PRTA

SEC source: 0001567619-21-012739 · doc1.xml · nonDerivative · entry 1

HENNEY CHRISTOPHER S · CIK 0001242880 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,000

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.

SEC source: 0001567619-21-012571 · doc1.xml · derivative · entry 10

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 68,750

Underlying: Ordinary Shares · 81,250 shares

Expires 2028-06-21

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 · kind: The transactions reported in the Form 4 were effected pursuant to a Rule 10b5-1 trading plan adopted by the Reporting Person.

F7 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 25% of the total number of shares subject to the option on June 21, 2019 and with respect to 1/48th of the total number of shares subject to the option in successive, equal monthly installments on each monthly anniversary thereafter, subject to the Reporting Person's continued employment with the Issuer on each such vesting date.

SEC source: 0001567619-21-012571 · doc1.xml · derivative · entry 9

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Ordinary Shares · 19,000 shares

Expires 2025-03-11

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 · kind: The transactions reported in the Form 4 were effected pursuant to a Rule 10b5-1 trading plan adopted by the Reporting Person.

F6 · derivative.exercise_date: The shares subject to the option were fully vested as of the date of the exercise.

SEC source: 0001567619-21-012571 · doc1.xml · derivative · entry 8

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Ordinary Shares · 15,000 shares

Expires 2023-09-03

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 · kind: The transactions reported in the Form 4 were effected pursuant to a Rule 10b5-1 trading plan adopted by the Reporting Person.

F6 · derivative.exercise_date: The shares subject to the option were fully vested as of the date of the exercise.

SEC source: 0001567619-21-012571 · doc1.xml · nonDerivative · entry 7

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

F1 · kind: The transactions reported in the Form 4 were effected pursuant to a Rule 10b5-1 trading plan adopted by the Reporting Person.

F5 · price: The transaction was executed in multiple trades in prices ranging from $48.31 to $49.11, inclusive. The price reported in Column 4 above reflects the weighted average sale price. The reporting person hereby undertakes to provide to the Securities and Exchange Commission staff, the Issuer, or a security holder of the Issuer, upon request, full information regarding the number of shares sold at each respective price within the range set forth in this footnote.

SEC source: 0001567619-21-012571 · doc1.xml · nonDerivative · entry 6

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 5,203

F1 · kind: The transactions reported in the Form 4 were effected pursuant to a Rule 10b5-1 trading plan adopted by the Reporting Person.

F4 · price: The transaction was executed in multiple trades in prices ranging from $47.31 to $48.30, inclusive. The price reported in Column 4 above reflects the weighted average sale price. The reporting person hereby undertakes to provide to the Securities and Exchange Commission staff, the Issuer, or a security holder of the Issuer, upon request, full information regarding the number of shares sold at each respective price within the range set forth in this footnote.

SEC source: 0001567619-21-012571 · doc1.xml · nonDerivative · entry 5

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 23,304

F1 · kind: The transactions reported in the Form 4 were effected pursuant to a Rule 10b5-1 trading plan adopted by the Reporting Person.

F3 · price: The transaction was executed in multiple trades in prices ranging from $46.03 to $46.89, inclusive. The price reported in Column 4 above reflects the weighted average sale price. The reporting person hereby undertakes to provide to the Securities and Exchange Commission staff, the Issuer, or a security holder of the Issuer, upon request, full information regarding the number of shares sold at each respective price within the range set forth in this footnote.

SEC source: 0001567619-21-012571 · doc1.xml · nonDerivative · entry 4

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 49,410

F1 · kind: The transactions reported in the Form 4 were effected pursuant to a Rule 10b5-1 trading plan adopted by the Reporting Person.

F2 · price: The transaction was executed in multiple trades in prices ranging from $45.015 to $46.00, inclusive. The price reported in Column 4 above reflects the weighted average sale price. The reporting person hereby undertakes to provide to the Securities and Exchange Commission staff, the Issuer, or a security holder of the Issuer, upon request, full information regarding the number of shares sold at each respective price within the range set forth in this footnote.

SEC source: 0001567619-21-012571 · doc1.xml · nonDerivative · entry 3

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 115,250

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 · kind: The transactions reported in the Form 4 were effected pursuant to a Rule 10b5-1 trading plan adopted by the Reporting Person.

