EX-4.3



 Exhibit 4.3 

AMENDMENT NO. 1 TO SECOND AMENDED AND RESTATED 

INVESTORS’ RIGHTS AGREEMENT 

This Amendment No. 1 to Second Amended and Restated Investors’ Rights Agreement (this “Amendment”) is made as of
April 20, 2015, by and among MyoKardia, Inc., a Delaware corporation (the “Company”), and the parties listed on the signature pages hereto. Capitalized terms used herein and not otherwise defined herein shall have the meanings
ascribed to such terms in the Second Amended and Restated Investors’ Rights Agreement, dated as of April 20, 2015, by and among the Company and the parties named therein (the “Agreement”). 

WHEREAS, pursuant to the terms of the Purchase Agreement, the Strategic Investor may, at its option, purchase certain shares of Series B
Preferred Stock in accordance with the terms of the Purchase Agreement (the “Strategic Investor Investment”); 
 WHEREAS,
pursuant to Section 6.6 of the Agreement, and subject to the qualifications set forth therein, the Agreement may be amended by a written instrument executed by (i) the Company and (ii) the holders of at least a majority of the
Registrable Securities then held by the Investors; and 
 WHEREAS, any such amendment so effected shall be binding on all Parties, even if
they do not execute such consent. 
 NOW, THEREFORE, for good and valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, the undersigned hereby agree as follows: 
 1. The defined term “Major Investor” is hereby deleted in its entirety from
Section 1.18 of the Agreement and replaced with the following: “1.18 Major Investor” means any Investor that, individually or together with such Investor’s Affiliates, holds at least 1,000,000 shares of Registrable
Securities (subject to appropriate adjustment in the event of any stock dividend, stock split, combination or other similar recapitalization); provided, however, that the Strategic Investor shall only be deemed a Major Investor for
purposes of Section 4 of this Agreement so long as (x) the Strategic Investor (together with its Affiliates) holds at least 1,000,000 shares of Registrable Securities (subject to appropriate adjustment in the event of any stock
dividend, stock split, combination or other similar recapitalization), (y) the Collaboration Agreement remains in full force and effect and (z) for any offering of New Securities after December 31, 2016, the Strategic Investor (or any
of its Affiliates) shall have taken all actions required under Section 9.3(a) of the Collaboration Agreement on or before January 31, 2017 (the conditions in clauses (x), (y) and (z) of the foregoing, the “Strategic
Investor Conditions”). For the avoidance of doubt, (A) if the Strategic Investor Conditions are not satisfied, the Strategic Investor shall not be deemed a Major Investor solely for purposes of Section 4 of this Agreement
and (B) clause (z) shall only be a Strategic Investor Condition following December 31, 2016.” 
 2. Section 4.1(b) of the Agreement
is hereby deleted in its entirety and replaced with the following: “By notification to the Company within twenty (20) days after the Offer Notice is given, each Major Investor may elect to purchase or otherwise acquire, at the price and on
the terms specified in the Offer Notice, up to that portion of such New Securities which equals the proportion that the Common Stock issued and held, or issuable (directly or indirectly) upon conversion and/or exercise, as applicable, of the Series
A Preferred Stock, Series A-1 Preferred Stock or Series B Preferred Stock and any other Derivative Securities (excluding Specified Preferred Stock) then held, by such Major Investor bears to the total number of shares of Common Stock of the Company
then outstanding (assuming full conversion and/or exercise, as applicable, of all Series A Preferred Stock, Series A-1 Preferred Stock and Series B Preferred Stock and other Derivative Securities). At the expiration of such twenty (20) day
period, the Company shall promptly notify each Major Investor that elects to purchase or acquire all the shares available to it (each, a “Fully Exercising Investor”) of any other Major Investor’s failure to do likewise. During
the ten (10) day period commencing after the Company 







