INCY

SEC source: 0001209191-22-037798 · doc4.xml · nonDerivative · entry 1

HARRIGAN EDMUND · CIK 0001177917 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 7,716

F1 · shares: This award of restricted stock units ("RSUs") vests in full on the first anniversary of the date of grant or, if earlier, the date of the next regular annual meeting of the Company's stockholders or upon a change of control (as defined in the Amended and Restated 2010 Stock Incentive Plan). The RSUs may be settled only for shares of common stock on a one-for-one basis.

SEC source: 0001209191-22-037797 · doc4.xml · derivative · entry 2

BIENAIME JEAN JACQUES · CIK 0001221590 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 9,124

Underlying: Common Stock · 9,124 shares

Expires 2032-06-14

F2 · derivative.exercise_date: This option vests in full on the first anniversary of the date of grant, or if earlier, the date of the next regular annual meeting of the Company's stockholders or upon change of control (as defined in the option plan).

SEC source: 0001209191-22-037797 · doc4.xml · nonDerivative · entry 1

BIENAIME JEAN JACQUES · CIK 0001221590 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,988

F1 · shares: This award of restricted stock units ("RSUs") vests in full on the first anniversary of the date of grant or, if earlier, the date of the next regular annual meeting of the Company's stockholders or upon a change of control (as defined in the RSU plan). The RSUs may be settled only for shares of common stock on a one-for-one basis.

SEC source: 0001209191-22-037793 · doc4.xml · derivative · entry 2

BRAWLEY OTIS W · CIK 0001213029 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 9,124

Underlying: Common Stock · 9,124 shares

Expires 2032-06-14

F2 · derivative.exercise_date: This option vests in full on the first anniversary of the date of grant, or if earlier, the date of the next regular annual meeting of the Company's stockholders or upon change of control (as defined in the option plan).

SEC source: 0001209191-22-037793 · doc4.xml · nonDerivative · entry 1

BRAWLEY OTIS W · CIK 0001213029 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 3,399

F1 · shares: This award of restricted stock units ("RSUs") vests in full on the first anniversary of the date of grant or, if earlier, the date of the next regular annual meeting of the Company's stockholders or upon a change of control (as defined in the RSU plan). The RSUs may be settled only for shares of common stock on a one-for-one basis.

SEC source: 0001209191-22-024137 · doc4.xml · nonDerivative · entry 1

Pasquale Maria E · CIK 0001736295 · EVP & General Counsel

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 53,058

F1 · shares: Represents shares withheld automatically by the Issuer to satisfy tax withholding obligations due at settlement of restricted stock units previously reported in Table I as common stock.

F2 · balance_after: Includes an aggregate of 46,929 shares of common stock issuable pursuant to previously reported earned performance stock units and restricted stock units that have not vested.

SEC source: 0001209191-22-024136 · doc4.xml · derivative · entry 8

Flannelly Barry P · CIK 0001615842 · EVP & General Manager US

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 21,348 shares

Expires 2029-01-03

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.

F4 · derivative.exercise_date: Beginning January 4, 2019, options become exercisable in 37 installments, with the first 25% vesting on July 2, 2019 and the remainder vesting monthly over three years.

SEC source: 0001209191-22-024136 · doc4.xml · derivative · entry 7

Flannelly Barry P · CIK 0001615842 · EVP & General Manager US

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 20,516 shares

Expires 2028-07-01

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_date: Beginning July 2, 2018, options become exercisable in 37 installments, with the first 25% vesting on July 2, 2019 and the remainder vesting monthly over three years.

SEC source: 0001209191-22-024136 · doc4.xml · nonDerivative · entry 6

Flannelly Barry P · CIK 0001615842 · EVP & General Manager US

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 65,163

F1 · price: This transaction was effected pursuant to a Rule 10b5-1 trading plan adopted by reporting person.

F2 · balance_after: Includes an aggregate of 64,148 shares of common stock issuable pursuant to previously reported restricted stock units and earned performance stock units that have not vested.

SEC source: 0001209191-22-024136 · doc4.xml · nonDerivative · entry 5

Flannelly Barry P · CIK 0001615842 · EVP & General Manager US

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 66,411

F1 · price: This transaction was effected pursuant to a Rule 10b5-1 trading plan adopted by reporting person.

