OrbiMed Capital GP V LLC

SEC source: 0001140361-18-031065 · form4.xml · nonDerivative · entry 5

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments V, LP

Disclosed balance after: 10,889,280

F2 · ownership.direct: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F2 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F3 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, David P. Bonita, an employee of Advisors, to serve on the Company's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

SEC source: 0001140361-18-031065 · form4.xml · nonDerivative · entry 4

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments V, LP

Disclosed balance after: 10,520,859

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · price: Each of the Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series C Convertible Preferred Stock and Series D Convertible Preferred Stock was convertible at any time at the option of the holder into Common Stock at a rate of 1/3.98, for no additional consideration, and had no expiration date. Each of the Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series C Convertible Preferred Stock and Series D Convertible Preferred Stock automatically converted into Common Stock, at a rate of 1/3.98 and for no additional consideration, upon closing of the Issuer's initial public offering of its Common Stock.

F2 · ownership.direct: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F2 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F3 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, David P. Bonita, an employee of Advisors, to serve on the Company's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

SEC source: 0001140361-18-031065 · form4.xml · nonDerivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments V, LP

Disclosed balance after: 9,451,684

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · price: Each of the Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series C Convertible Preferred Stock and Series D Convertible Preferred Stock was convertible at any time at the option of the holder into Common Stock at a rate of 1/3.98, for no additional consideration, and had no expiration date. Each of the Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series C Convertible Preferred Stock and Series D Convertible Preferred Stock automatically converted into Common Stock, at a rate of 1/3.98 and for no additional consideration, upon closing of the Issuer's initial public offering of its Common Stock.

F2 · ownership.direct: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F2 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F3 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, David P. Bonita, an employee of Advisors, to serve on the Company's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

SEC source: 0001140361-18-031065 · form4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments V, LP

Disclosed balance after: 5,860,490

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · price: Each of the Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series C Convertible Preferred Stock and Series D Convertible Preferred Stock was convertible at any time at the option of the holder into Common Stock at a rate of 1/3.98, for no additional consideration, and had no expiration date. Each of the Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series C Convertible Preferred Stock and Series D Convertible Preferred Stock automatically converted into Common Stock, at a rate of 1/3.98 and for no additional consideration, upon closing of the Issuer's initial public offering of its Common Stock.

F2 · ownership.direct: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F2 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F3 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, David P. Bonita, an employee of Advisors, to serve on the Company's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

SEC source: 0001140361-18-031065 · form4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments V, LP

Disclosed balance after: 1,559,716

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · price: Each of the Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series C Convertible Preferred Stock and Series D Convertible Preferred Stock was convertible at any time at the option of the holder into Common Stock at a rate of 1/3.98, for no additional consideration, and had no expiration date. Each of the Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series C Convertible Preferred Stock and Series D Convertible Preferred Stock automatically converted into Common Stock, at a rate of 1/3.98 and for no additional consideration, upon closing of the Issuer's initial public offering of its Common Stock.

F2 · ownership.direct: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F2 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F3 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, David P. Bonita, an employee of Advisors, to serve on the Company's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

SEC source: 0000947871-18-000542 · ss98060_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 5,193,946

F1 · price: These shares of the Issuer's common stock ("Shares") were purchased in a block order at a price of $3.85.

F2 · ownership.nature: These Shares are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power over the securities held by OPI V and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F3 · ownership.nature: Samuel D. Isaly, who was included as a Reporting Person on previous reports under Section 16 of the Exchange Act filed by GP V and Advisors, is no longer subject to Section 16 with respect to securities of the Issuer.

F4 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Chau Khuong, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-017726 · doc4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP IV LLC · CIK 0001502240 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments V, LP

Disclosed balance after: 409,547

F1 · shares: Pursuant to the Agreement and Plan of Merger (the "Merger Agreement"), dated May 9, 2018, by and among the Issuer, Eli Lilly and Company ("Parent") and Bluegill Acquisition Corporation ("Merger Sub"), a wholly-owned subsidiary of Parent, Merger Sub made a cash tender offer (the "Offer") to purchase each outstanding share of the Issuer's common stock for $50.00 per share (the "Offer Price"), net to the seller in cash, without interest and less any applicable tax withholding. These shares were tendered into the Offer and, after the expiration of the Offer at one minute after 11:59 pm Eastern Time on June 21, 2018, Merger Sub accepted all of the tendered shares and the holder was entitled to receive the Offer Price per share.

