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                                                                   Exhibit 4.2.2

                           SYNTA PHARMACEUTICALS CORP.

                                 FIRST AMENDMENT
                                     TO THE
                 AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

     This First Amendment (the "AMENDMENT") to the Amended and Restated Investor
Rights Agreement, dated December 13, 2002, by and among Synta Pharmaceuticals
Corp., a Delaware corporation (the "COMPANY"), and the Investors named therein
(the "INVESTOR RIGHTS AGREEMENT"), is made as of January 11, 2005, by and among
the Company and the Investors. Capitalized terms used herein but not defined
shall have the meanings ascribed to such terms in the Investor Rights Agreement.

     WHEREAS, Section 2 of the Investor Rights Agreement sets forth certain
rights granted to the Investors with respect to the registration of the
Registrable Securities;

     WHEREAS, the Company and the Investors wish to alter the registration
rights granted to the Investors as set forth in the Investor Rights Agreement;

     WHEREAS, the Company wishes to grant these registration rights to an
additional Investor by adding an additional party to the Investor Rights
Agreement, and the Company and the Investors wish to amend the Investor Rights
Agreement to add such additional Investor;

     WHEREAS, Section 4 of the Investor Rights Agreement sets forth certain
rights granted to the Investors with respect to the right of first refusal to
purchase certain securities issued by the Company;

     WHEREAS, the Company and the Investors wish to amend the Investor Rights
Agreement to provide that the rights set forth in Section 4 terminate upon the
closing of an Initial Offering; and

     WHEREAS, in accordance with Section 5.7 of the Investor Rights Agreement,
by executing and delivering this Amendment, the Company and each Investor has
approved this Amendment.

     NOW, THEREFORE, in consideration of the premises and the mutual covenants
contained in this Amendment and for other good and valuable consideration, the
receipt and sufficiency of which are hereby acknowledged, the parties hereto
agree as follows:

     1.    AMENDMENT OF INVESTOR RIGHTS AGREEMENT.

     (i)   The Investor Rights Agreement is hereby amended by deleting the
preamble in its entirety and by substituting in lieu thereof the following:

     "THIS AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT (this "AGREEMENT")
dated as of December 13, 2002, is by and among Synta Pharmaceuticals Corp., a
Delaware corporation (the "COMPANY"), Robert A. Day and Mountain Trail
Investments, LLC,

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(singly, a "DAY INVESTOR", and collectively, the "DAY INVESTOR"), Keith R.
Gollust, Gollust Trust II, and Wyandanch Partners, L.P. (singly, a "GOLLUST
INVESTOR", and collectively, the "GOLLUST INVESTOR") and Bruce Kovner and
Cxsynta LLC, an affiliate of Caxton Corporation (singly, a "CAXTON INVESTOR",
and collectively, the "CAXTON INVESTOR") (each an "INVESTOR" and, collectively,
the "INVESTORS")."

     (ii)  The Investor Rights Agreement is hereby amended by deleting Sections
1(d), (e), (h), (q), (r), (t), (u) and (v) in their entirety and by substituting
in lieu thereof the following:

           "(d)    The term "COMPANY INDEMNIFIED PARTIES" has the meaning set
     forth in SECTION 2.7(a) hereof."

           "(e)    [Intentionally omitted.]"

           "(h)    The term "HOLDER" means any person owning or having the right
     to acquire Registrable Securities, or any assignee thereof, in accordance
     with SECTION 2.9 hereof."

           "(q)    The term "REGISTRABLE SECURITIES" means (i) any shares of
     Common Stock held by an Investor (ii) any shares of capital stock of the
     Company acquired by an Investor (or any transferee of an Investor) after
     the date hereof pursuant to the Stockholders' Agreement and (iii) any
     Common Stock issued as (or issuable upon the conversion or exercise of any
     warrant, right or other security) a dividend or other distribution with
     respect to or because of stock splits, stock dividends, reclassifications,
     recapitalizations, or similar events, or in exchange for, or in replacement
     of the shares referenced in (i) and (ii) above, excluding in all cases,
     however, any Registrable Securities sold by a person in a transaction in
     which his, her or its rights under SECTION 2 hereof are not assigned.
     Registrable Securities shall exclude any shares which (A) have been
     registered under the Securities Act pursuant to an effective registration
     statement filed thereunder and disposed of in accordance with the
     registration statement covering them, or (B) may be publicly sold pursuant
     to and in compliance with SEC Rule 144 in any ninety (90) day period,
     provided that such shares shall not be excluded if (x) the number of shares
     proposed to be sold by such Investor is larger than the number of shares
     that may be sold in any single 90-day period pursuant to Rule 144 or (y)
     such Investor believes in good faith that a sale pursuant to Rule 144 will
     be less advantageous to it than a sale pursuant to SECTIONS 2.1, 2.2 or
     2.3."

