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. 2)¹

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

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).

(1) Includes 288,771 shares of Common Stock underlying certain A Warrants (defined in Item 4) owned by BVF. The A Warrants are subject to the A Warrants Blocker (defined in Item 4).

Includes 237,931 shares of Common Stock underlying certain B Warrants (defined in Item 4) owned by BVF. Excludes 50,839 shares of Common Stock underlying certain B Warrants owned by BVF, as a result of the B Warrants Blocker (defined in Item 4). As of the close of business on December 31, 2018, the B Warrants Blocker limits the aggregate exercise of B Warrants by the Reporting Persons to 237,931 out of the 624,999 shares of Common Stock underlying the B Warrants owned by the Reporting Persons in the aggregate.

Excludes 500,000 shares of Common Stock underlying certain New Warrants (defined in Item 4) owned by BVF, as a result of the New Warrants Blocker (defined in Item 4). As of the close of business on December 31, 2018, the New Warrants Blocker limits the aggregate exercise of New Warrants by the Reporting Persons to 0 out of the 1,000,000 shares of Common Stock underlying the New Warrants owned by the Reporting Persons in the aggregate.

See Item 4(a) for a full description of the Reporting Person’s beneficial ownership.  

(1) Includes 227,228 shares of Common Stock underlying certain A Warrants (defined in Item 4) owned by BVF2. The A Warrants are subject to the A Warrants Blocker (defined in Item 4).

Excludes 227,227 shares of Common Stock underlying certain B Warrants (defined in Item 4) owned by BVF2, as a result of the B Warrants Blocker (defined in Item 4). As of the close of business on December 31, 2018, the B Warrants Blocker limits the aggregate exercise of B Warrants by the Reporting Persons to 237,931 out of the 624,999 shares of Common Stock underlying the B Warrants owned by the Reporting Persons in the aggregate.

Excludes 410,000 shares of Common Stock underlying certain New Warrants (defined in Item 4) owned by BVF2, as a result of the New Warrants Blocker (defined in Item 4). As of the close of business on December 31, 2018, the New Warrants Blocker limits the aggregate exercise of New Warrants by the Reporting Persons to 0 out of the 1,000,000 shares of Common Stock underlying the Warrants owned by the Reporting Persons in the aggregate.

See Item 4(a) for a full description of the Reporting Person’s beneficial ownership.  

(1) Includes 44,132 shares of Common Stock underlying certain A Warrants (defined in Item 4) owned by Trading Fund OS. The A Warrants are subject to the A Warrants Blocker (defined in Item 4).

Excludes 44,132 shares of Common Stock underlying certain B Warrants (defined in Item 4) owned by Trading Fund OS, as a result of the B Warrants Blocker (defined in Item 4). As of the close of business on December 31, 2018, the B Warrants Blocker limits the aggregate exercise of B Warrants by the Reporting Persons to 237,931 out of the 624,999 shares of Common Stock underlying the B Warrants owned by the Reporting Persons in the aggregate.

Excludes 90,000 shares of Common Stock underlying certain New Warrants (defined in Item 4) owned by Trading Fund OS, as a result of the New Warrants Blocker (defined in Item 4). As of the close of business on December 31, 2018, the New Warrants Blocker limits the aggregate exercise of New Warrants by the Reporting Persons to 0 out of the 1,000,000 shares of Common Stock underlying the New Warrants owned by the Reporting Persons in the aggregate.

See Item 4(a) for a full description of the Reporting Person’s beneficial ownership.  

(1) Includes 44,132 shares of Common Stock underlying certain A Warrants (defined in Item 4) owned by Trading Fund OS. The A Warrants are subject to the A Warrants Blocker (defined in Item 4).

Excludes 44,132 shares of Common Stock underlying certain B Warrants (defined in Item 4) owned by Trading Fund OS, as a result of the B Warrants Blocker (defined in Item 4). As of the close of business on December 31, 2018, the B Warrants Blocker limits the aggregate exercise of B Warrants by the Reporting Persons to 237,931 out of the 624,999 shares of Common Stock underlying the B Warrants owned by the Reporting Persons in the aggregate.

Excludes 90,000 shares of Common Stock underlying certain New Warrants (defined in Item 4) owned by Trading Fund OS, as a result of the New Warrants Blocker (defined in Item 4). As of the close of business on December 31, 2018, the New Warrants Blocker limits the aggregate exercise of New Warrants by the Reporting Persons to 0 out of the 1,000,000 shares of Common Stock underlying the New Warrants owned by the Reporting Persons in the aggregate.

See Item 4(a) for a full description of the Reporting Person’s beneficial ownership.  

(1) Includes 625,001 shares of Common Stock underlying certain A Warrants (defined in Item 4) owned by the Reporting Persons. The A Warrants are subject to the A Warrants Blocker (defined in Item 4).

