SYNTA PHARMACEUTICALS CORP. AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

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Exhibit 4.2.1

SYNTA PHARMACEUTICALS CORP.

AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

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, (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

Cxsynta LLC, an affiliate of Caxton Corporation (the "Caxton Investor") (each an

"INVESTOR" and, collectively, the "INVESTORS").

Reference is hereby made to that certain Investor Rights Agreement dated

May 16, 2002 by and between the Company and Cxsynta LLC, which agreement is

hereby amended and restated in its entirety and shall be without further force

or effect as of the date hereof

RECITALS

WHEREAS, the Investors have purchased the number of shares (the "SHARES")

of the Common Stock, $.0001 par value, of the Company (the "COMMON STOCK") set

forth opposite their respective names on SCHEDULE A hereto;

WHEREAS, concurrently with the execution of this Agreement, the Investors

have executed the Amended and Restated Stockholders' Agreement of even date

herewith (the "STOCKHOLDERS' AGREEMENT") with the Company pursuant to which all

parties have agreed to provide for certain board of director representation and

meeting requirements, co-sale rights and rights of first refusal with respect to

the Common Stock; and

WHEREAS, the Company wishes to provide the Investors with certain

information rights, registration rights and rights of first refusal in

conjunction with the purchase of their respective Shares;

NOW, THEREFORE, in consideration of the mutual covenants and agreements

contained herein, and for other good and valuable consideration, the receipt and

sufficiency of which are hereby acknowledged, the parties hereto agree as

follows:

1. DEFINITIONS. For purposes of this Agreement:

(a) The term "AFFILIATE" means any general or limited partner of any

person that is a partnership, any member or manager of any person that is a

limited liability company or any person or entity that, directly or

indirectly, through one or more intermediaries, controls or is controlled

by, or is under common control with, such person.

(b) The term "ACT" means the Securities Act of 1933, as amended, or

any similar federal statute, and the rules and regulations of the SEC, all

as shall be in effect at the time.

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(c) The term "BUDGET" has the meaning set forth in SECTION 3.3

hereof.

(d) The term "COMPANY INDEMNIFIED PARTIES" has the meaning set forth

in SECTION 2.6(a) hereof.

(e) The term "DEMAND PERIOD" has the meaning set forth in SECTION

2.2(a) hereof.

(f) The term "FORM S-3" means such form under the Act as in effect on

the date hereof or any registration form under the act subsequently adopted

by the SEC that permits inclusion or incorporation of substantial

information by reference to other documents filed by the Company with the

SEC.

(g) The term "GAAP" means generally accepted accounting principles as

consistently applied by the Company.

(h) The term "HOLDER" means any person owning or having the right to

acquire Registrable Securities, or any assignee thereof, in accordance with

SECTION 2.8 hereof.

(i) The term "INITIAL OFFERING" means the Company's first firm

commitment underwritten public offering of its Common Stock under the Act.

(j) The term "1934 ACT" means the Securities Exchange Act of 1934, as

amended, or any similar federal statute, and the rules and regulations of

the SEC, all as shall be in effect at the time.

(k) The term "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,

HOWEVER that "New Securities" does not include: (i) securities offered to

the public pursuant to an Initial Offering; (ii) securities issued pursuant

to the acquisition of another corporation or entity by the Company by

merger, purchase of substantially all of the assets, or other

reorganization whereby the Company acquires a majority of the voting power

of such corporation or entity; (iii) up to ten million (10,000,000) shares

of Common Stock issued or issuable to employees, consultants or directors

of the Company pursuant to the Company's 2001 Stock Plan (including shares

issued or issuable upon exercise of options previously granted), which

number of shares may be adjusted upward by the affirmative vote of the

Company's Board of Directors; (iv) up to three hundred sixty eight thousand

eight hundred ninety four (368,894) shares of Common Stock issuable to

employees of the Company pursuant to the Company's 2002 Employee Stock

Purchase Plan; (v) securities issued to strategic partners of the Company,

such as biotechnology, pharmaceutical, drug manufacturing or clinical

research companies; (vi) securities issued to licensors of technology to

the Company; or (vii) securities issued in connection with any bank lines

of credit, equipment lease transactions, or real estate transactions; in

each case as approved by the Company's Board of Directors.