           "(r)    The term "REQUESTING HOLDERS" has the meaning set forth in
     SECTION 2.1(a) hereof."

           "(t)    The term "SELLING HOLDER" has the meaning set forth in
     SECTION 2.2(a) hereof."

           "(u)    The term "SELLING HOLDER INDEMNIFIED PARTIES" has the meaning
     set forth in SECTION 2.7(b) hereof."

           "(v)    The term "VIOLATION" has the meaning set forth in
     SECTION 2.7(a) hereof."

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     (iii) The Investor Rights Agreement is hereby amended by deleting Section 2
in its entirety and by substituting in lieu thereof the following:

"2.  Registration Rights. The Company covenants and agrees as follows:

     2.1   DEMAND REGISTRATION.

           (a)     Commencing upon the expiration of any lock-up agreement that
the Holders have entered into with the underwriters in connection with an
Initial Offering pursuant to SECTION 2.10, subject to the limitations set forth
in this SECTION 2, the Holders of not less than 60% of the then outstanding
Registrable Securities (the "REQUESTING HOLDERS") may at any time give to the
Company a written request for the registration (a "DEMAND REGISTRATION") by the
Company under the Act of all or any part of the Registrable Securities held by
such Requesting Holders. Within 15 business days after the receipt by the
Company of any such written request, the Company will give written notice of
such request to all Holders of Registrable Securities.

           (b)     Subject to the limitations set forth in this SECTION 2, after
the receipt of a written request for a Demand Registration, (i) the Company will
be obligated to include in such Demand Registration all Registrable Securities
with respect to which the Company receives from Holders of Registrable
Securities the written requests of such Holders for inclusion in such Demand
Registration, within 30 days after the date on which the Company gives to all
Holders a written notice of registration request pursuant to SECTION 2.1(a), and
(ii) the Company shall file a registration statement covering all such
Registrable Securities as soon as practicable after receipt of the written
requests of such Holders for inclusion in such Demand Registration, and shall
use its commercially reasonable efforts to effect the registration of all such
Registrable Securities. All written requests made by Holders of Registrable
Securities pursuant to this SECTION 2.1(b) will specify the number of
Registrable Securities to be registered and will also specify the intended
method of disposition thereof. If the Requesting Holders intend to distribute
the Registrable Securities by means of an underwriting, they shall so advise the
Company in their request. The underwriter shall be reasonably acceptable to the
Company.

           (c)     The registration statement filed pursuant to any Demand
Registration pursuant to this SECTION 2.1 may, subject to the limitations set
forth in this SECTION 2, include other securities of the Company which are held
by persons other than the Holders who, by virtue of agreements with the Company,
are entitled to include their securities in any such registration.

           (d)     The Company shall not be required to effect any Demand
Registration of any Registrable Securities pursuant to this SECTION 2.1 if the
anticipated aggregate offering price, net of underwriting discounts and
commissions, of the Registrable Securities will not equal or exceed fifteen
million dollars ($15,000,000).

           (e)     The Company shall not be required to effect more than two (2)
Demand Registrations pursuant to this SECTION 2.1.

           (f)     The Company will not be obligated to effect any Demand
Registration of any Registrable Securities pursuant to this SECTION 2.1 during
the period commencing on the date falling 90 days prior to the Company's
estimated date of filing of, and ending on the date 180

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days following the effective date of, any registration statement pertaining to
any registration initiated by the Company, for the account of the Company (other
than with respect to securities registered solely in connection with
acquisitions, employee benefit plans, and the like), if the written request of
the Requesting Holders for such Demand Registration pursuant to SECTION 2.1(a)
hereof is received by the Company after the Company has commenced an
underwritten registration initiated by the Company and provides reasonable
evidence that it commenced activities directly related to such filing before
receiving the written request of the Holders; PROVIDED, HOWEVER, that the
Company will use its commercially reasonable efforts in good faith to cause any
such registration statement to be filed and to become effective as expeditiously
as is reasonably possible.

