INCY

SEC source: 0001209191-18-041628 · doc4.xml · derivative · entry 2

SWAIN PAULA J · CIK 0001236934 · EVP, Human Resources

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 22,772

Underlying: Common Stock · 22,772 shares

Expires 2028-07-01

F3 · derivative.exercise_date: Beginning July 2, 2018, options become exercisable in 37 installments, with the first 25% vesting after one year and the remainder vesting monthly over three years.

SEC source: 0001209191-18-041610 · doc4.xml · derivative · entry 2

Wenqing Yao · CIK 0001624033 · EVP, Head of Discovery Chem

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 22,772

Underlying: Common Stock · 22,772 shares

Expires 2028-07-01

F3 · derivative.exercise_date: Beginning July 2, 2018, options become exercisable in 37 installments, with the first 25% vesting after one year and the remainder vesting monthly over three years.

SEC source: 0001209191-18-041613 · doc4.xml · derivative · entry 3

Trower Paul · CIK 0001642041 · Principal Accounting Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 6,297

Underlying: Common Stock · 6,297 shares

Expires 2028-07-01

F4 · derivative.exercise_date: Beginning July 2, 2018, options become exercisable in 37 installments, with the first 25% vesting after one year and the remainder vesting monthly over three years.

SEC source: 0001209191-18-041613 · doc4.xml · nonDerivative · entry 1

Trower Paul · CIK 0001642041 · Principal Accounting Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 14,469

F1 · shares: Represents award of restricted stock units ("RSUs") that will vest 25% annually over four years, subject to Mr. Trower's continued service with the Issuer through the applicable vesting dates. The RSUs may be settled only for shares of common stock on a one-for-one basis.

F2 · balance_after: Includes an aggregate of 3,526 shares of common stock issuable pursuant to previously reported restricted stock units that have not vested.

SEC source: 0001209191-18-040987 · doc4.xml · nonDerivative · entry 3

BROOKE PAUL A · CIK 0001175940 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 198,213

F3 · 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.

SEC source: 0001209191-18-040951 · doc4.xml · nonDerivative · entry 1

BIENAIME JEAN JACQUES · CIK 0001221590 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 5,459

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.

SEC source: 0001209191-18-040933 · doc4.xml · nonDerivative · entry 1

DIXON WENDY L · CIK 0001202283 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 9,709

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.

SEC source: 0001209191-18-040920 · doc4.xml · nonDerivative · entry 1

FOUSE JACQUALYN A · CIK 0001405288 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 336

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.

SEC source: 0001638599-18-000723 · doc4_5506.xml · nonDerivative · entry 6

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

14159, L.P. · CIK 0001551138 · Director · 10% owner

667, L.P. · CIK 0001551139 · 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

BAKER JULIAN · CIK 0001087939 · 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: 810,289

F4 · ownership.nature: 283 shares of common stock (the "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 director retainer fees of $19,000. 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 the Funds (as defined below).

F5 · ownership.nature: Pursuant to the policies of Baker Bros. Advisors LP (the "Adviser"), Julian C. Baker does not have any right to the pecuniary interest in the Issuer's securities issued in lieu of director retainer fees and the Funds (as defined below) are entitled to an indirect proportionate pecuniary interest in the securities issued in lieu of director fees. 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in the general partners of the general partners of 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 (ie. no direct pecuniary interest).

F8 · ownership.nature: As a result of Felix J. Baker's and Julian C. Baker's ownership interest in 14159 Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 810,289 shares of common stock of the Issuer beneficially owned by 14159, a limited partnership of which the sole general partner is 14159 Capital, L.P., a limited partnership of which the sole general partner is 14159 Capital (GP), LLC, due to 14159 Capital, L.P.'s right to receive an allocation of a portion of the profits from 14159. Includes beneficial ownership of 2,583 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 115,000 shares received previously from exercise of 115,000 stock options of the Issuer that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the fund may be deemed to own a portion.

F9 · ownership.nature: 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 principals 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. 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: The 283 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-18-000723 · doc4_5506.xml · nonDerivative · entry 5

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

14159, L.P. · CIK 0001551138 · Director · 10% owner

667, L.P. · CIK 0001551139 · 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

BAKER JULIAN · CIK 0001087939 · 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: 29,268,220

F4 · ownership.nature: 283 shares of common stock (the "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 director retainer fees of $19,000. 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 the Funds (as defined below).