F3 · ownership.nature: These Shares are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the general partner of OPI V, and Advisors is the managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power over the securities held by OPI V and as a result may be deemed to have beneficial ownership over such securities.

F4 · ownership.nature: Each of GP IV, GP V and Advisors disclaim beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Carl L. Gordon, a member of Advisors, to serve on the Issuer's board of directors. This report on Form 4 shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-017726 · doc4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP IV LLC · CIK 0001502240 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments IV, LP

Disclosed balance after: 3,709,356

F1 · shares: Pursuant to the Agreement and Plan of Merger (the "Merger Agreement"), dated May 9, 2018, by and among the Issuer, Eli Lilly and Company ("Parent") and Bluegill Acquisition Corporation ("Merger Sub"), a wholly-owned subsidiary of Parent, Merger Sub made a cash tender offer (the "Offer") to purchase each outstanding share of the Issuer's common stock for $50.00 per share (the "Offer Price"), net to the seller in cash, without interest and less any applicable tax withholding. These shares were tendered into the Offer and, after the expiration of the Offer at one minute after 11:59 pm Eastern Time on June 21, 2018, Merger Sub accepted all of the tendered shares and the holder was entitled to receive the Offer Price per share.

F2 · ownership.nature: These Shares are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP IV. By virtue of such relationships, GP IV and Advisors may be deemed to have voting and investment power over the securities held by OPI IV and as a result may be deemed to have beneficial ownership over such securities.

F4 · ownership.nature: Each of GP IV, GP V and Advisors disclaim beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Carl L. Gordon, a member of Advisors, to serve on the Issuer's board of directors. This report on Form 4 shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000492 · ss95078_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 4,901,310

F1 · security: Each American Depositary Share ("ADS") represents six ordinary shares, nominal value GBP 0.001 per share, of the Issuer. OrbiMed Private Investments V, LP ("OPI V") is the holder of record of the securities reported on this Form 4. OPI V's holdings consist of 25,408,300 ordinary shares held directly, and 666,593 ADSs representing 3,999,558 ordinary shares. Column 5 reports such holdings on an aggregate basis in terms of the corresponding number of ADSs.

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $13.49 to $13.50 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F4 · ownership.nature: These securities are held of record by OPI V. OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F5 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Peter A. Thompson, a Private Equity Partner of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000492 · ss95078_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 4,902,910

F1 · security: Each American Depositary Share ("ADS") represents six ordinary shares, nominal value GBP 0.001 per share, of the Issuer. OrbiMed Private Investments V, LP ("OPI V") is the holder of record of the securities reported on this Form 4. OPI V's holdings consist of 25,408,300 ordinary shares held directly, and 666,593 ADSs representing 3,999,558 ordinary shares. Column 5 reports such holdings on an aggregate basis in terms of the corresponding number of ADSs.

F2 · price: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were sold in multiple transactions at prices ranging from $13.50 to $13.69 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F4 · ownership.nature: These securities are held of record by OPI V. OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F5 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Peter A. Thompson, a Private Equity Partner of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000482 · ss94361_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 4,920,010

F1 · security: Each American Depositary Share ("ADS") represents six ordinary shares, nominal value GBP 0.001 per share, of the Issuer. OrbiMed Private Investments V, LP ("OPI V") is the holder of record of the securities reported on this Form 4. OPI V's holdings consist of 25,408,300 ordinary shares held directly, and 685,293 ADSs representing 4,111,758 ordinary shares. Column 5 reports such holdings on an aggregate basis in terms of the corresponding number of ADSs.

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $13.49 to $13.52 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F4 · ownership.nature: These securities are held of record by OPI V. OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F5 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Peter A. Thompson, a Private Equity Partner of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000482 · ss94361_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 4,970,010

F1 · security: Each American Depositary Share ("ADS") represents six ordinary shares, nominal value GBP 0.001 per share, of the Issuer. OrbiMed Private Investments V, LP ("OPI V") is the holder of record of the securities reported on this Form 4. OPI V's holdings consist of 25,408,300 ordinary shares held directly, and 685,293 ADSs representing 4,111,758 ordinary shares. Column 5 reports such holdings on an aggregate basis in terms of the corresponding number of ADSs.