           (g)     The Company will not be obligated to effect any Demand
Registration of any Registrable Securities pursuant to this SECTION 2.1 for not
more than a 120-day period, if: (i) in the good faith judgment of the Board of
Directors of the Company, such registration would be seriously detrimental to
the Company and the Board of Directors of the Company concludes, as a result,
that it is essential to defer the filing of such registration statement at such
time, and (ii) the Company shall furnish to such Holders a certificate signed by
the Chief Executive Officer of the Company stating that in the good faith
judgment of the Board of Directors of the Company, it would be seriously
detrimental to the Company for such registration statement to be filed in the
near future and that it is, therefore, essential to defer the filing for a
period of not more than 120 days after receipt of the request of the Requesting
Holders; and FURTHER PROVIDED, that the Company shall not defer its obligation
in this manner more than once in any twelve-month period.

           (h)     If the managing underwriters in any Demand Registration
advise the Company that the number of securities proposed to be included in such
registration exceeds, in the opinion of the managing underwriters of such
registration in light of marketing factors, the number of securities to which
such registration should be limited (the "UNDERWRITERS' MAXIMUM NUMBER"), then:
(i) the Company will be obligated to include in such registration that number of
Registrable Securities requested by Holders to be included in such registration
as does not exceed the Underwriters' Maximum Number, and such number of
Registrable Securities will be allocated PRO RATA among such Holders on the
basis of the number of Registrable Securities held by each such Holder; (ii) if
the Underwriters' Maximum Number exceeds the number of Registrable Securities
requested by Holders to be included in such registration, then the Company will
be entitled to include in such registration that number of securities as has
been requested by the Company to be included in such registration for the
account of the Company and that is not greater than such excess; and (iii) if
the Underwriters' Maximum Number exceeds the sum of the number of Registrable
Securities that the Company is obligated under clause (i) above to include in
such Demand Registration plus the number of securities that the Company proposes
to offer and sell for its own account in such registration, then the Company may
include in such registration that number of other securities as security holders
other than Holders may have requested be included in such registration and that
is not greater than such excess, and such number of excess securities will be
allocated PRO RATA among such security holders other than the Holders on the
basis of the number of such securities requested to be included in such
registration by each such security holder. Neither the Company nor any of its
other security holders will be entitled to include any securities in any
underwritten Demand Registration unless the Company or such security holders
(as the case may be) agree in writing to sell such securities

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on the same terms and conditions as apply to the Registrable Securities held by
Holders to be included in such Demand Registration.

     2.2   PIGGYBACK REGISTRATION.

           (a)     At any time subsequent to the expiration of any lock-up
agreement that the Holders have entered into with the underwriters in connection
with an Initial Offering pursuant to SECTION 2.10, if (but without any
obligation to do so) the Company proposes to register (including for this
purpose a registration effected by the Company for stockholders other than the
Holders) any of its stock or other securities under the Act (other than a
registration statement on Form S-8 or Form S-4, or their successors, or any
registration statement effected solely to implement an employee benefit plan or
covering only securities proposed to be issued in exchange for securities or
assets of another corporation), the Company shall, at such time, promptly give
each Holder written notice of such registration. Upon the written request of
each Holder (a "SELLING HOLDER") received within 30 days after the date on which
the Company gives such notice in accordance with the provisions hereof, the
Company shall, subject to the provisions of this SECTION 2, use all reasonable
efforts to cause to be registered under the Act all of the Registrable
Securities that each such Holder has requested to be registered.

           (b)     The Company shall have the right to terminate or withdraw any
registration initiated by it under this SECTION 2.2 prior to the effectiveness
of such registration whether or not any Holder has elected to include securities
in such registration. The expenses of such withdrawn registration shall be borne
by the Company in accordance with SECTION 2.6 hereof.