F5 · ownership.nature: Pursuant to the policies of Baker Bros. Advisors LP (the "Adviser"), Julian C. Baker does not have any right to the pecuniary interest in the Issuer's securities issued in lieu of director retainer fees and the Funds (as defined below) are entitled to an indirect proportionate pecuniary interest in the securities issued in lieu of director fees. 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in the general partners of the general partners of 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 (ie. no direct pecuniary interest).

F7 · ownership.nature: As a result of Felix J. Baker's and Julian C. Baker's ownership interest in Baker Brothers Life Sciences Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 29,268,220 shares of common stock of the Issuer beneficially owned 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 Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences. Includes beneficial ownership of 2,583 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 115,000 shares received previously from exercise of 115,000 stock options of the Issuer that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the fund may be deemed to own a portion.

F9 · ownership.nature: 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 principals 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. 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: The 283 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-18-000723 · doc4_5506.xml · nonDerivative · entry 4

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

14159, L.P. · CIK 0001551138 · Director · 10% owner

667, L.P. · CIK 0001551139 · 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

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 4,407,691

F4 · ownership.nature: 283 shares of common stock (the "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 director retainer fees of $19,000. 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 the Funds (as defined below).

F5 · ownership.nature: Pursuant to the policies of Baker Bros. Advisors LP (the "Adviser"), Julian C. Baker does not have any right to the pecuniary interest in the Issuer's securities issued in lieu of director retainer fees and the Funds (as defined below) are entitled to an indirect proportionate pecuniary interest in the securities issued in lieu of director fees. 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in the general partners of the general partners of 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 (ie. no direct pecuniary interest).

F6 · ownership.nature: As a result of Felix J. Baker's and Julian C. Baker's ownership interest in Baker Biotech Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 4,407,691 shares of common stock of the Issuer beneficially owned 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 Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667. Includes beneficial ownership of 2,583 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 115,000 shares received previously from exercise of 115,000 stock options of the Issuer that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the fund may be deemed to own a portion.

F9 · ownership.nature: 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 principals 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. 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: The 283 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001209191-18-040987 · doc4.xml · nonDerivative · entry 2

BROOKE PAUL A · CIK 0001175940 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · By the Paul Brooke Family Trusts

Disclosed balance after: 40,000

F2 · ownership.nature: As previously reported, the reporting person transferred certain directly owned shares of Common Stock to another family trust, the Paul Brooke Family Trust (the "Trust No. 1"). Collectively, Trust No. 1 and Trust No. 2 are referred to herein and will be referred to in future reports as "The Paul Brooke Family Trusts".

SEC source: 0001209191-18-040987 · doc4.xml · nonDerivative · entry 1

BROOKE PAUL A · CIK 0001175940 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 197,859

F1 · shares: On June 20, 2018, the reporting person transferred 20,000 directly owned shares of Common Stock to a family trust, The Kathleen McCarrigher and Paul A. Brooke 2012 Family Trust (the "Trust No. 2") for the benefit of the reporting person's descendants. The reporting person's spouse is the trustee of the Trust. The reporting person disclaims beneficial ownership of the shares of Common Stock held by Trust No. 2.

SEC source: 0001209191-18-036063 · doc4.xml · derivative · entry 2

BROOKE PAUL A · CIK 0001175940 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 20,000 shares

Expires 2019-05-19

F1 · 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 option plan).

SEC source: 0001209191-18-036063 · doc4.xml · nonDerivative · entry 1

BROOKE PAUL A · CIK 0001175940 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 217,859

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

SEC source: 0001209191-18-028548 · doc4.xml · nonDerivative · entry 2

BROOKE PAUL A · CIK 0001175940 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · By The Paul Brooke Family Trust

Disclosed balance after: 20,000

SEC source: 0001209191-18-028548 · doc4.xml · nonDerivative · entry 1

BROOKE PAUL A · CIK 0001175940 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 197,859

F1 · kind: On May 4, 2018, the reporting person transferred 20,000 directly owned shares of Common Stock to The Paul Brooke Family Trust (the "Trust") for the benefit of the reporting persons descendants. The reporting person's spouse is the trustee of the Trust. The reporting person disclaims beneficial ownership of the shares of Common Stock held by the Trust.

