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 UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 13G

(Rule 13d-102)

INFORMATION TO BE INCLUDED IN STATEMENTS FILED PURSUANT

TO RULES 13d-1(b), (c), AND (d) AND AMENDMENTS THERETO FILED

PURSUANT TO RULE 13d-2(b)

(Amendment No. 4)1

 

X4 Pharmaceuticals, Inc.

 (Name of Issuer)

Common Stock, par value $0.001 per share

 (Title of Class of Securities)

98420X103

 (CUSIP Number)

December 31, 2022

 (Date of Event Which Requires Filing of this Statement)

 

Check the appropriate box to designate the rule pursuant to which this Schedule is filed:

   ☐  Rule 13d-1(b)

   ☒  Rule 13d-1(c)

   ☐  Rule 13d-1(d)

 

 

 

1              The remainder of this cover page shall be filled out for a reporting person’s initial filing on this form with respect to the subject class of securities, and for any subsequent amendment containing information which would alter disclosures provided in a prior cover page.

The information required on the remainder of this cover page shall not be deemed to be “filed” for the purpose of Section 18 of the Securities Exchange Act of 1934 (“Act”) or otherwise subject to the liabilities of that section of the Act but shall be subject to all other provisions of the Act (however, see the Notes).

 

CUSIP No. 98420X103

 

  1   NAME OF REPORTING PERSON  
         
        Biotechnology Value Fund, L.P.  
  2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (a) ☒
        (b) ☐
           
  3   SEC USE ONLY    
           
             
  4   CITIZENSHIP OR PLACE OF ORGANIZATION  
         
        Delaware  
NUMBER OF   5   SOLE VOTING POWER  
SHARES          
BENEFICIALLY         0  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         1,172,223 (1)  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0  
    8   SHARED DISPOSITIVE POWER  
           
          1,172,223 (1)  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        1,172,223 (1)  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        Less than 1% (1)  
  12   TYPE OF REPORTING PERSON  
         
        PN  

  

(1) Includes 450,314 Shares (as defined below) underlying certain Class A Warrants (as defined below).

2

CUSIP No. 98420X103

  1   NAME OF REPORTING PERSON  
         
        BVF I GP LLC  
  2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (a) ☒
        (b) ☐
           
  3   SEC USE ONLY    
           
             
  4   CITIZENSHIP OR PLACE OF ORGANIZATION  
         
        Delaware  
NUMBER OF   5   SOLE VOTING POWER  
SHARES          
BENEFICIALLY         0  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         1,172,223 (1)  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0  
    8   SHARED DISPOSITIVE POWER  
           
          1,172,223 (1)  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        1,172,223 (1)  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        Less than 1% (1)  
  12   TYPE OF REPORTING PERSON  
         
        OO  

  

(1) Includes 450,314 Shares underlying certain Class A Warrants.

3

CUSIP No. 98420X103

 

  1   NAME OF REPORTING PERSON  
         
        Biotechnology Value Fund II, L.P.  
  2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (a) ☒
        (b) ☐
           
  3   SEC USE ONLY    
           
             
  4   CITIZENSHIP OR PLACE OF ORGANIZATION  
         
        Delaware  
NUMBER OF   5   SOLE VOTING POWER  
SHARES          
BENEFICIALLY         0  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         888,802 (1)  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0  
    8   SHARED DISPOSITIVE POWER  
           
          888,802 (1)  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        888,802 (1)  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        Less than 1% (1)  
  12   TYPE OF REPORTING PERSON  
         
        PN  

  

(1) Includes 363,810 Shares underlying certain Class A Warrants.

4

CUSIP No. 98420X103

 

  1   NAME OF REPORTING PERSON  
         
        BVF II GP LLC  
  2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (a) ☒
        (b) ☐
           
  3   SEC USE ONLY    
           
             
  4   CITIZENSHIP OR PLACE OF ORGANIZATION  
         
        Delaware  
NUMBER OF   5   SOLE VOTING POWER  
SHARES          
BENEFICIALLY         0  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         888,802 (1)  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0  
    8   SHARED DISPOSITIVE POWER  
           
          888,802 (1)  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        888,802 (1)  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        Less than 1% (1)  
  12   TYPE OF REPORTING PERSON  
         
        PN  

  

(1) Includes 363,810 Shares underlying certain Class A Warrants.

