14159, L.P.

SEC source: 0001638599-17-000381 · doc4_4670.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 FELIX · CIK 0001087940 · 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

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 2017-05-21

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 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.

SEC source: 0001638599-17-000381 · doc4_4670.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 FELIX · CIK 0001087940 · 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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 787,237

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 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: Includes beneficial ownership of 1,560 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 95,000 shares, 75,000 of which were 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.

F13 · 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.

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: 0001638599-17-000381 · doc4_4670.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 FELIX · CIK 0001087940 · 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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 29,161,795

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 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.

F12 · ownership.nature: Includes beneficial ownership of 1,560 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 95,000 shares, 75,000 of which were 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.

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: 0001638599-17-000381 · doc4_4670.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 FELIX · CIK 0001087940 · 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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 4,374,099

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 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. Includes beneficial ownership of 1,560 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 95,000 shares, 75,000 of which were 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.

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: 0001638599-17-000373 · doc4_4666.xml · derivative · entry 1

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

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

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

14159, L.P. · CIK 0001551138 · 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: 399,984

Underlying: Ordinary Shares · 399,984 shares

Expires 2027-04-18

F1 · derivative.exercise_price: In ordinary shares. Ordinary shares are convertible into American Depositary Shares ("ADS") on a 13:1 basis.

F1 · shares: In ordinary shares. Ordinary shares are convertible into American Depositary Shares ("ADS") on a 13:1 basis.

F2 · shares: 199,992 non-qualified share options ("Share Options") convertible solely into Ordinary Shares of BeiGene, Ltd. (the "Issuer") were granted to Michael Goller, an employee of Baker Bros. Advisors LP (the "Adviser") and 199,992 Share Options were granted to Ranjeev Krishana, an employee of the Adviser in their capacity as directors of the Issuer. The Share Options with a strike price of $2.84 vest in 3 equal annual installments beginning on April 19, 2017 and shall become exercisable in full on the date of the third annual meeting of shareholders following the grant date. The Share Options expire on April 18, 2027. Michael Goller and Ranjeev Krishana serve on the Board of Directors of the Issuer as representatives of Baker Brothers Life Sciences, L.P. ("Life Sciences"), 667, L.P. ("667") and 14159, L.P. ("14159", and together with 667 and Life Sciences, the "Funds").

F2 · derivative.exercise_date: 199,992 non-qualified share options ("Share Options") convertible solely into Ordinary Shares of BeiGene, Ltd. (the "Issuer") were granted to Michael Goller, an employee of Baker Bros. Advisors LP (the "Adviser") and 199,992 Share Options were granted to Ranjeev Krishana, an employee of the Adviser in their capacity as directors of the Issuer. The Share Options with a strike price of $2.84 vest in 3 equal annual installments beginning on April 19, 2017 and shall become exercisable in full on the date of the third annual meeting of shareholders following the grant date. The Share Options expire on April 18, 2027. Michael Goller and Ranjeev Krishana serve on the Board of Directors of the Issuer as representatives of Baker Brothers Life Sciences, L.P. ("Life Sciences"), 667, L.P. ("667") and 14159, L.P. ("14159", and together with 667 and Life Sciences, the "Funds").

F1 · ownership.nature: In ordinary shares. Ordinary shares are convertible into American Depositary Shares ("ADS") on a 13:1 basis.

F2 · ownership.nature: 199,992 non-qualified share options ("Share Options") convertible solely into Ordinary Shares of BeiGene, Ltd. (the "Issuer") were granted to Michael Goller, an employee of Baker Bros. Advisors LP (the "Adviser") and 199,992 Share Options were granted to Ranjeev Krishana, an employee of the Adviser in their capacity as directors of the Issuer. The Share Options with a strike price of $2.84 vest in 3 equal annual installments beginning on April 19, 2017 and shall become exercisable in full on the date of the third annual meeting of shareholders following the grant date. The Share Options expire on April 18, 2027. Michael Goller and Ranjeev Krishana serve on the Board of Directors of the Issuer as representatives of Baker Brothers Life Sciences, L.P. ("Life Sciences"), 667, L.P. ("667") and 14159, L.P. ("14159", and together with 667 and Life Sciences, the "Funds").

F3 · ownership.nature: Pursuant to the policies of the Adviser, Michael Goller and Ranjeev Krishana do not have any right to any of the Issuer's securities issued as part of their service on the Board and the Funds are entitled to receive all the pecuniary interest in the securities issued. The Funds each own an indirect proportionate pecuniary interest in the Share 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 Share Options (i.e. no direct pecuniary interest).

F4 · 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 have relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held by the Funds. Pursuant to agreements between both Michael Goller and Ranjeev Krishana and the Adviser, the Adviser has investment and dispositive power over the Share Options and any shares received as a result of the exercise of options.

SEC source: 0001638599-17-000353 · doc4_4647.xml · nonDerivative · entry 3

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director

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

BAKER JULIAN · CIK 0001087939 · Director

Baker Brothers Life Sciences LP · CIK 0001363364 · Director

14159, L.P. · CIK 0001551138 · Director

BAKER FELIX · CIK 0001087940 · Director

667, L.P. · CIK 0001551139 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 133,666

F1 · ownership.nature: 3,600 shares of common stock (the "Common Stock") issued to Julian C. Baker and 4,887 shares of Common Stock issued to Dr. Kelvin M. Neu, respectively, a principal and an employee of Baker Bros. Advisors LP (the "Adviser") pursuant to the Issuer's 2013 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $8,750 and $11,875, respectively. The shares of Common Stock are fully vested. Julian C. Baker and Dr. Neu serve on the Issuer's Board of Directors (the "Board") as representatives of the Funds (as defined below). Dr. Neu also serves on the Compensation Committee of the Board for which he receives additional director retainer fees.

F2 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker and Dr. Neu do 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 (i.e., no direct pecuniary interest).

F5 · 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 133,666 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 98,561 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees, of which the fund may be deemed to own a portion.

F6 · 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.