SEC source: 0001209191-22-024136 · doc4.xml · nonDerivative · entry 4

Flannelly Barry P · CIK 0001615842 · EVP & General Manager US

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 67,292

F1 · price: This transaction was effected pursuant to a Rule 10b5-1 trading plan adopted by reporting person.

SEC source: 0001209191-22-024136 · doc4.xml · nonDerivative · entry 3

Flannelly Barry P · CIK 0001615842 · EVP & General Manager US

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 88,640

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: 0001209191-22-024136 · doc4.xml · nonDerivative · entry 2

Flannelly Barry P · CIK 0001615842 · EVP & General Manager US

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 67,292

F1 · price: This transaction was effected pursuant to a Rule 10b5-1 trading plan adopted by reporting person.

SEC source: 0001209191-22-024136 · doc4.xml · nonDerivative · entry 1

Flannelly Barry P · CIK 0001615842 · EVP & General Manager US

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 87,808

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: 0001209191-22-022292 · doc4.xml · nonDerivative · entry 1

HARRIGAN EDMUND · CIK 0001177917 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 5,572

F1 · security: Restricted shares issued to the Reporting Person under the Issuer's Amended and Restated 2010 Stock Incentive Plan in lieu of quarterly director retainer fees pursuant to an election by the Reporting Person intended to comply with Rule 10b5-1. Restricted shares are fully vested.

F2 · balance_after: Includes an aggregate of 1,923 shares of common stock issuable pursuant to previously reported restricted stock units that have not vested.

SEC source: 0001209191-22-022469 · doc4.xml · nonDerivative · entry 5

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 33,419,495

F4 · price: 440 shares of Common Stock issued to Julian C. Baker pursuant to the Issuer's Amended and Restated 2010 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of quarterly director retainer fees of $32,000. The shares of Common Stock are fully vested. Julian C. Baker serves on the Issuer's board of directors (the "Board") as a representative of 667, L.P. ("667") and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds").

F4 · ownership.nature: 440 shares of Common Stock issued to Julian C. Baker pursuant to the Issuer's Amended and Restated 2010 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of quarterly director retainer fees of $32,000. The shares of Common Stock are fully vested. Julian C. Baker serves on the Issuer's board of directors (the "Board") as a representative of 667, L.P. ("667") and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds").

F6 · ownership.nature: The 440 shares are reported for each of the Funds as each has an indirect pecuniary interest.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock received previously from vested restricted stock units (each, an "RSU") and 195,000 shares of Common Stock received previously from exercise of 195,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to the Funds. In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F9 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F10 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F11 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F12 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

SEC source: 0001209191-22-022469 · doc4.xml · nonDerivative · entry 4

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 2,941,587

F4 · price: 440 shares of Common Stock issued to Julian C. Baker pursuant to the Issuer's Amended and Restated 2010 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of quarterly director retainer fees of $32,000. The shares of Common Stock are fully vested. Julian C. Baker serves on the Issuer's board of directors (the "Board") as a representative of 667, L.P. ("667") and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds").

F4 · ownership.nature: 440 shares of Common Stock issued to Julian C. Baker pursuant to the Issuer's Amended and Restated 2010 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of quarterly director retainer fees of $32,000. The shares of Common Stock are fully vested. Julian C. Baker serves on the Issuer's board of directors (the "Board") as a representative of 667, L.P. ("667") and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds").

F5 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Biotech Capital, L.P. and (ii) 667, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by 667, a limited partnership of which the sole general partner is Baker Biotech Capital, L.P., a limited partnership of which the sole general partner is Baker Biotech Capital (GP), LLC, due to their interest in 667 and Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667.

F6 · ownership.nature: The 440 shares are reported for each of the Funds as each has an indirect pecuniary interest.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock received previously from vested restricted stock units (each, an "RSU") and 195,000 shares of Common Stock received previously from exercise of 195,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to the Funds. In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F9 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F10 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F11 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

SEC source: 0001209191-22-022293 · doc4.xml · nonDerivative · entry 1

FOUSE JACQUALYN A · CIK 0001405288 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 8,511

F1 · security: Restricted shares issued to the Reporting Person under the Issuer's Amended and Restated 2010 Stock Incentive Plan in lieu of quarterly director retainer fees pursuant to an election by the Reporting Person intended to comply with Rule 10b5-1. Restricted shares are fully vested.