           (c)     In connection with any offering involving an underwriting of
shares of the Company's capital stock, the Company shall not be required under
this SECTION 2.2 to include any of the Holders' securities in such underwriting
unless they accept the terms of the underwriting as agreed upon between the
Company and the underwriters selected by it, which terms shall not contravene
any of the terms hereof without the consent of the Selling Holders holding at
least 50% of the Registrable Securities requested to be included in such
registration statement, and enter into such an underwriting agreement in
customary form with an underwriter or underwriters selected by the Company. In
connection with any such underwriting agreement, no Selling Holder shall be
required to make representations and warranties other than representations and
warranties regarding such Selling Holder's ownership and title to the
Registrable Securities being sold by it and its plan of distribution with
respect to its Registrable Securities. The number of securities which shall be
included in such registration shall be in such quantity as the managing
underwriter determines in its sole discretion will not materially and adversely
affect the offering by the Company. If the total number of securities, including
Registrable Securities, requested by stockholders to be included in such
offering exceeds the number of securities that the managing underwriter
determines in its sole discretion will not materially and adversely affect the
offering, then the Company shall be required to include in the offering only
that number of such securities, including Registrable Securities, that the
managing underwriter determines in writing in its sole discretion will not
materially and adversely affect the offering (the securities so included to be
apportioned pro rata among the Selling Holders according to the total amount of
securities entitled to be included therein owned by each Selling Holder or in
such other proportions as shall mutually be agreed to by such Selling Holders).

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Notwithstanding anything to the contrary contained in this Agreement, to the
extent the stockholders of the Company that have requested to have securities
included in such registration include stockholders other than Holders exercising
contractual demand registration rights, then the Company will include in such
registration, to the extent of the number and type which the Company is so
advised can be sold in such offering, (i) FIRST all Registrable Securities
requested for inclusion held by the stockholders exercising contractual demand
registration rights, and (ii) SECOND such securities requested to be included in
such registration statement by all other stockholders. For purposes of the
foregoing parenthetical concerning apportionment, for any selling stockholder
that is a Holder of Registrable Securities and that is a partnership, limited
liability company or corporation, the partners, members, retired partners,
retired members and stockholders of such Holder, or the estates and family
members of any such partners, members, retired partners and retired members and
any trusts for the benefit of any of the foregoing persons shall be deemed to be
a single Selling Holder, and any pro rata reduction with respect to such Selling
Holder shall be based upon the aggregate amount of Registrable Securities owned
by all such related entities and individuals.

     2.3   FORM S-3 REGISTRATION. At any time after the Company becomes eligible
to file a registration statement on Form S-3, a Holder or Holders of Registrable
Securities may request the Company, in writing, to effect the registration of
such Registrable Securities on Form S-3; PROVIDED, HOWEVER, that such
Registrable Securities are sufficient to result in an anticipated aggregate
offering price, net of underwriting discounts and commissions, of at least ten
million dollars ($10,000,000). Upon receipt of any such request, the Company
shall:

           (a)     promptly give written notice of the proposed registration,
and any related qualification or compliance, to all other Holders; and

           (b)     use its commercially reasonable efforts to effect such
registration to permit or facilitate the sale and distribution of all or such
portion of such Holder's or Holders' Registrable Securities as are specified in
such request, together with all or such portion of the Registrable Securities of
any other Holder or Holders joining in such request as are specified in a
written request given within 30 days after receipt of such written notice from
the Company; PROVIDED, HOWEVER, that the Company shall not be obligated to
effect any such registration pursuant to this SECTION 2.3: (i) if Form S-3 is
not available for such offering by the Holders; or (ii) for not more than a
120-day period, if: (A) in the good faith judgment of the Board of Directors of
the Company, such registration would be seriously detrimental to the Company and
the Board of Directors of the Company concludes, as a result, that it is
essential to defer the filing of such registration statement at such time, and
(B) the Company shall furnish to such Holders a certificate signed by the Chief
Executive Officer of the Company stating that in the good faith judgment of the
Board of Directors of the Company, it would be seriously detrimental to the
Company for such registration statement to be filed in the near future and that
it is, therefore, essential to defer the filing for a period of not more than
120 days after receipt of the request of the Holders; PROVIDED, HOWEVER, that
the Company shall not defer its obligation in this manner more than once in any
twelve-month period.

           (c)     The Company shall not be required to effect more than two (2)
registrations pursuant to this SECTION 2.3 in any rolling 12-month period.

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           (d)     Subject to the foregoing, the Company shall file a
registration statement covering the Registrable Securities and other securities
so requested to be registered as soon as practicable after receipt of the
request or requests of the Holders, and, in any event, shall use its
commercially reasonable efforts to effect the registration of all such
Registrable Securities and other securities.