SEC source: 0001567619-21-012571 · doc1.xml · nonDerivative · entry 2

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 34,000

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 · kind: The transactions reported in the Form 4 were effected pursuant to a Rule 10b5-1 trading plan adopted by the Reporting Person.

SEC source: 0001567619-21-012571 · doc1.xml · nonDerivative · entry 1

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

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 · kind: The transactions reported in the Form 4 were effected pursuant to a Rule 10b5-1 trading plan adopted by the Reporting Person.

SEC source: 0001567619-21-012482 · doc1.xml · derivative · entry 2

EcoR1 Capital, LLC · CIK 0001587114 · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Note 1

Disclosed balance after: 0

Underlying: Ordinary Shares · 250,000 shares

Expires 2021-06-18

F2 · kind: On June 18, 2021, the Filers exercised 2,500 call options to acquire 250,000 Ordinary Shares. Qualified Fund exercised 2,099 of those call options to acquire 209,900 Ordinary Shares. After this transaction, Qualified Fund owned 9,485,116 Ordinary Shares.

F2 · shares: On June 18, 2021, the Filers exercised 2,500 call options to acquire 250,000 Ordinary Shares. Qualified Fund exercised 2,099 of those call options to acquire 209,900 Ordinary Shares. After this transaction, Qualified Fund owned 9,485,116 Ordinary Shares.

F1 · ownership.nature: The filing persons (the "Filers") are EcoR1 Capital, LLC ("EcoR1"), Oleg Nodelman and EcoR1 Capital Fund Qualified, L.P. ("Qualified Fund"). EcoR1 is the general partner and investment adviser of private funds, including Qualified Fund (collectively, the "Funds"). Mr. Nodelman is the manager and controlling owner of EcoR1. EcoR1 is filing this Form 3 for itself, Mr. Nodelman and Qualified Fund. The Filers are filing this Form 4 jointly, but not as a group, and each expressly disclaims membership in a group, within the meaning of Rule 13d-5(b) under the Securities Exchange Act of 1934, as amended. The Funds hold these securities directly for the benefit of their investors. EcoR1 indirectly beneficially owns them as the investment adviser to the Funds, and Mr. Nodelman indirectly beneficially owns them as the control person of EcoR1. The Filers disclaim beneficial ownership of such securities except to the extent of their pecuniary interest therein.

SEC source: 0001567619-21-012482 · doc1.xml · nonDerivative · entry 1

EcoR1 Capital, LLC · CIK 0001587114 · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Note 1

Disclosed balance after: 11,284,280

F2 · kind: On June 18, 2021, the Filers exercised 2,500 call options to acquire 250,000 Ordinary Shares. Qualified Fund exercised 2,099 of those call options to acquire 209,900 Ordinary Shares. After this transaction, Qualified Fund owned 9,485,116 Ordinary Shares.

F2 · shares: On June 18, 2021, the Filers exercised 2,500 call options to acquire 250,000 Ordinary Shares. Qualified Fund exercised 2,099 of those call options to acquire 209,900 Ordinary Shares. After this transaction, Qualified Fund owned 9,485,116 Ordinary Shares.

F1 · ownership.nature: The filing persons (the "Filers") are EcoR1 Capital, LLC ("EcoR1"), Oleg Nodelman and EcoR1 Capital Fund Qualified, L.P. ("Qualified Fund"). EcoR1 is the general partner and investment adviser of private funds, including Qualified Fund (collectively, the "Funds"). Mr. Nodelman is the manager and controlling owner of EcoR1. EcoR1 is filing this Form 3 for itself, Mr. Nodelman and Qualified Fund. The Filers are filing this Form 4 jointly, but not as a group, and each expressly disclaims membership in a group, within the meaning of Rule 13d-5(b) under the Securities Exchange Act of 1934, as amended. The Funds hold these securities directly for the benefit of their investors. EcoR1 indirectly beneficially owns them as the investment adviser to the Funds, and Mr. Nodelman indirectly beneficially owns them as the control person of EcoR1. The Filers disclaim beneficial ownership of such securities except to the extent of their pecuniary interest therein.

SEC source: 0001567619-21-010961 · doc1.xml · derivative · entry 1

Patel Sanjiv · CIK 0001816210 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 30,000

Underlying: Ordinary Shares · 30,000 shares

Expires 2031-05-19

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 33 1/3% of the total number of shares subject to the option on the first anniversary of the grant date, 33 1/3% on the second anniversary of the grant date, and the remaining 33 1/3% on the earlier of the third anniversary of the grant date or the day of the annual general meeting in 2024 of the Issuer's shareholders, assuming continuous services as a director until each such vesting date.

