Document:

EX-10.5

 Exhibit 10.5 

REGISTRATION RIGHTS AGREEMENT 

This REGISTRATION RIGHTS AGREEMENT (this “Agreement”) is made and entered into as of July 3, 2022 by and among Syros Pharmaceuticals,
Inc., a Delaware corporation (the “Company”), and the “Investors” named in that certain Securities Purchase Agreement by and among the Company and the Investors, dated as of July 3, 2022 (the “Purchase
Agreement”). Capitalized terms used herein have the respective meanings ascribed thereto in the Purchase Agreement unless otherwise defined herein. 

The parties hereby agree as follows: 
 1. Definitions.

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

“Agreement” has the meaning set forth in the first paragraph. 

“Allowed Delay” has the meaning set forth in Section 2(c)(ii). 

“Company” has the meaning set forth in the first paragraph. 

“Constructive Primary Offering” has the meaning set forth in Section 2(e). 

“Cut Back Shares” has the meaning set forth in Section 2(e). 

“Effectiveness Deadline” means, with respect to the Registration Statement, the sixtieth (60th) calendar day following the Filing Deadline
(or, in the event the SEC reviews and has written comments to the Registration Statement, the one hundred and twentieth (120th) calendar day following the Filing Deadline); provided, however, that if the Effectiveness Deadline falls on a Saturday,
Sunday or other day that the Commission is closed for business, the Effectiveness Deadline shall be extended to the next Business Day on which the Commission is open for business. 

“Effectiveness Period” has the meaning set forth in Section 3(a). 

“Filing Deadline” has the meaning set forth in Section 2(a)(i). 

“Inspectors” has the meaning set forth in Section 3(j). 

“Investors” means the Investors identified in the Purchase Agreement and any Affiliate or permitted transferee of any Investor who is a
subsequent holder of Registrable Securities. 
 “Investor Information” has the meaning set forth in Section 5(b). 

“Liquidated Damages” has the meaning set forth in Section 2(d)(ii). 

“Losses” has the meaning set forth in Section 5(a). 

“Maintenance Failure” has the meaning set forth in Section 2(d)(ii). 

“Maintenance Liquidated Damages” has the meaning set forth in Section 2(d)(ii). 

“Prospectus” means (i) the prospectus included in any Registration Statement, as amended or supplemented by any prospectus supplement,
with respect to the terms of the offering of any portion of the Registrable Securities covered by such Registration Statement and by all other amendments and supplements to the prospectus, including post-effective amendments and all material
incorporated by reference in such prospectus, and (ii) any “free writing prospectus” as defined in Rule 405 under the 1933 Act. 

  
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 “Purchase Agreement” has the meaning set forth in the first paragraph. 

“Qualification Date” has the meaning set forth in Section 2(a)(ii). 

“Qualification Deadline” has the meaning set forth in Section 2(a)(ii). 

“Questionnaire” has the meaning set forth in Section 4(a). 

“Records” has the meaning set forth in Section 3(j). 

“Register,” “registered” and “registration” refer to a registration made by preparing and filing a
Registration Statement or similar document in compliance with the 1933 Act, and the declaration or ordering of effectiveness of such Registration Statement or document. 

“Registrable Securities” means (i) the Shares, (ii) the Warrant Shares and (iii) any other securities issued or issuable with
respect to or in exchange for Shares or Warrant Shares, whether by merger, charter amendment or otherwise; provided, that a security shall cease to be a Registrable Security upon (A) sale pursuant to a Registration Statement or Rule 144 under
the 1933 Act, or (B) such security becoming eligible for sale without restriction by the Investor holding such security pursuant to Rule 144, including without any manner of sale or volume limitations, and without the requirement to be in
compliance with Rule 144(c)(1) (or any successor thereto) promulgated under the 1933 Act. 
 “Registration Liquidated Damages” has the
meaning set forth in Section 2(d)(i). 
 “Registration Statement” means any registration statement of the Company under the 1933 Act
that covers the resale of any of the Registrable Securities pursuant to the provisions of this Agreement, amendments and supplements to such Registration Statement, including post-effective amendments, all exhibits and all material incorporated by
reference in such Registration Statement. 
 “Required Investors” means the Investors holding a majority of the Registrable Securities
outstanding from time to time. 
 “Restriction Termination Date” has the meaning set forth in Section 2(e). 

“SEC” means the U.S. Securities and Exchange Commission. 

“SEC Restrictions” has the meaning set forth in Section 2(e). 

“Shelf Registration Statement” has the meaning set forth in Section 2(a)(ii). 

2. Registration. 
 (a) Registration Statements.

 (i) Promptly following the Closing Date but no later than thirty (30) days after the Closing Date (the “Filing Deadline”), the
Company shall prepare and file with the SEC one Registration Statement covering the resale of all of the Registrable Securities. Subject to any SEC comments, such Registration Statement shall include the plan of distribution attached hereto as
Exhibit A; provided, however, that no Investor shall be named as an “underwriter” in such Registration Statement without the Investor’s prior written consent. Such Registration Statement also shall cover, to the extent allowable
under the 1933 Act and the rules promulgated thereunder (including Rule 416), such indeterminate number of additional shares of Common Stock resulting from stock splits, stock dividends or similar transactions with respect to the Registrable
Securities. Such Registration Statement shall not include any shares of Common Stock or other securities for the account of any other holder without the prior written consent of the Required Investors. Such Registration Statement (and each amendment
or supplement thereto, and each request for acceleration of effectiveness thereof) shall be provided in accordance with Section 3(c) to the Investors prior to its filing or other submission. 

  
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 (ii) The Registration Statement referred to in Section 2(a)(i) shall be on Form S-3. In the event that Form S-3 is not available for the registration of the resale of Registrable Securities hereunder, the Company shall (i) register the resale of the
Registrable Securities on such other form as is available to the Company and (ii) so long as Registrable Securities remain outstanding, promptly following the date (the “Qualification Date”) upon which the Company becomes
eligible to use a registration statement on Form S-3 to register the Registrable Securities for resale, but in no event more than thirty (30) days after the Qualification Date (the “Qualification
Deadline”), file a registration statement on Form S-3 covering the Registrable Securities (or a post-effective amendment on Form S-3 to a registration statement
on Form S-1) (a “Shelf Registration Statement”) and use commercially reasonable efforts to cause such Shelf Registration Statement to be declared effective as promptly as practicable
thereafter; provided that the Company shall maintain the effectiveness of the Registration Statement then in effect until such time as a Shelf Registration Statement covering the Registrable Securities has been declared effective by the SEC. 

(b) Expenses. The Company will pay all expenses associated with each Registration Statement, including filing and printing fees, the Company’s
counsel and accounting fees and expenses, costs associated with clearing the Registrable Securities for sale under applicable state securities laws and listing fees, but excluding discounts, commissions, fees of underwriters, selling brokers, dealer
managers or similar securities industry professionals with respect to the Registrable Securities being sold. 
 (c) Effectiveness. 

(i) The Company shall use commercially reasonable efforts to have each Registration Statement declared effective as soon as practicable after such
Registration Statement has been filed with the SEC, but no later than the Effectiveness Deadline. By 5:30 p.m. (Eastern time) on the second Business Day following the date on which the Registration Statement is declared effective by the SEC, the
Company shall file with the SEC, in accordance with Rule 424 under the 1933 Act, the final prospectus to be used in connection with sales pursuant to such Registration Statement. The Company shall notify the Investors by e-mail as promptly as practicable, and in any event within twenty-four (24) hours, after any Registration Statement is declared effective and shall simultaneously provide the Investors with copies of any
related Prospectus to be used in connection with the sale or other disposition of the securities covered thereby. 
 (ii) For not more than thirty
(30) consecutive days or for a total of not more than sixty (60) days in any twelve (12) month period, the Company may, on no more than two occasions, suspend the use of any Prospectus included in any Registration Statement
contemplated by this Section 2 in the event that the Company determines in good faith that such suspension is necessary to (A) delay the disclosure of material nonpublic information concerning the Company, the disclosure of which at the
time is not, in the good faith opinion of the Company, in the best interests of the Company or (B) amend or supplement the affected Registration Statement or the related Prospectus so that such Registration Statement or Prospectus shall not
include an untrue statement of a material fact or omit to state a material fact required to be stated therein or necessary to make the statements therein, in the case of the Prospectus in light of the circumstances under which they were made, not
misleading (an “Allowed Delay”); provided, that the Company shall promptly (a) notify each Investor in writing of the commencement of an Allowed Delay, but shall not (without the prior written consent of an Investor) disclose
to such Investor any material nonpublic information giving rise to an Allowed Delay, (b) advise the Investors in writing to cease all sales under such Registration Statement until the end of the Allowed Delay and (c) use commercially
reasonable efforts to terminate an Allowed Delay as promptly as practicable. 
 (d) Effect of Failure to File and Obtain and Maintain Effectiveness of
Registration Statement. 
 (i) If a Registration Statement covering the Registrable Securities is not filed with the SEC on or prior to the Filing
Deadline, the Company will make pro rata payments to each Investor then holding Registrable Securities, as liquidated damages and not as a penalty (the “Registration Liquidated Damages”), in an amount equal to one percent (1.0%) of
the aggregate amount invested by such Investor for the initial day of failure to file such Registration Statement by the Filing Deadline and for each 30-day period (or pro rata portion thereof with respect to
a final period, if any) thereafter during which no such Registration Statement is filed with respect to the Registrable Securities. Such payments shall be made to each Investor then holding Registrable Securities in cash no later than ten
(10) Business Days after the end of the date of the initial failure to file such Registration Statement by the Filing Deadline and each subsequent 30-day period (or portion thereof with respect to a final
period, if any) thereafter until such Registration Statement is filed with respect to the Registrable Securities. Interest shall accrue at the rate of one percent (1.0%) per month on any such liquidated damages payments that shall not be paid by the
applicable payment date until such amount is paid in full. 

  
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 (ii) If (A) a Registration Statement covering the Registrable Securities is not declared effective by
the SEC (x) prior to the earlier of five (5) Business Days after the SEC informs the Company that no review of such Registration Statement will be made or that the SEC has no further comments on such Registration Statement or (y) the
Effectiveness Deadline or (B) after a Registration Statement has been declared effective by the SEC, sales cannot be made pursuant to such Registration Statement for any reason (including, without limitation, by reason of a stop order or the
Company’s failure to update such Registration Statement), but excluding any Allowed Delay or the inability of any Investor to sell the Registrable Securities covered thereby due to market conditions (each of (A) and (B), a
“Maintenance Failure”), then the Company will make pro rata payments to each Investor then holding Registrable Securities, as liquidated damages and not as a penalty (the “Maintenance Liquidated Damages” and
together with the Registration Liquidated Damages, the “Liquidated Damages”), in an amount equal to one percent (1.0%) of the aggregate amount invested by such Investor for the Registrable Securities then held by such Investor for
the initial day of a Maintenance Failure and for each 30-day period (or pro rata portion thereof with respect to a final period, if any) thereafter until the Maintenance Failure is cured. The Maintenance
Liquidated Damages shall be paid monthly within ten (10) Business Days of the date of such Maintenance Failure and the end of each subsequent 30-day period (or portion thereof with respect to a final
period, if any) thereafter until the Maintenance Failure is cured. Such payments shall be made to each Investor then holding Registrable Securities in cash. Interest shall accrue at the rate of one percent (1%) per month on any such liquidated
damages payments that shall not be paid by the applicable payment date until such amount is paid in full. 
 (iii) The parties agree that
(1) notwithstanding anything to the contrary herein or in the Purchase Agreement, no Liquidated Damages shall be payable with respect to any period after the expiration of the Effectiveness Period (as defined below) (it being understood that
this sentence shall not relieve the Company of any Liquidated Damages accruing prior to the expiration of the Effectiveness Period), and in no event shall the aggregate amount of Liquidated Damages payable to an Investor exceed, in the aggregate,
six percent (6.0%) of the aggregate purchase price paid by such Investor pursuant to the Purchase Agreement and (2) in no event shall the Company be liable in any thirty (30) day period for Liquidated Damages under this Agreement in excess
of one percent (1.0%) of the aggregate purchase price paid by the Investors pursuant to the Purchase Agreement. 
 (iv) Notwithstanding the foregoing, the
Company and the Investors agree that the Company will not be liable for any liquidated damages under this Section 2(d) with respect to any Registrable Securities prior to their issuance. The Liquidated Damages described in this
Section 2(d) shall constitute the Investors’ exclusive monetary remedy for any failure to meet the Filing Deadline and for any Maintenance Failure, but shall not affect the right of the Investors to seek injunctive relief. 