     2.4   OBLIGATIONS OF THE COMPANY. Whenever required under this SECTION 2 to
effect the registration of any Registrable Securities, the Company shall, at the
earliest possible date:

           (a)     prepare and file with the SEC a registration statement with
respect to such Registrable Securities and use all reasonable efforts to cause
such registration statement to become effective, and, upon the request of the
Holders of a majority of the Registrable Securities registered thereunder, keep
such registration statement effective for 120 days from the effective date or
until the distribution contemplated in the Registration Statement has been
completed;

           (b)     as promptly as possible prepare and file with the SEC such
amendments and supplements to such registration statement and the prospectus
used in connection with such registration statement as may be necessary to
comply with the provisions of the Act with respect to the disposition of all
securities covered by such registration statement;

           (c)     as promptly as possible furnish to the Holders such numbers
of copies of the registration statement and amendments thereto, a prospectus,
including a preliminary prospectus, in conformity with the requirements of the
Act, and such other documents as they may reasonably request in order to
facilitate the disposition of Registrable Securities owned by them;

           (d)     as promptly as possible use all reasonable efforts to
register and qualify the securities covered by such registration statement under
such other securities or blue sky or other state securities laws of such
jurisdictions as shall be reasonably requested by the Holders, PROVIDED, that
the Company shall not be required in connection therewith or as a condition
thereto to qualify to do business or to file a general consent to service of
process in any such states or jurisdictions;

           (e)     as promptly as possible in the event of any underwritten
public offering, enter into and perform its obligations under an underwriting
agreement, in usual and customary form, with the managing underwriter of such
offering;

           (f)     as promptly as possible notify each Holder of Registrable
Securities covered by such registration statement at any time when a prospectus
relating thereto is required to be delivered under the Act of the happening of
any event as a result of which the prospectus included in such registration
statement, as then in effect, includes an untrue statement of a material fact or
omits to state 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;

           (g)     as promptly as possible cause all such Registrable Securities
registered pursuant hereto to be listed on each securities exchange on which
similar securities issued by the Company are then listed; and

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           (h)     if such securities are being sold in an underwritten
offering, as promptly as possible furnish at the request of any Holder
requesting registration of Registrable Securities pursuant hereto, on the date
that such Registrable Securities are delivered to the underwriters for sale in
connection with a registration pursuant hereto, (A) an opinion, dated such date,
of the counsel representing the Company for the purposes of such registration,
in form and substance as is customarily given to underwriters in an underwritten
public offering, addressed to the underwriters, and to the Holders requesting
registration of Registrable Securities, and (B) a letter dated such date, from
the independent certified public accountants of the Company, in form and
substance as is customarily given by independent certified public accountants to
underwriters in an underwritten public offering, addressed to the underwriters,
and to the Holders requesting registration of Registrable Securities.

     2.5   INFORMATION FROM HOLDER. It shall be a condition precedent to the
obligations of the Company to take any action pursuant to this SECTION 2 with
respect to the Registrable Securities of any Selling Holder that such Holder
shall furnish to the Company such information regarding itself, the Registrable
Securities held by it, and the intended method of disposition of such securities
as shall be required to effect the registration of such Holder's Registrable
Securities.

     2.6   EXPENSES OF REGISTRATION. All expenses (other than underwriting
discounts and commissions and the fees and expenses of counsel to the Holders)
incurred in connection with registrations, filings or qualifications pursuant to
this SECTION 2, including, without limitation, all registration, filing and
qualification fees, printers' and accounting fees, fees and disbursements of
counsel for the Company, shall be borne by the Company.

     2.7   INDEMNIFICATION. In the event any Registrable Securities are included
in a registration statement under this SECTION 2:

           (a)     The Company will indemnify and hold harmless each Holder, the
partners, members, managers, officers, directors and stockholders of each
Holder, any underwriter (as defined in the Act) for such Holder and each person,
if any, who controls such Holder or underwriter within the meaning of the Act or
the 1934 Act (collectively, the "COMPANY INDEMNIFIED PARTIES"), against any
losses, claims, damages or liabilities (joint or several) to which they may
become subject under the Act, the 1934 Act or any state securities laws, insofar
as such losses, claims, damages, or liabilities (or actions in respect thereof)
arise out of or are based upon any of the following statements, omissions or
violations (collectively, a "VIOLATION"): (i) any untrue statement or alleged
untrue statement of a material fact contained in such registration statement,
including any preliminary prospectus or final prospectus contained, therein or
any amendments or supplements thereto, (ii) the omission or alleged omission to
state therein a material fact required to be stated therein, or necessary to
make the statements therein not misleading, or (iii) any violation or alleged
violation by the Company of the Act, the 1934 Act, any blue sky or other state
securities laws or any rule or regulation promulgated under the Act, the 1934
Act or any blue sky or other state securities laws; and the Company will pay to
each such Company Indemnified Party any legal or other expenses reasonably
incurred by them in connection with investigating or defending any such loss,
claim, damage or liability (or actions in respect thereof); PROVIDED, HOWEVER,
that the indemnity agreement contained in this

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SECTION 2.7(a) shall not apply to amounts paid in settlement of any such loss,
claim, damage or liability if such settlement is effected without the consent of
the Company (which consent shall not be unreasonably withheld), nor shall the
Company be liable in any such case for any such loss, claim, damage, liability
or action to the extent that it arises out of or is based upon a Violation that
occurs in reliance upon and in conformity with written information furnished
expressly for use in connection with such registration by any such Company
Indemnified Party, and FURTHER PROVIDED, that the foregoing indemnity agreement
with respect to any preliminary prospectus shall not inure to the benefit of any
Company Indemnified Party, from whom the person asserting any such losses,
claims, damages or liabilities purchased shares in the offering, if a copy of
the prospectus (as then amended or supplemented if the Company shall have
furnished any amendments or supplements thereto) was not sent or given by or on
behalf of such Company Indemnified Party to such person, if required by law so
to have been delivered, at or prior to the written confirmation of the sale of
the shares to such person, and if the prospectus (as so amended or supplemented)
would have cured the defect giving rise to such loss, claim, damage or
liability.

           (b)     Each Holder selling securities in such registration statement
will indemnify and hold harmless the Company, each of its directors, each of its
officers who has signed the registration statement, each person, if any, who
controls the Company within the meaning of the Act, any underwriter, any other
Holder selling securities in such registration statement and any controlling
person of any such underwriter or other Holder (collectively, the "SELLING
HOLDER INDEMNIFIED PARTIES"), against any losses, claims, damages or liabilities
(joint or several) to which any of the foregoing Selling Holder Indemnified
Parties may become subject, under the Act, the 1934 Act or any state securities
laws, insofar as such losses, claims, damages or liabilities (or actions in
respect thereto) arise out of or are based upon any Violation, in each case to
the extent (and only to the extent) that such Violation occurs in reliance upon
and in conformity with written information furnished by such Holder expressly
for use in connection with such registration; and each such Holder will
reimburse a Selling Holder Indemnified Party for any legal or other expenses
reasonably incurred by such person in connection with investigating or defending
any such loss, claim, damage or liability (or actions in respect thereof);
PROVIDED, HOWEVER, that the indemnity agreement contained in this SECTION 2.7(b)
shall not apply to amounts paid in settlement of any such loss, claim, damage,
liability or action if such settlement is effected without the consent of such
indemnifying Holder (which consent shall not be unreasonably withheld); and
FURTHER PROVIDED, that in no event shall any indemnity under this SECTION 2.7(b)
exceed the net proceeds (after underwriting discounts and commissions) from the
offering received by such indemnifying Holder; and FURTHER PROVIDED, that the
foregoing indemnity agreement with respect to any preliminary prospectus shall
not inure to the benefit of a Selling Holder Indemnified Party from whom the
person asserting any such losses, claims, damages or liabilities purchased
shares in the offering, if a copy of the prospectus (as then amended or
supplemented if the Company shall have furnished any amendments or supplements
thereto) was not sent or given by or on behalf of such Selling Holder
Indemnified Party to such person, if required by law so to have been delivered,
at or prior to the written confirmation of the sale of the shares to such
person, and if the prospectus (as so amended or supplemented) would have cured
the defect giving rise to such loss, claim, damage or liability.