F7 · ownership.nature: The disclosure of the grant of Common Stock reported on this form is the sum of two grants totaling 8,487 shares. The 8,487 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000353 · doc4_4647.xml · nonDerivative · entry 2

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director

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

BAKER JULIAN · CIK 0001087939 · Director

Baker Brothers Life Sciences LP · CIK 0001363364 · Director

14159, L.P. · CIK 0001551138 · Director

BAKER FELIX · CIK 0001087940 · Director

667, L.P. · CIK 0001551139 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 9,331,989

F1 · ownership.nature: 3,600 shares of common stock (the "Common Stock") issued to Julian C. Baker and 4,887 shares of Common Stock issued to Dr. Kelvin M. Neu, respectively, a principal and an employee of Baker Bros. Advisors LP (the "Adviser") pursuant to the Issuer's 2013 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $8,750 and $11,875, respectively. The shares of Common Stock are fully vested. Julian C. Baker and Dr. Neu serve on the Issuer's Board of Directors (the "Board") as representatives of the Funds (as defined below). Dr. Neu also serves on the Compensation Committee of the Board for which he receives additional director retainer fees.

F2 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker and Dr. Neu do 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 (i.e., no direct pecuniary interest).

F4 · 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 9,331,989 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 98,561 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees, of which the fund may be deemed to own a portion.

F6 · 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.

F7 · ownership.nature: The disclosure of the grant of Common Stock reported on this form is the sum of two grants totaling 8,487 shares. The 8,487 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000353 · doc4_4647.xml · nonDerivative · entry 1

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director

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

BAKER JULIAN · CIK 0001087939 · Director

Baker Brothers Life Sciences LP · CIK 0001363364 · Director

14159, L.P. · CIK 0001551138 · Director

BAKER FELIX · CIK 0001087940 · Director

667, L.P. · CIK 0001551139 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 1,026,437

F1 · ownership.nature: 3,600 shares of common stock (the "Common Stock") issued to Julian C. Baker and 4,887 shares of Common Stock issued to Dr. Kelvin M. Neu, respectively, a principal and an employee of Baker Bros. Advisors LP (the "Adviser") pursuant to the Issuer's 2013 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $8,750 and $11,875, respectively. The shares of Common Stock are fully vested. Julian C. Baker and Dr. Neu serve on the Issuer's Board of Directors (the "Board") as representatives of the Funds (as defined below). Dr. Neu also serves on the Compensation Committee of the Board for which he receives additional director retainer fees.

F2 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker and Dr. Neu do 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 (i.e., no direct pecuniary interest).

F3 · 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 1,026,437 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 98,561 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees of which the fund may be deemed to own a portion.

F6 · 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.

F7 · ownership.nature: The disclosure of the grant of Common Stock reported on this form is the sum of two grants totaling 8,487 shares. The 8,487 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000333 · doc4_4646.xml · nonDerivative · 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 FELIX · CIK 0001087940 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

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

Baker Bros. Investments II, L.P. · CIK 0001551132 · Director · 10% owner

Baker Bros. Investments, L.P. · CIK 0001551136 · Director · 10% owner

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

Baker/Tisch Investments, LP · CIK 0001551137 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 320,627

F2 · ownership.nature: 317 shares of restricted stock (the "Restricted Stock") issued to Felix J. Baker and 317 shares of Restricted Stock issued to Julian C. Baker pursuant to the Issuer's 2005 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $10,000, respectively. The shares of Restricted Stock are fully vested. Felix J. Baker and Julian C. Baker serve on the Issuer's Board of Directors as representatives of the Funds (as defined below).

F3 · ownership.nature: Pursuant to the policies of the Adviser (as defined below), Felix J. Baker and Julian C. Baker do 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.

F4 · ownership.nature: Baker/Tisch Investments, L.P. ("Baker Tisch"), Baker Bros. Investments, L.P. ("Baker Bros. Investments"), Baker Bros. Investments II, L.P. ("Baker Bros. Investments II"), 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with Baker Tisch, Baker Bros. Investments, Baker Bros. Investments II, 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Restricted 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 Restricted Stock issued in lieu of director retainer fees (ie. no direct pecuniary interest).

F10 · 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 320,627 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 12,531 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 8,250 shares which were received from exercise of 8,250 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.

F11 · 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 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.

F12 · ownership.nature: The disclosure of the grant of Restricted Stock reported on this form is the sum of two grants totaling 634 shares. The 634 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000333 · doc4_4646.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 FELIX · CIK 0001087940 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

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

Baker Bros. Investments II, L.P. · CIK 0001551132 · Director · 10% owner

Baker Bros. Investments, L.P. · CIK 0001551136 · Director · 10% owner

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

Baker/Tisch Investments, LP · CIK 0001551137 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 11,350,962

F2 · ownership.nature: 317 shares of restricted stock (the "Restricted Stock") issued to Felix J. Baker and 317 shares of Restricted Stock issued to Julian C. Baker pursuant to the Issuer's 2005 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $10,000, respectively. The shares of Restricted Stock are fully vested. Felix J. Baker and Julian C. Baker serve on the Issuer's Board of Directors as representatives of the Funds (as defined below).

F3 · ownership.nature: Pursuant to the policies of the Adviser (as defined below), Felix J. Baker and Julian C. Baker do 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.

F4 · ownership.nature: Baker/Tisch Investments, L.P. ("Baker Tisch"), Baker Bros. Investments, L.P. ("Baker Bros. Investments"), Baker Bros. Investments II, L.P. ("Baker Bros. Investments II"), 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with Baker Tisch, Baker Bros. Investments, Baker Bros. Investments II, 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Restricted 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 Restricted Stock issued in lieu of director retainer fees (ie. no direct pecuniary interest).

F9 · 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 11,350,962 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 12,531 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 8,250 shares which were received from exercise of 8,250 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.

F11 · 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 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.