F2 · balance_after: Includes an aggregate of 1,923 shares of common stock issuable pursuant to previously reported restricted stock units that have not vested.

SEC source: 0001209191-22-022282 · doc4.xml · nonDerivative · entry 1

Clancy Paul J · CIK 0001409601 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 8,290

F1 · security: Restricted shares issued to the Reporting Person under the Issuer's Amended and Restated 2010 Stock Incentive Plan in lieu of quarterly director retainer fees pursuant to an election by the Reporting Person intended to comply with Rule 10b5-1. Restricted shares are fully vested.

F2 · balance_after: Includes an aggregate of 1,923 shares of common stock issuable pursuant to previously reported restricted stock units that have not vested.

SEC source: 0001209191-22-022285 · doc4.xml · nonDerivative · entry 1

DIXON WENDY L · CIK 0001202283 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 17,768

F1 · security: Restricted shares issued to the Reporting Person under the Issuer's Amended and Restated 2010 Stock Incentive Plan in lieu of quarterly director retainer fees pursuant to an election by the Reporting Person intended to comply with Rule 10b5-1. Restricted shares are fully vested.

F2 · balance_after: Includes an aggregate of 1,923 shares of common stock issuable pursuant to previously reported restricted stock units that have not vested.

SEC source: 0001209191-22-018023 · doc4.xml · nonDerivative · entry 15

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 33,419,055

F15 · price: The price reported in Column 4 is a weighted average price. These shares were traded by the Funds in multiple transactions at prices ranging from $72.92 to $73.48, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F10 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F11 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

SEC source: 0001209191-22-018023 · doc4.xml · nonDerivative · entry 14

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 2,941,147

F15 · price: The price reported in Column 4 is a weighted average price. These shares were traded by the Funds in multiple transactions at prices ranging from $72.92 to $73.48, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F4 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Biotech Capital, L.P. and (ii) 667, L.P. ("667"), Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by 667, a limited partnership of which the sole general partner is Baker Biotech Capital, L.P., a limited partnership of which the sole general partner is Baker Biotech Capital (GP), LLC, due to their interest in 667 and Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F10 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

SEC source: 0001209191-22-018023 · doc4.xml · nonDerivative · entry 13

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 33,243,260

F14 · price: The price reported in Column 4 is a weighted average price. These shares were traded by the Funds in multiple transactions at prices ranging from $71.94 to $71.97, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F10 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F11 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

SEC source: 0001209191-22-018023 · doc4.xml · nonDerivative · entry 12

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 2,926,657

F14 · price: The price reported in Column 4 is a weighted average price. These shares were traded by the Funds in multiple transactions at prices ranging from $71.94 to $71.97, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F4 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Biotech Capital, L.P. and (ii) 667, L.P. ("667"), Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by 667, a limited partnership of which the sole general partner is Baker Biotech Capital, L.P., a limited partnership of which the sole general partner is Baker Biotech Capital (GP), LLC, due to their interest in 667 and Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F10 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

SEC source: 0001209191-22-018023 · doc4.xml · nonDerivative · entry 11

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 33,242,243

F13 · price: The price reported in Column 4 is a weighted average price. These shares were traded by the Funds in multiple transactions at prices ranging from $71.76 to $72.13, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F10 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F11 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

SEC source: 0001209191-22-018023 · doc4.xml · nonDerivative · entry 10

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 2,926,573

F13 · price: The price reported in Column 4 is a weighted average price. These shares were traded by the Funds in multiple transactions at prices ranging from $71.76 to $72.13, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F4 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Biotech Capital, L.P. and (ii) 667, L.P. ("667"), Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by 667, a limited partnership of which the sole general partner is Baker Biotech Capital, L.P., a limited partnership of which the sole general partner is Baker Biotech Capital (GP), LLC, due to their interest in 667 and Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F10 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

SEC source: 0001209191-22-018023 · doc4.xml · nonDerivative · entry 9

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 33,217,136

F12 · price: The price reported in Column 4 is a weighted average price. These shares of Common Stock of the Issuer were traded by the Funds in multiple transactions at prices ranging from $71.42 to $72.10, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission (the "Staff"), upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F10 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F11 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