5

CUSIP No. 98420X103

 

  1   NAME OF REPORTING PERSON  
         
        Biotechnology Value Trading Fund OS LP  
  2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (a) ☒
        (b) ☐
           
  3   SEC USE ONLY    
           
             
  4   CITIZENSHIP OR PLACE OF ORGANIZATION  
         
        Cayman Islands  
NUMBER OF   5   SOLE VOTING POWER  
SHARES          
BENEFICIALLY         0  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         148,010 (1)  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0  
    8   SHARED DISPOSITIVE POWER  
           
          148,010 (1)  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        148,010 (1)  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        Less than 1% (1)  
  12   TYPE OF REPORTING PERSON  
         
        PN  

  

(1) Includes 64,996 Shares underlying certain Class A Warrants.

6

CUSIP No. 98420X103

 

  1   NAME OF REPORTING PERSON  
         
        BVF Partners OS Ltd.  
  2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (a) ☒
        (b) ☐
           
  3   SEC USE ONLY    
           
             
  4   CITIZENSHIP OR PLACE OF ORGANIZATION  
         
        Cayman Islands  
NUMBER OF   5   SOLE VOTING POWER  
SHARES          
BENEFICIALLY         0  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         148,010 (1)  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0  
    8   SHARED DISPOSITIVE POWER  
           
          148,010 (1)  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        148,010 (1)  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        Less than 1% (1)  
  12   TYPE OF REPORTING PERSON  
         
        CO  

  

(1) Includes 64,996 Shares underlying certain Class A Warrants.

7

CUSIP No. 98420X103

 

  1   NAME OF REPORTING PERSON  
         
        BVF GP Holdings LLC  
  2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (a) ☒
        (b) ☐
           
  3   SEC USE ONLY    
           
             
  4   CITIZENSHIP OR PLACE OF ORGANIZATION  
         
        Delaware  
NUMBER OF   5   SOLE VOTING POWER  
SHARES          
BENEFICIALLY         0  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         2,061,025 (1)  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0  
    8   SHARED DISPOSITIVE POWER  
           
          2,061,025 (1)  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        2,061,025 (1)  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        1.7% (1)  
  12   TYPE OF REPORTING PERSON  
         
        OO  

  

(1) Includes 814,124 Shares underlying certain Class A Warrants.

8

CUSIP No. 98420X103

 

  1   NAME OF REPORTING PERSON  
         
        BVF Partners L.P.  
  2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (a) ☒
        (b) ☐
           
  3   SEC USE ONLY    
           
             
  4   CITIZENSHIP OR PLACE OF ORGANIZATION  
         
        Delaware  
NUMBER OF   5   SOLE VOTING POWER  
SHARES          
BENEFICIALLY         0  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         2,258,400 (1)  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0  
    8   SHARED DISPOSITIVE POWER  
           
          2,258,400 (1)  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        2,258,400 (1)  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        1.9% (1)  
  12   TYPE OF REPORTING PERSON  
         
        PN, IA  

  

(1) Includes 910,750 Shares underlying certain Class A Warrants.

9

CUSIP No. 98420X103

 

  1   NAME OF REPORTING PERSON  
         
        BVF Inc.  
  2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (a) ☒
        (b) ☐
           
  3   SEC USE ONLY    
           
             
  4   CITIZENSHIP OR PLACE OF ORGANIZATION  
         
        Delaware  
NUMBER OF   5   SOLE VOTING POWER  
SHARES          
BENEFICIALLY         0  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         2,258,400 (1)  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0  
    8   SHARED DISPOSITIVE POWER  
           
          2,258,400 (1)  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        2,258,400 (1)  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        1.9% (1)  
  12   TYPE OF REPORTING PERSON  
         
        CO  

  

(1) Includes 910,750 Shares underlying certain Class A Warrants.