SEC source: 0001567619-21-010960 · doc1.xml · derivative · entry 1

COLLIER RICHARD T · CIK 0001110751 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Ordinary Shares · 15,000 shares

Expires 2031-05-19

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 100% of the total number of shares subject to the option on the earlier of the first anniversary of the grant date or the day of the annual general meeting in 2022 of the Issuer's shareholders, assuming continuous service as a director until such vesting date.

SEC source: 0001567619-21-010951 · doc1.xml · derivative · entry 1

HENNEY CHRISTOPHER S · CIK 0001242880 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Ordinary Shares · 15,000 shares

Expires 2031-05-19

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 100% of the total number of shares subject to the option on the earlier of the first anniversary of the grant date or the day of the annual general meeting in 2022 of the Issuer's shareholders, assuming continuous service as a director until such vesting date.

SEC source: 0001567619-21-010955 · doc1.xml · derivative · entry 1

Ekman Lars · CIK 0001376117 · Director · Chairman of the Board

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Ordinary Shares · 15,000 shares

Expires 2031-05-19

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 100% of the total number of shares subject to the option on the earlier of the first anniversary of the grant date or the day of the annual general meeting in 2022 of the Issuer's shareholders, assuming continuous service as a director until such vesting date.

SEC source: 0001567619-21-010962 · doc1.xml · derivative · entry 1

Cooke Shane · CIK 0001524823 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Ordinary Shares · 15,000 shares

Expires 2031-05-19

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 100% of the total number of shares subject to the option on the earlier of the first anniversary of the grant date or the day of the annual general meeting in 2022 of the Issuer's shareholders, assuming continuous service as a director until such vesting date.

SEC source: 0001567619-21-010953 · doc1.xml · derivative · entry 1

Selkoe Dennis J. · CIK 0001582306 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Ordinary Shares · 15,000 shares

Expires 2031-05-19

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 100% of the total number of shares subject to the option on the earlier of the first anniversary of the grant date or the day of the annual general meeting in 2022 of the Issuer's shareholders, assuming continuous service as a director until such vesting date.

SEC source: 0001567619-21-010957 · doc1.xml · derivative · entry 1

Cobb Paula K · CIK 0001763372 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Ordinary Shares · 15,000 shares

Expires 2031-05-19

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 100% of the total number of shares subject to the option on the earlier of the first anniversary of the grant date or the day of the annual general meeting in 2022 of the Issuer's shareholders, assuming continuous service as a director until such vesting date.

SEC source: 0001567619-21-010949 · doc1.xml · derivative · entry 1

Harfstrand Karl Anders Olof · CIK 0001646451 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Ordinary Shares · 15,000 shares

Expires 2031-05-19

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 100% of the total number of shares subject to the option on the earlier of the first anniversary of the grant date or the day of the annual general meeting in 2022 of the Issuer's shareholders, assuming continuous service as a director until such vesting date.

SEC source: 0001567619-21-007776 · doc1.xml · derivative · entry 1

Garren Hideki · CIK 0001854126 · Chief Medical Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 250,000

Underlying: Ordinary Shares · 250,000 shares

Expires 2031-04-05

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 25% of the total number of shares subject to the option on April 5, 2022 and with respect to 1/48th of the total number of shares subject to the option in successive, equal monthly installments on each monthly anniversary thereafter, subject to the Reporting Person's continued employment with the Issuer on each such vesting date.

SEC source: 0001567619-21-006927 · doc1.xml · nonDerivative · entry 1

EcoR1 Capital, LLC · CIK 0001587114 · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Note 1

Disclosed balance after: 11,034,280

F2 · shares: Qualified Fund purchased 746,500 of the Ordinary Shares purchased in this transaction. After this transaction, Qualified Fund owned 9,275,216 Ordinary Shares.