F2 · price: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were sold in multiple transactions at prices ranging from $13.12 to $13.64 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F4 · ownership.nature: These securities are held of record by OPI V. OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F5 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Peter A. Thompson, a Private Equity Partner of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000450 · ss93582_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner · See Remarks

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner · See Remarks

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 2,750,079

F2 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $30.90 to $31.10 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F3 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F4 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000450 · ss93582_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner · See Remarks

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner · See Remarks

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 2,751,679

F1 · price: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were sold in multiple transactions at prices ranging from $29.90 to $30.89 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F3 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F4 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000439 · ss93205_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 2,769,659

F2 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $30.75 to $31.27 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F3 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F4 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000439 · ss93205_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 2,832,159

F1 · price: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were sold in multiple transactions at prices ranging from $30.44 to $31.35 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F3 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F4 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000422 · ss92647_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 5,091,010

F1 · security: Each American Depositary Share ("ADS") represents six ordinary shares, nominal value GBP 0.001 per share, of the Issuer. OrbiMed Private Investments V, LP ("OPI V") is the holder of record of the securities reported on this Form 4. OPI V's holdings consist of 25,408,300 ordinary shares held directly, and 856,293 ADSs representing 5,137,758 ordinary shares. Column 5 reports such holdings on an aggregate basis in terms of the corresponding number of ADSs.

F2 · price: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were sold in multiple transactions at prices ranging from $13.50 to $13.51 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares purchased at each separate price within the range set forth in this footnote. Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F3 · ownership.nature: These securities are held of record by OPI V. OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act").

F4 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Peter A. Thompson, a Private Equity Partner of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001104659-18-031867 · a4.xml · derivative · entry 5

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 548,817 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F2 · derivative.exercise_price: Shares of Series F Convertible Preferred Stock automatically converted into shares of the Issuer's Common Stock at a 1-for-0.1504 conversion rate immediately prior to the closing of the Issuer's IPO for no additional consideration (subject to the payment of cash in lieu of any fractional shares in accordance with the Issuer's Certificate of Incorporation). These shares had no expiration date.

F2 · derivative.exercise_date: Shares of Series F Convertible Preferred Stock automatically converted into shares of the Issuer's Common Stock at a 1-for-0.1504 conversion rate immediately prior to the closing of the Issuer's IPO for no additional consideration (subject to the payment of cash in lieu of any fractional shares in accordance with the Issuer's Certificate of Incorporation). These shares had no expiration date.

F2 · derivative.expiration_date: Shares of Series F Convertible Preferred Stock automatically converted into shares of the Issuer's Common Stock at a 1-for-0.1504 conversion rate immediately prior to the closing of the Issuer's IPO for no additional consideration (subject to the payment of cash in lieu of any fractional shares in accordance with the Issuer's Certificate of Incorporation). These shares had no expiration date.

F3 · ownership.direct: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F4 · ownership.direct: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Chau Khuong, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

SEC source: 0001104659-18-031867 · a4.xml · derivative · entry 4

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 1,582,904 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · derivative.exercise_price: Shares of Series E Convertible Preferred Stock automatically converted into shares of the Issuer's Common Stock at a 1-for-0.1728 conversion rate immediately prior to the closing of the Issuer's initial public offering ("IPO") for no additional consideration (subject to the payment of cash in lieu of any fractional shares in accordance with the Issuer's Sixth Amended and Restated Certificate of Incorporation (as amended, the "Certificate of Incorporation")). These shares had no expiration date.

F1 · derivative.exercise_date: Shares of Series E Convertible Preferred Stock automatically converted into shares of the Issuer's Common Stock at a 1-for-0.1728 conversion rate immediately prior to the closing of the Issuer's initial public offering ("IPO") for no additional consideration (subject to the payment of cash in lieu of any fractional shares in accordance with the Issuer's Sixth Amended and Restated Certificate of Incorporation (as amended, the "Certificate of Incorporation")). These shares had no expiration date.

F1 · derivative.expiration_date: Shares of Series E Convertible Preferred Stock automatically converted into shares of the Issuer's Common Stock at a 1-for-0.1728 conversion rate immediately prior to the closing of the Issuer's initial public offering ("IPO") for no additional consideration (subject to the payment of cash in lieu of any fractional shares in accordance with the Issuer's Sixth Amended and Restated Certificate of Incorporation (as amended, the "Certificate of Incorporation")). These shares had no expiration date.