10

CUSIP No. 98420X103

 

  1   NAME OF REPORTING PERSON  
         
        Mark N. Lampert  
  2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (a) ☒
        (b) ☐
           
  3   SEC USE ONLY    
           
             
  4   CITIZENSHIP OR PLACE OF ORGANIZATION  
         
        United States  
NUMBER OF   5   SOLE VOTING POWER  
SHARES          
BENEFICIALLY         0  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         2,258,400 (1)  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0  
    8   SHARED DISPOSITIVE POWER  
           
          2,258,400 (1)  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        2,258,400 (1)  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        1.9% (1)  
  12   TYPE OF REPORTING PERSON  
         
        IN  

  

(1) Includes 910,750 Shares underlying certain Class A Warrants.

11

CUSIP No. 98420X103

 

Item 1(a).Name of Issuer:

 

X4 Pharmaceuticals, Inc., a Delaware corporation (the “Issuer”).

 

Item 1(b).Address of Issuer’s Principal Executive Offices:

 

61 North Beacon Street, 4th Floor

Boston, Massachusetts 02134

 

Item 2(a).Name of Person Filing
Item 2(b).Address of Principal Business Office or, if None, Residence
Item 2(c).Citizenship

 

Biotechnology Value Fund, L.P. (“BVF”)

44 Montgomery St., 40th Floor

San Francisco, California 94104

Citizenship: Delaware

 

BVF I GP LLC (“BVF GP”)

44 Montgomery St., 40th Floor

San Francisco, California 94104

Citizenship: Delaware

 

Biotechnology Value Fund II, L.P. (“BVF2”)

44 Montgomery St., 40th Floor

San Francisco, California 94104

Citizenship: Delaware

 

BVF II GP LLC (“BVF2 GP”)

44 Montgomery St., 40th Floor

San Francisco, California 94104

Citizenship: Delaware

 

Biotechnology Value Trading Fund OS LP (“Trading Fund OS”)

PO Box 309 Ugland House

Grand Cayman, KY1-1104

Cayman Islands

Citizenship: Cayman Islands

 

BVF Partners OS Ltd. (“Partners OS”)

PO Box 309 Ugland House

Grand Cayman, KY1-1104

Cayman Islands

Citizenship: Cayman Islands

 

BVF GP Holdings LLC (“BVF GPH”)

44 Montgomery St., 40th Floor

San Francisco, California 94104

Citizenship: Delaware

 

BVF Partners L.P. (“Partners”)

44 Montgomery St., 40th Floor

San Francisco, California 94104

Citizenship: Delaware

12

CUSIP No. 98420X103

 

BVF Inc.

44 Montgomery St., 40th Floor

San Francisco, California 94104

Citizenship: Delaware

 

Mark N. Lampert (“Mr. Lampert”)

44 Montgomery St., 40th Floor

San Francisco, California 94104

Citizenship: United States

 

Each of the foregoing is referred to as a “Reporting Person” and collectively as the “Reporting Persons.”

 

Item 2(d).Title of Class of Securities:

 

Common Stock, par value $0.001 per share (the “Shares”)

 

Item 2(e).CUSIP Number:

 

98420X103

 

Item 3.If This Statement is Filed Pursuant to Rule 13d-1(b), or 13d-2(b) or (c), Check Whether the Person Filing is a:

 

    /x/ Not applicable.
       
  (a) / / Broker or dealer registered under Section 15 of the Exchange Act.
       
  (b) / / Bank as defined in Section 3(a)(6) of the Exchange Act.
       
  (c) / / Insurance company as defined in Section 3(a)(19) of the Exchange Act.
       
  (d) / / Investment company registered under Section 8 of the Investment Company Act.
       
  (e) / / An investment adviser in accordance with Rule 13d-1(b)(1)(ii)(E).
       
  (f) / / An employee benefit plan or endowment fund in accordance with Rule 13d-1(b)(1)(ii)(F).
       
  (g) / / A parent holding company or control person in accordance with Rule 13d-1(b)(1)(ii)(G).
       
  (h) / / A savings association as defined in Section 3(b) of the Federal Deposit Insurance Act.
       
  (i) / / A church plan that is excluded from the definition of an investment company under Section 3(c)(14) of the Investment Company Act.
       
  (j) / / A non-U.S. institution in accordance with Rule 13d-1(b)(1)(ii)(J).
       