F1 · ownership.nature: The filing persons (the "Filers") are EcoR1 Capital, LLC ("EcoR1"), Oleg Nodelman and EcoR1 Capital Fund Qualified, L.P. ("Qualified Fund"). EcoR1 is the general partner and investment adviser of private funds, including Qualified Fund (collectively, the "Funds"). Mr. Nodelman is the manager and controlling owner of EcoR1. EcoR1 is filing this Form 4 for itself, Mr. Nodelman and Qualified Fund. The Filers are filing this Form 4 jointly, but not as a group, and each expressly disclaims membership in a group, within the meaning of Rule 13d-5(b) under the Securities Exchange Act of 1934, as amended. The Funds hold these securities directly for the benefit of their investors. EcoR1 indirectly beneficially owns them as the investment adviser to the Funds, and Mr. Nodelman indirectly beneficially owns them as the control person of EcoR1. The Filers disclaim beneficial ownership of such securities except to the extent of their pecuniary interest therein.

SEC source: 0001567619-21-005089 · doc1.xml · derivative · entry 1

Smith Brandon S. · CIK 0001805226 · Chief Business Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 56,000

Underlying: Ordinary Shares · 56,000 shares

Expires 2031-02-25

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 25% of the total number of shares subject to the option on February 25, 2022 and with respect to 1/48th of the total number of shares subject to the option in successive, equal monthly installments on each monthly anniversary thereafter, subject to the Reporting Person's continued employment with the Issuer on each such vesting date.

SEC source: 0001567619-21-005077 · doc1.xml · derivative · entry 1

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 56,000

Underlying: Ordinary Shares · 56,000 shares

Expires 2031-02-25

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 25% of the total number of shares subject to the option on February 25, 2022 and with respect to 1/48th of the total number of shares subject to the option in successive, equal monthly installments on each monthly anniversary thereafter, subject to the Reporting Person's continued employment with the Issuer on each such vesting date.

SEC source: 0001567619-21-005082 · doc1.xml · derivative · entry 1

Karp Carol D. · CIK 0001692214 · Chief Regulatory Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 56,000

Underlying: Ordinary Shares · 56,000 shares

Expires 2031-02-25

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 25% of the total number of shares subject to the option on February 25, 2022 and with respect to 1/48th of the total number of shares subject to the option in successive, equal monthly installments on each monthly anniversary thereafter, subject to the Reporting Person's continued employment with the Issuer on each such vesting date.

SEC source: 0001567619-21-005091 · doc1.xml · derivative · entry 1

Nguyen Tran · CIK 0001457013 · See Remarks

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 84,000

Underlying: Ordinary Shares · 84,000 shares

Expires 2031-02-25

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 25% of the total number of shares subject to the option on February 25, 2022 and with respect to 1/48th of the total number of shares subject to the option in successive, equal monthly installments on each monthly anniversary thereafter, subject to the Reporting Person's continued employment with the Issuer on each such vesting date.

SEC source: 0001567619-21-005088 · doc1.xml · derivative · entry 2

Kinney Gene G. · CIK 0001564380 · President and CEO

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 50,000

Underlying: Ordinary Shares · 50,000 shares

Expires 2030-02-25

F2 · derivative.exercise_date: On February 25, 2020, the reporting person was granted an option to purchase 50,000 ordinary shares. The shares subject to the option vested in full based on the achievement of certain performance criteria.

SEC source: 0001567619-21-005088 · doc1.xml · derivative · entry 1

Kinney Gene G. · CIK 0001564380 · President and CEO

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 250,000

Underlying: Ordinary Shares · 250,000 shares

Expires 2031-02-25

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 25% of the total number of shares subject to the option on February 25, 2022 and with respect to 1/48th of the total number of shares subject to the option in successive, equal monthly installments on each monthly anniversary thereafter, subject to the Reporting Person's continued employment with the Issuer on each such vesting date.

SEC source: 0001567619-21-005085 · doc1.xml · derivative · entry 1

Tripuraneni Radhika · CIK 0001761114 · Chief Development Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 56,000

Underlying: Ordinary Shares · 56,000 shares

Expires 2031-02-25

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 25% of the total number of shares subject to the option on February 25, 2022 and with respect to 1/48th of the total number of shares subject to the option in successive, equal monthly installments on each monthly anniversary thereafter, subject to the Reporting Person's continued employment with the Issuer on each such vesting date.

SEC source: 0001567619-21-005083 · doc1.xml · derivative · entry 1

Malecek Michael J · CIK 0001779336 · See Remarks

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 56,000

Underlying: Ordinary Shares · 56,000 shares

Expires 2031-02-25

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 25% of the total number of shares subject to the option on February 25, 2022 and with respect to 1/48th of the total number of shares subject to the option in successive, equal monthly installments on each monthly anniversary thereafter, subject to the Reporting Person's continued employment with the Issuer on each such vesting date.