F3 · ownership.direct: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F4 · ownership.direct: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Chau Khuong, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

SEC source: 0001104659-18-031867 · a4.xml · nonDerivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 2,444,221

F3 · ownership.direct: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F4 · ownership.direct: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Chau Khuong, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

SEC source: 0001104659-18-031867 · a4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 2,131,721

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F2 · price: Shares of Series F Convertible Preferred Stock automatically converted into shares of the Issuer's Common Stock at a 1-for-0.1504 conversion rate immediately prior to the closing of the Issuer's IPO for no additional consideration (subject to the payment of cash in lieu of any fractional shares in accordance with the Issuer's Certificate of Incorporation). These shares had no expiration date.

F3 · ownership.direct: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F4 · ownership.direct: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Chau Khuong, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

SEC source: 0001104659-18-031867 · a4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 1,582,904

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · price: Shares of Series E Convertible Preferred Stock automatically converted into shares of the Issuer's Common Stock at a 1-for-0.1728 conversion rate immediately prior to the closing of the Issuer's initial public offering ("IPO") for no additional consideration (subject to the payment of cash in lieu of any fractional shares in accordance with the Issuer's Sixth Amended and Restated Certificate of Incorporation (as amended, the "Certificate of Incorporation")). These shares had no expiration date.

F3 · ownership.direct: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F4 · ownership.direct: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Chau Khuong, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

SEC source: 0000947871-18-000307 · ss86018_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 5,101,310

F1 · security: Each American Depositary Share ("ADS") represents six ordinary shares, nominal value GBP 0.001 per share, of the Issuer. OrbiMed Private Investments V, LP ("OPI V") is the holder of record of the securities reported on this Form 4. OPI V's holdings consist of 25,408,300 ordinary shares held directly, and, 866,593 ADSs representing 5,199,558 ordinary shares. Column 5 reports such holdings on an aggregate basis in terms of the corresponding number of ADSs.

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $11.50 to $11.59 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F4 · ownership.nature: These securities are held of record by OPI V. OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F5 · ownership.nature: Samuel D. Isaly, who was included as a Reporting Person on previous reports under Section 16 of the Exchange Act filed by GP V and Advisors, is no longer subject to Section 16 with respect to securities of the Issuer.

F6 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Peter A. Thompson, a Private Equity Partner of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000307 · ss86018_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 5,133,293

F1 · security: Each American Depositary Share ("ADS") represents six ordinary shares, nominal value GBP 0.001 per share, of the Issuer. OrbiMed Private Investments V, LP ("OPI V") is the holder of record of the securities reported on this Form 4. OPI V's holdings consist of 25,408,300 ordinary shares held directly, and, 866,593 ADSs representing 5,199,558 ordinary shares. Column 5 reports such holdings on an aggregate basis in terms of the corresponding number of ADSs.

F2 · price: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were sold in multiple transactions at prices ranging from $11.50 to $11.70 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F4 · ownership.nature: These securities are held of record by OPI V. OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F5 · ownership.nature: Samuel D. Isaly, who was included as a Reporting Person on previous reports under Section 16 of the Exchange Act filed by GP V and Advisors, is no longer subject to Section 16 with respect to securities of the Issuer.

F6 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Peter A. Thompson, a Private Equity Partner of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000244 · ss83909_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 5,967,584

F1 · price: These shares of the Issuer's common stock ("Shares") were purchased in a block order at a price of $8.50.

F2 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F3 · ownership.nature: Samuel D. Isaly, who was included as a Reporting Person on previous reports under Section 16 of the Exchange Act filed by GP V and Advisors, is no longer subject to Section 16 with respect to securities of the Issuer.

F4 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Peter A. Thompson, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

SEC source: 0000899243-18-002286 · doc4.xml · derivative · entry 9

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP IV LLC · CIK 0001502240 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments V, LP

Disclosed balance after: 0

Underlying: Common Stock · 31,315 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F3 · derivative.exercise_price: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F3 · derivative.exercise_date: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F3 · derivative.expiration_date: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F5 · ownership.nature: These Shares are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the general partner of OPI V, and Advisors is the managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power over the securities held by OPI V and as a result may be deemed to have beneficial ownership over such securities.