  (k) / / Group, in accordance with Rule 13d-1(b)(1)(ii)(K). If filing as a non-U.S. institution in accordance with Rule 13d-1(b)(1)(ii)(J), please specify the type of institution: ____

 

13

CUSIP No. 98420X103

Item 4.Ownership

 

(a)Amount beneficially owned:

 

As of the close of business on December 31, 2022, the Reporting Persons held 910,750 Class A Warrants (the “Class A Warrants”) exercisable into an aggregate of 910,750 Shares. Each Class A Warrant has an exercise price per Share equal to $13.20 and expires on April 16, 2024. The Class A Warrants are exercisable, at the option of each holder, provided that the holder will be prohibited, subject to certain exceptions, from exercising the Class A Warrants for Shares to the extent that immediately prior to or after giving effect to such exercise, the holder, together with its affiliates and other attribution parties, would own more than 9.99% of the total number of Shares then issued and outstanding (the “Class A Blocker”). As of the close of business on December 31, 2022, the Class A Blocker does not limit the exercise of any of the Class A Warrants held by the Reporting Persons.

 

As of the close of business on December 31, 2022, (i) BVF beneficially owned 1,172,223 Shares, including 450,314 Shares issuable upon conversion of certain Class A Warrants held by it, (ii) BVF2 beneficially owned 888,802 Shares, including 363,810 Shares issuable upon conversion of certain Class A Warrants held by it, and (iii) Trading Fund OS beneficially owned 148,010 Shares, including 64,996 Shares issuable upon conversion of certain Class A Warrants held by it.

 

BVF GP, as the general partner of BVF, may be deemed to beneficially own the 1,172,223 Shares beneficially owned by BVF.

 

BVF2 GP, as the general partner of BVF2, may be deemed to beneficially own the 888,802 Shares beneficially owned by BVF2.

 

Partners OS, as the general partner of Trading Fund OS, may be deemed to beneficially own the 148,010 Shares beneficially owned by Trading Fund OS.

 

BVF GPH, as the sole member of each of BVF GP and BVF2 GP, may be deemed to beneficially own the 2,061,025 Shares beneficially owned in the aggregate by BVF and BVF2.

 

Partners, as the investment manager of BVF, BVF2 and Trading Fund OS, and the sole member of Partners OS, may be deemed to beneficially own the 2,258,400 Shares beneficially owned in the aggregate by BVF, BVF2 and Trading Fund OS and held in a certain Partners managed account (the “Partners Managed Account”), including 49,365 Shares held in the Partners Managed Account, which includes 31,630 Shares issuable upon conversion of certain Class A Warrants held in the Partners Managed Account.

 

BVF Inc., as the general partner of Partners, may be deemed to beneficially own the 2,258,400 Shares beneficially owned by Partners.

14

CUSIP No. 98420X103

 

Mr. Lampert, as a director and officer of BVF Inc., may be deemed to beneficially own the 2,258,400 Shares beneficially owned by BVF Inc.

 

The foregoing should not be construed in and of itself as an admission by any Reporting Person as to beneficial ownership of any Shares owned by another Reporting Person. BVF GP disclaims beneficial ownership of the Shares beneficially owned by BVF. BVF2 GP disclaims beneficial ownership of the Shares beneficially owned by BVF2. Partners OS disclaims beneficial ownership of the Shares beneficially owned by Trading Fund OS. BVF GPH disclaims beneficial ownership of the Shares beneficially owned by BVF and BVF2. Each of Partners, BVF Inc. and Mr. Lampert disclaims beneficial ownership of the Shares beneficially owned by BVF, BVF2 and Trading Fund OS and held in the Partners Managed Account, and the filing of this statement shall not be construed as an admission that any such person or entity is the beneficial owner of any such securities.

 

(b)Percent of class:

 

The following percentages are based on a denominator that is the sum of (i) 121,034,553 Shares outstanding which is the total number of Shares outstanding as disclosed in the Issuer’s Prospectus Supplement on Form 424B5 filed with the Securities and Exchange Commission on December 9, 2022 and (ii) certain or all of 910,750 Shares issuable upon the exercise of the Class A Warrants held by the Reporting Persons, as applicable.