(e) Rule 415; Cutback. If at any time the SEC takes the position that the offering of some or all of the Registrable Securities in a Registration
Statement is a primary offering or not eligible to be made on a delayed or continuous basis under the provisions of Rule 415 under the 1933 Act, or requires any Investor to be named as an “underwriter,” the Company shall use commercially
reasonable efforts to advocate before the SEC its reasonable position that the offering contemplated by such Registration Statement is a valid secondary offering and not an offering “by or on behalf of the issuer” as defined in Rule 415 (a
“Constructive Primary Offering”) and that none of the Investors is an “underwriter.” The Investors shall have the right to review and oversee any registration or matters pursuant to this Section 2(e), including
participation in any meetings or discussions with the SEC regarding the SEC’s position and to comment on any written submission made to the SEC with respect thereto. In the event that, despite the Company’s commercially reasonable efforts,
the SEC does not alter its position, the Company shall (i) remove from such Registration Statement such portion of the Registrable Securities (the “Cut Back Shares”) and/or (ii) agree to such restrictions and limitations
on the registration and resale of the Registrable Securities as the SEC may require to assure the Company’s compliance with the requirements of Rule 415 (collectively, the “SEC Restrictions”); provided, however, that the
Company shall not agree to name any Investor as an “underwriter” in such Registration Statement without the prior written consent of such Investor. Any cut-back imposed on the Investors pursuant to
this Section 2(e) shall be allocated among the Investors on a pro rata basis and shall be applied first to any of the Registrable Securities of such Investor as such Investor shall designate, unless the SEC Restrictions otherwise require or
provide or the Investors otherwise agree. The parties agree that the Company’s 

  
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delay or failure to have a Registration Statement declared effective due to the SEC taking the position that the offering is a Constructive Primary Offering shall not be a breach of any provision
of this Agreement and no liquidated damages shall accrue as to any Cut Back Shares. From and after such date as the Company is able to effect the registration of such Cut Back Shares in accordance with any SEC Restrictions applicable to such Cut
Back Shares (such date, the “Restriction Termination Date”), all of the provisions of this Section 2 (including the Company’s obligations with respect to the filing of a Registration Statement and its obligations to use
commercially reasonable efforts to have such Registration Statement declared effective within the time periods set forth herein and the liquidated damages provisions relating thereto) shall again be applicable to such Cut Back Shares; provided,
however, (i) that the Filing Deadline and/or the Qualification Deadline, as applicable, for such Registration Statement including such Cut Back Shares shall be ten (10) Business Days after such Restriction Termination Date, and
(ii) the date by which the Company is required to obtain effectiveness with respect to such Cut Back Shares under Section 2(c) shall be the 90th day immediately after the Restriction Termination Date (or the 120th day if the SEC reviews
such Registration Statement). 
 3. Company Obligations. The Company will use commercially reasonable efforts to effect the registration of the
Registrable Securities in accordance with the terms hereof, and pursuant thereto the Company will, as expeditiously as possible: 
 (a) use commercially
reasonable efforts to cause such Registration Statement to become effective and to remain continuously effective for a period that will terminate upon the earlier of (i) the date on which all Registrable Securities covered by such Registration
Statement, as amended from time to time, have been sold, and (ii) the date on which all Shares and Warrant Shares cease to be Registrable Securities (the “Effectiveness Period”); 

(b) prepare and file with the SEC such amendments and post-effective amendments to such Registration Statement and the related Prospectus as may be necessary
to keep such Registration Statement effective for the Effectiveness Period and to comply with the provisions of the 1933 Act and the 1934 Act with respect to the distribution of all of the Registrable Securities covered thereby; 

(c) provide copies to and permit each Investor to review each Registration Statement and all amendments and supplements thereto prior to their filing with the
SEC and a reasonable opportunity to furnish comments thereon; 
 (d) furnish to each Investor whose Registrable Securities are included in any Registration
Statement (i) promptly after the same is prepared and filed with the SEC, if requested by the Investor, one (1) copy of any Registration Statement and any amendment thereto, each preliminary prospectus and Prospectus and each amendment or
supplement thereto, and each letter written by or on behalf of the Company to the SEC or the staff of the SEC, and each item of correspondence from the SEC or the staff of the SEC, in each case relating to such Registration Statement (other than any
portion thereof which contains information for which the Company has sought confidential treatment), and (ii) such number of copies of a Prospectus, including a preliminary prospectus, and all amendments and supplements thereto and such other
documents as each Investor may reasonably request in order to facilitate the disposition of the Registrable Securities owned by such Investor that are covered by such Registration Statement; 

(e) use commercially reasonable efforts to (i) prevent the issuance of any stop order or other suspension of effectiveness and, (ii) if such order
is issued, obtain the withdrawal of any such order at the earliest practical moment; 
 (f) use commercially reasonable efforts to cause all Registrable
Securities covered by a Registration Statement to be listed on each securities exchange, interdealer quotation system or other market on which similar securities issued by the Company are then listed; 

(g) promptly notify the Investors, at any time prior to the end of the Effectiveness Period, upon discovery that, or upon the happening of any event as a
result of which, the Prospectus includes an untrue statement of a material fact or omits to state any material fact required to be stated therein or necessary to make the statements therein not misleading in light of the circumstances then existing
(provided that such notice shall not, without the prior written consent of an Investor, disclose to such Investor any material nonpublic information regarding the Company), and promptly prepare, file with the SEC and furnish to such holder a
supplement to or an amendment of such Prospectus as may be necessary so that such Prospectus shall not include an untrue statement of a material fact or omit to state a material fact required to be stated therein or necessary to make the statements
therein not misleading in light of the circumstances then existing; 

  
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 (h) otherwise use commercially reasonable efforts to comply with all applicable rules and regulations of the
SEC under the 1933 Act and the 1934 Act, including, without limitation, Rule 172 under the 1933 Act, file any final Prospectus, including any supplement or amendment thereof, with the SEC pursuant to Rule 424 under the 1933 Act, promptly inform the
Investors in writing if, at any time during the Effectiveness Period, the Company does not satisfy the conditions specified in Rule 172 and, as a result thereof, the Investors are required to deliver a Prospectus in connection with any disposition
of Registrable Securities and take such other actions as may be reasonably necessary to facilitate the registration of the Registrable Securities hereunder; and make available to its security holders, as soon as reasonably practicable, an earnings
statement covering satisfying the provisions of Section 11(a) of the 1933 Act; 
 (i) if requested by an Investor, the Company shall (i) as soon
as practicable, incorporate in a prospectus supplement or post-effective amendment such information as an Investor reasonably requests to be included therein relating to the sale and distribution of Registrable Securities, including, without
limitation, information with respect to the number of Registrable Securities being offered or sold, the purchase price being paid therefor and any other terms of the offering of the Registrable Securities to be sold in such offering; (ii) as
soon as practicable, make all required filings of such prospectus supplement or post-effective amendment after being notified of the matters to be incorporated in such prospectus supplement or post-effective amendment; and (iii) as soon as
practicable, supplement or make amendments to any Registration Statement if reasonably requested by an Investor holding any Registrable Securities; 
 (j)
within two (2) Business Days after a Registration Statement which covers Registrable Securities is ordered effective by the SEC, the Company shall deliver to the transfer agent for such Registrable Securities (with copies to the Investors whose
Registrable Securities are included in such Registration Statement) confirmation that such Registration Statement has been declared effective by the SEC; 

(k) make available upon reasonable prior notice during normal business hours and for reasonable periods for inspection by the Investors and by any attorney,
accountant or other agent retained by the Investors and who is reasonably acceptable to the Company (collectively, the “Inspectors”), all pertinent financial and other records and pertinent corporate documents and properties of the
Company (collectively, the “Records”) as may be reasonably necessary for the purpose of such review, and cause the Company’s officers, directors and employees and the independent public accountants who have certified its
financial statements to make themselves available to discuss the business of the Company and to supply all information reasonably requested by the Inspectors for the sole purpose of conducting initial and ongoing due diligence with respect to the
Company and the accuracy of the Registration Statement; provided, however, that each Investor shall agree to, and to direct its Inspectors to, hold in strict confidence and shall not make any disclosure or use of any Record or other information
which the Company determines in good faith to be confidential, and of which determination the Inspectors are so notified, unless (a) the disclosure of such Records is necessary to avoid or correct a misstatement or omission in any Registration
Statement or is otherwise required under the 1933 Act, (b) the release of such Records is ordered pursuant to a final, non-appealable subpoena or order from a court or government body of competent
jurisdiction, or (c) the information in such Records has been made generally available to the public other than by disclosure in violation of this Section 3(j). Notwithstanding the foregoing, the Company shall not disclose material
nonpublic information to the Investors, or to advisors to or representatives of the Investors, unless prior to disclosure of such information the Company identifies such information as being material nonpublic information and provides the Investors,
such advisors and such representatives with the opportunity to accept or refuse to accept such material nonpublic information for review and any Investor wishing to obtain such information enters into an appropriate confidentiality agreement with
the Company with respect thereto; and 
 (l) with a view to making available to the Investors the benefits of Rule 144 (or its successor rule) and any other
rule or regulation of the SEC that may at any time permit the Investors to sell shares of Common Stock to the public without registration, the Company covenants and agrees to: (i) make and keep adequate current public information available, as
those terms are understood and defined in Rule 144, until the earlier of (A) six months after such date as all of the Registrable Securities may be sold without restriction by the holders thereof pursuant to Rule

  
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144 or any other rule of similar effect or (B) such date as all of the Registrable Securities shall have been resold; (ii) file with the SEC in a timely manner all reports and other
documents required of the Company under the 1934 Act; and (iii) furnish to each Investor upon request, as long as such Investor owns any Registrable Securities, (A) a written statement by the Company that it has complied with the reporting
requirements of the 1934 Act, (B) a copy of the Company’s most recent Annual Report on Form 10-K or Quarterly Report on Form 10-Q, and (C) such other
information as may be reasonably requested in order to avail such Investor of any rule or regulation of the SEC that permits the selling of any such Registrable Securities without registration. 