SEC source: 0001567619-21-005080 · doc1.xml · derivative · entry 1

Walker Karin L · CIK 0001559422 · Chief Accounting Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 28,000

Underlying: Ordinary Shares · 28,000 shares

Expires 2031-02-25

F1 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 25% of the total number of shares subject to the option on February 25, 2022 and with respect to 1/48th of the total number of shares subject to the option in successive, equal monthly installments on each monthly anniversary thereafter, subject to the Reporting Person's continued employment with the Issuer on each such vesting date.

SEC source: 0001567619-21-004963 · doc1.xml · nonDerivative · entry 2

EcoR1 Capital, LLC · CIK 0001587114 · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Note 1

Disclosed balance after: 10,159,280

F3 · shares: Qualified Fund purchased 9,067 of the Ordinary Shares purchased in this transaction. After this transaction, Qualified Fund owned 8,528,716 Ordinary Shares.

F1 · ownership.nature: The filing persons (the "Filers") are EcoR1 Capital, LLC ("EcoR1"), Oleg Nodelman and EcoR1 Capital Fund Qualified, L.P. ("Qualified Fund"). EcoR1 is the general partner and investment adviser of private funds, including Qualified Fund (collectively, the "Funds"). Mr. Nodelman is the manager and controlling owner of EcoR1. EcoR1 is filing this Form 4 for itself, Mr. Nodelman and Qualified Fund. The Filers are filing this Form 4 jointly, but not as a group, and each expressly disclaims membership in a group, within the meaning of Rule 13d-5(b) under the Securities Exchange Act of 1934, as amended. The Funds hold these securities directly for the benefit of their investors. EcoR1 indirectly beneficially owns them as the investment adviser to the Funds, and Mr. Nodelman indirectly beneficially owns them as the control person of EcoR1. The Filers disclaim beneficial ownership of such securities except to the extent of their pecuniary interest therein.

SEC source: 0001567619-21-004963 · doc1.xml · nonDerivative · entry 1

EcoR1 Capital, LLC · CIK 0001587114 · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Note 1

Disclosed balance after: 10,148,480

F2 · shares: Qualified Fund purchased 37,274 of the Ordinary Shares purchased in this transaction. After this transaction, Qualified Fund owned 8,519,649 Ordinary Shares.

F1 · ownership.nature: The filing persons (the "Filers") are EcoR1 Capital, LLC ("EcoR1"), Oleg Nodelman and EcoR1 Capital Fund Qualified, L.P. ("Qualified Fund"). EcoR1 is the general partner and investment adviser of private funds, including Qualified Fund (collectively, the "Funds"). Mr. Nodelman is the manager and controlling owner of EcoR1. EcoR1 is filing this Form 4 for itself, Mr. Nodelman and Qualified Fund. The Filers are filing this Form 4 jointly, but not as a group, and each expressly disclaims membership in a group, within the meaning of Rule 13d-5(b) under the Securities Exchange Act of 1934, as amended. The Funds hold these securities directly for the benefit of their investors. EcoR1 indirectly beneficially owns them as the investment adviser to the Funds, and Mr. Nodelman indirectly beneficially owns them as the control person of EcoR1. The Filers disclaim beneficial ownership of such securities except to the extent of their pecuniary interest therein.

SEC source: 0001567619-21-004526 · doc1.xml · derivative · entry 3

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Ordinary Shares · 7,540 shares

Expires 2023-01-29

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 · kind: The transactions reported in the Form 4 were effected pursuant to a Rule 10b5-1 trading plan adopted by the Reporting Person.

F2 · derivative.exercise_date: The shares subject to the option were fully vested as of the date of the exercise.

SEC source: 0001567619-21-004526 · doc1.xml · nonDerivative · entry 2

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

F1 · kind: The transactions reported in the Form 4 were effected pursuant to a Rule 10b5-1 trading plan adopted by the Reporting Person.

SEC source: 0001567619-21-004526 · doc1.xml · nonDerivative · entry 1

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 7,540

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 · kind: The transactions reported in the Form 4 were effected pursuant to a Rule 10b5-1 trading plan adopted by the Reporting Person.