F12 · ownership.nature: The disclosure of the grant of Restricted Stock reported on this form is the sum of two grants totaling 634 shares. The 634 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000333 · doc4_4646.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 FELIX · CIK 0001087940 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

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

Baker Bros. Investments II, L.P. · CIK 0001551132 · Director · 10% owner

Baker Bros. Investments, L.P. · CIK 0001551136 · Director · 10% owner

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

Baker/Tisch Investments, LP · CIK 0001551137 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 1,760,293

F2 · ownership.nature: 317 shares of restricted stock (the "Restricted Stock") issued to Felix J. Baker and 317 shares of Restricted Stock issued to Julian C. Baker pursuant to the Issuer's 2005 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $10,000, respectively. The shares of Restricted Stock are fully vested. Felix J. Baker and Julian C. Baker serve on the Issuer's Board of Directors as representatives of the Funds (as defined below).

F3 · ownership.nature: Pursuant to the policies of the Adviser (as defined below), Felix J. Baker and Julian C. Baker do 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.

F4 · ownership.nature: Baker/Tisch Investments, L.P. ("Baker Tisch"), Baker Bros. Investments, L.P. ("Baker Bros. Investments"), Baker Bros. Investments II, L.P. ("Baker Bros. Investments II"), 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with Baker Tisch, Baker Bros. Investments, Baker Bros. Investments II, 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Restricted 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 Restricted 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 Baker Biotech Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 1,760,293 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 12,531 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 8,250 shares which were received from exercise of 8,250 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.

F11 · 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 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.

F12 · ownership.nature: The disclosure of the grant of Restricted Stock reported on this form is the sum of two grants totaling 634 shares. The 634 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000333 · doc4_4646.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 FELIX · CIK 0001087940 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

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

Baker Bros. Investments II, L.P. · CIK 0001551132 · Director · 10% owner

Baker Bros. Investments, L.P. · CIK 0001551136 · Director · 10% owner

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

Baker/Tisch Investments, LP · CIK 0001551137 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 34,019

F2 · ownership.nature: 317 shares of restricted stock (the "Restricted Stock") issued to Felix J. Baker and 317 shares of Restricted Stock issued to Julian C. Baker pursuant to the Issuer's 2005 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $10,000, respectively. The shares of Restricted Stock are fully vested. Felix J. Baker and Julian C. Baker serve on the Issuer's Board of Directors as representatives of the Funds (as defined below).

F3 · ownership.nature: Pursuant to the policies of the Adviser (as defined below), Felix J. Baker and Julian C. Baker do 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.

F4 · ownership.nature: Baker/Tisch Investments, L.P. ("Baker Tisch"), Baker Bros. Investments, L.P. ("Baker Bros. Investments"), Baker Bros. Investments II, L.P. ("Baker Bros. Investments II"), 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with Baker Tisch, Baker Bros. Investments, Baker Bros. Investments II, 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Restricted 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 Restricted 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 Bros. Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 34,019 shares of Common Stock of the Issuer beneficially owned by Baker Bros. Investments II, a limited partnership of which the sole general partner is Baker Bros. Capital, L.P., a limited partnership of which the sole general partner is Baker Bros. Capital (GP), LLC, due to Baker Bros. Capital, L.P.'s right to receive an allocation of a portion of the profits from Baker Bros. Investments II. Includes beneficial ownership of 12,531 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 8,250 shares which were received from exercise of 8,250 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.

F11 · 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 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.

F12 · ownership.nature: The disclosure of the grant of Restricted Stock reported on this form is the sum of two grants totaling 634 shares. The 634 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000333 · doc4_4646.xml · nonDerivative · entry 3

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 FELIX · CIK 0001087940 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

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

Baker Bros. Investments II, L.P. · CIK 0001551132 · Director · 10% owner

Baker Bros. Investments, L.P. · CIK 0001551136 · Director · 10% owner

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

Baker/Tisch Investments, LP · CIK 0001551137 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 194,678

F2 · ownership.nature: 317 shares of restricted stock (the "Restricted Stock") issued to Felix J. Baker and 317 shares of Restricted Stock issued to Julian C. Baker pursuant to the Issuer's 2005 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $10,000, respectively. The shares of Restricted Stock are fully vested. Felix J. Baker and Julian C. Baker serve on the Issuer's Board of Directors as representatives of the Funds (as defined below).

F3 · ownership.nature: Pursuant to the policies of the Adviser (as defined below), Felix J. Baker and Julian C. Baker do 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.

F4 · ownership.nature: Baker/Tisch Investments, L.P. ("Baker Tisch"), Baker Bros. Investments, L.P. ("Baker Bros. Investments"), Baker Bros. Investments II, L.P. ("Baker Bros. Investments II"), 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with Baker Tisch, Baker Bros. Investments, Baker Bros. Investments II, 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Restricted 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 Restricted 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 Bros. Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 194,678 shares of Common Stock of the Issuer beneficially owned by Baker Bros. Investments, a limited partnership of which the sole general partner is Baker Bros. Capital, L.P., a limited partnership of which the sole general partner is Baker Bros. Capital (GP), LLC, due to Baker Bros. Capital, L.P.'s right to receive an allocation of a portion of the profits from Baker Bros. Investments. Includes beneficial ownership of 12,531 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 8,250 shares which were received from exercise of 8,250 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.

F11 · 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 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.

F12 · ownership.nature: The disclosure of the grant of Restricted Stock reported on this form is the sum of two grants totaling 634 shares. The 634 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000333 · doc4_4646.xml · nonDerivative · entry 2

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 FELIX · CIK 0001087940 · Director · 10% owner

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

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

Baker Bros. Investments II, L.P. · CIK 0001551132 · Director · 10% owner

Baker Bros. Investments, L.P. · CIK 0001551136 · Director · 10% owner

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

Baker/Tisch Investments, LP · CIK 0001551137 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 214,942

F2 · ownership.nature: 317 shares of restricted stock (the "Restricted Stock") issued to Felix J. Baker and 317 shares of Restricted Stock issued to Julian C. Baker pursuant to the Issuer's 2005 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $10,000, respectively. The shares of Restricted Stock are fully vested. Felix J. Baker and Julian C. Baker serve on the Issuer's Board of Directors as representatives of the Funds (as defined below).