4. Obligations of the Investors. 
 (a) Notwithstanding
any other provision of the Agreement, no Investor may include any of its Registrable Securities in the Registration Statement pursuant to this Agreement unless such Investor furnishes to the Company a completed questionnaire substantially in the
form of Exhibit B (the “Questionnaire”) for use in connection with the Registration Statement at least five (5) Business Days prior to the anticipated filing date of the Registration Statement if such Investor elects to have
any of the Registrable Securities included in such Registration Statement. In addition to the Questionnaire, each Investor shall furnish such other information as shall be reasonably required to effect the registration of such Registrable
Securities, and shall execute such documents in connection with such registration as the Company may reasonably request. 
 (b) Each Investor, by its
acceptance of the Registrable Securities, agrees to cooperate with the Company as reasonably requested by the Company in connection with the preparation and filing of a Registration Statement hereunder, unless such Investor has notified the Company
in writing of its election to exclude all of its Registrable Securities from such Registration Statement. 
 (c) Each Investor agrees that, upon receipt of
any notice from the Company of either (i) the commencement of an Allowed Delay pursuant to Section 2(c)(ii) or (ii) the happening of an event pursuant to Section 3(g) hereof, such
Investor will immediately discontinue disposition of Registrable Securities pursuant to any Registration Statement covering such Registrable Securities, until the Investor is advised by the Company that such dispositions may again be made, provided
that, no Holder shall be required to discontinue disposition of Registrable Securities under a Registration Statement by virtue of the delivery by the Company of a notice of the occurrence of any event of the kind described in
Section 2(c)(ii) on more than two occasions or for more than thirty (30) consecutive days or for more than sixty (60) total calendar days, in each case during any twelve-month period. 

(d) Each Investor covenants and agrees that it will comply with the prospectus delivery requirements of the 1933 Act as applicable to it or an exemption
therefrom in connection with sales of Registrable Securities pursuant to any Registration Statement. 
 5. Indemnification. 

(a) Indemnification by the Company. The Company will indemnify and hold harmless each Investor and its officers, directors, members, employees and
agents, and each other person, if any, who controls such Investor within the meaning of the 1933 Act, against any losses, claims, damages or liabilities (collectively, “Losses”), joint or several, to which they may become subject
under the 1933 Act or otherwise, insofar as such Losses (or actions in respect thereof) arise out of or are based upon (i) any untrue or alleged untrue statement of any material fact contained in any Registration Statement, any preliminary
Prospectus or final Prospectus, or any amendment or supplement thereof, (ii) any omission or alleged omission of a material fact required to be stated therein or necessary to make the statements in any preliminary Prospectus or final
Prospectus, or any amendment or supplement thereof, in light of the circumstances under which they were made not misleading or (iii) any violation or alleged violation by the Company or any of its subsidiaries of any federal, state, foreign or
common law rule or regulation applicable to the Company or any of its subsidiaries and relating to action or inaction in connection with any such registration, disclosure document or other document or report, except to the extent that any such
Losses arise out of or are based upon (i) an untrue statement or alleged untrue statement or omission or alleged omission so made in conformity with Investor Information, (ii) the use by an Investor of an outdated or defective Prospectus
after the Company has notified such Investor in writing that such Prospectus is outdated or defective; or (iii) an Investor’s failure to send or give a copy of the Prospectus or supplement (as then amended or supplemented), if required
(and not exempted) to the Persons asserting an untrue statement or omission or alleged untrue statement or omission at or prior to the written confirmation of the sale of Registrable Securities. 

  
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 (b) Indemnification by the Investors. Each Investor agrees, severally but not jointly, to indemnify
and hold harmless, to the fullest extent permitted by law, the Company, its directors, officers, employees, stockholders and each person who controls the Company (within the meaning of the 1933 Act) against any Losses resulting from any untrue
statement of a material fact or any omission of a material fact required to be stated in any Registration Statement or Prospectus or preliminary Prospectus or amendment or supplement thereto or necessary to make the statements therein not
misleading, to the extent, but only to the extent that such untrue statement or omission is contained in any information furnished in writing by such Investor, relating to such Investor, to the Company specifically for inclusion in such Registration
Statement or Prospectus or amendment or supplement thereto (“Investor Information”). In no event shall the liability of an Investor be greater in amount than the dollar amount of the proceeds (net of all expense paid by such
Investor in connection with any claim relating to this Section 5 and the amount of any damages such Investor has otherwise been required to pay by reason of such untrue statement or omission) received by such Investor upon the sale of the
Registrable Securities included in such Registration Statement giving rise to such indemnification obligation. 
 (c) Conduct of Indemnification
Proceedings. Any person entitled to indemnification hereunder shall (i) give prompt written notice to the indemnifying party of any claim with respect to which it seeks indemnification and (ii) permit such indemnifying party to assume
the defense of such claim with counsel reasonably satisfactory to the indemnified party; provided that any person entitled to indemnification hereunder shall have the right to employ separate counsel and to participate in the defense of such claim,
but the fees and expenses of such counsel shall be at the expense of such person unless (a) the indemnifying party has agreed in writing to pay such fees or expenses, (b) the indemnifying party shall have failed to assume the defense of
such claim and employ counsel reasonably satisfactory to such person or (c) in the reasonable judgment of any such person, based upon written advice of its counsel, a conflict of interest exists between such person and the indemnifying party
with respect to such claims (in which case, if the person notifies the indemnifying party in writing that such person elects to employ separate counsel at the expense of the indemnifying party, the indemnifying party shall not have the right to
assume the defense of such claim on behalf of such person); and provided, further, that the failure of any indemnified party to give written notice as provided herein shall not relieve the indemnifying party of its obligations hereunder, except to
the extent that such failure to give notice shall materially adversely affect the indemnifying party in the defense of any such claim or litigation. It is understood that the indemnifying party shall not, in connection with any proceeding in the
same jurisdiction, be liable for fees or expenses of more than one separate firm of attorneys at any time for all such indemnified parties. No indemnifying party will, except with the consent of the indemnified party, which shall not be unreasonably
withheld or conditioned, consent to entry of any judgment or enter into any settlement that 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. 
 (d) Contribution. If for any reason the indemnification provided for in the preceding paragraphs (a) and
(b) is unavailable to an indemnified party or insufficient to hold it harmless, other than as expressly specified therein, then the indemnifying party shall contribute to the amount paid or payable by the indemnified party as a result of such loss,
claim, damage or liability in such proportion as is appropriate to reflect the relative fault of the indemnified party and the indemnifying party, as well as any other relevant equitable considerations. No person guilty of fraudulent
misrepresentation within the meaning of Section 11(f) of the 1933 Act shall be entitled to contribution from any person not guilty of such fraudulent misrepresentation. In no event shall the contribution obligation of an Investor be greater in
amount than the dollar amount of the proceeds (net of all expenses paid by such holder in connection with any claim relating to this Section 5 and the amount of any damages such holder has otherwise been required to pay by reason of such untrue
or alleged untrue statement or omission or alleged omission) received by it upon the sale of the Registrable Securities giving rise to such contribution obligation. 

6. Miscellaneous. 
 (a) Effective Date. This
Agreement shall be effective as of the Closing. If, prior to the Closing, (i) the Purchase Agreement is terminated with respect to all parties thereto pursuant to Section 6.3 therein, then this Agreement shall be null and void; or
(ii) any Investor (with respect to itself only) terminates its obligations under the Purchase Agreement pursuant to Section 6.3(a)(ii) therein, then such Investor’s rights and obligations under this Agreement shall also be terminated,
in each case, unless otherwise mutually agreed. 

  
 8 

 (b) Amendments and Waivers. This Agreement may be amended only by a writing signed by the Company and
the Required Investors. The Company may take any action herein prohibited, or omit to perform any act herein required to be performed by it, only if the Company shall have obtained the written consent to such amendment, action or omission to act of
the Required Investors. 
 (c) Notices. All notices and other communications provided for or permitted hereunder shall be made as set forth in
Section 9.4 of the Purchase Agreement. 
 (d) Assignments and Transfers by Investors. The provisions of this Agreement shall be binding upon and
inure to the benefit of the Investors and their respective successors and assigns. An Investor may transfer or assign, in whole or from time to time in part, to one or more persons its rights hereunder in connection with the transfer of Registrable
Securities by such Investor to such person, provided that such Investor complies with all laws applicable thereto, and the provisions of the Purchase Agreement, and provides written notice of assignment to the Company promptly after such assignment
is effected, and such person agrees in writing to be bound by all of the provisions contained herein. 
 (e) Assignments and Transfers by the
Company. This Agreement may not be assigned by the Company (whether by operation of law or otherwise) without the prior written consent of the Required Investors, provided, however, that in the event that the Company is a party to a merger,
consolidation, share exchange or similar business combination transaction in which the Common Stock is converted into the equity securities of another Person, from and after the effective time of such transaction, such Person shall, by virtue of
such transaction, be deemed to have assumed the obligations of the Company hereunder, the term “Company” shall be deemed to refer to such Person and the term “Registrable Securities” shall be deemed to include the securities
received by the Investors in connection with such transaction unless such securities are otherwise freely tradable by the Investors after giving effect to such transaction. 

(f) Benefits of the Agreement. The terms and conditions of this Agreement shall inure to the benefit of and be binding upon the respective permitted
successors and assigns of the parties. Nothing in this Agreement, express or implied, is intended to confer upon any party other than the parties hereto or their respective successors and assigns any rights, remedies, obligations, or liabilities
under or by reason of this Agreement, except as expressly provided in this Agreement. 
 (g) Counterparts. This Agreement may be executed in two or
more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. Counterparts may be delivered via facsimile, electronic mail (including pdf or any electronic signatures complying
with the U.S. federal ESIGN Act of 2000, e.g., www.docusign.com) or other transmission method and any counterpart so delivered shall be deemed to have been duly and validly delivered and be valid and effective for all purposes. 

(h) Titles and Subtitles. The titles and subtitles used in this Agreement are used for convenience only and are not to be considered in construing or
interpreting this Agreement. 
 (i) Severability. Any provision of this Agreement that is prohibited or unenforceable in any jurisdiction shall, as
to such jurisdiction, be ineffective to the extent of such prohibition or unenforceability without invalidating the remaining provisions hereof but shall be interpreted as if it were written so as to be enforceable to the maximum extent permitted by
applicable law, and any such prohibition or unenforceability in any jurisdiction shall not invalidate or render unenforceable such provision in any other jurisdiction. To the extent permitted by applicable law, the parties hereby waive any provision
of law which renders any provisions hereof prohibited or unenforceable in any respect. 

  
 9 

 (j) Further Assurances. The parties shall execute and deliver all such further instruments and
documents and take all such other actions as may reasonably be required to carry out the transactions contemplated hereby and to evidence the fulfillment of the agreements herein contained. 

(k) Entire Agreement. This Agreement is intended by the parties as a final expression of their agreement and intended to be a complete and exclusive
statement of the agreement and understanding of the parties hereto in respect of the subject matter contained herein. This Agreement supersedes all prior agreements and understandings between the parties with respect to such subject matter. 

(l) Governing Law. This Agreement shall be governed by, and construed in accordance with, the laws of the State of Delaware. Service of process in
connection with any such suit, action or proceeding may be served on each party hereto anywhere in the world by the same methods as are specified for the giving of notices under this Agreement. 

(m) Cumulative Remedies. The remedies provided herein are cumulative and not exclusive of any remedies provided by law. 

[remainder of page intentionally left blank] 

  
 10 

 IN WITNESS WHEREOF, the parties have executed this Agreement or caused their duly authorized officers to
execute this Agreement as of the date first above written. 
  

					
	COMPANY:	 		 	
		
		 	 SYROS PHARMACEUTICALS, INC.