SEC source: 0001209191-22-018023 · doc4.xml · nonDerivative · entry 8

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 2,924,503

F12 · price: The price reported in Column 4 is a weighted average price. These shares of Common Stock of the Issuer were traded by the Funds in multiple transactions at prices ranging from $71.42 to $72.10, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission (the "Staff"), upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F4 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Biotech Capital, L.P. and (ii) 667, L.P. ("667"), Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by 667, a limited partnership of which the sole general partner is Baker Biotech Capital, L.P., a limited partnership of which the sole general partner is Baker Biotech Capital (GP), LLC, due to their interest in 667 and Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F10 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

SEC source: 0001209191-22-018023 · doc4.xml · derivative · entry 17

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 0

Underlying: Common Stock · 20,000 shares

Expires 2022-05-29

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.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F8 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F9 · ownership.nature: Common Stock received upon exercise of 20,000 Stock Options that were issued to Julian C. Baker in his capacity as a director of the Issuer. Julian C. Baker, pursuant to the policies of the Adviser, does not have any right to the pecuniary interest in the Stock Options issued for his service on the Board or the Common Stock received upon exercise of such Stock Options. Each of the Funds owns an indirect proportionate pecuniary interest in the Common Stock received upon exercise of the Stock Options issued in connection with Julian C. Baker's service on the Board less the exercise cost of those Stock Options.

F10 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F11 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

SEC source: 0001209191-22-018023 · doc4.xml · derivative · entry 16

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 0

Underlying: Common Stock · 20,000 shares

Expires 2022-05-29

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.

F4 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Biotech Capital, L.P. and (ii) 667, L.P. ("667"), Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by 667, a limited partnership of which the sole general partner is Baker Biotech Capital, L.P., a limited partnership of which the sole general partner is Baker Biotech Capital (GP), LLC, due to their interest in 667 and Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F8 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F9 · ownership.nature: Common Stock received upon exercise of 20,000 Stock Options that were issued to Julian C. Baker in his capacity as a director of the Issuer. Julian C. Baker, pursuant to the policies of the Adviser, does not have any right to the pecuniary interest in the Stock Options issued for his service on the Board or the Common Stock received upon exercise of such Stock Options. Each of the Funds owns an indirect proportionate pecuniary interest in the Common Stock received upon exercise of the Stock Options issued in connection with Julian C. Baker's service on the Board less the exercise cost of those Stock Options.

F10 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

SEC source: 0001209191-22-018023 · doc4.xml · nonDerivative · entry 7

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 33,151,989

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F10 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F11 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

SEC source: 0001209191-22-018023 · doc4.xml · nonDerivative · entry 6

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 2,919,133

F4 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Biotech Capital, L.P. and (ii) 667, L.P. ("667"), Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by 667, a limited partnership of which the sole general partner is Baker Biotech Capital, L.P., a limited partnership of which the sole general partner is Baker Biotech Capital (GP), LLC, due to their interest in 667 and Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F10 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

SEC source: 0001209191-22-018023 · doc4.xml · nonDerivative · entry 5

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 33,059,604

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.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F9 · ownership.nature: Common Stock received upon exercise of 20,000 Stock Options that were issued to Julian C. Baker in his capacity as a director of the Issuer. Julian C. Baker, pursuant to the policies of the Adviser, does not have any right to the pecuniary interest in the Stock Options issued for his service on the Board or the Common Stock received upon exercise of such Stock Options. Each of the Funds owns an indirect proportionate pecuniary interest in the Common Stock received upon exercise of the Stock Options issued in connection with Julian C. Baker's service on the Board less the exercise cost of those Stock Options.

F10 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F11 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

SEC source: 0001209191-22-018023 · doc4.xml · nonDerivative · entry 4

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 2,911,518

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.

F4 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Biotech Capital, L.P. and (ii) 667, L.P. ("667"), Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by 667, a limited partnership of which the sole general partner is Baker Biotech Capital, L.P., a limited partnership of which the sole general partner is Baker Biotech Capital (GP), LLC, due to their interest in 667 and Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F9 · ownership.nature: Common Stock received upon exercise of 20,000 Stock Options that were issued to Julian C. Baker in his capacity as a director of the Issuer. Julian C. Baker, pursuant to the policies of the Adviser, does not have any right to the pecuniary interest in the Stock Options issued for his service on the Board or the Common Stock received upon exercise of such Stock Options. Each of the Funds owns an indirect proportionate pecuniary interest in the Common Stock received upon exercise of the Stock Options issued in connection with Julian C. Baker's service on the Board less the exercise cost of those Stock Options.

