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. 1)1

 

Principia Biopharma Inc.

 (Name of Issuer)

Common Stock, $0.0001 par value

 (Title of Class of Securities)

74257L108

 (CUSIP Number)

December 31, 2019

 (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. 74257L108

 

  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 shares  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         866,814  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0 shares  
    8   SHARED DISPOSITIVE POWER  
           
          866,814  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        866,814  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        2.6%  
  12   TYPE OF REPORTING PERSON  
         
        PN  

  

2

CUSIP No. 74257L108

  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 shares  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         866,814  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0 shares  
    8   SHARED DISPOSITIVE POWER  
           
          866,814  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        866,814  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        2.6%  
  12   TYPE OF REPORTING PERSON  
         
        OO  

  

3

CUSIP No. 74257L108

 

  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 shares  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         679,147  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0 shares  
    8   SHARED DISPOSITIVE POWER  
           
          679,147  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        679,147  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        2.1%  
  12   TYPE OF REPORTING PERSON  
         
        PN  

  

4

CUSIP No. 74257L108

 

  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 shares  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         679,147  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0 shares  
    8   SHARED DISPOSITIVE POWER  
           
          679,147  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        679,147  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        2.1%  
  12   TYPE OF REPORTING PERSON  
         
        OO  

  

5

CUSIP No. 74257L108

 

  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 shares  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         118,362  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0 shares  
    8   SHARED DISPOSITIVE POWER  
           
          118,362  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        118,362  
  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%  
  12   TYPE OF REPORTING PERSON  
         
        PN  

  

6

CUSIP No. 74257L108

 

  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 shares  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         118,362  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0 shares  
    8   SHARED DISPOSITIVE POWER  
           
          118,362  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        118,362  
  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%  
  12   TYPE OF REPORTING PERSON  
         
        CO  

  

7

CUSIP No. 74257L108

 

  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 shares  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         1,545,961  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0 shares  
    8   SHARED DISPOSITIVE POWER  
           
          1,545,961  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        1,545,961  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        4.7%  
  12   TYPE OF REPORTING PERSON  
         
        OO  

  

8

CUSIP No. 74257L108

 

  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 shares  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         1,716,734  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0 shares  
    8   SHARED DISPOSITIVE POWER  
           
          1,716,734  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        1,716,734  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        5.2%  
  12   TYPE OF REPORTING PERSON  
         
        PN, IA  

  

9

CUSIP No. 74257L108

 

  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 shares  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         1,716,734  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0 shares  
    8   SHARED DISPOSITIVE POWER  
           
          1,716,734  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        1,716,734  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        5.2%  
  12   TYPE OF REPORTING PERSON  
         
        CO  

  

10

CUSIP No. 74257L108

 

  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 shares  
OWNED BY   6   SHARED VOTING POWER  
EACH          
REPORTING         1,716,734  
PERSON WITH   7   SOLE DISPOSITIVE POWER  
         
          0 shares  
    8   SHARED DISPOSITIVE POWER  
           
          1,716,734  
  9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON  
         
        1,716,734  
  10   CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES     ☐
       
           
  11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)  
         
        5.2%  
  12   TYPE OF REPORTING PERSON  
         
        IN  

  

11

CUSIP No. 74257L108

Item 1(a).Name of Issuer:

 

Principia Biopharma Inc., a Delaware corporation (the “Issuer”).

 

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

 

220 East Grand Avenue

South San Francisco, California 94080

 

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

 

12

CUSIP No. 74257L108

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

 

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, $0.0001 par value per share (the “Shares”).

 

Item 2(e).CUSIP Number:

 

74257L108

 

13

CUSIP No. 74257L108

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) / / Group, in accordance with Rule 13d-1(b)(1)(ii)(J).
       
  (k) / / Group, in accordance with Rule 240.13d-1(b)(1)(ii)(K). If filing as a non-U.S. institution in accordance with Rule 240.13d-1(b)(1)(ii)(J), please specify the type of institution: ____

 

Item 4.Ownership

 

(a)Amount beneficially owned:

 

As of the close of business on December 31, 2019, (i) BVF beneficially owned 866,814 Shares, (ii) BVF2 beneficially owned 679,147 Shares, and (iii) Trading Fund OS beneficially owned 118,362 Shares.

 

BVF GP, as the general partner of BVF, may be deemed to beneficially own the 866,814 Shares beneficially owned by BVF.

 

BVF2 GP, as the general partner of BVF2, may be deemed to beneficially own the 679,147 Shares beneficially owned by BVF2.

 

14

CUSIP No. 74257L108

Partners OS, as the general partner of Trading Fund OS, may be deemed to beneficially own the 118,362 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 1,545,961 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 1,716,734 Shares beneficially owned in the aggregate by BVF, BVF2, Trading Fund OS, and a certain Partners managed account (the “Partners Managed Account”), including 52,411 Shares held in the Partners Managed Account.

 

BVF Inc., as the general partner of Partners, may be deemed to beneficially own the 1,716,734 Shares beneficially owned by Partners.

 

Mr. Lampert, as a director and officer of BVF Inc., may be deemed to beneficially own the 1,716,734 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, Trading Fund OS, and 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 32,786,610 Shares outstanding as of October 31, 2019, as reported in the Issuer’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 5, 2019.

 

As of the close of business on December 31, 2019, (i) BVF beneficially owned approximately 2.6% of the outstanding Shares, (ii) BVF2 beneficially owned approximately 2.1% 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 approximately 2.6% of the outstanding Shares, (v) BVF2 GP may be deemed to beneficially own approximately 2.1% 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 4.7% of the outstanding Shares, and (viii) each of Partners, BVF Inc. and Mr. Lampert may be deemed to beneficially own approximately 5.2% of the outstanding Shares (less than 1% of the outstanding Shares is held in the Partners Managed Account).

 

15

CUSIP No. 74257L108

(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.

 

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

 

Not Applicable.

 

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

 

BVF GPH, Partners, BVF Inc. and Mr. Lampert share voting and dispositive power over the Shares beneficially owned by BVF and BVF2. Partners, BVF Inc. and Mr. Lampert share voting and dispositive power over the Shares beneficially owned by Trading Fund OS and the Partners Managed Account.

 

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.

 

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. 74257L108

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, 2020

 

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 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 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 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

Exhibit 99.1

 

Joint Filing Agreement

 

The undersigned hereby agree that the Statement on Schedule 13G dated February 14, 2020 with respect to the shares of Common Stock of Principia Biopharma Inc., and any further amendments thereto executed by each and any of the undersigned shall be filed on behalf of each of the undersigned pursuant to and in accordance with the provisions of Rule 13d-1(k)(1) under the Securities Exchange Act of 1934, as amended.

 

Dated: February 14, 2020

  

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 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 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 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