F6 · ownership.nature: Each of GP IV, GP V and Advisors disclaim beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Carl L. Gordon, a member of Advisors, to serve on the Issuer's board of directors. This report on Form 4 shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-002286 · doc4.xml · derivative · entry 8

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP IV LLC · CIK 0001502240 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments V, LP

Disclosed balance after: 0

Underlying: Common Stock · 45,961 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F3 · derivative.exercise_price: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F3 · derivative.exercise_date: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F3 · derivative.expiration_date: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F5 · ownership.nature: These Shares are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the general partner of OPI V, and Advisors is the managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power over the securities held by OPI V and as a result may be deemed to have beneficial ownership over such securities.

F6 · ownership.nature: Each of GP IV, GP V and Advisors disclaim beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Carl L. Gordon, a member of Advisors, to serve on the Issuer's board of directors. This report on Form 4 shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-002286 · doc4.xml · derivative · entry 7

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP IV LLC · CIK 0001502240 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments V, LP

Disclosed balance after: 0

Underlying: Common Stock · 332,271 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F3 · derivative.exercise_price: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F3 · derivative.exercise_date: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F3 · derivative.expiration_date: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F5 · ownership.nature: These Shares are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the general partner of OPI V, and Advisors is the managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power over the securities held by OPI V and as a result may be deemed to have beneficial ownership over such securities.

F6 · ownership.nature: Each of GP IV, GP V and Advisors disclaim beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Carl L. Gordon, a member of Advisors, to serve on the Issuer's board of directors. This report on Form 4 shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-002286 · doc4.xml · derivative · entry 6

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP IV LLC · CIK 0001502240 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments IV, LP

Disclosed balance after: 0

Underlying: Common Stock · 283,627 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F3 · derivative.exercise_price: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F3 · derivative.exercise_date: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F3 · derivative.expiration_date: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F4 · ownership.nature: These Shares are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP IV. By virtue of such relationships, GP IV and Advisors may be deemed to have voting and investment power over the securities held by OPI IV and as a result may be deemed to have beneficial ownership over such securities.

F6 · ownership.nature: Each of GP IV, GP V and Advisors disclaim beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Carl L. Gordon, a member of Advisors, to serve on the Issuer's board of directors. This report on Form 4 shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-002286 · doc4.xml · derivative · entry 5

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP IV LLC · CIK 0001502240 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments IV, LP

Disclosed balance after: 0

Underlying: Common Stock · 415,869 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F3 · derivative.exercise_price: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F3 · derivative.exercise_date: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F3 · derivative.expiration_date: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F4 · ownership.nature: These Shares are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP IV. By virtue of such relationships, GP IV and Advisors may be deemed to have voting and investment power over the securities held by OPI IV and as a result may be deemed to have beneficial ownership over such securities.

F6 · ownership.nature: Each of GP IV, GP V and Advisors disclaim beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Carl L. Gordon, a member of Advisors, to serve on the Issuer's board of directors. This report on Form 4 shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-002286 · doc4.xml · derivative · entry 4

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP IV LLC · CIK 0001502240 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments IV, LP

Disclosed balance after: 0

Underlying: Common Stock · 1,226,156 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F3 · derivative.exercise_price: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F3 · derivative.exercise_date: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F3 · derivative.expiration_date: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F4 · ownership.nature: These Shares are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP IV. By virtue of such relationships, GP IV and Advisors may be deemed to have voting and investment power over the securities held by OPI IV and as a result may be deemed to have beneficial ownership over such securities.

F6 · ownership.nature: Each of GP IV, GP V and Advisors disclaim beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Carl L. Gordon, a member of Advisors, to serve on the Issuer's board of directors. This report on Form 4 shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-002286 · doc4.xml · derivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP IV LLC · CIK 0001502240 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments IV, LP

Disclosed balance after: 0

Underlying: Common Stock · 1,783,704 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F3 · derivative.exercise_price: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F3 · derivative.exercise_date: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F3 · derivative.expiration_date: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F4 · ownership.nature: These Shares are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP IV. By virtue of such relationships, GP IV and Advisors may be deemed to have voting and investment power over the securities held by OPI IV and as a result may be deemed to have beneficial ownership over such securities.

