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

Lexicon Pharmaceuticals, Inc.

 (Name of Issuer)

Common Stock, par value $0.001

 (Title of Class of Securities)

528872302

 (CUSIP Number)

December 31, 2021

 (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. 528872302

	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					7,557,501
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					7,557,501
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			7,557,501
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			5.1%
	12	TYPE OF REPORTING PERSON
			PN

2

CUSIP No. 528872302

	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					7,557,501
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					7,557,501
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			7,557,501
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			5.1%
	12	TYPE OF REPORTING PERSON
			OO

3

CUSIP No. 528872302

	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					5,665,077
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					5,665,077
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			5,665,077
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			3.8%
	12	TYPE OF REPORTING PERSON
			PN

4

CUSIP No. 528872302

	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					5,665,077
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					5,665,077
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			5,665,077
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			3.8%
	12	TYPE OF REPORTING PERSON
			OO

5

CUSIP No. 528872302

	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					869,596
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					869,596
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			869,596
	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. 528872302

	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					869,596
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					869,596
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			869,596
	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. 528872302

	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					13,222,578
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					13,222,578
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			13,222,578
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			8.9%
	12	TYPE OF REPORTING PERSON
			OO

8

CUSIP No. 528872302

	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					14,360,000
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					14,360,000
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			14,360,000
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			9.6%
	12	TYPE OF REPORTING PERSON
			PN, IA

9

CUSIP No. 528872302

	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					14,360,000
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					14,360,000
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			14,360,000
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			9.6%
	12	TYPE OF REPORTING PERSON
			CO

10

CUSIP No. 528872302

	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					14,360,000
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					14,360,000
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			14,360,000
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			9.6%
	12	TYPE OF REPORTING PERSON
			IN

11

CUSIP No. 528872302

Item 1(a). Name of Issuer:

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

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

2445 Technology Forest Blvd.

11th Floor

The Woodlands, Texas 77381

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. 528872302

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 (the “Shares”).

Item 2(e). CUSIP Number:

528872302

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: ____

13

CUSIP No. 528872302

Item 4. Ownership

(a) Amount beneficially owned:

As of the close of business on December 31, 2021, (i) BVF beneficially owned 7,557,501 Shares, (ii) BVF2 beneficially owned 5,665,077 Shares and (iii) Trading Fund OS beneficially owned 869,596 Shares.

BVF GP, as the general partner of BVF, may be deemed to beneficially own the 7,557,501 Shares beneficially owned by BVF.

BVF2 GP, as the general partner of BVF2, may be deemed to beneficially own the 5,665,077 Shares beneficially owned by BVF2.

Partners OS, as the general partner of Trading Fund OS, may be deemed to beneficially own the 869,596 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 13,222,578 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 14,360,000 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 267,826 Shares held in the Partners Managed Account.

BVF Inc., as the general partner of Partners, may be deemed to beneficially own the 14,360,000 Shares beneficially owned by Partners.

Mr. Lampert, as a director and officer of BVF Inc., may be deemed to beneficially own the 14,360,000 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 148,895,707 Shares outstanding, which is the total number of Shares outstanding as disclosed in the Issuer’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 9, 2021.

14

CUSIP No. 528872302

As of the close of business on December 31, 2021, (i) BVF beneficially owned approximately 5.1% of the outstanding Shares, (ii) BVF2 beneficially owned approximately 3.8% 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 5.1% of the outstanding Shares, (v) BVF2 GP may be deemed to beneficially own approximately 3.8% 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 8.9% of the outstanding Shares and (viii) each of Partners, BVF Inc. and Mr. Lampert may be deemed to beneficially own approximately 9.6% 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.

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 GP, BVF GPH, Partners, BVF Inc. and Mr. Lampert share voting and dispositive power over the Shares beneficially owned by BVF. BVF GPH, Partners, BVF Inc. and Mr. Lampert share voting and dispositive power over the Shares beneficially owned BVF2. Partners, BVF Inc. and Mark Lampert share voting and dispositive power over the Shares beneficially owned by Trading Fund OS and the Shares held in 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 to the Schedule 13G filed on December 21, 2020.

15

CUSIP No. 528872302

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. 528872302

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 11, 2022

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