F3 · ownership.nature: Pursuant to the policies of the Adviser (as defined below), Felix J. Baker and Julian C. Baker do 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.

F4 · ownership.nature: Baker/Tisch Investments, L.P. ("Baker Tisch"), Baker Bros. Investments, L.P. ("Baker Bros. Investments"), Baker Bros. Investments II, L.P. ("Baker Bros. Investments II"), 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with Baker Tisch, Baker Bros. Investments, Baker Bros. Investments II, 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Restricted 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 Restricted Stock issued in lieu of director retainer fees (ie. no direct pecuniary interest).

F5 · ownership.nature: As a result of Felix J. Baker's and Julian C. Baker's ownership interest in Baker/Tisch Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 214,942 shares of Common Stock of the Issuer beneficially owned by Baker Tisch, a limited partnership of which the sole general partner is Baker/Tisch Capital, L.P., a limited partnership of which the sole general partner is Baker/Tisch Capital (GP), LLC, due to Baker/Tisch Capital, L.P.'s right to receive an allocation of a portion of the profits from Baker Tisch. Includes beneficial ownership of 12,531 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 8,250 shares which were received from exercise of 8,250 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.

F11 · 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 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.

F12 · ownership.nature: The disclosure of the grant of Restricted Stock reported on this form is the sum of two grants totaling 634 shares. The 634 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000334 · doc4_4645.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 FELIX · CIK 0001087940 · 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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 767,237

F4 · ownership.nature: 142 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 767,237 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 1,560 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 75,000 shares received previously from exercise of 75,000 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 142 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000334 · doc4_4645.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 FELIX · CIK 0001087940 · 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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 29,141,795

F4 · ownership.nature: 142 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 29,141,795 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 1,560 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 75,000 shares received previously from exercise of 75,000 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 142 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000334 · doc4_4645.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 FELIX · CIK 0001087940 · 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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 4,354,099

F4 · ownership.nature: 142 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 4,354,099 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 1,560 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 75,000 shares received previously from exercise of 75,000 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 142 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000213 · doc4_4560.xml · derivative · entry 15

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 0

Underlying: Common Stock · 121,672 shares

Expires 2020-11-15

F10 · price: Pursuant to the Exchange Agreement, 14159 exchanged $5,674,000 principal amount of 2018 Notes for 111,514 shares of common stock of the Issuer and exchanged $6,050,000 principal amount of 2020 Notes for 121,672 shares of common stock of the Issuer.

F12 · derivative.exercise_date: Immediately

F4 · ownership.nature: On February 17, 2017, the Issuer entered into a letter agreement with 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") for the exchange of $533.5 million aggregate principal amount of its convertible senior notes ("Exchange Agreement") consisting of $259 million aggregate principal amount of 0.375% convertible Senior Notes due November 15, 2018 (the "2018 Notes") and $274.5 million aggregate principal amount of 1.25% convertible senior notes due November 15, 2020 (the "2020 Notes") in exchange for an aggregate of 10,610,782 shares of common stock of the Issuer. The shares of common stock of the Issuer issued in exchange for the 2018 and 2020 Notes represent the number of shares into which these notes were convertible together with an additional negotiated number of shares.

SEC source: 0001638599-17-000213 · doc4_4560.xml · derivative · entry 14

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 0

Underlying: Common Stock · 111,514 shares

Expires 2018-11-15

F10 · price: Pursuant to the Exchange Agreement, 14159 exchanged $5,674,000 principal amount of 2018 Notes for 111,514 shares of common stock of the Issuer and exchanged $6,050,000 principal amount of 2020 Notes for 121,672 shares of common stock of the Issuer.

F12 · derivative.exercise_date: Immediately

F4 · ownership.nature: On February 17, 2017, the Issuer entered into a letter agreement with 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") for the exchange of $533.5 million aggregate principal amount of its convertible senior notes ("Exchange Agreement") consisting of $259 million aggregate principal amount of 0.375% convertible Senior Notes due November 15, 2018 (the "2018 Notes") and $274.5 million aggregate principal amount of 1.25% convertible senior notes due November 15, 2020 (the "2020 Notes") in exchange for an aggregate of 10,610,782 shares of common stock of the Issuer. The shares of common stock of the Issuer issued in exchange for the 2018 and 2020 Notes represent the number of shares into which these notes were convertible together with an additional negotiated number of shares.

SEC source: 0001638599-17-000213 · doc4_4560.xml · derivative · entry 13

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 0

Underlying: Common Stock · 4,896,067 shares

Expires 2020-11-15

F7 · price: Pursuant to the Exchange Agreement, Life Sciences exchanged $228,326,000 principal amount of 2018 Notes for 4,487,412 shares of common stock of the Issuer and exchanged $243,450,000 principal amount of 2020 Notes for 4,896,067 shares of common stock of the Issuer.

F12 · derivative.exercise_date: Immediately

F4 · ownership.nature: On February 17, 2017, the Issuer entered into a letter agreement with 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") for the exchange of $533.5 million aggregate principal amount of its convertible senior notes ("Exchange Agreement") consisting of $259 million aggregate principal amount of 0.375% convertible Senior Notes due November 15, 2018 (the "2018 Notes") and $274.5 million aggregate principal amount of 1.25% convertible senior notes due November 15, 2020 (the "2020 Notes") in exchange for an aggregate of 10,610,782 shares of common stock of the Issuer. The shares of common stock of the Issuer issued in exchange for the 2018 and 2020 Notes represent the number of shares into which these notes were convertible together with an additional negotiated number of shares.

SEC source: 0001638599-17-000213 · doc4_4560.xml · derivative · entry 12

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 0

Underlying: Common Stock · 4,487,412 shares

Expires 2018-11-15

F7 · price: Pursuant to the Exchange Agreement, Life Sciences exchanged $228,326,000 principal amount of 2018 Notes for 4,487,412 shares of common stock of the Issuer and exchanged $243,450,000 principal amount of 2020 Notes for 4,896,067 shares of common stock of the Issuer.