F10 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

SEC source: 0001209191-22-011843 · doc4.xml · nonDerivative · entry 11

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 33,039,604

F15 · price: The price reported in Column 4 is a weighted average price. These shares were traded by the Funds in multiple transactions at prices ranging from $67.88 to $68.21, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667, L.P. ("667") and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

F7 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F8 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock, 2,802 of which were received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F9 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F10 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

SEC source: 0001209191-22-011843 · doc4.xml · nonDerivative · entry 10

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 2,891,518

F15 · price: The price reported in Column 4 is a weighted average price. These shares were traded by the Funds in multiple transactions at prices ranging from $67.88 to $68.21, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667, L.P. ("667") and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F7 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F8 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock, 2,802 of which were received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F9 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F10 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F13 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Biotech Capital, L.P. and (ii) 667, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by 667, a limited partnership of which the sole general partner is Baker Biotech Capital, L.P., a limited partnership of which the sole general partner is Baker Biotech Capital (GP), LLC, due to their interest in 667 and Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667.

SEC source: 0001209191-22-011843 · doc4.xml · nonDerivative · entry 9

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 32,947,370

F14 · price: The price reported in Column 4 is a weighted average price. These shares were traded by the Funds in multiple transactions at prices ranging from $68.34 to $68.51, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667, L.P. ("667") and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

F7 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F8 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock, 2,802 of which were received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F9 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F10 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

SEC source: 0001209191-22-011843 · doc4.xml · nonDerivative · entry 8

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 2,883,952

F14 · price: The price reported in Column 4 is a weighted average price. These shares were traded by the Funds in multiple transactions at prices ranging from $68.34 to $68.51, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667, L.P. ("667") and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F7 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F8 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock, 2,802 of which were received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F9 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F10 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F13 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Biotech Capital, L.P. and (ii) 667, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by 667, a limited partnership of which the sole general partner is Baker Biotech Capital, L.P., a limited partnership of which the sole general partner is Baker Biotech Capital (GP), LLC, due to their interest in 667 and Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667.

SEC source: 0001209191-22-011843 · doc4.xml · nonDerivative · entry 7

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 32,925,192

F12 · price: The price reported in Column 4 is a weighted average price. These shares were traded by the Funds in multiple transactions at prices ranging from $67.75 to $68.53, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667, L.P. ("667") and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

F7 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F8 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock, 2,802 of which were received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F9 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F10 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

SEC source: 0001209191-22-011843 · doc4.xml · nonDerivative · entry 6

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 2,882,125

F12 · price: The price reported in Column 4 is a weighted average price. These shares were traded by the Funds in multiple transactions at prices ranging from $67.75 to $68.53, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667, L.P. ("667") and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F7 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F8 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock, 2,802 of which were received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F9 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F10 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F13 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Biotech Capital, L.P. and (ii) 667, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by 667, a limited partnership of which the sole general partner is Baker Biotech Capital, L.P., a limited partnership of which the sole general partner is Baker Biotech Capital (GP), LLC, due to their interest in 667 and Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667.

SEC source: 0001209191-22-011843 · doc4.xml · nonDerivative · entry 5

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 32,824,461

F11 · price: The price reported in Column 4 is a weighted average price. These shares were traded by Life Sciences in multiple transactions at prices ranging from $67.24 to $68.06, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667, L.P. ("667") and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

F7 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F8 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock, 2,802 of which were received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F9 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F10 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

SEC source: 0001209191-22-011843 · doc4.xml · nonDerivative · entry 4

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 32,538,789

F4 · price: The price reported in Column 4 is a weighted average price. These shares of Common Stock of the Issuer were traded by Life Sciences in multiple transactions at prices ranging from $67.37 to $67.40, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission (the "Staff"), upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667, L.P. ("667") and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

F7 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F8 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock, 2,802 of which were received previously from vested restricted stock units (each, an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F9 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F10 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

SEC source: 0001209191-22-009411 · doc4.xml · nonDerivative · entry 11

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 32,531,489

F17 · price: The price reported in Column 4 is a weighted average price. These shares were traded by Life Sciences in multiple transactions at prices ranging from $65.89 to $66.23, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock, 2,802 of which were received previously from vested restricted stock units (each an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F9 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F11 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