F6 · ownership.nature: Each of GP IV, GP V and Advisors disclaim beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Carl L. Gordon, a member of Advisors, to serve on the Issuer's board of directors. This report on Form 4 shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-002286 · doc4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP IV LLC · CIK 0001502240 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments V, LP

Disclosed balance after: 409,547

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F2 · shares: The total represents shares received upon conversion of shares of Series B-1, C and C-1 Convertible Preferred Stock.

F3 · price: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F5 · ownership.nature: These Shares are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the general partner of OPI V, and Advisors is the managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power over the securities held by OPI V and as a result may be deemed to have beneficial ownership over such securities.

F6 · ownership.nature: Each of GP IV, GP V and Advisors disclaim beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Carl L. Gordon, a member of Advisors, to serve on the Issuer's board of directors. This report on Form 4 shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-002286 · doc4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP IV LLC · CIK 0001502240 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · By OrbiMed Private Investments IV, LP

Disclosed balance after: 3,709,356

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · shares: The total represents shares received upon conversion of shares of Series A, B, C and C-1 Convertible Preferred Stock.

F3 · price: Each share of Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, Series B-1 Convertible Preferred Stock, Series C Convertible Preferred Stock and Series C-1 Convertible Preferred Stock automatically converted into one share of Issuer's Common Stock for no additional consideration immediately prior to the completion of the Issuer's initial public offering. The Convertible Preferred Stock had no expiration date.

F4 · ownership.nature: These Shares are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP IV. By virtue of such relationships, GP IV and Advisors may be deemed to have voting and investment power over the securities held by OPI IV and as a result may be deemed to have beneficial ownership over such securities.

F6 · ownership.nature: Each of GP IV, GP V and Advisors disclaim beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Carl L. Gordon, a member of Advisors, to serve on the Issuer's board of directors. This report on Form 4 shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000998 · ss71524_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

ISALY SAMUEL D · CIK 0001055949 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 941,000

F1 · price: These shares of the Issuer's common stock ("Shares") were sold in a block order at a price of $82.50.

F2 · ownership.nature: These Shares are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act").

F3 · ownership.nature: This report on Form 4 is jointly filed by GP V, Advisors and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently, David P. Bonita, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000969 · ss69206_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

ISALY SAMUEL D · CIK 0001055949 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 1,191,000

F1 · price: These shares of the Issuer's common stock ("Shares") were sold in a block order at a price of $75.00.

F2 · ownership.nature: These Shares are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act").

F3 · ownership.nature: This report on Form 4 is jointly filed by GP V, Advisors and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently, David P. Bonita, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000953 · ss68467_4.xml · nonDerivative · entry 5

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

ISALY SAMUEL D · CIK 0001055949 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 1,458,000

F5 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $76.00 to $76.69 inclusive. Upon request, the Reporting Persons undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F6 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act").

F7 · ownership.nature: Each of the Reporting Persons, GP V, Advisors and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently, David P. Bonita, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any such entity or person, including the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000953 · ss68467_4.xml · nonDerivative · entry 4

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

ISALY SAMUEL D · CIK 0001055949 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 1,466,377

F4 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $75.00 to $75.95 inclusive. Upon request, the Reporting Persons undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F6 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act").

F7 · ownership.nature: Each of the Reporting Persons, GP V, Advisors and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently, David P. Bonita, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any such entity or person, including the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000953 · ss68467_4.xml · nonDerivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

ISALY SAMUEL D · CIK 0001055949 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 1,537,975

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $74.00 to $74.99 inclusive. Upon request, the Reporting Persons undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F6 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act").

F7 · ownership.nature: Each of the Reporting Persons, GP V, Advisors and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently, David P. Bonita, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any such entity or person, including the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000953 · ss68467_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

ISALY SAMUEL D · CIK 0001055949 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 1,638,020

F2 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $73.00 to $73.97 inclusive. Upon request, the Reporting Persons undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F6 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act").

F7 · ownership.nature: Each of the Reporting Persons, GP V, Advisors and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently, David P. Bonita, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any such entity or person, including the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000953 · ss68467_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

ISALY SAMUEL D · CIK 0001055949 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 1,681,320

F1 · price: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were purchased in multiple transactions at prices ranging from $72.00 to $72.99 inclusive. Upon request, the Reporting Persons undertake to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F6 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act").