           (c)     Promptly after receipt by an indemnified party under this
SECTION 2.7 of notice of the commencement of any action (including any
governmental action), such

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indemnified party will, if a claim in respect thereof is to be made against any
indemnifying party under this SECTION 2.7, deliver to the indemnifying party a
written notice of the commencement thereof and the indemnifying party shall have
the right to participate in, and, to the extent the indemnifying party so
desires, jointly with any other indemnifying party similarly noticed, to assume
the defense thereof with counsel mutually satisfactory to the parties; PROVIDED,
HOWEVER, that an indemnified party (together with all other indemnified parties
that may be represented without conflict by one counsel) shall have the right to
retain one separate counsel, with the fees and expenses to be paid by the
indemnifying party, if representation of such indemnified party by the counsel
retained by the indemnifying party would be inappropriate due to actual conflict
of interests between such indemnified party and any other party represented by
such counsel in such proceeding. The failure to deliver written notice to the
indemnifying party within a reasonable time of the commencement of any such
action, if prejudicial to its ability to defend such action, shall relieve such
indemnifying party of any liability to the indemnified party under this SECTION
2.7 but the omission so to deliver written notice to the indemnifying party will
not relieve it of any liability that it may have to any indemnified party
otherwise than under this SECTION 2.7.

           (d)     If the indemnification provided for in this SECTION 2.7 is
held by a court of competent jurisdiction to be unavailable to an indemnified
party with respect to any loss, liability, claim, damage or expense referred to
herein, then the indemnifying party, in lieu of indemnifying such indemnified
party hereunder, shall contribute to the amount paid or payable by such
indemnified party as a result of such loss, liability, claim, damage or expense
in such proportion as is appropriate to reflect the relative fault of the
indemnifying party on the one hand and of the indemnified party on the other in
connection with the statements or omissions that resulted in such loss,
liability, claim, damage or expense, as well as any other relevant equitable
considerations. The relative fault of the indemnifying party and of the
indemnified party shall be determined by reference to, among other things,
whether the untrue or alleged untrue statement of a material fact or the
omission to state a material fact relates to information supplied by the
indemnifying party or by the indemnified party, and the parties' relative
intent, knowledge, access to information and opportunity to correct or prevent
such statement or omission; PROVIDED, HOWEVER, that, in any such case (A) no
such Holder will be required to contribute any amount in excess of the net
proceeds (after underwriting discounts and commissions) from the offering
received by such Holder, and (B) no person or entity guilty of fraudulent
misrepresentation (within the meaning of Section 11(f) of the Act) will be
entitled to contribution from any person or entity who was not guilty of such
fraudulent misrepresentation.

           (e)     Notwithstanding anything to the contrary in the foregoing, to
the extent that the provisions on indemnification and contribution contained in
the underwriting agreement entered into in connection with the underwritten
public offering are in conflict with the foregoing provisions, the provisions in
the underwriting agreement shall control.

           (f)     The obligations of the Company and Holders under this
SECTION 2.7 shall survive the completion of any offering of Registrable
Securities in a registration statement under this SECTION 2, and otherwise.

     2.8   REPORTS UNDER SECURITIES EXCHANGE ACT OF 1934. With a view to making
available to the Holders the benefits of SEC Rule 144 and any other rule or
regulation of the SEC that may at any time permit a Holder to sell securities of
the Company to the public without

                                       10
<Page>

registration or pursuant to a registration on Form S-3, the Company agrees to:

           (a)     make and keep public information available, as those terms
are understood and defined in SEC Rule 144, at all times after 90 days after the
effective date of the Initial Offering;

           (b)     file with the SEC in a timely manner all reports and other
documents required of the Company under the Act and the 1934 Act; and

           (c)     furnish to any Holder, so long as the Holder owns any
Registrable Securities, promptly upon request (i) a written statement by the
Company that it has complied with the reporting requirements of SEC Rule 144 (at
any time after 90 days after the effective date of the Initial Offering), the
Act and the 1934 Act (at any time after it has become subject to such reporting
requirements), or that it qualifies as a registrant whose securities may be
resold pursuant to Form S-3 (at any time after it so qualifies), (ii) a copy of
the most recent annual or quarterly report of the Company and such other reports
and documents so filed by the Company, and (iii) such other information as may
be reasonably requested in availing any Holder of any rule or regulation of the
SEC that permits the selling of any such securities without registration or
pursuant to such form.