(1) The term "NOTICE OF ACCEPTANCE" has the meaning set forth in

SECTION 4.3

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hereof.

(m) The term "OFFER" has the meaning set forth in SECTION 4.2 hereof.

(n) The term "PRO RATA AMOUNT" has the meaning set forth in SECTION

4.1 hereof.

(o) The term "REFUSED SECURITIES" has the meaning set forth in

SECTION 4.4 hereof.

(p) The term "REGISTER," "REGISTERED," and "REGISTRATION" refer to a

registration effected by preparing and filing a registration statement or

similar document in compliance with the Act, and the declaration or

ordering of effectiveness of such registration statement or document.

(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 Section 2.1 or 2.2.

(r) The term "REQUESTING HOLDERS" has the meaning set forth in

SECTION 2.2(a) hereof.

(s) The term "SEC" means the Securities and Exchange Commission.

(t) The term "SELLING HOLDER" has the meaning set forth in SECTION

2.1(a) hereof.

(u) The term "SELLING HOLDER INDEMNIFIED PARTIES" has the meaning set

forth in SECTION 2.6(b) hereof.

(v) The term "VIOLATION" has the meaning set forth in SECTION 2.6(a)

hereof.

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

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2.1 PIGGYBACK REGISTRATION.

(a) 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 in connection with the public offering of such securities (other than a

registration statement on Form S-8 or Form S-4, or their successors, or any

registration statement 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") given within thirty (30)

days after mailing of such notice by the Company in accordance with the

provisions hereof, the Company shall, subject to the provisions of SECTION

2.1(c), 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 2.1 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 2.5 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 2.1 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 fifty

percent (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).

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 Holders exercising contractual demand

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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.

(d) In the event a Selling Holder (i) is unable to include in a

registration by the Company under this SECTION 2.1 all of the Registrable

Securities that such Holder has requested, or (ii) disapproves the terms of the

underwriting as agreed upon between the Company and the underwriters selected by

it, the Selling Holder will have the demand registration rights set forth in

SECTION 2.2.

2.2 DEMAND REGISTRATION.

(a) Commencing at least one hundred eighty (180) days from the

effective date of a registration statement that could have included Registrable

Securities under SECTION 2.1 and expiring two (2) years from such effective date

or until such time as the registration statement delayed pursuant to Section

2.2.(b) has been granted effectiveness (the "DEMAND PERIOD"), any Holders

entitled to demand registration rights under Section 2.1(d) (the "REQUESTING

HOLDERS") shall be entitled to request in writing during the Demand Period that

the Company effect the registration, qualification or compliance of the

Registrable Securities owned by such Requesting Holders; PROVIDED, HOWEVER, that

the expected aggregate price to the public of the Registrable Securities will

equal or exceed five million dollars ($5,000,000). 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.

(b) The Company shall file a registration statement covering the

Registrable Securities so requested to be registered as soon as practicable

after receipt of the request or requests of the Requesting Holders, and shall

use its commercially reasonable efforts to effect such registration,

qualification or compliance (including, without limitation, the execution of an

undertaking to file post-effective amendments, appropriate qualification under

applicable blue sky or other state securities laws and appropriate compliance

with applicable regulations issued under the Securities Act and any other

governmental requirements or regulations) as may be so requested and as would

permit or facilitate the sale and distribution of all or such portion of such

Registrable Securities as are specified in such request; PROVIDED, HOWEVER, that

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

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and that it is, therefore, essential to defer the filing for a period of not

more than one hundred twenty (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.

(c) The Company shall not be required to effect more than one (1)

registration pursuant to this SECTION 2.2 during the Demand Period.

2.3 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 one hundred twenty (120) days from the

effective date or, if earlier, 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 hereunder to be listed on each securities exchange on which

similar securities issued by

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the Company are then listed;

(h) as promptly as possible. provide a transfer agent and registrar

for all Registrable Securities registered pursuant hereunder and a CUSIP number

for all such Registrable Securities, in each case not later than the effective

date of such registration; and

(i) 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.

2.4 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 th