 

As of the close of business on December 31, 2022, (i) BVF beneficially owned less than 1% of the outstanding Shares, (ii) BVF2 beneficially owned less than 1% of the outstanding Shares, (iii) Trading Fund OS beneficially owned less than 1% of the outstanding Shares, (iv) BVF GP may be deemed to beneficially own less than 1% of the outstanding Shares, (v) BVF2 GP may be deemed to beneficially own less than 1% of the outstanding Shares, (vi) Partners OS may be deemed to beneficially own less than 1% of the outstanding Shares, (vii) BVF GPH may be deemed to beneficially own approximately 1.7% of the outstanding Shares, and (viii) each of Partners, BVF Inc. and Mr. Lampert may be deemed to beneficially own approximately 1.9% of the outstanding Shares (less than 1% of the outstanding Shares are held in the Partners Managed Account).

 

(c)Number of shares as to which such person has:

 

(i)Sole power to vote or to direct the vote

 

See Cover Pages Items 5-9.

 

(ii)Shared power to vote or to direct the vote

 

See Cover Pages Items 5-9.

 

(iii)Sole power to dispose or to direct the disposition of

 

See Cover Pages Items 5-9.

 

(iv)Shared power to dispose or to direct the disposition of

 

See Cover Pages Items 5-9.

15

CUSIP No. 98420X103

 

Item 5.Ownership of Five Percent or Less of a Class.

 

If this statement is being filed to report the fact that as of the date hereof the Reporting Persons have ceased to be the beneficial owner of more than five percent of the Shares, check the following [X].

 

Item 6.Ownership of More than Five Percent on Behalf of Another Person.

 

Not Applicable.

 

Item 7.Identification and Classification of the Subsidiary That Acquired the Security Being Reported on by the Parent Holding Company or Control Person.

 

Not Applicable.

 

Item 8.Identification and Classification of Members of the Group.

 

See Exhibit 99.1 to Amendment No. 1 to the Schedule 13G filed with the Securities and Exchange Commission on February 14, 2020.

 

Item 9.Notice of Dissolution of Group.

 

Not Applicable.

 

Item 10.Certifications.

 

By signing below each of the undersigned certifies that, to the best of its knowledge and belief, the securities referred to above were not acquired and are not held for the purpose of or with the effect of changing or influencing the control of the issuer of the securities and were not acquired and are not held in connection with or as a participant in any transaction having that purpose or effect.

16

CUSIP No. 98420X103

SIGNATURE

 

After reasonable inquiry and to the best of his knowledge and belief, each of the undersigned certifies that the information set forth in this statement is true, complete and correct.

Dated: February 14, 2023

 

BIOTECHNOLOGY VALUE FUND, L.P.   BIOTECHNOLOGY VALUE TRADING FUND OS LP
       
By: BVF I GP LLC, its general partner   By: BVF Partners L.P., its investment manager
      By: BVF Inc., its general partner
By:

/s/ Mark N. Lampert

      
  Mark N. Lampert   By: /s/ Mark N. Lampert
  Chief Executive Officer     Mark N. Lampert
        President
         
BVF I GP LLC      
      BVF GP HOLDINGS LLC
By: /s/ Mark N. Lampert    
  Mark N. Lampert   By: /s/ Mark N. Lampert
  Chief Executive Officer     Mark N. Lampert
        Chief Executive Officer
         
BIOTECHNOLOGY VALUE FUND II, L.P.    
      BVF PARTNERS L.P.
By: BVF II GP LLC, its general partner    
      By: BVF Inc., its general partner
By:

/s/ Mark N. Lampert

      
  Mark N. Lampert   By: /s/ Mark N. Lampert
  Chief Executive Officer     Mark N. Lampert
        President
         
BVF II GP LLC      
      BVF INC.
By: /s/ Mark N. Lampert    
  Mark N. Lampert   By: /s/ Mark N. Lampert
  Chief Executive Officer     Mark N. Lampert
        President
         
BVF PARTNERS OS LTD.      
      /s/ Mark N. Lampert
By: BVF Partners L.P., its sole member   MARK N. LAMPERT
By: BVF Inc., its general partner    
         
By:

/s/ Mark N. Lampert

    
  Mark N. Lampert    
  President      

 

17