F12 · derivative.exercise_date: Immediately

F4 · ownership.nature: On February 17, 2017, the Issuer entered into a letter agreement with 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") for the exchange of $533.5 million aggregate principal amount of its convertible senior notes ("Exchange Agreement") consisting of $259 million aggregate principal amount of 0.375% convertible Senior Notes due November 15, 2018 (the "2018 Notes") and $274.5 million aggregate principal amount of 1.25% convertible senior notes due November 15, 2020 (the "2020 Notes") in exchange for an aggregate of 10,610,782 shares of common stock of the Issuer. The shares of common stock of the Issuer issued in exchange for the 2018 and 2020 Notes represent the number of shares into which these notes were convertible together with an additional negotiated number of shares.

SEC source: 0001638599-17-000213 · doc4_4560.xml · derivative · entry 11

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 0

Underlying: Common Stock · 502,779 shares

Expires 2020-11-15

F5 · price: Pursuant to the Exchange Agreement, 667 exchanged $25,000,000 principal amount of 2018 Notes for 491,338 shares of common stock of the Issuer and exchanged $25,000,000 principal amount of 2020 Notes for 502,779 shares of common stock of the Issuer.

F12 · derivative.exercise_date: Immediately

F4 · ownership.nature: On February 17, 2017, the Issuer entered into a letter agreement with 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") for the exchange of $533.5 million aggregate principal amount of its convertible senior notes ("Exchange Agreement") consisting of $259 million aggregate principal amount of 0.375% convertible Senior Notes due November 15, 2018 (the "2018 Notes") and $274.5 million aggregate principal amount of 1.25% convertible senior notes due November 15, 2020 (the "2020 Notes") in exchange for an aggregate of 10,610,782 shares of common stock of the Issuer. The shares of common stock of the Issuer issued in exchange for the 2018 and 2020 Notes represent the number of shares into which these notes were convertible together with an additional negotiated number of shares.

SEC source: 0001638599-17-000213 · doc4_4560.xml · derivative · entry 10

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 0

Underlying: Common Stock · 491,338 shares

Expires 2018-11-15

F5 · price: Pursuant to the Exchange Agreement, 667 exchanged $25,000,000 principal amount of 2018 Notes for 491,338 shares of common stock of the Issuer and exchanged $25,000,000 principal amount of 2020 Notes for 502,779 shares of common stock of the Issuer.

F12 · derivative.exercise_date: Immediately

F4 · ownership.nature: On February 17, 2017, the Issuer entered into a letter agreement with 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") for the exchange of $533.5 million aggregate principal amount of its convertible senior notes ("Exchange Agreement") consisting of $259 million aggregate principal amount of 0.375% convertible Senior Notes due November 15, 2018 (the "2018 Notes") and $274.5 million aggregate principal amount of 1.25% convertible senior notes due November 15, 2020 (the "2020 Notes") in exchange for an aggregate of 10,610,782 shares of common stock of the Issuer. The shares of common stock of the Issuer issued in exchange for the 2018 and 2020 Notes represent the number of shares into which these notes were convertible together with an additional negotiated number of shares.

SEC source: 0001638599-17-000213 · doc4_4560.xml · nonDerivative · entry 9

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 767,095

F10 · price: Pursuant to the Exchange Agreement, 14159 exchanged $5,674,000 principal amount of 2018 Notes for 111,514 shares of common stock of the Issuer and exchanged $6,050,000 principal amount of 2020 Notes for 121,672 shares of common stock of the Issuer.

F4 · ownership.nature: On February 17, 2017, the Issuer entered into a letter agreement with 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") for the exchange of $533.5 million aggregate principal amount of its convertible senior notes ("Exchange Agreement") consisting of $259 million aggregate principal amount of 0.375% convertible Senior Notes due November 15, 2018 (the "2018 Notes") and $274.5 million aggregate principal amount of 1.25% convertible senior notes due November 15, 2020 (the "2020 Notes") in exchange for an aggregate of 10,610,782 shares of common stock of the Issuer. The shares of common stock of the Issuer issued in exchange for the 2018 and 2020 Notes represent the number of shares into which these notes were convertible together with an additional negotiated number of shares.

F10 · ownership.nature: Pursuant to the Exchange Agreement, 14159 exchanged $5,674,000 principal amount of 2018 Notes for 111,514 shares of common stock of the Issuer and exchanged $6,050,000 principal amount of 2020 Notes for 121,672 shares of common stock of the Issuer.

F11 · ownership.nature: Following the transactions reported herein, 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 767,095 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 1,418 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 75,000 shares received previously from exercise of 75,000 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.

F13 · 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.

F14 · ownership.nature: 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: 0001638599-17-000213 · doc4_4560.xml · nonDerivative · entry 8

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 645,423

F10 · price: Pursuant to the Exchange Agreement, 14159 exchanged $5,674,000 principal amount of 2018 Notes for 111,514 shares of common stock of the Issuer and exchanged $6,050,000 principal amount of 2020 Notes for 121,672 shares of common stock of the Issuer.

F4 · ownership.nature: On February 17, 2017, the Issuer entered into a letter agreement with 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") for the exchange of $533.5 million aggregate principal amount of its convertible senior notes ("Exchange Agreement") consisting of $259 million aggregate principal amount of 0.375% convertible Senior Notes due November 15, 2018 (the "2018 Notes") and $274.5 million aggregate principal amount of 1.25% convertible senior notes due November 15, 2020 (the "2020 Notes") in exchange for an aggregate of 10,610,782 shares of common stock of the Issuer. The shares of common stock of the Issuer issued in exchange for the 2018 and 2020 Notes represent the number of shares into which these notes were convertible together with an additional negotiated number of shares.

F10 · ownership.nature: Pursuant to the Exchange Agreement, 14159 exchanged $5,674,000 principal amount of 2018 Notes for 111,514 shares of common stock of the Issuer and exchanged $6,050,000 principal amount of 2020 Notes for 121,672 shares of common stock of the Issuer.

