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. 3)¹

Regulus Therapeutics Inc.

 (Name of Issuer)

Common Stock, $0.001 par value

 (Title of Class of Securities)

75915K200

 (CUSIP Number)

December 31, 2018

 (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. 75915K200

	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					511,693
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					511,693
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			511,693
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			5.8%
	12	TYPE OF REPORTING PERSON
			PN

2

CUSIP NO. 75915K200

	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					326,555
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					326,555
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			326,555
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			3.7%
	12	TYPE OF REPORTING PERSON
			PN

3

CUSIP NO. 75915K200

	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					87,461
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					87,461
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			87,461
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			1.0%
	12	TYPE OF REPORTING PERSON
			PN

4

CUSIP NO. 75915K200

	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					87,461
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					87,461
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			87,461
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			1.0%
	12	TYPE OF REPORTING PERSON
			CO

5

CUSIP NO. 75915K200

	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					1,051,940
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					1,051,940
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			1,051,940
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			12.0%
	12	TYPE OF REPORTING PERSON
			PN, IA

6

CUSIP NO. 75915K200

	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					1,051,940
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					1,051,940
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			1,051,940
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			12.0%
	12	TYPE OF REPORTING PERSON
			CO

7

CUSIP NO. 75915K200

	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					1,051,940
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					1,051,940
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			1,051,940
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			12.0%
	12	TYPE OF REPORTING PERSON
			IN

8

CUSIP NO. 75915K200

Item 1(a). Name of Issuer:

Regulus Therapeutics Inc., a Delaware corporation (the “Issuer”).

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

10614 Science Center Drive

San Diego, California 92121

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

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

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 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.”

9

CUSIP NO. 75915K200

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

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

Item 2(e). CUSIP Number:

75915K200

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, 2018 (i) BVF beneficially owned 511,693 shares of Common Stock, (ii) BVF2 beneficially owned 326,555 shares of Common Stock, and (iii) Trading Fund OS beneficially owned 87,461 shares of Common Stock.

Partners OS, as the general partner of Trading Fund OS, may be deemed to beneficially own the 87,461 shares of Common Stock beneficially owned by Trading Fund OS.

10

CUSIP NO. 75915K200

Partners, as the general partner of BVF, BVF2, the investment manager of Trading Fund OS, and the sole member of Partners OS, may be deemed to beneficially own the 1,051,940 shares of Common Stock beneficially owned in the aggregate by BVF, BVF2, Trading Fund OS, and a certain Partners managed account (the “Partners Managed Account”), including 126,231 shares of Common Stock held in the Partners Managed Account.

BVF Inc., as the general partner of Partners, may be deemed to beneficially own the 1,051,940 Common Stock beneficially owned by Partners.

Mr. Lampert, as a director and officer of BVF Inc., may be deemed to beneficially own the 1,051,940 Common Stock 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 Common Stock owned by another Reporting Person. Partners OS disclaims beneficial ownership of the Common Stock beneficially owned by Trading Fund OS. Each of Partners, BVF Inc. and Mr. Lampert disclaims beneficial ownership of the Common Stock 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 8,750,343 shares of Common Stock outstanding as of November 2, 2018, which is the total number of shares of Common Stock outstanding as reported in the Issuer’s Quarterly Report filed on Form 10-Q with the Securities and Exchange Commission on November 9, 2018.

As of the close of business on December 31, 2018 (i) BVF beneficially owned approximately 5.8% of the outstanding Common Stock, (ii) BVF2 beneficially owned approximately 3.7% of the outstanding Common Stock, (iii) Trading Fund OS beneficially owned approximately 1.0% of the outstanding Common Stock, (iv) Partners OS may be deemed to beneficially own approximately 1.0% of the outstanding Common Stock, and (v) each of Partners, BVF Inc. and Mr. Lampert may be deemed to beneficially own approximately 12.0% of the outstanding Common Stock (approximately 1.4% of the outstanding Common Stock is 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.

11

CUSIP NO. 75915K200

(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.

Partners, BVF Inc. and Mr. Lampert share voting and dispositive power over the shares of Common Stock beneficially owned by BVF, BVF2, 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 to Schedule 13G filed with the Securities and Exchange Commission on May 5, 2017.

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.

12

CUSIP NO. 75915K200

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, 2019

BIOTECHNOLOGY VALUE FUND, L.P.		BVF INC.
By:	BVF Partners L.P., its general partner	By:	/s/ Mark N. Lampert
By:	BVF Inc., its general partner		Mark N. Lampert
			President
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President	/s/ Mark N. Lampert
		MARK N. LAMPERT
BIOTECHNOLOGY VALUE FUND II, L.P.
By:	BVF Partners L.P., its general partner
By:	BVF Inc., its general partner
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President
BVF PARTNERS L.P.
By:	BVF Inc., its general partner
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President
BVF PARTNERS OS LTD.
By:	BVF Partners L.P., its sole member
By:	BVF Inc., its general partner
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President
Biotechnology Value Trading Fund OS LP
By:	BVF Partners L.P., its investment manager
By:	BVF Inc., its general partner
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President

13