SEC source: 0001209191-22-009411 · doc4.xml · nonDerivative · entry 10

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 32,349,163

F16 · price: The price reported in Column 4 is a weighted average price. These shares were traded by Life Sciences in multiple transactions at prices ranging from $65.66 to $66.19, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock, 2,802 of which were received previously from vested restricted stock units (each an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F9 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F11 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

SEC source: 0001209191-22-009411 · doc4.xml · nonDerivative · entry 9

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 32,028,637

F15 · price: The price reported in Column 4 is a weighted average price. These shares were traded by Life Sciences in multiple transactions at prices ranging from $66.82 to $67.00, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock, 2,802 of which were received previously from vested restricted stock units (each an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F9 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F11 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

SEC source: 0001209191-22-009411 · doc4.xml · nonDerivative · entry 8

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 32,017,652

F14 · price: The price reported in Column 4 is a weighted average price. These shares were traded by Life Sciences in multiple transactions at prices ranging from $66.54 to $67.32, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock, 2,802 of which were received previously from vested restricted stock units (each an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F9 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F11 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

SEC source: 0001209191-22-009777 · doc4.xml · nonDerivative · entry 2

Stamoulis Christiana · CIK 0001502917 · EVP & Chief Financial Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 56,285

F1 · shares: Represents shares withheld to satisfy tax withholding obligations due at settlement of restricted stock units previously reported in Table I as common stock.

F2 · balance_after: This includes an aggregate of 47,506 shares of common stock issuable pursuant to previously reported restricted stock units and earned performance shares that have not vested.

SEC source: 0001209191-22-009777 · doc4.xml · nonDerivative · entry 1

Stamoulis Christiana · CIK 0001502917 · EVP & Chief Financial Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 56,616

F1 · shares: Represents shares withheld to satisfy tax withholding obligations due at settlement of restricted stock units previously reported in Table I as common stock.

SEC source: 0001209191-22-009411 · doc4.xml · nonDerivative · entry 7

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 31,752,130

F13 · price: The price reported in Column 4 is a weighted average price. These shares were traded by Life Sciences in multiple transactions at prices ranging from $66.85 to $67.85, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock, 2,802 of which were received previously from vested restricted stock units (each an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F9 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F11 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

SEC source: 0001209191-22-009411 · doc4.xml · nonDerivative · entry 6

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

667, L.P. · CIK 0001551139 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

Baker Bros. Advisors (GP) LLC · CIK 0001580575 · Director · 10% owner

Baker Brothers Life Sciences LP · CIK 0001363364 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · 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: 30,979,379

F12 · price: The price reported in Column 4 is a weighted average price. These shares were traded by Life Sciences in multiple transactions at prices ranging from $67.10 to $67.43, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer, or the Staff, upon request, full information regarding the number of shares traded at each separate price within the range set forth in this footnote.

F5 · ownership.nature: Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held by the Funds. Baker Bros. Advisors (GP) LLC (the ''Adviser GP'') is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds.

F6 · ownership.nature: Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any other purpose.

F7 · ownership.nature: Includes beneficial ownership of 7,233 shares of Common Stock previously issued to Julian C. Baker pursuant to the Stock Incentive Plan in lieu of director retainer fees, 4,725 shares of Common Stock, 2,802 of which were received previously from vested restricted stock units (each an "RSU") and 175,000 shares of Common Stock received previously from exercise of 175,000 non-qualified stock options to purchase Common Stock of the Issuer ("Stock Options") that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the Funds may be deemed to own a portion.

F8 · ownership.nature: Pursuant to agreements between Julian C. Baker and the Adviser and the policies of the Adviser, the Adviser has voting and dispositive power over the Common Stock received in lieu of director retainer fees, Stock Options, RSUs and any Common Stock received as a result of the exercise of Stock Options or vesting of RSUs.

F9 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker does not have a right to any of the Issuer's securities issued in lieu of director retainer fees and the Funds are entitled to an indirect proportionate pecuniary interest in the securities. The Funds each own an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in (i) the general partners of the Funds and (ii) the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares of Common Stock issued in lieu of director retainer fees, Stock Options, Common Stock issued upon exercise of Stock Options, RSU's payable solely in Common Stock and Common Stock received upon vesting of RSUs (ie. no direct pecuniary interest).

F11 · ownership.nature: After giving effect to the transaction reported herein and as a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in Common Stock reported in column 5 of Table I directly held by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.