SEC source: 0001567619-21-004588 · doc1.xml · nonDerivative · entry 1

EcoR1 Capital, LLC · CIK 0001587114 · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Note 1

Disclosed balance after: 10,104,080

F2 · shares: 37,022 of the Ordinary Shares purchased in this transaction were purchased by Qualified Fund. After this transaction, Qualified Fund owned 8,482,375 Ordinary Shares.

F1 · ownership.nature: The filing persons (the "Filers") are EcoR1 Capital, LLC ("EcoR1"), Oleg Nodelman and EcoR1 Capital Fund Qualified, L.P. ("Qualified Fund"). EcoR1 is the general partner and investment adviser of private funds, including Qualified Fund (collectively, the "Funds"). Mr. Nodelman is the manager and controlling owner of EcoR1. EcoR1 is filing this Form 4 for itself, Mr. Nodelman and Qualified Fund. The Filers are filing this Form 4 jointly, but not as a group, and each expressly disclaims membership in a group, within the meaning of Rule 13d-5(b) under the Securities Exchange Act of 1934, as amended. The Funds hold these securities directly for the benefit of their investors. EcoR1 indirectly beneficially owns them as the investment adviser to the Funds, and Mr. Nodelman indirectly beneficially owns them as the control person of EcoR1. The Filers disclaim beneficial ownership of such securities except to the extent of their pecuniary interest therein.

SEC source: 0001567619-21-004660 · doc1.xml · nonDerivative · entry 1

EcoR1 Capital, LLC · CIK 0001587114 · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Note 1

Disclosed balance after: 10,104,080

F2 · shares: 37,022 of the Ordinary Shares purchased in this transaction were purchased by Qualified Fund. After this transaction, Qualified Fund owned 8,482,375 Ordinary Shares.

F3 · price: The Filers are filing this amendment to correct the price at which the Ordinary Shares were purchased.

F1 · ownership.nature: The filing persons (the "Filers") are EcoR1 Capital, LLC ("EcoR1"), Oleg Nodelman and EcoR1 Capital Fund Qualified, L.P. ("Qualified Fund"). EcoR1 is the general partner and investment adviser of private funds, including Qualified Fund (collectively, the "Funds"). Mr. Nodelman is the manager and controlling owner of EcoR1. EcoR1 is filing this Form 4 for itself, Mr. Nodelman and Qualified Fund. The Filers are filing this Form 4 jointly, but not as a group, and each expressly disclaims membership in a group, within the meaning of Rule 13d-5(b) under the Securities Exchange Act of 1934, as amended. The Funds hold these securities directly for the benefit of their investors. EcoR1 indirectly beneficially owns them as the investment adviser to the Funds, and Mr. Nodelman indirectly beneficially owns them as the control person of EcoR1. The Filers disclaim beneficial ownership of such securities except to the extent of their pecuniary interest therein.

SEC source: 0001567619-21-004320 · doc1.xml · derivative · entry 5

EcoR1 Capital, LLC · CIK 0001587114 · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Note 1

Disclosed balance after: 2,500

Underlying: Ordinary Shares · 250,000 shares

Expires 2021-06-30

F6 · shares: 2,099 of the options purchased in this transaction were purchased by Qualified Fund. After this transaction, Qualified Fund owned 2,099 options to acquire 209,900 Ordinary Shares.

F1 · ownership.nature: The filing persons (the "Filers") are EcoR1 Capital, LLC ("EcoR1"), Oleg Nodelman and EcoR1 Capital Fund Qualified, L.P. ("Qualified Fund"). EcoR1 is the general partner and investment adviser of private funds, including Qualified Fund (collectively, the "Funds"). Mr. Nodelman is the manager and controlling owner of EcoR1. EcoR1 is filing this Form 3 for itself, Mr. Nodelman and Qualified Fund. The Filers are filing this Form 4 jointly, but not as a group, and each expressly disclaims membership in a group, within the meaning of Rule 13d-5(b) under the Securities Exchange Act of 1934, as amended. The Funds hold these securities directly for the benefit of their investors. EcoR1 indirectly beneficially owns them as the investment adviser to the Funds, and Mr. Nodelman indirectly beneficially owns them as the control person of EcoR1. The Filers disclaim beneficial ownership of such securities except to the extent of their pecuniary interest therein.