F13 · 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.

F14 · ownership.nature: 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: 0001638599-17-000213 · doc4_4560.xml · nonDerivative · entry 7

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 29,141,653

F7 · price: Pursuant to the Exchange Agreement, Life Sciences exchanged $228,326,000 principal amount of 2018 Notes for 4,487,412 shares of common stock of the Issuer and exchanged $243,450,000 principal amount of 2020 Notes for 4,896,067 shares of common stock of the Issuer.

F4 · ownership.nature: On February 17, 2017, the Issuer entered into a letter agreement with 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") for the exchange of $533.5 million aggregate principal amount of its convertible senior notes ("Exchange Agreement") consisting of $259 million aggregate principal amount of 0.375% convertible Senior Notes due November 15, 2018 (the "2018 Notes") and $274.5 million aggregate principal amount of 1.25% convertible senior notes due November 15, 2020 (the "2020 Notes") in exchange for an aggregate of 10,610,782 shares of common stock of the Issuer. The shares of common stock of the Issuer issued in exchange for the 2018 and 2020 Notes represent the number of shares into which these notes were convertible together with an additional negotiated number of shares.

F7 · ownership.nature: Pursuant to the Exchange Agreement, Life Sciences exchanged $228,326,000 principal amount of 2018 Notes for 4,487,412 shares of common stock of the Issuer and exchanged $243,450,000 principal amount of 2020 Notes for 4,896,067 shares of common stock of the Issuer.

F8 · ownership.nature: Following the transactions reported herein, 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 29,141,653 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.

F9 · ownership.nature: Includes beneficial ownership of 1,418 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 75,000 shares received previously from exercise of 75,000 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.

F13 · 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.

F14 · ownership.nature: 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: 0001638599-17-000213 · doc4_4560.xml · nonDerivative · entry 6

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 24,245,586

F7 · price: Pursuant to the Exchange Agreement, Life Sciences exchanged $228,326,000 principal amount of 2018 Notes for 4,487,412 shares of common stock of the Issuer and exchanged $243,450,000 principal amount of 2020 Notes for 4,896,067 shares of common stock of the Issuer.

F4 · ownership.nature: On February 17, 2017, the Issuer entered into a letter agreement with 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") for the exchange of $533.5 million aggregate principal amount of its convertible senior notes ("Exchange Agreement") consisting of $259 million aggregate principal amount of 0.375% convertible Senior Notes due November 15, 2018 (the "2018 Notes") and $274.5 million aggregate principal amount of 1.25% convertible senior notes due November 15, 2020 (the "2020 Notes") in exchange for an aggregate of 10,610,782 shares of common stock of the Issuer. The shares of common stock of the Issuer issued in exchange for the 2018 and 2020 Notes represent the number of shares into which these notes were convertible together with an additional negotiated number of shares.

F7 · ownership.nature: Pursuant to the Exchange Agreement, Life Sciences exchanged $228,326,000 principal amount of 2018 Notes for 4,487,412 shares of common stock of the Issuer and exchanged $243,450,000 principal amount of 2020 Notes for 4,896,067 shares of common stock of the Issuer.

F13 · 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.

F14 · ownership.nature: 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: 0001638599-17-000213 · doc4_4560.xml · nonDerivative · entry 5

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 4,353,957

F5 · price: Pursuant to the Exchange Agreement, 667 exchanged $25,000,000 principal amount of 2018 Notes for 491,338 shares of common stock of the Issuer and exchanged $25,000,000 principal amount of 2020 Notes for 502,779 shares of common stock of the Issuer.

F4 · ownership.nature: On February 17, 2017, the Issuer entered into a letter agreement with 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") for the exchange of $533.5 million aggregate principal amount of its convertible senior notes ("Exchange Agreement") consisting of $259 million aggregate principal amount of 0.375% convertible Senior Notes due November 15, 2018 (the "2018 Notes") and $274.5 million aggregate principal amount of 1.25% convertible senior notes due November 15, 2020 (the "2020 Notes") in exchange for an aggregate of 10,610,782 shares of common stock of the Issuer. The shares of common stock of the Issuer issued in exchange for the 2018 and 2020 Notes represent the number of shares into which these notes were convertible together with an additional negotiated number of shares.

F5 · ownership.nature: Pursuant to the Exchange Agreement, 667 exchanged $25,000,000 principal amount of 2018 Notes for 491,338 shares of common stock of the Issuer and exchanged $25,000,000 principal amount of 2020 Notes for 502,779 shares of common stock of the Issuer.

F6 · ownership.nature: Following the transactions reported herein, 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 4,353,957 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 1,418 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 75,000 shares received previously from exercise of 75,000 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.

F13 · 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.

F14 · ownership.nature: 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: 0001638599-17-000213 · doc4_4560.xml · nonDerivative · entry 4

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 3,851,178

F5 · price: Pursuant to the Exchange Agreement, 667 exchanged $25,000,000 principal amount of 2018 Notes for 491,338 shares of common stock of the Issuer and exchanged $25,000,000 principal amount of 2020 Notes for 502,779 shares of common stock of the Issuer.

F4 · ownership.nature: On February 17, 2017, the Issuer entered into a letter agreement with 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") for the exchange of $533.5 million aggregate principal amount of its convertible senior notes ("Exchange Agreement") consisting of $259 million aggregate principal amount of 0.375% convertible Senior Notes due November 15, 2018 (the "2018 Notes") and $274.5 million aggregate principal amount of 1.25% convertible senior notes due November 15, 2020 (the "2020 Notes") in exchange for an aggregate of 10,610,782 shares of common stock of the Issuer. The shares of common stock of the Issuer issued in exchange for the 2018 and 2020 Notes represent the number of shares into which these notes were convertible together with an additional negotiated number of shares.