F1 · shares: On May 4, 2018, the reporting person transferred 20,000 directly owned shares of Common Stock to The Paul Brooke Family Trust (the "Trust") for the benefit of the reporting persons descendants. The reporting person's spouse is the trustee of the Trust. The reporting person disclaims beneficial ownership of the shares of Common Stock held by the Trust.

SEC source: 0001209191-18-027697 · doc4.xml · nonDerivative · entry 1

Hoppenot Herve · CIK 0001596492 · Director · Chairman / CEO · President

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 276,690

F1 · balance_after: Includes an aggregate of 173,657 shares of common stock issuable pursuant to previously reported restricted stock units that have not vested.

SEC source: 0001638599-18-000457 · doc4_5364.xml · derivative · entry 10

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

14159, L.P. · CIK 0001551138 · Director · 10% owner

667, L.P. · CIK 0001551139 · 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

BAKER JULIAN · CIK 0001087939 · 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 2018-05-21

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

F8 · price: These non-qualified stock options are not priced.

F7 · ownership.nature: As a result of their ownership interest in 14159 Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 20,000 shares of Common Stock of the Issuer received upon the exercise of stock options of the Issuer held by 14159, L.P. ("14159" and together with 667 and Life Sciences, the "Funds"), a limited partnership of which the sole general partner is 14159 Capital, L.P., a limited partnership of which the sole general partner is 14159 Capital (GP), LLC, due to 14159 Capital, L.P.'s right to receive an allocation of a portion of the profits from 14159. The policy of the Funds and the Adviser, does not permit full-time employees or principals of the Adviser to receive compensation for serving as Directors of the Issuer.

F9 · ownership.nature: The disclosure of the exercise of directors options for shares of common stock reported on this form is a single exercise of 20,000 shares. The 20,000 shares is reported for each of the Funds as each has an indirect pecuniary interest.

F14 · ownership.nature: 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 principals 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. 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.

SEC source: 0001638599-18-000457 · doc4_5364.xml · derivative · entry 9

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

14159, L.P. · CIK 0001551138 · Director · 10% owner

667, L.P. · CIK 0001551139 · 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

BAKER JULIAN · CIK 0001087939 · 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 2018-05-21

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

F8 · price: These non-qualified stock options are not priced.

F6 · ownership.nature: As a result of their ownership interest in Baker Brothers Life Sciences Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 20,000 shares of Common Stock of the Issuer received upon the exercise of stock options of the Issuer held by Baker Brothers Life Sciences, L.P. ("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 Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences. The policy of the Funds (defined below) and the Adviser, does not permit full-time employees or principals of the Adviser to receive compensation for serving as Directors of the Issuer.

F9 · ownership.nature: The disclosure of the exercise of directors options for shares of common stock reported on this form is a single exercise of 20,000 shares. The 20,000 shares is reported for each of the Funds as each has an indirect pecuniary interest.

F14 · ownership.nature: 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 principals 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. 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.

SEC source: 0001638599-18-000457 · doc4_5364.xml · derivative · entry 8

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

14159, L.P. · CIK 0001551138 · Director · 10% owner

667, L.P. · CIK 0001551139 · 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

BAKER JULIAN · CIK 0001087939 · 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 2018-05-21

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

F8 · price: These non-qualified stock options are not priced.

F4 · ownership.nature: As a result of their ownership interest in Baker Biotech Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 20,000 shares of Common Stock of the Issuer received upon the exercise of stock options of the Issuer held by 667, L.P. ("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 Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667. The policy of the Funds (defined below) and Baker Bros. Advisors LP (the "Adviser"), does not permit full-time employees or principals of the Adviser to receive compensation for serving as Directors of the Issuer.

F9 · ownership.nature: The disclosure of the exercise of directors options for shares of common stock reported on this form is a single exercise of 20,000 shares. The 20,000 shares is reported for each of the Funds as each has an indirect pecuniary interest.

F14 · ownership.nature: 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 principals 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. 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.

SEC source: 0001638599-18-000457 · doc4_5364.xml · nonDerivative · entry 6

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

14159, L.P. · CIK 0001551138 · Director · 10% owner

667, L.P. · CIK 0001551139 · 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

BAKER JULIAN · CIK 0001087939 · 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: 810,006

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: The shares of common stock were 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 of Directors of the Issuer (the "Board") or the shares of common stock received upon exercise of such stock options. Each of the Funds owns an indirect proportionate pecuniary interest in the shares of 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 options. Solely as a result of their ownership interest in the general partners of the general partners of the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares issued upon exercise of the stock options (i.e. no direct pecuniary interest).