Includes 237,931 shares of Common Stock underlying certain B Warrants (defined in Item 4) owned by the Reporting Persons. Excludes 387,068 shares of Common Stock underlying certain B Warrants owned by the Reporting Persons, as a result of the B Warrants Blocker (defined in Item 4). As of the close of business on December 31, 2018, the B Warrants Blocker limits the aggregate exercise of B Warrants by the Reporting Persons to 237,931 out of the 624,999 shares of Common Stock underlying the B Warrants owned by the Reporting Persons in the aggregate.

Excludes 1,000,000 shares of Common Stock underlying certain New Warrants (defined in Item 4) owned by the Reporting Persons, as a result of the New Warrants Blocker (defined in Item 4). As of the close of business on December 31, 2018, the New Warrants Blocker limits the aggregate exercise of New Warrants by the Reporting Persons to 0 out of the 1,000,000 shares of Common Stock underlying the New Warrants owned by the Reporting Persons in the aggregate.  

(1) Includes 625,001 shares of Common Stock underlying certain A Warrants (defined in Item 4) owned by the Reporting Persons. The A Warrants are subject to the A Warrants Blocker (defined in Item 4).

Includes 237,931 shares of Common Stock underlying certain B Warrants (defined in Item 4) owned by the Reporting Persons. Excludes 387,068 shares of Common Stock underlying certain B Warrants owned by the Reporting Persons, as a result of the B Warrants Blocker (defined in Item 4). As of the close of business on December 31, 2018, the B Warrants Blocker limits the aggregate exercise of B Warrants by the Reporting Persons to 237,931 out of the 624,999 shares of Common Stock underlying the B Warrants owned by the Reporting Persons in the aggregate.

Excludes 1,000,000 shares of Common Stock underlying certain New Warrants (defined in Item 4) owned by the Reporting Persons, as a result of the New Warrants Blocker (defined in Item 4). As of the close of business on December 31, 2018, the New Warrants Blocker limits the aggregate exercise of New Warrants by the Reporting Persons to 0 out of the 1,000,000 shares of Common Stock underlying the New Warrants owned by the Reporting Persons in the aggregate.

See Item 4(a) for a full description of the Reporting Person’s beneficial ownership.  

(1) Includes 625,001 shares of Common Stock underlying certain A Warrants (defined in Item 4) owned by the Reporting Persons. The A Warrants are subject to the A Warrants Blocker (defined in Item 4).

Includes 237,931 shares of Common Stock underlying certain B Warrants (defined in Item 4) owned by the Reporting Persons. Excludes 387,068 shares of Common Stock underlying certain B Warrants owned by the Reporting Persons, as a result of the B Warrants Blocker (defined in Item 4). As of the close of business on December 31, 2018, the B Warrants Blocker limits the aggregate exercise of B Warrants by the Reporting Persons to 237,931 out of the 624,999 shares of Common Stock underlying the B Warrants owned by the Reporting Persons in the aggregate.

Excludes 1,000,000 shares of Common Stock underlying certain New Warrants (defined in Item 4) owned by the Reporting Persons, as a result of the New Warrants Blocker (defined in Item 4). As of the close of business on December 31, 2018, the New Warrants Blocker limits the aggregate exercise of New Warrants by the Reporting Persons to 0 out of the 1,000,000 shares of Common Stock underlying the New Warrants owned by the Reporting Persons in the aggregate.

See Item 4(a) for a full description of the Reporting Person’s beneficial ownership.  

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

7707 Gateway Boulevard, Suite 140

Newark, California 94560

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

44 Montgomery St., 40^th Floor

San Francisco, California 94104

Citizenship: Delaware

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

44 Montgomery St., 40^th 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., 40^th Floor

San Francisco, California 94104

Citizenship: Delaware

BVF Inc.

44 Montgomery St., 40^th Floor

San Francisco, California 94104

Citizenship: Delaware

Mark N. Lampert (“Mr. Lampert”)

44 Montgomery St., 40^th 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.”

Common Stock, $0.00001 par value (the “Common Stock”)

74366E102

The Reporting Persons hold 625,001 Class A Warrants (the “A Warrants”) exercisable for an aggregate of 625,001 shares of Common Stock. The A Warrants have an exercise price of $10 per share and expire on August 8, 2023. The A Warrants may not be exercised if, after such exercise, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Exchange Act, more than 9.99% of the number of shares of Common Stock then issued and outstanding (the “A Warrants Blocker”). In providing beneficial ownership described herein, the Reporting Persons have assumed the A Warrants owned by each of BVF, BVF2 and Trading Fund OS and held in Partners managed accounts (the “Partners Managed Accounts”) would be fully exercised.

In addition to the A Warrants, the Reporting Persons hold 624,999 Class B Warrants (the “B Warrants”) exercisable for an aggregate of 624,999 shares of Common Stock. The B Warrants have an exercise price of $15 per share and expire on August 8, 2023. The B Warrants may not be exercised if, after such exercise, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Exchange Act, more than 9.99% of the number of shares of Common Stock then issued and outstanding (the “B Warrants Blocker”). As of the close of business on December 31, 2018, the B Warrants Blocker limits the aggregate exercise of B Warrants by the Reporting Persons to 237,931 out of the 624,999 shares of Common Stock underlying the B Warrants owned by the Reporting Persons in the aggregate. In providing beneficial ownership described herein, the Reporting Persons have assumed that 237,931 of certain B Warrants owned by BVF have been exercised and the remaining B Warrants owned by BVF, BVF2 and Trading Fund OS and held in the Partners Managed Accounts would not be exercised due to the B Warrants Blocker.