 
has given such notice, each Fully Exercising Investor may, by giving notice to the Company, elect to purchase or acquire, in addition to the number of shares specified above, up to that portion
of the New Securities for which Major Investors were entitled to subscribe but that were not subscribed for by the Major Investors, which is equal to the proportion that the Common Stock issued and held, or issuable upon conversion of Series A
Preferred Stock, Series A-1 Preferred Stock and Series B Preferred Stock and any other Derivative Securities (excluding Specified Preferred Stock) then held, by such Fully Exercising Investor bears to the total number of shares of Common Stock
issued and held, or issuable (directly or indirectly) upon conversion of the Series A Preferred Stock, Series A-1 Preferred Stock and Series B Preferred Stock and any other Derivative Securities (excluding Specified Preferred Stock) then
held, by all Fully Exercising Investors who wish to purchase such unsubscribed shares. The closing of any sale pursuant to this Section 4.1(b) shall occur within the later of one hundred twenty (120) days after the date that the Offer
Notice is given and the date of initial sale of New Securities pursuant to Section 4.1(c).” 
 3. The Agreement is hereby amended to add a new
Section 4.3 as follows: “4.3 Strategic Investor Limitation. The Investors and the Company hereby agree that if the Strategic Investor exercises its right to participate in a financing of the Company as contemplated in
Section 9.3 of the Collaboration Agreement, then for such financing, such participation rights will be in lieu of the Strategic Investor’s participation rights in an offer of New Securities as contemplated by this Section 4, and the
Strategic Investor shall not be considered a Major Investor under this Section 4 solely for purposes of such financing.” 
 4. This Amendment
shall become effective upon the consummation of the Strategic Investor Investment. If the Strategic Investor Investment is not consummated on or prior to the Strategic Investor Outside Date (as defined in the Purchase Agreement) in accordance with
the terms of the Purchase Agreement, this Amendment shall be void ab initio and the Agreement shall remain in full force and effect without the amendments contemplated herein. 

5. Except as expressly amended herein, the Agreement shall remain in full force and effect. 

6. This Amendment shall be governed by and construed in accordance with the General Corporation Law of the State of Delaware as to matters within the scope
thereof, and as to all other matters shall be governed by and construed in accordance with the internal laws of the State of California, without regard to conflict of law principles that would result in the application of any law other than the law
of the State of California. 
 7. This Amendment 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. This Amendment may also be executed and delivered by facsimile signature and 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. 
 8. Sections 6.1, 6.5, 6.7, 6.8, 6.10 and 6.11 of the Agreement are hereby incorporated by reference (mutatis
mutandis) as if set forth herein 
 [Remainder of Page Intentionally Left Blank]. 

  
 2 








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

  

			
	MYOKARDIA, INC.
		
	By:	 	 /s/ T. Anastasios Gianakakos

		 	Name: T. Anastasios Gianakakos
		 	Title: President and Chief Executive Officer









 
			
	INVESTOR:
	
	FIDELITY ADVISOR SERIES VII: FIDELITY ADVISOR BIOTECHNOLOGY FUND
		
	By:	 	 /s/ Kenneth Robins

		 	Name: Kenneth Robins
		 	Title: Authorized Signatory
	
	Address:
	 State Street Bank & Trust

PO Box 5756
 Boston, Massachusetts 02206

Attn: Bangle & Co fbo Fidelity Advisor Series VII: Fidelity Advisor Biotechnology Fund

Email: SSBCORPACTIONS@StateStreet.com
 Fax number:
617-988-9110










 
			
	INVESTOR:
	
	FIDELITY SELECT PORTFOLIOS: BIOTECHNOLOGY PORTFOLIO
		
	By:	 	 /s/ Kenneth Robins

		 	Name: Kenneth Robins
		 	Title: Authorized Signatory
	
	Address:
	 Brown Brothers Harriman & Co.

525 Washington Blvd

Jersey City NJ 07310

Attn: Michael Lerman 15th Floor

Corporate Actions

Email: michael.lerman@bbh.com

Fax number: 617 772-2418
















 
					
	 INVESTOR:

	
	 THIRD ROCK VENTURES II, L.P.