F7 · ownership.nature: As a result of their ownership interest in 14159 Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 20,000 shares of Common Stock of the Issuer received upon the exercise of stock options of the Issuer held by 14159, L.P. ("14159" and together with 667 and Life Sciences, the "Funds"), a limited partnership of which the sole general partner is 14159 Capital, L.P., a limited partnership of which the sole general partner is 14159 Capital (GP), LLC, due to 14159 Capital, L.P.'s right to receive an allocation of a portion of the profits from 14159. The policy of the Funds and the Adviser, does not permit full-time employees or principals of the Adviser to receive compensation for serving as Directors of the Issuer.

F9 · ownership.nature: The disclosure of the exercise of directors options for shares of common stock reported on this form is a single exercise of 20,000 shares. The 20,000 shares is reported for each of the Funds as each has an indirect pecuniary interest.

F12 · ownership.nature: After giving effect to the transactions reported herein, and as a result of their ownership interest in 14159 Capital (GP), LLC, Julian C. Baker and Felix J. Baker may be deemed to have an indirect pecuniary interest in the Issuer's shares of Common Stock reported in column 5 of Table I directly held by 14159, a limited partnership of which the sole general partner is 14159 Capital, L.P., a limited partnership of which the sole general partner is 14159 Capital (GP), LLC, due to 14159, L.P.'s right to receive an allocation of a portion of the profits from 14159.

F13 · ownership.nature: Includes beneficial ownership of 2,300 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 115,000 shares, 95,000 of which were received previously, from exercise of 115,000 stock options of the Issuer that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the fund may be deemed to own a portion.

F14 · ownership.nature: 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 principals 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. 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.

SEC source: 0001638599-18-000457 · doc4_5364.xml · nonDerivative · entry 5

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

14159, L.P. · CIK 0001551138 · Director · 10% owner

667, L.P. · CIK 0001551139 · 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

BAKER JULIAN · CIK 0001087939 · 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: 29,267,937

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: The shares of common stock were 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 of Directors of the Issuer (the "Board") or the shares of common stock received upon exercise of such stock options. Each of the Funds owns an indirect proportionate pecuniary interest in the shares of 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 options. Solely as a result of their ownership interest in the general partners of the general partners of the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares issued upon exercise of the stock options (i.e. no direct pecuniary interest).

F6 · ownership.nature: As a result of their ownership interest in Baker Brothers Life Sciences Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 20,000 shares of Common Stock of the Issuer received upon the exercise of stock options of the Issuer held by Baker Brothers Life Sciences, L.P. ("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 Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences. The policy of the Funds (defined below) and the Adviser, does not permit full-time employees or principals of the Adviser to receive compensation for serving as Directors of the Issuer.

F9 · ownership.nature: The disclosure of the exercise of directors options for shares of common stock reported on this form is a single exercise of 20,000 shares. The 20,000 shares is reported for each of the Funds as each has an indirect pecuniary interest.

F11 · ownership.nature: After giving effect to the transactions reported herein, and as a result of their ownership interest in Baker Brothers Life Sciences Capital (GP), LLC, Julian C. Baker and Felix J. Baker may be deemed to have an indirect pecuniary interest in the Issuer's shares of 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 Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences.

F13 · ownership.nature: Includes beneficial ownership of 2,300 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 115,000 shares, 95,000 of which were received previously, from exercise of 115,000 stock options of the Issuer that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the fund may be deemed to own a portion.

F14 · ownership.nature: 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 principals 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. 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.

SEC source: 0001638599-18-000457 · doc4_5364.xml · nonDerivative · entry 4

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

14159, L.P. · CIK 0001551138 · Director · 10% owner

667, L.P. · CIK 0001551139 · 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

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 4,407,408

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: As a result of their ownership interest in Baker Biotech Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 20,000 shares of Common Stock of the Issuer received upon the exercise of stock options of the Issuer held by 667, L.P. ("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 Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667. The policy of the Funds (defined below) and Baker Bros. Advisors LP (the "Adviser"), does not permit full-time employees or principals of the Adviser to receive compensation for serving as Directors of the Issuer.