SEC source: 0001567619-21-004320 · doc1.xml · nonDerivative · entry 4

EcoR1 Capital, LLC · CIK 0001587114 · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Note 1

Disclosed balance after: 10,059,980

F5 · shares: 166,926 of the Ordinary Shares purchased in this transaction were purchased by Qualified Fund. After this transaction, Qualified Fund owned 8,445,353 Ordinary Shares.

F1 · ownership.nature: The filing persons (the "Filers") are EcoR1 Capital, LLC ("EcoR1"), Oleg Nodelman and EcoR1 Capital Fund Qualified, L.P. ("Qualified Fund"). EcoR1 is the general partner and investment adviser of private funds, including Qualified Fund (collectively, the "Funds"). Mr. Nodelman is the manager and controlling owner of EcoR1. EcoR1 is filing this Form 3 for itself, Mr. Nodelman and Qualified Fund. The Filers are filing this Form 4 jointly, but not as a group, and each expressly disclaims membership in a group, within the meaning of Rule 13d-5(b) under the Securities Exchange Act of 1934, as amended. The Funds hold these securities directly for the benefit of their investors. EcoR1 indirectly beneficially owns them as the investment adviser to the Funds, and Mr. Nodelman indirectly beneficially owns them as the control person of EcoR1. The Filers disclaim beneficial ownership of such securities except to the extent of their pecuniary interest therein.

SEC source: 0001567619-21-005004 · doc1.xml · derivative · entry 1

EcoR1 Capital, LLC · CIK 0001587114 · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Note 1

Disclosed balance after: 2,500

Underlying: Ordinary Shares · 250,000 shares

Expires 2021-06-18

F2 · shares: 2,099 of the options purchased in this transaction were purchased by Qualified Fund. After this transaction, Qualified Fund owned 2,099 options to acquire 209,900 Ordinary Shares.

F3 · derivative.expiration_date: The Filers are filing this amendment to correct the expiration date of the options, which was reported as 6/30/2021 in the Form 4 filed on 2/17/2021.

F1 · ownership.nature: The filing persons (the "Filers") are EcoR1 Capital, LLC ("EcoR1"), Oleg Nodelman and EcoR1 Capital Fund Qualified, L.P. ("Qualified Fund"). EcoR1 is the general partner and investment adviser of private funds, including Qualified Fund (collectively, the "Funds"). Mr. Nodelman is the manager and controlling owner of EcoR1. EcoR1 is filing this Form 3 for itself, Mr. Nodelman and Qualified Fund. The Filers are filing this Form 4 jointly, but not as a group, and each expressly disclaims membership in a group, within the meaning of Rule 13d-5(b) under the Securities Exchange Act of 1934, as amended. The Funds hold these securities directly for the benefit of their investors. EcoR1 indirectly beneficially owns them as the investment adviser to the Funds, and Mr. Nodelman indirectly beneficially owns them as the control person of EcoR1. The Filers disclaim beneficial ownership of such securities except to the extent of their pecuniary interest therein.

SEC source: 0001567619-21-004320 · doc1.xml · nonDerivative · entry 3

EcoR1 Capital, LLC · CIK 0001587114 · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Note 1

Disclosed balance after: 9,861,140

F4 · shares: 80,040 of the Ordinary Shares purchased in this transaction were purchased by Qualified Fund. After this transaction, Qualified Fund owned 8,278,427 Ordinary Shares.

F1 · ownership.nature: The filing persons (the "Filers") are EcoR1 Capital, LLC ("EcoR1"), Oleg Nodelman and EcoR1 Capital Fund Qualified, L.P. ("Qualified Fund"). EcoR1 is the general partner and investment adviser of private funds, including Qualified Fund (collectively, the "Funds"). Mr. Nodelman is the manager and controlling owner of EcoR1. EcoR1 is filing this Form 3 for itself, Mr. Nodelman and Qualified Fund. The Filers are filing this Form 4 jointly, but not as a group, and each expressly disclaims membership in a group, within the meaning of Rule 13d-5(b) under the Securities Exchange Act of 1934, as amended. The Funds hold these securities directly for the benefit of their investors. EcoR1 indirectly beneficially owns them as the investment adviser to the Funds, and Mr. Nodelman indirectly beneficially owns them as the control person of EcoR1. The Filers disclaim beneficial ownership of such securities except to the extent of their pecuniary interest therein.