In addition to the A and B Warrants, the Reporting Persons hold 1,000,000 Warrants (the “New Warrants”) exercisable for an aggregate of 1,000,000 shares of Common Stock. The New Warrants are pre-funded warrants and have an exercise price of $0.00001 per share and expire on December 21, 2028. The New Warrants may not be exercised if, after such exercise, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Exchange Act, more than 9.99% of the number of shares of Common Stock then issued and outstanding (the “New Warrants Blocker”). As of the close of business on December 31, 2018, the New Warrants Blocker limits the aggregate exercise of New Warrants by the Reporting Persons to 0 out of the 1,000,000 shares of Common Stock underlying the New Warrants owned by the Reporting Persons in the aggregate. In providing beneficial ownership described herein, the Reporting Persons have assumed the New Warrants owned by each of BVF, BVF2 and Trading Fund OS and held in the Partners Managed Accounts would not be exercised due to the New Warrants Blocker.

As of the close of business on December 31, 2018 (i) BVF beneficially owned 1,247,629 shares of Common Stock, including (a) 288,771 shares of Common Stock underlying certain A Warrants held by it and (b) 237,931 shares of Common Stock underlying certain B Warrants held by it, and excluding (a) 50,839 shares of Common Stock underlying certain B Warrants held by it and (b) 500,000 shares of Common Stock underlying certain New Warrants held by it; (ii) BVF2 beneficially owned 785,039 shares of Common Stock, including 227,228 shares of Common Stock underlying certain A Warrants held by it, and excluding (a) 227,227 shares of Common Stock underlying certain B Warrants held by it and (b) 410,000 shares of Common Stock underlying certain New Warrants held by it; and (iii) Trading Fund OS beneficially owned 153,328 shares of Common Stock, including 44,132 shares of Common Stock underlying certain A Warrants held by it, and excluding (a) 44,132 shares of Common Stock underlying certain B Warrants held by it and (b) 90,000 shares of Common Stock underlying certain New Warrants held by it.

Partners OS, as the general partner of Trading Fund OS, may be deemed to beneficially own the 153,328 shares of Common Stock beneficially owned by Trading Fund OS.

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 2,502,390 shares of Common Stock beneficially owned in the aggregate by BVF, BVF2, Trading Fund OS, including 316,394 shares of Common Stock held in the Partners Managed Accounts, which includes 64,870 shares of Common Stock underlying certain A Warrants and excludes 64,870 shares of Common Stock underlying certain B Warrants.

BVF Inc., as the general partner of Partners, may be deemed to beneficially own the 2,502,390 shares of Common Stock beneficially owned by Partners.

Mr. Lampert, as a director and officer of BVF Inc., may be deemed to beneficially own the 2,502,390 shares of 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 shares of Common Stock owned by another Reporting Person. Partners OS disclaims beneficial ownership of the shares of Common Stock beneficially owned by Trading Fund OS. Each of Partners, BVF Inc. and Mr. Lampert disclaims beneficial ownership of the shares of Common Stock beneficially owned by BVF, BVF2, Trading Fund OS, and held in the Partners Managed Accounts, 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.

The following percentages are based on a denominator which is the sum of: (i) 24,186,019 shares of Common Stock outstanding, as of October 31, 2018, which is the total number of shares of Common Stock outstanding as disclosed in the Issuer’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 6, 2018, (ii) certain or all of the 625,001 shares of Common Stock underlying the A Warrants, as applicable, and (iii) 237,931 shares of Common Stock underlying the B Warrants, as applicable.

As of the close of business on December 31, 2018 (i) BVF beneficially owned approximately 5.1% of the outstanding shares of Common Stock, (ii) BVF2 beneficially owned approximately 3.2% of the outstanding shares of Common Stock, (iii) Trading Fund OS beneficially owned less than 1% of the outstanding shares of Common Stock, (iv) Partners OS may be deemed to beneficially own less than 1% of the outstanding shares of Common Stock, and (v) each of Partners, BVF Inc. and Mr. Lampert may be deemed to beneficially own approximately 9.99% of the outstanding shares of Common Stock (1.3% of the outstanding shares of Common Stock are held in the Partners Managed Accounts).

See Cover Pages Items 5-9.

See Cover Pages Items 5-9.

See Cover Pages Items 5-9.

See Cover Pages Items 5-9.

Not Applicable.

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 Accounts.

Not Applicable.

See Exhibit 99.1 to the Schedule 13G filed with the Securities and Exchange Commission on May 24, 2018.

Not Applicable.

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.

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