F5 · ownership.nature: Pursuant to the Exchange Agreement, 667 exchanged $25,000,000 principal amount of 2018 Notes for 491,338 shares of common stock of the Issuer and exchanged $25,000,000 principal amount of 2020 Notes for 502,779 shares of common stock of the Issuer.

F13 · 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.

F14 · ownership.nature: 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: 0001638599-17-000048 · doc4_4456.xml · nonDerivative · entry 3

BAKER JULIAN · CIK 0001087939 · Director

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

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director

Baker Brothers Life Sciences LP · CIK 0001363364 · Director

14159, L.P. · CIK 0001551138 · Director

BAKER FELIX · CIK 0001087940 · Director

667, L.P. · CIK 0001551139 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 125,179

F1 · ownership.nature: 5,835 shares of common stock (the "Common Stock") issued to Julian C. Baker and 8,334 shares of Common Stock issued to Dr. Kelvin M. Neu, respectively, a principal and an employee of Baker Bros. Advisors LP (the "Adviser") pursuant to the Issuer's 2013 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $8,750 and $12,500, respectively. The shares of Common Stock are fully vested. Julian C. Baker and Dr. Neu serve on the Issuer's Board of Directors (the "Board") as representatives of the Funds (as defined below). Dr. Neu also serves on the Compensation Committee of the Board for which he receives additional director retainer fees.

F2 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker and Dr. Neu do 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 (i.e., no direct pecuniary interest).

F5 · 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 125,179 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 90,074 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees, of which the fund may be deemed to own a portion.

F6 · 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.

F7 · ownership.nature: The disclosure of the grant of Common Stock reported on this form is the sum of two grants totaling 14,169 shares. The 14,169 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000048 · doc4_4456.xml · nonDerivative · entry 2

BAKER JULIAN · CIK 0001087939 · Director

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

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director

Baker Brothers Life Sciences LP · CIK 0001363364 · Director

14159, L.P. · CIK 0001551138 · Director

BAKER FELIX · CIK 0001087940 · Director

667, L.P. · CIK 0001551139 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 9,323,502

F1 · ownership.nature: 5,835 shares of common stock (the "Common Stock") issued to Julian C. Baker and 8,334 shares of Common Stock issued to Dr. Kelvin M. Neu, respectively, a principal and an employee of Baker Bros. Advisors LP (the "Adviser") pursuant to the Issuer's 2013 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $8,750 and $12,500, respectively. The shares of Common Stock are fully vested. Julian C. Baker and Dr. Neu serve on the Issuer's Board of Directors (the "Board") as representatives of the Funds (as defined below). Dr. Neu also serves on the Compensation Committee of the Board for which he receives additional director retainer fees.

F2 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker and Dr. Neu do 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 (i.e., no direct pecuniary interest).

F4 · 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 9,323,502 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 90,074 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees, of which the fund may be deemed to own a portion.

F6 · 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.

F7 · ownership.nature: The disclosure of the grant of Common Stock reported on this form is the sum of two grants totaling 14,169 shares. The 14,169 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000048 · doc4_4456.xml · nonDerivative · entry 1

BAKER JULIAN · CIK 0001087939 · Director

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

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director

Baker Brothers Life Sciences LP · CIK 0001363364 · Director

14159, L.P. · CIK 0001551138 · Director

BAKER FELIX · CIK 0001087940 · Director

667, L.P. · CIK 0001551139 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 1,017,950

F1 · ownership.nature: 5,835 shares of common stock (the "Common Stock") issued to Julian C. Baker and 8,334 shares of Common Stock issued to Dr. Kelvin M. Neu, respectively, a principal and an employee of Baker Bros. Advisors LP (the "Adviser") pursuant to the Issuer's 2013 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $8,750 and $12,500, respectively. The shares of Common Stock are fully vested. Julian C. Baker and Dr. Neu serve on the Issuer's Board of Directors (the "Board") as representatives of the Funds (as defined below). Dr. Neu also serves on the Compensation Committee of the Board for which he receives additional director retainer fees.

F2 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker and Dr. Neu do 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 (i.e., no direct pecuniary interest).

F3 · 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 1,017,950 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 90,074 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees,of which the fund may be deemed to own a portion.

F6 · 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.

F7 · ownership.nature: The disclosure of the grant of Common Stock reported on this form is the sum of two grants totaling 14,169 shares. The 14,169 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000029 · doc4_4448.xml · nonDerivative · entry 7

BAKER FELIX · CIK 0001087940 · Director · 10% owner

14159, L.P. · CIK 0001551138 · 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 BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

Baker Bros. Investments II, L.P. · CIK 0001551132 · Director · 10% owner

Baker Bros. Investments, L.P. · CIK 0001551136 · Director · 10% owner

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

Baker/Tisch Investments, LP · CIK 0001551137 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 319,993

F2 · ownership.nature: 340 shares of restricted stock (the "Restricted Stock") issued to Felix J. Baker and 340 shares of Restricted Stock issued to Julian C. Baker pursuant to the Issuer's 2005 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $10,000, respectively. The shares of Restricted Stock are fully vested. Felix J. Baker and Julian C. Baker serve on the Issuer's Board of Directors as representatives of the Funds (as defined below).

F3 · ownership.nature: Pursuant to the policies of the Adviser (as defined below), Felix J. Baker and Julian C. Baker do 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.

F4 · ownership.nature: Baker/Tisch Investments, L.P. ("Baker Tisch"), Baker Bros. Investments, L.P. ("Baker Bros. Investments"), Baker Bros. Investments II, L.P. ("Baker Bros. Investments II"), 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with Baker Tisch, Baker Bros. Investments, Baker Bros. Investments II, 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Restricted 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 Restricted Stock issued in lieu of director retainer fees (ie. no direct pecuniary interest).

F10 · 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 319,993 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 11,897 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 8,250 shares which were received from exercise of 8,250 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.

F11 · 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 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.

