:

<PAGE>

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

                           THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                           THE STOCKHOLDERS:

                                /s/ W. ELLIOTT WALDEN
                                ----------------------------------------
                                By its duly authorized officer:

                                W. Elliot Walden
                                ----------------------------------------
                                Name:
                                Title:

<PAGE>

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

                           THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                           THE STOCKHOLDERS:

                                ________________________________________
                                By its duly authorized officer:

                                /s/ STELIOS PAPADOPOULOS
                                ----------------------------------------
                                Name: Stelios Papadopoulos
                                Title:

<PAGE>

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

                           THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                           THE STOCKHOLDERS:

                                ________________________________________
                                By its duly authorized officer:

                                /s/ JOSEPH H. FLOM
                                ----------------------------------------
                                Name: Joseph H. Flom
                                Title:

<PAGE>

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

                           THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                           THE STOCKHOLDERS:

                                /s/ DICKON AND LISA POWNALL-GRAY
                                ----------------------------------------
                                By its duly authorized officer:

                                Dickon and Lisa Pownall-Gray
                                ----------------------------------------
                                Name:
                                Title:
<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    -------------------------------------------
                                   Name: Michael Kauffman
                                   Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                /s/ LEON D. GOULD
                                    -------------------------------------------
                                By its duly authorized officer:

                                WHITEHALL FINANCIAL GROUP INC
                                    -------------------------------------------
                                Name: LEON D. GOULD
                                Title: SECRETARY

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                /s/ CHARLENE LEDBETTER
                                -----------------------------------
                                By its duly authorized officer:

                                CHARLENE LEDBETTER
                                -----------------------------------
                                Name: CHAIRMAN
                                Title:

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    ----------------------------------------
                                Name: Michael Kauffman
                                Title: President and Chief Executive Officer

                                THE STOCKHOLDERS:

                                /s/ WALTER W. HESS, JR.
                                ---------------------------------
                                By its duly authorized officer:

                                WALTER W. HESS, JR.
                                ---------------------------------
                                Name:
                                Title:

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                Danziger Capital Partners
                                ------------------------------
                                By its duly authorized officer:

                                /s/ FREDERICK M. DANZIGER
                                ------------------------------
                                Name: Frederick M. Danziger
                                Title: General Partner

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                /s/ RICHARD M. DANZIGER
                                -----------------------------------
                                By its duly authorized officer:
                                ___________________________________
                                Name: Richard M. Danziger
                                Title:

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                /s/ GEORGE D. GOULD
                                -------------------------------
                                By its duly authorized officer:

                                George D. Gould
                                -------------------------------
                                Name:
                                Title:

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                DELAWARE CHARTER GUARANTEE TRUST,
                                CUSTODIAN ROBERT F. SHAPIRO, IRA
                                ----------------------------------
                                By its duly authorized officer:

                                /s/ ROBERT F. SHAPIRO
                                ----------------------------------
                                Name:
                                Title:

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                NORTH FORK ASSOCIATES
                                ------------------------------------
                                By its duly authorized officer:

                                /s/ ROBERT F. SHAPIRO
                                ------------------------------------
                                Name:
                                Title: MANAGING PARTNER

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:
                                ________________________________________
                                By its duly authorized officer:

                                /s/ ROBERT F. SHAPIRO
                                ---------------------------------------
                                Name:
                                Title:

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                ________________________________________
                                By its duly authorized officer:

                                /s/ HAIM AVIV
                                ----------------------------------------
                                Name: HAIM AVIV C/O AYELET AVIV
                                Title:

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                _______________________________
                                By its duly authorized officer:

                                /s/ HAIM AVIV
                                -------------------------------
                                Name: HAIM AVIV
                                Title:

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                ________________________________
                                By its duly authorized officer:

                                /s/ HAIM AVIV
                                --------------------------------
                                Name: c/o TZVI AVIV
                                Title:

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                AEOW 96 LLC
                                -------------------------------
                                By its duly authorized officer:

                                /s/ BERNARD OSHER
                                -------------------------------
                                Name: Bernard Osher
                                Title: Partner

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                Forward Ventures V, LP
                                -------------------------------
                                By its duly authorized officer:
                                By Forward V Associates LLC