F5 · ownership.nature: The shares of common stock were 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 of Directors of the Issuer (the "Board") or the shares of common stock received upon exercise of such stock options. Each of the Funds owns an indirect proportionate pecuniary interest in the shares of 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 options. Solely as a result of their ownership interest in the general partners of the general partners of the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the shares issued upon exercise of the stock options (i.e. no direct pecuniary interest).

F9 · ownership.nature: The disclosure of the exercise of directors options for shares of common stock reported on this form is a single exercise of 20,000 shares. The 20,000 shares is reported for each of the Funds as each has an indirect pecuniary interest.

F10 · ownership.nature: After giving effect to the transactions reported herein, and as a result of their ownership interest in Baker Biotech Capital (GP), LLC, Julian C. Baker and Felix J. Baker may be deemed to have an indirect pecuniary interest in the Issuer's shares of 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 Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667.

F13 · ownership.nature: Includes beneficial ownership of 2,300 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 115,000 shares, 95,000 of which were received previously, from exercise of 115,000 stock options of the Issuer that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the fund may be deemed to own a portion.

F14 · ownership.nature: 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 principals 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. 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.

SEC source: 0001209191-18-027769 · doc4.xml · derivative · entry 1

FRIEDMAN PAUL A · CIK 0001236927 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Stock · 15,000 shares

Expires 2028-04-30

F1 · 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 option plan).

SEC source: 0001209191-18-027762 · doc4.xml · derivative · entry 1

FOUSE JACQUALYN A · CIK 0001405288 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Stock · 15,000 shares

Expires 2028-04-30

F1 · 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 option plan).

SEC source: 0001209191-18-027750 · doc4.xml · derivative · entry 1

DIXON WENDY L · CIK 0001202283 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Stock · 15,000 shares

Expires 2028-04-30

F1 · 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 option plan).

SEC source: 0001209191-18-027732 · doc4.xml · derivative · entry 1

Clancy Paul J · CIK 0001409601 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Stock · 15,000 shares

Expires 2028-04-30

F1 · 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 option plan).

SEC source: 0001209191-18-027724 · doc4.xml · derivative · entry 1

BROOKE PAUL A · CIK 0001175940 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Stock · 15,000 shares

Expires 2028-04-30

F1 · 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 option plan).

SEC source: 0001209191-18-027713 · doc4.xml · derivative · entry 1

BIENAIME JEAN JACQUES · CIK 0001221590 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Stock · 15,000 shares

Expires 2028-04-30

F1 · 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 option plan).

SEC source: 0001638599-18-000457 · doc4_5364.xml · derivative · entry 7

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

14159, L.P. · CIK 0001551138 · Director · 10% owner

667, L.P. · CIK 0001551139 · 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

BAKER JULIAN · CIK 0001087939 · 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: 15,000

Underlying: Common Stock · 15,000 shares

Expires 2028-04-30

F8 · price: These non-qualified stock options are not priced.

F14 · ownership.nature: 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 principals 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. 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.

F15 · ownership.nature: 15,000 non-qualified stock options (the "Stock Options") convertible solely into common shares were granted to Julian C. Baker. The Stock Options have a strike price of $60.85 and vest on the first anniversary of the grant date or, if earlier, the date of the next regular annual meeting of the Issuer stockholders or upon a change in control of the Issuer (as defined in the Issuer's Amended and Restated 2010 Stock Incentive Plan). Julian C. Baker serves on the Board as a representative of the Funds. Pursuant to the policies of the Adviser, Julian C. Baker does not have any right to any of the Issuer's securities issued as part of his service on the Board and the Funds are entitled to receive all the pecuniary interest in the securities issued.

F16 · ownership.nature: The Funds each own an indirect proportionate pecuniary interest in the Stock Options. Solely as a result of Felix J. Baker's and Julian C. Baker's ownership interest in the general partners of the general partners of the Funds, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in the Stock Options (i.e. no direct pecuniary interest).