     2.9   ASSIGNMENT OF REGISTRATION RIGHTS. The rights to cause the Company to
register Registrable Securities pursuant to this SECTION 2 may be assigned (but
only with all related obligations) by a Holder to a transferee or assignee of
such securities that (i) is an Affiliate of the Holder or (ii) after such
assignment or transfer, holds at least one percent (1%) of the issued and
outstanding shares of the Company's Common Stock, PROVIDED, that: (a) the
Company is, within a reasonable time after such transfer, furnished with written
notice of the name and address of such transferee or assignee and the securities
with respect to which such registration rights are being assigned; and (b) such
transferee or assignee agrees in writing to be bound by and subject to the terms
and conditions of this Agreement, including without limitation the provisions of
SECTION 2.10 below.

     2.10  "MARKET STAND-OFF' AGREEMENT. Each Holder hereby agrees that, if
requested by the managing underwriter, it will not, without the prior written
consent of the managing underwriter, sell or otherwise transfer or dispose of
(subject to customary exceptions) any shares of Common Stock or any securities
convertible into or exercisable or exchangeable for Common Stock (whether such
shares or any such securities are then owned by the Holder or are thereafter
acquired) during the period commencing on the date of the final prospectus
relating to the Initial Offering and ending on the date specified by the Company
and the managing underwriter (such period not to exceed 180 days); PROVIDED,
HOWEVER, that all executive officers and directors of the Company and all other
holders of at least one percent (1%) of Common Stock enter into similar
agreements. The underwriters in connection with the Initial Offering are
intended third-party beneficiaries of this SECTION 2.10 and shall have the
right, power and authority to enforce the provisions hereof as though they were
a party hereto.

     In order to enforce the foregoing covenant, the Company may impose
stop-transfer instructions with respect to the Registrable Securities of each
Holder (and the shares or securities of every other person subject to the
foregoing restriction) until the end of such period.

                                       11
<Page>

     2.11  TERMINATION OF REGISTRATION RIGHTS. No Holder shall be entitled to
exercise any right provided for in this SECTION 2 after the later to occur of
(a) the date that is five (5) years following the consummation of the Initial
Offering, and (b) the date on which all of such Holder's Registrable Securities
may be sold within a 90-day period pursuant to SEC Rule 144."

     (iv)  The Investor Rights Agreement is hereby amended by adding the
following Section 4.7:

     "4.7  The obligations and covenants set forth in this SECTION 4 shall
terminate and be of no further force and effect upon the closing of an Initial
Offering."

     (v)   The Investor Rights Agreement is hereby amended by adding the
following address to Section 5.5:

     "If to Bruce Kovner, at Bruce Kovner, c/o Caxton Corporation, Princeton
Plaza, Building 2, 731 Alexander Road, Princeton, New Jersey 08540, facsimile
number 609-419-0470, or at such other address as may be furnished in writing by
the Investor to the Company."

     (vi)  Except as amended hereby, all of the terms and conditions of the
Investor Rights Agreement shall remain in full force and effect.

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

                   REMAINDER OF PAGE INTENTIONALLY LEFT BLANK

                                       12
<Page>

     IN WITNESS WHEREOF, the undersigned have executed this Amendment as of the
date first above written.

                                    COMPANY:

                                    SYNTA PHARMACEUTICALS CORP.

                                    By: /s/ Safi R. Bahcall
                                       ----------------------------
                                    Name:  Safi R. Bahcall
                                    Title: Chief Executive Officer

                                       13
<Page>

     [First Amendment to the Amended and Restated Investor Rights Agreement,
                           Signature Page, CONTINUED]

                                    INVESTORS:

                                    CxSYNTA LLC

                                    By: /s/ Bruce Kovner
                                       ---------------------------
                                    Name:  Bruce Kovner
                                    Title:

                                    /s/ Bruce Kovner
                                    ------------------------------
                                    Bruce Kovner

                                    MOUNTAIN TRAIL INVESTMENTS, LLC

                                    By: /s/ Richard N. Foster
                                       ---------------------------
                                    Name:  Richard N. Foster
                                    Title: Partner

                                    GOLLUST TRUST II

                                    By: /s/ Kenneth S. Davidson
                                       ---------------------------
                                    Name:  Kenneth S. Davidson
                                    Title: Trustee

                                    WYANDANCH PARTNERS, L.P.

                                    By: /s/ Keith R. Gollust
                                       ---------------------------
                                    Name:  Keith R. Gollust
                                    Title:

                                    /s/ Keith R. Gollust
                                    ------------------------------
                                    Keith R. Gollust

                                       14