			
		 	By:	 	/s/ Nancy Simonian
		 		 	Name: Nancy Simonian
		 		 	Title: Chief Executive Officer
		
	INVESTOR:	 	 667, L.P.

			
		 	By:	 	BAKER BROS. ADVISORS LP, management company and investment adviser to 667, L.P., pursuant to authority granted to it by Baker Biotech Capital, L.P., general partner to 667, L.P., and not as the general partner.
			
		 	By:	 	/s/ Scott Lessing
		 		 	Name: Scott Lessing
		 		 	Title: President
		
	INVESTOR:	 	 BAKER BROTHERS LIFE SCIENCES, L.P.

			
		 	By:	 	BAKER BROS. ADVISORS LP, management company and investment adviser to Baker Brothers Life Sciences, L.P., pursuant to authority granted to it by Baker Brothers Life Sciences Capital, L.P., general partner to Baker Brothers Life
Sciences, L.P., and not as the general partner.
			
		 	By:	 	/s/ Scott Lessing
		 		 	Name: Scott Lessing
		 		 	Title: President
		
	INVESTOR:	 	 AVIDITY MASTER FUND LP

			
		 	By:	 	Avidity Capital Partners Fund (GP) LP, its general partner
			
		 	By:	 	Avidity Capital Partners (GP) LLC, its general partner
			
		 	By:	 	/s/ Michael Gregory
		 		 	Name: Michael Gregory
		 		 	Title: Managing Member

  
 [Signature Page to
Registration Rights Agreement] 

					
		
	INVESTOR:	 	AVIDITY CAPITAL FUND II LP
			
		 	 By:
	 	 Avidity Capital Partners Fund (GP) LP, its general partner

			
		 	 By:
	 	 Avidity Capital Partners (GP) LLC, its general partner

			
		 	 By:
	 	 /s/ Michael Gregory

		 		 	 Name: Michael Gregory

		 		 	 Title:   Managing Member

		
	INVESTOR:	 	AVIDITY CAPITAL HL SUB FUND III LLC
			
		 	 By:
	 	 Avidity Master Fund III LP, its managing member

			
		 	 By:
	 	 Avidity Capital Partners Fund (GP) LP, its general partner

			
		 	 By:
	 	 Avidity Capital Partners (GP) LLC, its general partner

			
		 	 By:
	 	 /s/ Michael Gregory

		 		 	 Name: Michael Gregory

		 		 	 Title:  Managing Member

		
	INVESTOR:	 	AVIDITY PRIVATE MASTER FUND I LP
			
		 	 By:
	 	 Avidity Capital Partners Fund (GP) LP, its general partner

			
		 	 By:
	 	 Avidity Capital Partners (GP) LLC, its general partner

			
		 	 By:
	 	 /s/ Michael Gregory

		 		 	 Name: Michael Gregory

		 		 	 Title:   Managing Member

		
	INVESTOR:	 	FLAGSHIP PIONEERING FUND VII, L.P.
			
		 	 By:
	 	 Flagship Pioneering Fund VII General Partner, LLC, its General Partner

			
		 	 By:
	 	 /s/ Charles Carelli

		 		 	 Name: Charles Carelli

		 		 	 Title:   Authorized Signatory

		
	INVESTOR:	 	DEEP TRACK BIOTECHNOLOGY MASTER FUND, LTD.
			
		 	 By:
	 	 /s/ Nir Messafi

		 		 	 Name: Nir Messafi

		 		 	 Title:Authorized Signatory

  
 [Signature Page to
Registration Rights Agreement] 

							
	INVESTOR:	 		 	 INVUS PUBLIC EQUITIES, L.P. 

				
		 		 	 By:
	 	 /s/ Khalil Barrage

		 		 		 	 Name: Khalil Barrage

		 		 		 	 Title: VP of the General Partner

			
	INVESTOR:	 		 	 BCLS II EQUITY OPPORTUNITIES, LP 

				
		 		 	 By:
	 	 BCLS II Equity Opportunities GP, LLC, its general partner

				
		 		 	 By:
	 	 Bain Capital Life Sciences Fund II, L.P., its manager

				
		 		 	 By:
	 	 Bain Capital Life Sciences Investors II, LLC, its general partner

				
		 		 	 By:
	 	 Bain Capital Life Sciences Investors, LLC, its manager

				
		 		 	 By:
	 	 /s/ Ricky Sun

		 		 		 	 Name: Ricky Sun

		 		 		 	 Title: Managing Director

			
	INVESTOR:	 		 	 SAMSARA BIOCAPITAL, LP 

				
		 		 	 By:
	 	 /s/ Srinivas Akkaraju

		 		 		 	 Name: Srinivas Akkaraju, PhD

		 		 		 	 Title: Managing Director,

		 		 		 	 Samsara BioCapital GP, LLC

			
	INVESTOR:	 		 	 CHI IV PUBLIC INVESTMENTS LP 

				
		 		 	 By:
	 	 CHI Advisors LLC, its investment manager

				
		 		 	 By:
	 	 /s/ Kevin Raidy

		 		 		 	 Name: Kevin Raidy

		 		 		 	 Title: Managing Partner

			
	INVESTOR:	 		 	 ALLY BRIDGE MEDALPHA MASTER FUND L.P. 

				
		 		 	 By:
	 	 Ally Bridge MedAlpha General Partner L.P., its general partner

				
		 		 	 By:
	 	 Ally Bridge MedAlpha GP, LLC, its general partner

				
		 		 	By:	 	/s/ Fan Yu
		 		 		 	Name: Fan Yu
		 		 		 	Title: Manager

  
 [Signature Page to
Registration Rights Agreement] 

					
		
	INVESTOR:	 	ADAGE CAPITAL PARTNERS LP
			
		 	By:	 	/s/ Dan Lehan
		 		 	Name: Dan Lehan
		 		 	Title: COO
		
	INVESTOR:	 	CVI INVESTMENTS, INC.
			
		 	By:	 	Heights Capital Management, Inc.,
		 		 	its authorized agent
			
		 	By:	 	/s/ Martin Kobinger
		 		 	Name: Martin Kobinger
		 		 	Title: President
		
	INVESTOR:	 	ALTIUM GROWTH FUND, LP
			
		 	By:	 	/s/ Mark Gottlieb
		 		 	Name: Mark Gottlieb
		 		 	Title: COO
		
	INVESTOR:	 	DAFNA LIFESCIENCE LP
			
		 	By:	 	/s/ Nathan Fischel
		 		 	Name: Nathan Fischel
		 		 	Title: CEO
		
	INVESTOR:	 	DAFNA LIFESCIENCE SELECT LP
			
		 	By:	 	/s/ Nathan Fischel
		 		 	Name: Nathan Fischel
		 		 	Title: CEO
		
	INVESTOR:	 	JALAA EQUITIES, LP
			
		 	By:	 	/s/ Jason Aryeh
		 		 	Name: JALAA Equities, LP
		 		 	Title: General Partner

 [Signature Page to Registration Rights Agreement] 

 EXHIBIT A 

Plan of Distribution 
 The selling
stockholders, which as used herein includes donees, pledgees, transferees or other successors-in-interest selling shares of common stock or interests in shares of common
stock received after the date of this prospectus from a selling stockholder as a gift, pledge, partnership distribution or other transfer, may, from time to time, sell, transfer or otherwise dispose of any or all of their shares of common stock or
interests in shares of common stock on any stock exchange, market or trading facility on which the shares are traded or in private transactions. These dispositions may be at fixed prices, at prevailing market prices at the time of sale, at prices
related to the prevailing market price, at varying prices determined at the time of sale, or at negotiated prices. 
 The selling stockholders may use any
one or more of the following methods when disposing of shares or interests therein: 
  

	 	•	 	 ordinary brokerage transactions and transactions in which the broker-dealer solicits purchasers;

  

	 	•	 	 block trades in which the broker-dealer will attempt to sell the shares as agent, but may position and resell a
portion of the block as principal to facilitate the transaction; 

  

	 	•	 	 purchases by a broker-dealer as principal and resale by the broker-dealer for its account; 

 

	 	•	 	 an exchange distribution in accordance with the rules of the applicable exchange; 

 

	 	•	 	 privately negotiated transactions; 

 

	 	•	 	 short sales; 

  

	 	•	 	 through the writing or settlement of options or other hedging transactions, whether through an options exchange
or otherwise; 

  

	 	•	 	 broker-dealers may agree with the selling stockholders to sell a specified number of such shares at a stipulated
price per share; 

  

	 	•	 	 a combination of any such methods of sale; and 

 

	 	•	 	 any other method permitted by applicable law. 

The selling stockholders may, from time to time, pledge or grant a security interest in some or all of the shares of common stock owned by them and, if they
default in the performance of their secured obligations, the pledgees or secured parties may offer and sell the shares of common stock, from time to time, under this prospectus, or under an amendment to this prospectus under Rule 424(b)(3) or other
applicable provision of the Securities Act of 1933, as amended (the “Securities Act”), amending the list of selling stockholders to include the pledgee, transferee or other successors in interest as selling stockholders under this
prospectus. The selling stockholders also may transfer the shares of common stock in other circumstances, in which case the transferees, pledgees, donees or other successors in interest will be the selling beneficial owners for purposes of this
prospectus. 
 In connection with the sale of our common stock or interests therein, the selling stockholders may enter into hedging transactions with
broker-dealers or other financial institutions, which may in turn engage in short sales of the common stock in the course of hedging the positions they assume. The selling stockholders may also sell shares of our common stock short and deliver these
securities to close out their short positions, or loan or pledge the common stock to broker-dealers that in turn may sell these securities. The selling stockholders may also enter into option or other transactions with broker-dealers or 

other financial institutions or the creation of one or more derivative securities which require the delivery to such broker-dealer or other financial
institution of shares offered by this prospectus, which shares such broker-dealer or other financial institution may resell pursuant to this prospectus (as supplemented or amended to reflect such transaction). 

The aggregate proceeds to the selling stockholders from the sale of the common stock offered by them will be the purchase price of the common stock less
discounts or commissions, if any. Each of the selling stockholders reserves the right to accept and, together with their agents from time to time, to reject, in whole or in part, any proposed purchase of common stock to be made directly or through
agents. We will not receive any of the proceeds from this offering. Upon any exercise of the warrants by payment of cash, however, we will receive the exercise price of the warrants. 

 The selling stockholders also may resell all or a portion of the shares in open market transactions in
reliance upon Rule 144 under the Securities Act of 1933, provided that they meet the criteria and conform to the requirements of that rule. 
 The selling
stockholders and any underwriters, broker-dealers or agents that participate in the sale of the common stock or interests therein may be “underwriters” within the meaning of Section 2(11) of the Securities Act. Any discounts,
commissions, concessions or profit they earn on any resale of the shares may be underwriting discounts and commissions under the Securities Act. Selling stockholders who are “underwriters” within the meaning of Section 2(11) of the
Securities Act will be subject to the prospectus delivery requirements of the Securities Act. 
 To the extent required, the shares of our common stock to
be sold, the names of the selling stockholders, the respective purchase prices and public offering prices, the names of any agents, dealer or underwriter, and any applicable commissions or discounts with respect to a particular offer will be set
forth in an accompanying prospectus supplement or, if appropriate, a post-effective amendment to the registration statement that includes this prospectus. 

In order to comply with the securities laws of some states, if applicable, the common stock may be sold in these jurisdictions only through registered or
licensed brokers or dealers. In addition, in some states the common stock may not be sold unless it has been registered or qualified for sale or an exemption from registration or qualification requirements is available and is complied with. 