		
		 	By: Third Rock Ventures GP II, L.P., its general partner
		 	By: TRV GP II, LLC, its general partner
			
		 	By:	 	 /s/ Kevin Gillis

		 		 	Name: Kevin Gillis
		 		 	Title: CFO
			
	 Address:
	 		 	    29 Newbury Street; 3rd Floor
		 		 	     Boston, MA 02116

		 		 	     Phone: (617) 585-2000

		 		 	     Fax: (617) 859-2891










 
					
	 INVESTOR:

	
	 THIRD ROCK VENTURES III, L.P.

		
		 	By: Third Rock Ventures GP II, L.P., its general partner
		 	By: TRV GP II, LLC, its general partner
			
		 	By:	 	 /s/ Kevin Gillis

		 		 	Name: Kevin Gillis
		 		 	Title: CFO
			
	 Address:
	 		 	    29 Newbury Street; 3rd Floor
		 		 	     Boston, MA 02116

		 		 	     Phone: (617) 585-2000

		 		 	     Fax: (617) 859-2891










 SCHEDULE A 

Name and Contact of Investors 

THIRD ROCK VENTURES II, L.P. 

29 Newbury Street; 3rd Floor 

Boston, MA 02116 
 Phone:
(617)585-2000 
 Fax: (617) 859-2891 

http://www.thirdrockventures.com 

ALEXANDRIA EQUITIES, LLC, 

Alexandria Real Estate Equities, Inc. 

385 East Colorado Blvd., Suite 299 

Pasadena, CA 91101 
 Attn: Natasha
Moon 
 Phone: (626) 578-0777, x. 1619 

Fax: (626) 578-7252 
 http:/
/www.are.com 
 THIRD ROCK VENTURES III, L.P. 

29 Newbury Street; 3rd Floor 

Boston, MA 02116 
 Phone:
(617)585-2000 
 Fax: (617) 859-2891 

http://www.thirdrockventures.com 

AVENTIS INC. 
 c/o Sanofi
S.A. 
 54 rue La Boetie, 75008 Paris, France 

Facsimile: +33 1 53 77 44 53 

Attention: Vice President, Legal Operations 

BRIDGEBIO LLC 
 1 Maritime
Plaza, Suite 1940 
 San Francisco, CA 94111 

CORMORANT ASSET MANAGEMENT HEALTHCARE MASTER FUND, LP 

200 Clarendon Street 52nd Floor 

Boston, MA 02116 
 COWEN MK
INVESTMENT LLC 
 599 Lexington Avenue 

New York, NY 10022 
 Attn: Owen
Littman 
 FIDELITY SELECT PORTFOLIOS: BIOTECHNOLOGY PORTFOLIO 

Brown Brothers Harriman & Co. 

525 Washington Blvd 
 Jersey City NJ
07310 







 Attn: Michael Lerman 15th Floor 

Corporate Actions 
 Email:
michael.lerman@bbh.com 
 Fax number: 617 772-2418 

FIDELITY ADVISOR SERIES VII: FIDELITY ADVISOR BIOTECHNOLOGY FUND 

State Street Bank & Trust 

PO Box 5756 
 Boston, Massachusetts
02206 
 Attn: Bangle & Co fbo Fidelity Advisor Series VII: Fidelity Advisor Biotechnology Fund 

Email: SSBCORPACTIONS@StateStreet.com 

Fax number: 617-988-9110 

PERCEPTIVE LIFE SCIENCES MASTER FUND LTD 

499 Park Avenue, 25th Floor 
 New
York, NY 10022 
 Attn: James H. Mannix 

Phone: (646) 205-5340 
 Fax:
(646) 205-5301 
 TITAN PERC, LLC 

750 Washington Blvd., 10th Floor 

Stamford, CT 06901 
 Attn: Darren
Ross 
 Phone: (203) 327-8650 

Email: dross@titanadvisors.com 

Fax: (203) 327-8599 

Casdin Partners Master Fund LP 

1345 Avenue of the Americas, Suite 1140 

New York, NY 10019