SEC source: 0001567619-21-004315 · doc1.xml · derivative · entry 6

COLLIER RICHARD T · CIK 0001110751 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 6,315

Underlying: Ordinary Shares · 6,315 shares

Expires 2027-05-18

F4 · price: On February 12, 2021, the issuer canceled, pursuant to the issuer's option exchange program, an option for 12,000 of the issuer's ordinary shares granted to the reporting person on May 18, 2017. In exchange, the reporting person received a replacement option, for 6,315 ordinary shares, having an exercise price of $22.85 per ordinary share.

F2 · derivative.exercise_date: The shares subject to the option will vest and become exercisable on the one year anniversary of the date of grant, subject to the reporting person's continued service with the issuer through such one year anniversary.

SEC source: 0001567619-21-004315 · doc1.xml · derivative · entry 5

COLLIER RICHARD T · CIK 0001110751 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Ordinary Shares · 12,000 shares

Expires 2027-05-18

F4 · price: On February 12, 2021, the issuer canceled, pursuant to the issuer's option exchange program, an option for 12,000 of the issuer's ordinary shares granted to the reporting person on May 18, 2017. In exchange, the reporting person received a replacement option, for 6,315 ordinary shares, having an exercise price of $22.85 per ordinary share.

SEC source: 0001567619-21-004315 · doc1.xml · derivative · entry 4

COLLIER RICHARD T · CIK 0001110751 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 8,426

Underlying: Ordinary Shares · 8,426 shares

Expires 2026-05-20

F3 · price: On February 12, 2021, the issuer canceled, pursuant to the issuer's option exchange program, an option for 15,000 of the issuer's ordinary shares granted to the reporting person on May 20, 2016. In exchange, the reporting person received a replacement option, for 8,426 ordinary shares, having an exercise price of $22.85 per ordinary share.

F2 · derivative.exercise_date: The shares subject to the option will vest and become exercisable on the one year anniversary of the date of grant, subject to the reporting person's continued service with the issuer through such one year anniversary.

SEC source: 0001567619-21-004315 · doc1.xml · derivative · entry 3

COLLIER RICHARD T · CIK 0001110751 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Ordinary Shares · 15,000 shares

Expires 2026-05-20

F3 · price: On February 12, 2021, the issuer canceled, pursuant to the issuer's option exchange program, an option for 15,000 of the issuer's ordinary shares granted to the reporting person on May 20, 2016. In exchange, the reporting person received a replacement option, for 8,426 ordinary shares, having an exercise price of $22.85 per ordinary share.

SEC source: 0001567619-21-004315 · doc1.xml · derivative · entry 2

COLLIER RICHARD T · CIK 0001110751 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 9,803

Underlying: Ordinary Shares · 9,803 shares

Expires 2025-05-22

F1 · price: On February 12, 2021, the issuer canceled, pursuant to the issuer's option exchange program, an option for 15,000 of the issuer's ordinary shares granted to the reporting person on May 22, 2015. In exchange, the reporting person received a replacement option, for 9,803 ordinary shares, having an exercise price of $22.85 per ordinary share.

F2 · derivative.exercise_date: The shares subject to the option will vest and become exercisable on the one year anniversary of the date of grant, subject to the reporting person's continued service with the issuer through such one year anniversary.

SEC source: 0001567619-21-004315 · doc1.xml · derivative · entry 1

COLLIER RICHARD T · CIK 0001110751 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Ordinary Shares · 15,000 shares

Expires 2025-05-22

F1 · price: On February 12, 2021, the issuer canceled, pursuant to the issuer's option exchange program, an option for 15,000 of the issuer's ordinary shares granted to the reporting person on May 22, 2015. In exchange, the reporting person received a replacement option, for 9,803 ordinary shares, having an exercise price of $22.85 per ordinary share.

SEC source: 0001567619-21-004318 · doc1.xml · derivative · entry 6

Zago Wagner M. · CIK 0001708681 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 31,250

Underlying: Ordinary Shares · 18,750 shares

Expires 2029-02-27

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 · kind: The sales reported in the Form 4 was effected pursuant to a Rule 10b5-1 trading plan adopted by the Reporting Person.

F4 · derivative.exercise_date: The shares subject to the option will vest and become exercisable as to 25% of the total number of shares subject to the option on February 27, 2020 and with respect to 1/48th of the total number of shares subject to the option in successive, equal monthly installments on each monthly anniversary thereafter, subject to the Reporting Person's continued employment with the Issuer on each such vesting date.