We have advised the selling stockholders that the anti-manipulation rules of Regulation M under the Securities Exchange Act of 1934, as amended, may apply to
sales of shares in the market and to the activities of the selling stockholders and their affiliates. In addition, to the extent applicable, we will make copies of this prospectus (as it may be supplemented or amended from time to time) available to
the selling stockholders for the purpose of satisfying the prospectus delivery requirements of the Securities Act. The selling stockholders may indemnify any broker-dealer that participates in transactions involving the sale of the shares against
certain liabilities, including liabilities arising under the Securities Act. 
 We have agreed to indemnify the selling stockholders against liabilities,
including liabilities under the Securities Act and state securities laws, relating to the registration of the shares offered by this prospectus. 
 We have
agreed with the selling stockholders to use commercially reasonable efforts to cause the registration statement of which this prospectus constitutes a part effective and to remain continuously effective until the earlier of (1) such time as all
of the shares covered by this prospectus have been disposed of pursuant to and in accordance with such registration statement or (2) the date on which all of the shares may be sold without restriction pursuant to Rule 144 of the Securities Act.

 EXHIBIT B 

FORM OF 
 SELLING
SECURITYHOLDER QUESTIONNAIRE 
 Reference is made to that certain registration rights agreement (the “Registration Rights Agreement”),
dated as of July 3, 2022, by and among Syros Pharmaceuticals, Inc. (the “Company”), and
[                        ]. Capitalized terms used and not defined herein shall have the meanings given to such terms in
the Registration Rights Agreement. 
 The undersigned Holder (the “Selling Securityholder”) of the Registrable Securities is providing this
Selling Securityholder Questionnaire pursuant to Section 4(a) of the Registration Rights Agreement. The Selling Securityholder, by signing and returning this Selling Securityholder Questionnaire, understands that it will be bound by the terms
and conditions of this Selling Securityholder Questionnaire and the Registration Rights Agreement. The Selling Securityholder hereby acknowledges its indemnity obligations pursuant to Section 5(b) of the Registration Rights Agreement. 

The Selling Securityholder provides the following information to the Company and represents and warrants that such information is accurate and complete: 

 

	(1)	 (a)       Full Legal Name of Selling Securityholder: 

 

                      
                   
  

	 	(b)	 Full Legal Name of Registered Holder (if not the same as (a) above) through which Registrable Securities
listed in (3) below are held: 

  

                       
                  
  

	 	(c)	 Full Legal Name of DTC Participant (if applicable and if not the same as (b) above) through which
Registrable Securities listed in (3) below are held: 

  

                       
                  
  

	(2)	 Address for Notices to Selling Securityholder: 

 

                       
                  
  

                       
                  
 Telephone (including area code):
                                        

 Fax (including area code):
                                        

 Contact Person:
                                        

  

	(3)	 Beneficial Ownership of Registrable Securities: 

 

	 	(a)	 Type and Principal Amount/Number of Registrable Securities beneficially owned: 

 

                       
                  

	 	(b)	 CUSIP No(s). of such Registrable Securities beneficially owned: 

 

                       
                  
  

	(4)	 Beneficial Ownership of Other Securities of the Company Owned by the Selling Securityholder:

 Except as set forth below in this Item (4), the Selling Securityholder is not the beneficial or registered owner of
any securities of the Company other than the Registrable Securities listed above in Item (3). 
  

	 	(a)	 Type and Amount of Other Securities beneficially owned by the Selling Securityholder: 

 

                       
                  
  

	 	(b)	 CUSIP No(s). of such Other Securities beneficially owned: 

 

                       
                  
  

	(5)	 Relationship with the Company: 

Except as set forth below, neither the Selling Securityholder nor any of its affiliates, officers, directors or principal equity holders (5%
or more) has held any position or office or has had any other material relationship with the Company (or its predecessors or affiliates) during the past three years. 

State any exceptions here: 
  

                       
                  
  

	(6)	 Is the Selling Securityholder a registered broker-dealer? 

Yes     ☐ 

No      ☐ 

If “Yes”, please answer subsection (a) and subsection (b): 

 

	 	(a)	 Did the Selling Securityholder acquire the Registrable Securities as compensation for
underwriting/broker-dealer activities to the Company? 

 Yes     ☐ 

No      ☐ 
  

	 	(b)	 If you answered “No” to question 6(a), please explain your reason for acquiring the Registrable
Securities: 

  

                       
                  
  

                       
                  
  

	(7)	 Is the Selling Securityholder an affiliate of a registered broker-dealer? 

Yes     ☐ 

No      ☐ 

 If “Yes”, please identify the registered broker-dealer(s), describe the nature of
the affiliation(s) and answer subsection (a) and subsection (b): 
  

                       
                  
  

                       
                  
  

	 	(a)	 Did the Selling Securityholder purchase the Registrable Securities in the ordinary course of business (if no,
please explain)? 

  

	 	Yes	         ☐ 

 

	 	No	         ☐ 

 

                       
                  
  

                       
                  
  

	 	(b)	 Did the Selling Securityholder have an agreement or understanding, directly or indirectly, with any person to
distribute the Registrable Securities at the same time the Registrable Securities were originally purchased (if yes, please explain)? 

  

	 	Yes	         ☐ 

 

	 	No	         ☐ 

 

                       
                  
  

                       
                  
  

	(8)	 Is the Selling Securityholder a non-public entity?

 Yes        ☐ 

No         ☐ 

If “Yes”, please answer subsection (a): 
  

	 	(a)	 Identify the natural person or persons that have voting or investment control over the Registrable Securities
that the non-public entity owns: 

  

                       
                  
  

                       
                  
  

	(9)	 Plan of Distribution: 

The Selling Securityholder (including its transferees, donees, pledgees and other successors in interest) intends to distribute the Registrable Securities
listed above in Item (3) pursuant to the Registration Statement in accordance with the Plan of Distribution attached as Exhibit A to the Registration Rights Agreement ☐. 

The Selling Securityholder acknowledges that it understands its obligations to comply with the provisions of the Securities Exchange Act of 1934, as amended,
and the rules thereunder relating to stock manipulation, particularly Regulation M thereunder (or any successor rules or regulations), in connection with any offering of Registrable Securities pursuant to the Shelf Registration Agreement. The
Selling Securityholder agrees that neither it nor any person acting on its behalf will engage in any transaction in violation of such provisions. 

 Pursuant to the Registration Rights Agreement, the Company has agreed under certain circumstances to
indemnify the Selling Securityholder against certain liabilities. 
 In the event the Selling Securityholder transfers all or any portion of the Registrable
Securities listed in Item (3) above after the date on which such information is provided to the Company other than pursuant to the Registration Statement, the Selling Securityholder agrees to notify the transferee(s) at the time of the transfer
of its rights and obligations under this Selling Securityholder Questionnaire and the Registration Rights Agreement. 
 In accordance with the Selling
Securityholder’s obligation under the Registration Rights Agreement to provide such information as may be required by law or by the staff of the SEC for inclusion in the Registration Statement, the Selling Securityholder agrees to promptly
notify the Company of any inaccuracies or changes in the information provided herein that may occur subsequent to the date hereof at anytime while the Registration Statement remains effective. All notices to the Selling Securityholder pursuant to
the Registration Rights Agreement shall be made in writing, by hand-delivery, first-class mail, or air courier guaranteeing overnight delivery to the address set forth below. 

By signing below, the Selling Securityholder consents to the disclosure of the information contained herein in its answers to Items (1) through (9) above
and the inclusion of such information in the Registration Statement and the related Prospectus. The undersigned understands that such information will be relied upon by the Company in connection with the preparation or amendment of the Registration
Statement and the related Prospectus. 
 By signing below, the undersigned agrees that if the Company notifies the undersigned that the Registration
Statement is not available pursuant to the terms of the Registration Rights Agreement, the undersigned will suspend use of the Prospectus until notice from the Company that the Prospectus is again available. 

Once this Selling Securityholder Questionnaire is executed by the undersigned and received by the Company, the terms of this Selling Securityholder
Questionnaire, and the representations, warranties and agreements contained herein, shall be binding on, shall inure to the benefit of and shall be enforceable by the respective successors, heirs, personal representatives, and assigns of the Company
and the undersigned with respect to the Registrable Securities beneficially owned by the undersigned and listed in Item (3) above. This Selling Securityholder Questionnaire shall be governed by and construed in accordance with the laws of the
State of New York without regard to choice of laws or conflicts of laws provisions thereof that would require the application of the laws of any other jurisdiction. 

PLEASE RETURN THE COMPLETED AND EXECUTED 

SELLING SECURITYHOLDER QUESTIONNAIRE TO THE COMPANY AT: 

[___________________]EX-10.6

 Exhibit 10.6 

REGISTRATION RIGHTS AGREEMENT 
 This
Registration Rights Agreement (this “Agreement”) is made as of July 3, 2022 by and between Syros Pharmaceuticals, Inc., a Delaware corporation (the “Company”), and the persons listed on the attached
Schedule A who are signatories to this Agreement (collectively, the “Investors”). Unless otherwise defined herein, capitalized terms used in this Agreement have the respective meanings ascribed to them in
Section 1. 
 RECITALS 

WHEREAS, the Company and the Investors wish to provide for certain arrangements with respect to the registration of the Registrable Securities (as
defined below) by the Company under the Securities Act (as defined below). 
 NOW, THEREFORE, in consideration of the mutual promises and covenants
set forth herein, and other consideration, the receipt and adequacy of which are hereby acknowledged, the parties hereto agree as follows: 

Section 1. 

Definitions 
 1.1. Certain
Definitions. In addition to the terms defined elsewhere in this Agreement, as used in this Agreement, the following terms have the respective meanings set forth below: 

(a) “Block Trade” shall mean an offering of Registrable Securities which requires both the Investors and the Company to enter into a sale
agreement and is limited in scope of selling efforts as compared to an Underwritten Offering. 
 (b) “Board” shall mean the Board of
Directors of the Company. 
 (c) “Commission” shall mean the Securities and Exchange Commission or any other federal agency at the time
administering the Securities Act. 
 (d) “Common Stock” shall mean the common stock of the Company, par value $0.001 per share. 

(e) “Effective Date” shall mean the first date following the closing of the transactions contemplated by that certain Securities Purchase
Agreement, dated as of July 3, 2022, by and between the Company and the purchasers named therein when any of the Investors either has a nominee on the Board or beneficially owns at least one share of Common Stock. 

(f) “Exchange Act” shall mean the Securities Exchange Act of 1934, as amended, or any similar successor federal statute and the rules and
regulations thereunder, all as the same shall be in effect from time to time. 
 (g) “Existing Registration Rights Agreement” shall mean
that certain Registration Rights Agreement, dated as of July 3, 2022, by and among the Company and the “Investors” named in that certain Securities Purchase Agreement, dated as of July 3, 2022, by and among the Company and the
investors named therein. 