SEC source: 0001209191-18-027410 · doc4.xml · derivative · entry 6

SWAIN PAULA J · CIK 0001236934 · EVP, Human Resources

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 73,900 shares

Expires 2019-01-18

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 · derivative.exercise_date: Beginning January 19, 2012, options become exercisable in 25 installments, with the first 33.33% vesting after one year and the remainder vesting monthly over two years

SEC source: 0001209191-18-027410 · doc4.xml · derivative · entry 5

SWAIN PAULA J · CIK 0001236934 · EVP, Human Resources

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 6,100 shares

Expires 2019-01-18

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 · derivative.exercise_date: Beginning January 19, 2012, options become exercisable in 25 installments, with the first 33.33% vesting after one year and the remainder vesting monthly over two years

SEC source: 0001209191-18-027410 · doc4.xml · nonDerivative · entry 4

SWAIN PAULA J · CIK 0001236934 · EVP, Human Resources

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 33,367

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

F2 · price: Represents weighted average sale price. Actual sale prices ranged from $61.88 - $63.09.

F3 · price: Reporting person undertakes to provide upon request by Securites and Exchange Commission, the issuer or a securityholder of the issuer detailed information regarding the price and number of shares sold within range indicated.

F4 · balance_after: Includes an aggregate of 10,294 shares of common stock issuable pursuant to previously reported restricted stock units that have not vested.

SEC source: 0001209191-18-027410 · doc4.xml · nonDerivative · entry 3

SWAIN PAULA J · CIK 0001236934 · EVP, Human Resources

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 107,267

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: 0001209191-18-027410 · doc4.xml · nonDerivative · entry 2

SWAIN PAULA J · CIK 0001236934 · EVP, Human Resources

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 33,367

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

F2 · price: Represents weighted average sale price. Actual sale prices ranged from $61.88 - $63.09.

F3 · price: Reporting person undertakes to provide upon request by Securites and Exchange Commission, the issuer or a securityholder of the issuer detailed information regarding the price and number of shares sold within range indicated.

SEC source: 0001209191-18-027410 · doc4.xml · nonDerivative · entry 1

SWAIN PAULA J · CIK 0001236934 · EVP, Human Resources

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 39,467

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: 0001209191-18-024652 · doc4.xml · derivative · entry 2

Pasquale Maria E · CIK 0001736295 · EVP & General Counsel

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 41,193

Underlying: Common Stock · 41,193 shares

Expires 2028-04-09

F2 · derivative.exercise_date: Beginning April 9, 2018, options become exercisable in 37 installments, with the first 25% vesting after one year and the remainder vesting monthly over three years.

SEC source: 0001209191-18-024652 · doc4.xml · nonDerivative · entry 1

Pasquale Maria E · CIK 0001736295 · EVP & General Counsel

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 6,141

F1 · shares: Represents award of restricted stock units ("RSUs") that will vest 25% annually over four years, subject to Maria Pasquale's continued service with the issuer through the applicable vesting dates. The RSUs may be settled only for shares of common stock on a one-for-one basis.

SEC source: 0001209191-18-024363 · doc4.xml · derivative · entry 2

BROOKE PAUL A · CIK 0001175940 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 20,000 shares

Expires 2018-05-22

F1 · 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 option plan).

SEC source: 0001209191-18-024363 · doc4.xml · nonDerivative · entry 1

BROOKE PAUL A · CIK 0001175940 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 217,859

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

SEC source: 0001638599-18-000388 · doc4_5343.xml · nonDerivative · entry 6

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

14159, L.P. · CIK 0001551138 · Director · 10% owner

667, L.P. · CIK 0001551139 · 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

BAKER JULIAN · CIK 0001087939 · 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: 790,006

F4 · ownership.nature: 228 shares of common stock (the "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 director retainer fees of $19,000. 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 the Funds (as defined below).

F5 · ownership.nature: Pursuant to the policies of Baker Bros. Advisors LP (the "Adviser"), Julian C. Baker does not have any right to the pecuniary interest in the Issuer's securities issued in lieu of director retainer fees and the Funds (as defined below) are entitled to an indirect proportionate pecuniary interest in the securities issued in lieu of director fees. 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in the general partners of the general partners of 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 (ie. no direct pecuniary interest).

F8 · ownership.nature: As a result of Felix J. Baker's and Julian C. Baker's ownership interest in 14159 Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 790,006 shares of common stock of the Issuer beneficially owned by 14159, a limited partnership of which the sole general partner is 14159 Capital, L.P., a limited partnership of which the sole general partner is 14159 Capital (GP), LLC, due to 14159 Capital, L.P.'s right to receive an allocation of a portion of the profits from 14159. Includes beneficial ownership of 2,300 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 95,000 shares received previously from exercise of 95,000 stock options of the Issuer that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the fund may be deemed to own a portion.