                                /s/ STANDISH FLEMING
                                -------------------------------
                                Name: Standish Fleming
                                Title: Managing Member

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                S.R. One Limited
                                ---------------------------------
                                By its duly authorized officer:

                                /s/ DONALD F. PARMAN
                                ---------------------------------
                                Name: Donald F. Parman
                                Title: Vice President & Secretary

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                CMEA Ventures VI, L.P.
                                CMEA Ventures VI GmbH & Co. KG
                                CMEA Ventures Life Sciences 2000, L.P.
                                CMEA Ventures Life Sciences 2000, Civil Law
                                Partnership

                                By: /s/ DAVID J. COLLIER
                                    ----------------------------------------
                                David J. Collier, MD,

                                General Partner, CMEA Ventures VI Management,
                                L.P., the General Partner of CMEA
                                Ventures VI, L.P.

                                General Partner, CMEA Ventures VI Management,
                                L.P., the Managing Limited Partner of CMEA
                                Ventures VI GmbH & Co. KG

                                General Partner, CMEA Ventures LS Management
                                2000, L.P., the General Partner of CMEA Ventures
                                Life Sciences 2000, L.P.

                                General Partner, CMEA Ventures LS Management
                                2000, L.P., the Managing Partner of CMEA
                                Ventures Life Sciences 2000, Civil Law
                                Partnership

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                         Foulon Limited
                         ------------------------------------
                         By its duly authorized officer:

                                /s/ Illegible             /s/ Illegible
                                ---------------           ---------------------
                         Name: FOR HILL SAMUEL            FOR HILL SAMUEL
                                (GUERNSEY)               (GUERNSEY)
                         Title: SERVICES LIMITED          MANAGEMENT LIMITED
                                DIRECTOR                   DIRECTOR

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                /s/ YIGAL ERLICH
                                --------------------------------
                                By its duly authorized officer:

                                PCM Venture Capital L.P.
                                --------------------------------
                                Name: Yigal Erlich
                                Title: General Partner

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                YOZMA VENTURE CAPITAL
                                -----------------------------------
                                By its duly authorized officer:

                                /s/ YOAV DOPPELT
                                -----------------------------------
                                Name: Yoav Doppelt
                                Title: CEO

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                /s/ YIGAL ERLICH
                                ------------------------------
                                By its duly authorized officer:

                                Yozma II (ISRAEL) LP.
                                ------------------------------
                                Name: Yigal Erlich
                                Title: General Partner

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                Yozma II (BVI) L.P.
                                -------------------------------
                                By its duly authorized officer:

                                /s/ YIGAL ERLICH
                                -------------------------------
                                Name: Yigal Erlich
                                Title: General Partner

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                Mulligan BioCapital AG
                                -------------------------------
                                By its duly authorized officer:

                                /s/ H.H. MUENCHMEYER
                                -------------------------------
                                Name: Hans Hermann Muenchmeyer
                                Title: Managing Director

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                JAFCO LIFE SCIENCE NO.1 INVESTMENT
                                ENTERPRISE PARTNERSHIP
                                ----------------------------------
                                By its duly authorized officer:

                                /s/ HISAJI AGATA
                                ----------------------------------
                                Name: Hisaji Agata
                                Title: Managing Director
                                       JAFCO Co. Ltd.,
                                       Its General Partner

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                SLRB-1
                                -------------------------------
                                By its duly authorized officer:

                                /s/ THOMAS W. STRAUSS
                                -------------------------------
                                Name: Thomas W. Strauss
                                Title: General Partner

<PAGE>

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

                         THE COMPANY

                                PREDIX PHARMACEUTICALS HOLDINGS, INC.

                                By: /s/ MICHAEL KAUFFMAN
                                    --------------------------------------------
                                    Name: Michael Kauffman
                                    Title: President and Chief Executive Officer

                         THE STOCKHOLDERS:

                                /s/ DETLEF BIERBAUM
                                -------------------------------
                                By its duly authorized officer:

                                BIERBAUM
                                -------------------------------
                                Name:
                                Title: Partner

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00088-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00088-of-00352.parquet"}]]