 (h) “Governmental Entity” shall mean any federal, state, local or foreign government, or
any department, agency, or instrumentality of any government; any public international organization, any transnational governmental organization; any court of competent jurisdiction, arbitral, administrative agency, commission, or other governmental
regulatory authority or quasi-governmental authority, any political party; and any national securities exchange or national quotation system. 
 (i)
“Other Securities” shall mean securities of the Company, other than Registrable Securities (as defined below). 
 (j)
“Person” shall mean any individual, partnership, corporation, company, association, trust, joint venture, limited liability company, unincorporated organization, entity or division, or any government, governmental department or
agency or political subdivision thereof. 
 (k) “Registrable Securities” shall mean the shares of Common Stock and any Common Stock issued
or issuable upon the exercise or conversion of any other securities (whether equity, debt or otherwise) of the Company now owned or hereafter acquired by any of the Investors. Registrable Securities shall cease to be Registrable Securities upon the
earliest to occur of the following events: (i) such Registrable Securities have been sold pursuant to an effective Registration Statement; (ii) such Registrable Securities have been sold by the Investors pursuant to Rule 144 (or other
similar rule), (iii) at any time after any of the Investors become an affiliate of the Company, such Registrable Securities may be resold by the Investor holding such Registrable Securities without limitations as to volume or manner of sale pursuant
to Rule 144; or (iv) ten (10) years after the Effective Date. For purposes of this definition, in order to determine whether an Investor is an “affiliate” (as such term is defined and used in Rule 144, and including for determining
whether volume or manner of sale limitations of Rule 144 apply) the parties will assume that all convertible securities (whether equity, debt or otherwise) have been converted into Common Stock. 

(l) The terms “register,” “registered” and “registration” shall refer to a registration effected by
preparing and filing a Registration Statement in compliance with the Securities Act, and such Registration Statement becoming effective under the Securities Act. 

(m) “Registration Expenses” shall mean all expenses incurred by the Company in effecting any registration pursuant to this Agreement,
including, without limitation, all registration, qualification, and filing fees, printing expenses, escrow fees, fees and disbursements of counsel for the Company, up to $50,000 of reasonable legal expenses of one special counsel for Investors (if
different from the Company’s counsel and if such counsel is reasonably approved by the Company) in connection with the preparation and filing of the Resale Registration Shelf (as defined below), and up to $50,000 of reasonable legal expenses of
one special counsel for the Investors (if different from the Company’s counsel and if such counsel is reasonably approved by the Company) per Underwritten Offering, blue sky fees and expenses, and expenses of any regular or special audits
incident to or required by any such registration, but shall not include Selling Expenses. 

  
 2 

 (n) “Registration Statement” means any registration statement of the Company filed with, or
to be filed with, the Commission under the Securities Act, including the related prospectus, amendments and supplements to such registration statement, including pre- and post-effective amendments, and all
exhibits and all material incorporated by reference in such registration statement as may be necessary to comply with applicable securities laws other than a registration statement (and related prospectus) filed on Form S-4 or Form S-8 or any successor forms thereto. 
 (o) “Rule 144”
shall mean Rule 144 as promulgated by the Commission under the Securities Act, as such rule may be amended from time to time, or any similar successor rule that may be promulgated by the Commission. 

(p) “Securities Act” shall mean the Securities Act of 1933, as amended, or any similar successor federal statute and the rules and
regulations thereunder, all as the same shall be in effect from time to time. 
 (q) “Selling Expenses” shall mean all underwriting
discounts and selling commissions applicable to the sale of Registrable Securities, the fees and expenses of any legal counsel (except as provided in the definition of “Registration Expenses”) and any other advisors any of the Investors
engage and all similar fees and commissions relating to the Investors’ disposition of the Registrable Securities. 
 (r) “Underwritten
Offering” shall mean a public offering of Registrable Securities pursuant to an effective registration statement under the Securities Act (other than pursuant to a registration statement on Form S-4
or S-8 or any similar or successor form) which requires the Investors and the Company to enter into an underwriting agreement. 

Section 2. 
 Resale
Registration Rights 
 2.1. Resale Registration Rights. 

(a) Beginning on the Effective Date, following demand by any Investor, the Company shall file with the Commission a Registration Statement on Form S-3 (except if the Company is not then eligible to register for resale the Registrable Securities on Form S-3, in which case such registration shall be on another appropriate
form in accordance with the Securities Act) covering the resale of the Registrable Securities by the Investors (the “Resale Registration Shelf”), and the Company shall file such Resale Registration Shelf as promptly as reasonably
practicable following such demand, and in any event within sixty (60) days of such demand. Such Resale Registration Shelf shall include a “final” prospectus, including the information required by Item 507 of Regulation S-K of the Securities Act, as provided by the Investors in accordance with Section 2.7. Notwithstanding the foregoing, before filing the Resale Registration Shelf, the Company shall furnish to the Investors a
copy of the Resale Registration Shelf and afford the Investors an opportunity to review and comment on the Resale Registration Shelf. The Company’s obligation pursuant to this Section 2.1(a) is conditioned upon the
Investors providing the information contemplated in Section 2.7. 

  
 3 

 (b) The Company shall use its reasonable best efforts to cause the Resale Registration Shelf and related
prospectuses to become effective as promptly as practicable after filing. The Company shall use its reasonable best efforts to cause such Registration Statement to remain effective under the Securities Act until the earlier of the date (i) all
Registrable Securities covered by the Resale Registration Shelf have been sold or may be sold freely without limitations or restrictions as to volume or manner of sale pursuant to Rule 144 or (ii) all Registrable Securities covered by the
Resale Registration Shelf otherwise cease to be Registrable Securities pursuant to the definition of Registrable Securities. The Company shall promptly, and within two (2) business days after the Company confirms effectiveness of the Resale
Registration Shelf with the Commission, notify the Investors of the effectiveness of the Resale Registration Shelf. 
 (c) Notwithstanding anything
contained herein to the contrary, the Company shall not be obligated to effect, or to take any action to effect, a registration pursuant to Section 2.1(a): 

(i) if the Company then currently has and maintains an effective Registration Statement on Form S-3ASR
that provides for the resale of an unlimited number of securities by selling stockholders (a “Company Registration Shelf”); 

(ii) during the period forty-five (45) days prior to the Company’s good faith estimate of the date of filing of a Company
Registration Shelf; or 
 (iii) if the Company has caused a Registration Statement to become effective pursuant to this
Section 2.1 or pursuant to the Existing Registration Rights Agreement which then includes all the Registrable Securities then owned by the Investors. 

(d) If the Company has a Company Registration Shelf in place at any time in which the Investors make a demand pursuant to
Section 2.1(a), the Company shall file with the Commission, as promptly as practicable, and in any event within fifteen (15) business days after such demand, a “final” prospectus supplement to its Company
Registration Shelf covering the resale of the Registrable Securities by the Investors (the “Prospectus”); provided, however, that the Company shall not be obligated to file more than one Prospectus pursuant to this
Section 2.1(d) in any six month period to add additional Registrable Securities to the Company Registration Shelf that were acquired by the Investors other than directly from the Company or in an underwritten public
offering by the Company. The Prospectus shall include the information required under Item 507 of Regulation S-K of the Securities Act, which information shall be provided by the Investors in accordance with
Section 2.7. Notwithstanding the foregoing, before filing the Prospectus, the Company shall furnish to the Investors a copy of the Prospectus and afford the Investors an opportunity to review and comment on the Prospectus.

 (e) Deferral and Suspension. At any time after being obligated pursuant to this Agreement to file a Resale Registration Shelf or Prospectus, or
after any Resale Registration Shelf has become effective or a Prospectus is filed with the Commission, the Company may defer the filing of or suspend the use of any such Resale Registration Shelf or Prospectus, upon giving written notice of such
action to the Investors with a certificate signed by the Principal Executive Officer or the Principal Financial Officer of the Company stating that in the good faith judgment of the Board, the filing or use of any such Resale Registration Shelf or
Prospectus covering the Registrable Securities would be seriously detrimental to the Company or its stockholders at such time and that the Board concludes, as a result, that it is in the best interests of the Company and its

  
 4 

 
stockholders to defer the filing or suspend the use of such Resale Registration Shelf or Prospectus at such time. The Company shall have the right to defer the filing of or suspend the use of
such Resale Registration Shelf or Prospectus for a period of not more than one hundred twenty (120) days from the date the Company notifies the Investors of such deferral or suspension; provided that the Company shall not exercise the
right contained in this Section 2.1(e) more than once in any twelve month period. In the case of the suspension of use of any effective Resale Registration Shelf or Prospectus, the Investors, immediately upon receipt of
notice thereof from the Company, shall discontinue any offers or sales of Registrable Securities pursuant to such Resale Registration Shelf or Prospectus until advised in writing by the Company that the use of such Resale Registration Shelf or
Prospectus may be resumed. In the case of a deferred Prospectus or Resale Registration Shelf filing, the Company shall provide prompt written notice to the Investors of (i) the Company’s decision to file or seek effectiveness of the
Prospectus or Resale Registration Shelf, as the case may be, following such deferral and (ii) in the case of a Resale Registration Shelf, the effectiveness of such Resale Registration Shelf. In the case of either a suspension of use of, or
deferred filing of, any Resale Registration Shelf or Prospectus, the Company shall not, during the pendency of such suspension or deferral, be required to take any action hereunder (including any action pursuant to
Section 2.2 hereof) with respect to the registration or sale of any Registrable Securities pursuant to any such Resale Registration Shelf, Company Registration Shelf or Prospectus. 

(f) Other Securities. Subject to Section 2.2(e) below, any Resale Registration Shelf or Prospectus may include Other
Securities, and may include securities of the Company being sold for the account of the Company; provided such Other Securities are excluded first from such Registration Statement (except as may be required pursuant to the Existing Registration
Rights Agreement) in order to comply with any applicable laws or request from any Government Entity, Nasdaq or any applicable listing agency. For the avoidance of doubt, no Other Securities may be included in an Underwritten Offering pursuant to
Section 2.2 without the consent of the Investors. 
 (g) Suspension of Rights. From the Effective Date through the
termination of this Agreement, the Investors’ rights under the Existing Registration Agreement shall be suspended. 
 2.2. Sales and Underwritten
Offerings of the Registrable Securities. 
 (a) Notwithstanding any provision contained herein to the contrary, the Investors, collectively, shall and
subject to the limitations set forth in this Section 2.2, be permitted (i) one Underwritten Offering per calendar year, but no more than three Underwritten Offerings in total, and (ii) no more than two
Underwritten Offerings or Block Trades in any twelve month period, to effect the sale or distribution of Registrable Securities. 
 (b) If the Investors
intend to effect an Underwritten Offering or Block Trade pursuant to a Resale Registration Shelf or Company Registration Shelf to sell or otherwise distribute Registrable Securities, they shall so advise the Company and provide as much notice to the
Company as reasonably practicable (and, in either case, not less than fifteen (15) business days prior to the Investors’ request that the Company file a prospectus supplement to a Resale Registration Shelf or Company Registration Shelf).