F7 · ownership.nature: Each of the Reporting Persons, GP V, Advisors and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently, David P. Bonita, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any such entity or person, including the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001104659-17-061573 · a4.xml · derivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 2,546,295 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · derivative.exercise_price: In connection with the closing of the Issuer's initial public offering, each share of the Issuer's series A convertible preferred stock (the "Series A Preferred") converted into the Issuer's common stock on a 9.17-for-one basis without payment or consideration. The Series A Preferred had no expiration date.

F4 · shares: Reflects the number of shares of Series A Preferred held by the Reporting Person on an as-converted to common stock basis.

F1 · derivative.exercise_date: In connection with the closing of the Issuer's initial public offering, each share of the Issuer's series A convertible preferred stock (the "Series A Preferred") converted into the Issuer's common stock on a 9.17-for-one basis without payment or consideration. The Series A Preferred had no expiration date.

F1 · derivative.expiration_date: In connection with the closing of the Issuer's initial public offering, each share of the Issuer's series A convertible preferred stock (the "Series A Preferred") converted into the Issuer's common stock on a 9.17-for-one basis without payment or consideration. The Series A Preferred had no expiration date.

F4 · derivative.underlying_shares: Reflects the number of shares of Series A Preferred held by the Reporting Person on an as-converted to common stock basis.

F2 · ownership.nature: The reportable securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly") a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V and as a result, may be deemed to have beneficial ownership over such shares.

F3 · ownership.nature: This report on Form 4 is jointly filed by GP V, Advisors and Isaly. Each of OPI V, GP V, Advisors and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001104659-17-061573 · a4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 2,901,295

F2 · ownership.nature: The reportable securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly") a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V and as a result, may be deemed to have beneficial ownership over such shares.

F3 · ownership.nature: This report on Form 4 is jointly filed by GP V, Advisors and Isaly. Each of OPI V, GP V, Advisors and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001104659-17-061573 · a4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 2,546,295

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · price: In connection with the closing of the Issuer's initial public offering, each share of the Issuer's series A convertible preferred stock (the "Series A Preferred") converted into the Issuer's common stock on a 9.17-for-one basis without payment or consideration. The Series A Preferred had no expiration date.

F2 · ownership.nature: The reportable securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly") a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V and as a result, may be deemed to have beneficial ownership over such shares.

F3 · ownership.nature: This report on Form 4 is jointly filed by GP V, Advisors and Isaly. Each of OPI V, GP V, Advisors and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000255 · ss36710_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP V LLC · CIK 0001615374 · Director

ISALY SAMUEL D · CIK 0001055949 · Director

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 6,149,377

F1 · security: Each American Depositary Share ("ADS") represents six ordinary shares, nominal value GBP 0.001 per share, of the Issuer. OrbiMed Private Investments V, LP ("OPI V") is the holder of record of the securities reported on this Form 4. OPI V's holdings consist of 25,408,300 ordinary shares held directly, and, 1,914,660 ADSs representing 11,487,960 ordinary shares. Column 5 reports such holdings on an aggregate basis in terms of the corresponding number of ADSs.

F2 · ownership.nature: These securities are held of record by OPI V. OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act").

F3 · ownership.nature: This report on Form 4 is jointly filed by GP V, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Peter A. Thompson, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-17-008159 · doc4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · Director · 10% owner

ISALY SAMUEL D · CIK 0001055949 · Director · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 4,416,446

F1 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to have beneficial ownership over such securities.

F2 · ownership.nature: This report on Form 4 is jointly filed by GP V, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Chau Khuong, an employee of Advisors, to serve on the Company's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000160 · ss31932_4.xml · nonDerivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 1,469,524

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were purchased in multiple transactions at prices ranging from $5.25 to $5.50 inclusive. Upon request, the Reporting Persons undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F4 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act").

F5 · ownership.nature: This report on Form 4 is jointly filed by GP V, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000160 · ss31932_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 1,462,524

F2 · price: The price reported in Column 4 is a weighted average price. These Shares were purchased in multiple transactions at prices ranging from $5.10 to $5.25 inclusive. Upon request, the Reporting Persons undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F4 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act").

F5 · ownership.nature: This report on Form 4 is jointly filed by GP V, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000160 · ss31932_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

Joint disclosure: these amounts are not allocated separately to each reporting owner.

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 1,390,724

F1 · price: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were purchased in multiple transactions at prices ranging from $4.97 to $5.10 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F4 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act").

F5 · ownership.nature: This report on Form 4 is jointly filed by GP V, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.