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

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 (i) 185,933 American Depositary Shares (“ADSs”), each of which represents twenty-five Shares (as defined below in Item 2) and in the aggregate 4,648,325 Shares and (ii) 1,139,568 Shares issuable upon the exercise of certain Warrants (as defined below in Item 4).

¹ Includes (i) 120,333 ADSs, each of which represents twenty-five Shares and in the aggregate 3,008,325 Shares and (ii) 737,512 Shares issuable upon the exercise of certain Warrants.

¹ Includes (i) 21,800 ADSs, each of which represents twenty-five Shares and in the aggregate 545,000 Shares and (ii) 133,610 Shares issuable upon the exercise of certain Warrants.

¹ Includes (i) 21,800 ADSs, each of which represents twenty-five Shares and in the aggregate 545,000 Shares and (ii) 133,610 Shares issuable upon the exercise of certain Warrants.

¹ Includes (i) 360,866 ADS, each of which represents twenty-five Shares and in the aggregate 9,021,650 Shares and (ii) 2,451,563 Shares issuable upon the exercise of certain Warrants.

¹ Includes (i) 360,866 ADS, each of which represents twenty-five Shares and in the aggregate 9,021,650 Shares and (ii) 2,451,563 Shares issuable upon the exercise of certain Warrants.

¹ Includes (i) 360,866 ADS, each of which represents twenty-five Shares and in the aggregate 9,021,650 Shares and (ii) 2,451,563 Shares issuable upon the exercise of certain Warrants.

Realm Therapeutics plc, incorporated under the law of England and Wales (the “Issuer”).

267 Great Valley Parkway

Malvern, PA 19355

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

1 Sansome Street, 30^th Floor

San Francisco, California 94104

Citizenship: Delaware

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

1 Sansome Street, 30^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”)

1 Sansome Street, 30th Floor

San Francisco, California 94104

Citizenship: Delaware

BVF Inc.

1 Sansome Street, 30^th Floor

San Francisco, California 94104

Citizenship: Delaware

Mark N. Lampert (“Mr. Lampert”)

1 Sansome Street, 30^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.”

Ordinary shares, nominal value of £0.10 per share (the “Shares”)

75606L103

As of the close of business on July 18, 2018, the Reporting Persons held 6,128,906 Warrants exercisable for an aggregate of 2,451,563 Shares (the “Warrants”). Each Warrant is convertible into 0.4 of a Share. Such Warrants have an initial exercise price of £0.58 per Share, subject to adjustment pursuant to the terms of the Warrants, and expire in April 2020.

As of the close of business on July 18, 2018 (i) BVF beneficially owned 8,261,869 Shares, including 1,139,568 Shares issuable upon the exercise of Warrants, (ii) BVF2 beneficially owned 5,346,960 Shares, including 737,512 Shares issuable upon the exercise of Warrants and (iii) Trading Fund OS beneficially owned 968,673 Shares, including 133,610 Shares issuable upon the exercise of Warrants.

Partners OS, as the general partner of Trading Fund OS, may be deemed to beneficially own the 968,673 Shares 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 17,773,829 Shares beneficially owned in the aggregate by BVF, BVF2, Trading Fund OS, and certain Partners managed accounts (the “Partners Managed Accounts”), including 3,196,327 Shares, which includes (i) 32,800 ADSs representing 820,000 Shares in the aggregate and (ii) 440,873 Shares issuable upon the exercise of Warrants, held in the Partners Managed Accounts.

BVF Inc., as the general partner of Partners, may be deemed to beneficially own the 17,773,829 Shares beneficially owned by Partners.

Mr. Lampert, as a director and officer of BVF Inc., may be deemed to beneficially own the 17,773,829 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. Partners OS disclaims beneficial ownership of the Shares beneficially owned by Trading Fund OS. 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 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) 116,561,917 Shares outstanding, as of March 31, 2018, which is the total number of Shares outstanding as reported in the Prospectus on Form 424B4 filed with the Securities and Exchange Commission on July 3, 2018 and (ii) certain or all of the 2,451,563 Shares underlying certain Warrants, as applicable.

As of the close of business on July 18, 2018 (i) BVF beneficially owned approximately 7.0% of the outstanding Shares, (ii) BVF2 beneficially owned approximately 4.6% of the outstanding Shares, (iii) Trading Fund OS beneficially owned less than 1% of the outstanding Shares, (iv) Partners OS may be deemed to beneficially own less than 1% of the outstanding Shares, and (v) each of Partners, BVF Inc. and Mr. Lampert may be deemed to beneficially own approximately 14.9% of the outstanding Shares (2.7% of the outstanding Shares 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 beneficially owned by BVF, BVF2, Trading Fund OS, and the Partners Managed Accounts.

Not Applicable.

See Exhibit 99.1.

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: July 18, 2018

Exhibit 99.1

Joint Filing Agreement

The undersigned hereby agree that the Statement on Schedule 13G dated July 18, 2018 with respect to the Ordinary shares, nominal value of £0.10 per share of Realm Therapeutics plc, 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: July 18, 2018