  
 5 

 (c) In connection with any offering initiated by the Investors pursuant to this Section 2.2
involving an underwriting of shares of Registrable Securities, the Investors shall be entitled to select the underwriter or underwriters for such offering, subject to the consent of the Company, such consent not to be unreasonably withheld,
conditioned or delayed. 
 (d) In connection with any offering initiated by the Investors pursuant to this Section 2.2
involving an Underwritten Offering of Registrable Securities, the Company shall not be required to include any of the Registrable Securities in such underwriting unless the Investors (i) enter into an underwriting agreement in customary
form with the underwriter or underwriters, (ii) accept customary terms in such underwriting agreement with regard to representations and warranties relating to ownership of the Registrable Securities and authority and power to enter into such
underwriting agreement and (iii) complete and execute all questionnaires, powers of attorney, custody agreements, indemnities and other documents as may be requested by such underwriter or underwriters. Further, the Company shall not be
required to include any of the Registrable Securities in such underwriting if (Y) the underwriting agreement proposed by the underwriter or underwriters contains representations, warranties or conditions that are not reasonable in light of the
Company’s then-current business or (Z) the underwriter, underwriters or the Investors require the Company to participate in any marketing, road show or comparable activity that may be required to complete the orderly sale of shares by the
underwriter or underwriters. 
 (e) If the total amount of securities to be sold in any offering initiated by the Investors pursuant to this
Section 2.2 involving an underwriting of shares of Registrable Securities exceeds the amount that the underwriters determine in their sole discretion is compatible with the success of the offering, then the Company shall be
required to include in the offering only that number of such securities, including Registrable Securities (subject in each case to the cutback provisions set forth in this Section 2.2(e)), that the underwriters and the
Company determine in their sole discretion shall not jeopardize the success of the offering. If the Underwritten Offering has been requested pursuant to Section 2.2(a) hereof, the number of shares that are entitled to be
included in the registration and underwriting shall be allocated in the following manner: (a) first, shares of Company equity securities that the Company desires to include in such registration shall be excluded and
(b) second, Registrable Securities requested to be included in such registration by the Investors shall be excluded. For the avoidance of doubt, no other person besides the Investors shall be entitled to participate in any Block Trade.
To facilitate the allocation of shares in accordance with the above provisions, the Company or the underwriters may round down the number of shares allocated to any of the Investors to the nearest 100 shares. 

2.3. Fees and Expenses. All Registration Expenses incurred in connection with registrations pursuant to this Agreement shall be borne by the Company.
All Selling Expenses relating to securities registered on behalf of the Investors shall be borne by the Investors. 

  
 6 

 2.4. Registration Procedures. In the case of each registration of Registrable Securities effected by
the Company pursuant to Section 2.1 hereof, the Company shall keep the Investors advised as to the initiation of each such registration and as to the status thereof. The Company shall use its reasonable best efforts, within
the limits set forth in this Section 2.4, to: 
 (a) prepare and file with the Commission such amendments and supplements to such
Registration Statement and the prospectuses used in connection with such Registration Statement as may be necessary to keep such Registration Statement effective and current and comply with the provisions of the Securities Act with respect to the
disposition of all securities covered by such Registration Statement; 
 (b) furnish to the Investors such numbers of copies of a prospectus, including
preliminary prospectuses, in conformity with the requirements of the Securities Act, and such other documents as the Investors may reasonably request in order to facilitate the disposition of Registrable Securities; 

(c) use its reasonable best efforts to register and qualify the Registrable Securities covered by such Registration Statement under such other securities or
blue sky laws of such jurisdictions in the United States as shall be reasonably requested by the Investors, 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; 
 (d) in the event of an Underwritten Offering or Block Trade, and subject to
Section 2.2(d), enter into and perform its obligations under an underwriting agreement or Block Trade sale agreement, in usual and customary form (including any “lock-ups”
on behalf of the Company and its directors and officers), with the managing underwriter of such offering and take such other usual and customary action as the Investors may reasonably request in order to facilitate the disposition of such
Registrable Securities; 
 (e) notify the Investors at any time when a prospectus relating to a Registration Statement covering any Registrable Securities
is required to be delivered under the Securities 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. The Company shall use its reasonable best efforts to amend or supplement such prospectus in order
to cause such prospectus not to include any untrue statement of a material fact or omit 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; 
 (f) provide a transfer agent and registrar for all Registrable Securities registered pursuant to such Registration Statement and, if required,
a CUSIP number for all such Registrable Securities, in each case not later than the effective date of such registration; 
 (g) if requested by an Investor,
use reasonable best efforts to cause the Company’s transfer agent to remove any restrictive legend from any Registrable Securities, within two business days following such request; 

(h) cause to be furnished, at the request of the Investors, on the date that Registrable Securities are delivered to underwriters for sale in connection with
an Underwritten Offering or Block Trade, (i) 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

  
 7 

 
underwritten public offering, addressed to the underwriters, and (ii) a letter or letters 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 
 (i)
cause all such Registrable Securities included in a Registration Statement pursuant to this Agreement to be listed on each securities exchange or other securities trading markets on which Common Stock is then listed. 

2.5. The Investors Obligations. 
 (a) Discontinuance
of Distribution. The Investors agree that, upon receipt of any notice from the Company of the occurrence of any event of the kind described in Section 2.4(e) hereof, the Investors shall immediately discontinue disposition of
Registrable Securities pursuant to any Registration Statement covering such Registrable Securities until the Investors’ receipt of the copies of the supplemented or amended prospectus contemplated by Section 2.4(e) hereof or receipt
of notice that no supplement or amendment is required and that the Investors’ disposition of the Registrable Securities may be resumed. The Company may provide appropriate stop orders to enforce the provisions of this
Section 2.5(a). 
 (b) Compliance with Prospectus Delivery Requirements. The Investors covenant and agree that they shall
comply with the prospectus delivery requirements of the Securities Act as applicable to them or an exemption therefrom in connection with sales of Registrable Securities pursuant to any Registration Statement filed by the Company pursuant to this
Agreement. 
 (c) Notification of Sale of Registrable Securities. The Investors covenant and agree that they shall notify the Company following the
sale of Registrable Securities to a third party as promptly as reasonably practicable, and in any event within thirty (30) days, following the sale of such Registrable Securities. 

2.6. Indemnification. 
 (a) To the extent permitted by
law, the Company shall indemnify the Investors, and, as applicable, their officers, directors, and constituent partners, legal counsel for each Investor and each Person controlling the Investors, with respect to which registration, related
qualification, or related compliance of Registrable Securities has been effected pursuant to this Agreement, and each underwriter, if any, and each Person who controls any underwriter within the meaning of the Securities Act against all claims,
losses, damages, or liabilities (or actions in respect thereof) to the extent such claims, losses, damages, or liabilities arise out of or are based upon (i) any untrue statement (or alleged untrue statement) of a material fact contained in any
prospectus or other document (including any related Registration Statement) incident to any such registration, qualification, or compliance, or (ii) any 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 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 applicable to the Company and relating to action or inaction required of the Company in connection with any such registration, qualification, or

  
 8 

 
compliance; and the Company shall pay as incurred to the Investors, each such underwriter, and each Person who controls the Investors or underwriter, any legal and any other expenses reasonably
incurred in connection with investigating or defending any such claim, loss, damage, liability, or action; provided, however, that the indemnity contained in this Section 2.6(a) shall not apply to amounts paid
in settlement of any such claim, loss, damage, liability, or action if settlement is effected without the consent of the Company (which consent shall not unreasonably be withheld); and provided, further, that the Company shall not be liable in any
such case to the extent that any such claim, loss, damage, liability, or expense arises out of or is based upon any violation by such Investor of the obligations set forth in Section 2.5 hereof or any untrue statement or
omission contained in such prospectus or other document based upon written information furnished to the Company by the Investors, such underwriter, or such controlling Person and stated to be for use therein. 

(b) To the extent permitted by law, each Investor (severally and not jointly) shall, if Registrable Securities held by such Investor are included for sale in
the registration and related qualification and compliance effected pursuant to this Agreement, indemnify the Company, each of its directors, each officer of the Company who signs the applicable Registration Statement, each legal counsel and each
underwriter of the Company’s securities covered by such a Registration Statement, each Person who controls the Company or such underwriter within the meaning of the Securities Act against all claims, losses, damages, and liabilities (or actions
in respect thereof) arising out of or based upon (i) any untrue statement (or alleged untrue statement) of a material fact contained in any such Registration Statement, or related document, or (ii) any 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 such Investor of Section 2.5 hereof, 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 applicable to such Investor and relating to action or inaction required of such Investor in
connection with any such registration and related qualification and compliance, and shall pay as incurred to such persons, any legal and any other expenses reasonably incurred in connection with investigating or defending any such claim, loss,
damage, liability, or action, in each case only to the extent that such untrue statement (or alleged untrue statement) or omission (or alleged omission) is made in (and such violation pertains to) such Registration Statement or related document in
reliance upon and in conformity with written information furnished to the Company by such Investor and stated to be specifically for use therein; provided, however, that the indemnity contained in this
Section 2.6(b) shall not apply to amounts paid in settlement of any such claim, loss, damage, liability, or action if settlement is effected without the consent of such Investor (which consent shall not unreasonably be
withheld); provided, further, that such Investor’s liability under this Section 2.6(b) (when combined with any amounts such Investor is liable for under Section 2.6(d)) shall not exceed such
Investor’s net proceeds from the offering of securities made in connection with such registration. 
 (c) Promptly after receipt by an indemnified
party under this Section 2.6 of notice of the commencement of any action, such indemnified party shall, if a claim in respect thereof is to be made against an indemnifying party under this
Section 2.6, notify the indemnifying party in writing of the commencement thereof and generally summarize such action. The indemnifying party shall have the right to participate in and to assume the defense of such claim;
provided, 

  
 9 

 
however, that the indemnifying party shall be entitled to select counsel for the defense of such claim with the approval of any parties entitled to indemnification, which approval shall
not be unreasonably withheld; provided further, however, that if either party reasonably determines that there may be a conflict between the position of the Company and the Investors in conducting the defense of such action, suit, or proceeding by
reason of recognized claims for indemnity under this Section 2.6, then counsel for such party shall be entitled to conduct the defense to the extent reasonably determined by such counsel to be necessary to protect the
interest of such party. The failure to notify an indemnifying party promptly of the commencement of any such action, if prejudicial to the ability of the indemnifying party to defend such action, shall relieve such indemnifying party, to the extent
so prejudiced, of any liability to the indemnified party under this Section 2.6, but the omission so to notify the indemnifying party shall not relieve such party of any liability that such party may have to any indemnified
party otherwise than under this Section 2.6. 
 (d) If the indemnification provided for in this
Section 2.6 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 therein, 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. In no event,
however, shall (i) any amount due for contribution hereunder be in excess of the amount that would otherwise be due under Section 2.6(a) or Section 2.6(b), as applicable, based on the
limitations of such provisions and (ii) a Person guilty of fraudulent misrepresentation (within the meaning of the Securities Act) be entitled to contribution from a Person who was not guilty of such fraudulent misrepresentation. 

(e) Notwithstanding the foregoing, to the extent that the provisions on indemnification and contribution contained in the underwriting agreement entered into
in connection with an Underwritten Offering, or the Block Trade sale agreement, are in conflict with the foregoing provisions, the provisions in the underwriting agreement or Block Trade sale agreement shall control; provided, however,
that the failure of the underwriting agreement to provide for or address a matter provided for or addressed by the foregoing provisions shall not be a conflict between the underwriting agreement or the Block Trade sale agreement and the foregoing
provisions. 
 (f) The obligations of the Company and the Investors under this Section 2.6 shall survive the completion of any
offering of Registrable Securities in a Registration Statement under this Agreement or otherwise. 