F9 · ownership.nature: 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 principals 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. 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: The 228 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-18-000388 · doc4_5343.xml · nonDerivative · entry 5

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

14159, L.P. · CIK 0001551138 · Director · 10% owner

667, L.P. · CIK 0001551139 · 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

BAKER JULIAN · CIK 0001087939 · 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: 29,247,937

F4 · ownership.nature: 228 shares of common stock (the "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 director retainer fees of $19,000. 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 the Funds (as defined below).

F5 · ownership.nature: Pursuant to the policies of Baker Bros. Advisors LP (the "Adviser"), Julian C. Baker does not have any right to the pecuniary interest in the Issuer's securities issued in lieu of director retainer fees and the Funds (as defined below) are entitled to an indirect proportionate pecuniary interest in the securities issued in lieu of director fees. 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in the general partners of the general partners of 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 (ie. no direct pecuniary interest).

F7 · ownership.nature: As a result of Felix J. Baker's and Julian C. Baker's ownership interest in Baker Brothers Life Sciences Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest 29,247,937 shares of common stock of the Issuer beneficially owned 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 Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences. Includes beneficial ownership of 2,300 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 95,000 shares received previously from exercise of 95,000 stock options of the Issuer that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the fund may be deemed to own a portion.

F9 · ownership.nature: 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 principals 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. 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: The 228 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-18-000388 · doc4_5343.xml · nonDerivative · entry 4

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

14159, L.P. · CIK 0001551138 · Director · 10% owner

667, L.P. · CIK 0001551139 · 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

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 4,387,408

F4 · ownership.nature: 228 shares of common stock (the "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 director retainer fees of $19,000. 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 the Funds (as defined below).

F5 · ownership.nature: Pursuant to the policies of Baker Bros. Advisors LP (the "Adviser"), Julian C. Baker does not have any right to the pecuniary interest in the Issuer's securities issued in lieu of director retainer fees and the Funds (as defined below) are entitled to an indirect proportionate pecuniary interest in the securities issued in lieu of director fees. 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Common Stock. Solely as a result of their ownership interest in the general partners of the general partners of 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 (ie. no direct pecuniary interest).

F6 · ownership.nature: As a result of Felix J. Baker's and Julian C. Baker's ownership interest in Baker Biotech Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 4,387,408 shares of common stock of the Issuer beneficially owned 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 Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667. Includes beneficial ownership of 2,300 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 95,000 shares received previously from exercise of 95,000 stock options of the Issuer that were issued to Julian C. Baker in his capacity as a director of the Issuer, of which the fund may be deemed to own a portion.

F9 · ownership.nature: 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 principals 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. 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: The 228 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001209191-18-022963 · doc4.xml · nonDerivative · entry 1

DIXON WENDY L · CIK 0001202283 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 9,467

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.

SEC source: 0001209191-18-022973 · doc4.xml · nonDerivative · entry 1

FOUSE JACQUALYN A · CIK 0001405288 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 150

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.

SEC source: 0001209191-18-022953 · doc4.xml · nonDerivative · entry 1

BROOKE PAUL A · CIK 0001175940 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 197,859

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.

SEC source: 0001209191-18-022918 · doc4.xml · nonDerivative · entry 1

BIENAIME JEAN JACQUES · CIK 0001221590 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 5,243

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.

SEC source: 0001209191-18-017263 · doc4.xml · nonDerivative · entry 1

Stein Steven H · CIK 0001673776 · EVP & Chief Medical Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,459

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 10,294 shares of common stock issuable pursuant to previously reported restricted stock units that have not vested.

SEC source: 0001209191-18-012484 · doc4.xml · nonDerivative · entry 2

GRYSKA DAVID W · CIK 0001202335 · Executive Vice President, CFO

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,970

F2 · shares: Reporting person undertakes to provide upon request by Securites and Exchange Commission, the issuer or a securityholder of the issuer detailed information regarding the price and number of shares sold within range indicated.

F3 · shares: This transaction was effected pursuant to a Rule 10b5-1 trading plan adopted by reporting person.

F4 · shares: Represents weighted average sale price. Actual sale prices ranged from $85.11 - $86.28.

F5 · balance_after: Includes an aggregate of 10,294 shares of common stock issuable pursuant to previously reported restricted stock units that have not vested.