  
 10 

 2.7. Information. The Investors shall furnish to the Company such information regarding the Investors
and the distribution proposed by the Investors as the Company may reasonably request and as shall be reasonably required in connection with any registration referred to in this Agreement. The Investors agree to, as promptly as practicable (and in
any event prior to any sales made pursuant to a prospectus), furnish to the Company all information required to be disclosed in order to make the information previously furnished to the Company by the Investors not misleading. The Investors agree to
keep confidential the receipt of any notice received pursuant to Section 2.4(e) and the contents thereof, except as required pursuant to applicable law. Notwithstanding anything to the contrary herein, the Company shall be under no
obligation to name the Investors in any Registration Statement if the Investors have not provided the information required by this Section 2.7 with respect to the Investors as a selling securityholder in such Registration
Statement or any related prospectus. 
 2.8. Rule 144 Requirements. With a view to making available to the Investors the benefits of Rule 144 and any
other rule or regulation of the Commission that may at any time permit the Investors to sell Registrable Securities to the public without registration, the Company agrees to use its reasonable best efforts to: 

(a) make and keep public information available, as those terms are understood and defined in Rule 144 at all times after the date hereof; 

(b) 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; 

(c) prior to the filing of the Registration Statement or any amendment thereto (whether pre-effective or post-effective), and prior to the filing of any prospectus or prospectus supplement related thereto, to provide the Investors with copies of all of the pages thereof (if any) that reference the Investors; and 

(d) furnish to any Investor, so long as the Investor owns any Registrable Securities, forthwith upon request (i) a written statement by the Company that
it has complied with the reporting requirements of Rule 144, (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 by an Investor in availing itself of any rule or regulation of the Commission which permits an Investor to sell any such securities without registration. 

2.9. Limitations on Subsequent Registration Rights. From and after the date of this Agreement, the Company shall not, without prior written consent of
the Investors, enter into any agreement with any holder or prospective holder of any securities of the Company which would provide to such holder rights with respect to the registration of such securities under the Securities Act or the Exchange Act
that would conflict with or adversely affect any of the rights provided to the Investors in this Section 2; it being understood and agreed that any subsequent agreement of the Company with any holder or prospective holder
of any securities of the Company of the same class (or convertible into or exchange for securities of the same class) as the Registrable Securities granting such Person rights under this Section 2 equivalent to the rights
of the Investors under this Section 2 will not be prohibited by the terms of this Section 2.9. 

  
 11 

 Section 3. 

Miscellaneous 
 3.1. Amendment. No
amendment, alteration or modification of any of the provisions of this Agreement shall be binding unless made in writing and signed by each of the Company and the Investors. 

3.2. Injunctive Relief. It is hereby agreed and acknowledged that it shall be impossible to measure in money the damages that would be suffered if the
parties fail to comply with any of the obligations herein imposed on them and that in the event of any such failure, an aggrieved Person shall be irreparably damaged and shall not have an adequate remedy at law. Any such Person shall, therefore, be
entitled (in addition to any other remedy to which it may be entitled in law or in equity) to injunctive relief, including, without limitation, specific performance, to enforce such obligations, and if any action should be brought in equity to
enforce any of the provisions of this Agreement, none of the parties hereto shall raise the defense that there is an adequate remedy at law. 
 3.3.
Notices. All notices required or permitted under this Agreement must be in writing and sent to the address or e-mail address identified below. Notices must be given: (a) by personal delivery, with
receipt acknowledged; (b) by email followed by hard copy delivered by the methods under clause (c) or (d); (c) by prepaid certified or registered mail, return receipt requested; or (d) by prepaid reputable overnight
delivery service. Notices shall be effective upon receipt. Either party may change its notice address by providing the other party written notice of such change. Notices shall be delivered as follows: 

 

			
	If to the Investors:	  	At such Investor’s address as set forth on Schedule A hereto
		
	If to the Company:	  	 Syros Pharmaceuticals, Inc.
 Attention: Chief
Financial Officer
 Address: 35 CambridgePark Drive, 4th Floor

Cambridge, MA 02140

E-mail: jhaas@syros.com

		
	with a copy to:	  	 Wilmer Cutler Pickering Hale and Dorr LLP

Attention: Cynthia Mazareas 60 State Street
 Boston, MA 02109

E-mail: cynthia.mazareas@wilmerhale.com

 3.4. Governing Law; Jurisdiction; Venue; Jury Trial. 

(a) This Agreement shall be governed by, and construed in accordance with, the law of the State of New York without giving effect to any choice or conflict of
law provision or rule (whether of the State of New York or any other jurisdiction) that would cause the application of the laws of any jurisdiction other than the State of New York. 

  
 12 

 (b) Each of the Company and the Investors irrevocably and unconditionally submits, for itself and its
property, to the nonexclusive jurisdiction of the courts of the State of New York sitting in the Borough of Manhattan, New York and of the United States District Court of the Southern District of New York, and any appellate court from any thereof,
in any action or proceeding arising out of or relating to this Agreement and the transactions contemplated herein, or for recognition or enforcement of any judgment, and each of the Company and the Investors irrevocably and unconditionally agrees
that all claims in respect of any such action or proceeding may be heard and determined in such New York state court or, to the fullest extent permitted by applicable law, in such federal court. Each of the Company and the Investors hereto agrees
that a final judgment in any such action or proceeding shall be conclusive and may be enforced in other jurisdictions by suit on the judgment or in any other manner provided by law. 

(c) Each of the Company and the Investors irrevocably and unconditionally waives, to the fullest extent permitted by applicable law, any objection that it may
now or hereafter have to the laying of venue of any action or proceeding arising out of or relating to this Agreement and the transactions contemplated herein in any court referred to in Section 3.4(b) hereof. Each of the
Company and the Investors hereby irrevocably waives, to the fullest extent permitted by applicable law, the defense of an inconvenient forum to the maintenance of such action or proceeding in any such court. 

(d) EACH OF THE COMPANY AND THE INVESTORS HEREBY IRREVOCABLY WAIVES, TO THE FULLEST EXTENT PERMITTED BY APPLICABLE LAW, ANY RIGHT IT MAY HAVE TO A TRIAL BY
JURY IN ANY LEGAL PROCEEDING DIRECTLY OR INDIRECTLY ARISING OUT OF OR RELATING TO THIS AGREEMENT OR THE TRANSACTIONS CONTEMPLATED HEREBY (WHETHER BASED ON CONTRACT, TORT OR ANY OTHER THEORY). EACH OF THE COMPANY AND THE INVESTORS (A) CERTIFIES
THAT NO REPRESENTATIVE, AGENT OR ATTORNEY OF ANY OTHER PERSON HAS REPRESENTED, EXPRESSLY OR OTHERWISE, THAT SUCH OTHER PERSON WOULD NOT, IN THE EVENT OF LITIGATION, SEEK TO ENFORCE THE FOREGOING WAIVER AND (B) ACKNOWLEDGES THAT EACH OF THE
COMPANY AND THE INVESTORS HAS BEEN INDUCED TO ENTER INTO THIS AGREEMENT BY, AMONG OTHER THINGS, THE MUTUAL WAIVERS AND CERTIFICATIONS IN THIS SECTION. 

3.5. Successors, Assigns and Transferees. Any and all rights, duties and obligations hereunder shall not be assigned, transferred, delegated or
sublicensed by any party hereto without the prior written consent of the other party; provided, however, that the Investors shall be entitled to transfer Registrable Securities to one or more of their affiliates and, solely in
connection therewith, may assign their rights hereunder in respect of such transferred Registrable Securities, in each case, so long as such Investor is not relieved of any liability or obligations hereunder, without the prior consent of the
Company. Any transfer or assignment made other than as provided in the first sentence of this Section 3.5 shall be null and void. Subject to the foregoing and except as otherwise provided herein, the provisions of this
Agreement shall inure to the benefit of, and be binding upon, the successors, permitted assigns, heirs, executors and administrators of the parties hereto. The Company shall not consummate any recapitalization, merger, consolidation, reorganization
or other similar transaction whereby stockholders of the Company receive (either directly, through an exchange, via dividend from the Company or otherwise) equity (the “Other Equity”) in any other entity (the “Other
Entity”) with respect to Registrable Securities hereunder, unless prior to the consummation thereof, the Other Entity assumes, by written instrument, the obligations under this Agreement with respect to such Other Equity as if such Other
Equity were Registrable Securities hereunder. 

  
 13 

 3.6. Entire Agreement. This Agreement, together with any exhibits hereto, constitute the entire
agreement between the parties relating to the subject matter hereof and all previous agreements or arrangements between the parties, written or oral, relating to the subject matter hereof are superseded. 

3.7. Waiver. No failure on the part of either party hereto to exercise any power, right, privilege or remedy under this Agreement, and no delay on the
part of either party hereto in exercising any power, right, privilege or remedy under this Agreement, shall operate as a waiver thereof; and no single or partial exercise of any such power, right, privilege or remedy shall preclude any other or
further exercise thereof or of any other power, right, privilege or remedy. 
 3.8. Severability. If any part of this Agreement is declared invalid
or unenforceable by any court of competent jurisdiction, such declaration shall not affect the remainder of the Agreement and the invalidated provision shall be revised in a manner that shall render such provision valid while preserving the
parties’ original intent to the maximum extent possible. 
 3.9. Titles and Subtitles. The titles and subtitles used in this Agreement are used
for convenience only and are not to be considered in construing or interpreting this Agreement. All references in this Agreement to sections, paragraphs and exhibits shall, unless otherwise provided, refer to sections and paragraphs hereof and
exhibits attached hereto. 
 3.10. Counterparts. This Agreement may be executed in any number of counterparts, each of which shall be enforceable
against the parties that execute such counterparts (including by facsimile or other electronic means), and all of which together shall constitute one instrument. 

3.11. Term and Termination. The Investors’ rights to demand the registration of the Registrable Securities under this Agreement, as well as the
Company’s obligations hereunder other than pursuant to Section 2.6 hereof, shall terminate automatically once all Registrable Securities cease to be Registrable Securities pursuant to the terms of this Agreement. 

[Remainder of Page Intentionally Left Blank; Signature Page Follows] 

  
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 IN WITNESS WHEREOF, the parties hereto have executed this Registration Rights Agreement effective as of the
day, month and year first above written. 
  

			
	SYROS PHARMACEUTICALS, INC.
		
	By:	 	/s/ Nancy Simonian
	Name:	 	Nancy Simonian
	Title:	 	Chief Executive Officer

 [Signature Page to Registration Rights Agreement] 

 IN WITNESS WHEREOF, the parties hereto have executed this Registration Rights Agreement effective as of the
day, month and year first above written. 
  

			
	667, L.P.
		
	By:	 	BAKER BROS. ADVISORS LP, management company and investment adviser to 667, L.P., pursuant to authority granted to it by Baker Biotech Capital, L.P., general partner to 667, L.P., and not as the general partner
		
	By:	 	/s/ Scott L. Lessing
		 	Scott L. Lessing
		 	President
	
	BAKER BROTHERS LIFE SCIENCES, L.P.
		
	By:	 	BAKER BROS. ADVISORS LP, management company and investment adviser to BAKER BROTHERS LIFE SCIENCES, L.P., pursuant to authority granted to it by Baker Brothers Life Sciences Capital, L.P., general partner to BAKER BROTHERS LIFE
SCIENCES, L.P., and not as the general partner
		
	By:	 	/s/ Scott L. Lessing
		 	Scott L. Lessing
		 	President

 [Signature Page to Registration Rights Agreement] 

 Schedule A 

The Investors 
 667, L.P. 

BAKER BROTHERS LIFE SCIENCES, L.P. 
 To the above Investors: 

Baker Brothers Investments 
 860 Washington Street 

New York, NY 10014 
 Attn: Scott Lessing 

Email: slessing@BBInvestments.com 
 With a copy to: 

Paul, Weiss, Rifkind, Wharton & Garrison LLP 
 Attn:
Jeffrey Kochian 
 Email: jkochian@paulweiss.com 
 1285 Avenue
of the Americas 
 New York, NY 10019-6064

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