F12 · ownership.nature: The disclosure of the grant of Restricted Stock reported on this form is the sum of two grants totaling 680 shares. The 680 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000029 · doc4_4448.xml · nonDerivative · entry 6

BAKER FELIX · CIK 0001087940 · Director · 10% owner

14159, L.P. · CIK 0001551138 · 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 BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

Baker Bros. Investments II, L.P. · CIK 0001551132 · Director · 10% owner

Baker Bros. Investments, L.P. · CIK 0001551136 · Director · 10% owner

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

Baker/Tisch Investments, LP · CIK 0001551137 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 11,350,328

F2 · ownership.nature: 340 shares of restricted stock (the "Restricted Stock") issued to Felix J. Baker and 340 shares of Restricted Stock issued to Julian C. Baker pursuant to the Issuer's 2005 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $10,000, respectively. The shares of Restricted Stock are fully vested. Felix J. Baker and Julian C. Baker serve on the Issuer's Board of Directors as representatives of the Funds (as defined below).

F3 · ownership.nature: Pursuant to the policies of the Adviser (as defined below), Felix J. Baker and Julian C. Baker do 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.

F4 · ownership.nature: Baker/Tisch Investments, L.P. ("Baker Tisch"), Baker Bros. Investments, L.P. ("Baker Bros. Investments"), Baker Bros. Investments II, L.P. ("Baker Bros. Investments II"), 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with Baker Tisch, Baker Bros. Investments, Baker Bros. Investments II, 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Restricted 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 Restricted Stock issued in lieu of director retainer fees (ie. no direct pecuniary interest).

F9 · 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 11,350,328 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 11,897 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 8,250 shares which were received from exercise of 8,250 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.

F11 · 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 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.

F12 · ownership.nature: The disclosure of the grant of Restricted Stock reported on this form is the sum of two grants totaling 680 shares. The 680 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000029 · doc4_4448.xml · nonDerivative · entry 5

BAKER FELIX · CIK 0001087940 · Director · 10% owner

14159, L.P. · CIK 0001551138 · 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 BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

Baker Bros. Investments II, L.P. · CIK 0001551132 · Director · 10% owner

Baker Bros. Investments, L.P. · CIK 0001551136 · Director · 10% owner

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

Baker/Tisch Investments, LP · CIK 0001551137 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 1,759,659

F2 · ownership.nature: 340 shares of restricted stock (the "Restricted Stock") issued to Felix J. Baker and 340 shares of Restricted Stock issued to Julian C. Baker pursuant to the Issuer's 2005 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $10,000, respectively. The shares of Restricted Stock are fully vested. Felix J. Baker and Julian C. Baker serve on the Issuer's Board of Directors as representatives of the Funds (as defined below).

F3 · ownership.nature: Pursuant to the policies of the Adviser (as defined below), Felix J. Baker and Julian C. Baker do 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.

F4 · ownership.nature: Baker/Tisch Investments, L.P. ("Baker Tisch"), Baker Bros. Investments, L.P. ("Baker Bros. Investments"), Baker Bros. Investments II, L.P. ("Baker Bros. Investments II"), 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with Baker Tisch, Baker Bros. Investments, Baker Bros. Investments II, 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Restricted 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 Restricted 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 Baker Biotech Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 1,759,659 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 11,897 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 8,250 shares which were received from exercise of 8,250 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.

F11 · 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 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.

F12 · ownership.nature: The disclosure of the grant of Restricted Stock reported on this form is the sum of two grants totaling 680 shares. The 680 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000029 · doc4_4448.xml · nonDerivative · entry 4

BAKER FELIX · CIK 0001087940 · Director · 10% owner

14159, L.P. · CIK 0001551138 · 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 BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

Baker Bros. Investments II, L.P. · CIK 0001551132 · Director · 10% owner

Baker Bros. Investments, L.P. · CIK 0001551136 · Director · 10% owner

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

Baker/Tisch Investments, LP · CIK 0001551137 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 33,385

F2 · ownership.nature: 340 shares of restricted stock (the "Restricted Stock") issued to Felix J. Baker and 340 shares of Restricted Stock issued to Julian C. Baker pursuant to the Issuer's 2005 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $10,000, respectively. The shares of Restricted Stock are fully vested. Felix J. Baker and Julian C. Baker serve on the Issuer's Board of Directors as representatives of the Funds (as defined below).

F3 · ownership.nature: Pursuant to the policies of the Adviser (as defined below), Felix J. Baker and Julian C. Baker do 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.

F4 · ownership.nature: Baker/Tisch Investments, L.P. ("Baker Tisch"), Baker Bros. Investments, L.P. ("Baker Bros. Investments"), Baker Bros. Investments II, L.P. ("Baker Bros. Investments II"), 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with Baker Tisch, Baker Bros. Investments, Baker Bros. Investments II, 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Restricted 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 Restricted 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 Bros. Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 33,385 shares of Common Stock of the Issuer beneficially owned by Baker Bros. Investments II, a limited partnership of which the sole general partner is Baker Bros. Capital, L.P., a limited partnership of which the sole general partner is Baker Bros. Capital (GP), LLC, due to Baker Bros. Capital, L.P.'s right to receive an allocation of a portion of the profits from Baker Bros. Investments II. Includes beneficial ownership of 11,897 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 8,250 shares which were received from exercise of 8,250 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.

F11 · 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 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.

F12 · ownership.nature: The disclosure of the grant of Restricted Stock reported on this form is the sum of two grants totaling 680 shares. The 680 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000029 · doc4_4448.xml · nonDerivative · entry 3

BAKER FELIX · CIK 0001087940 · Director · 10% owner

14159, L.P. · CIK 0001551138 · 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 BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

Baker Bros. Investments II, L.P. · CIK 0001551132 · Director · 10% owner

Baker Bros. Investments, L.P. · CIK 0001551136 · Director · 10% owner

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

Baker/Tisch Investments, LP · CIK 0001551137 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 194,044

F2 · ownership.nature: 340 shares of restricted stock (the "Restricted Stock") issued to Felix J. Baker and 340 shares of Restricted Stock issued to Julian C. Baker pursuant to the Issuer's 2005 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $10,000, respectively. The shares of Restricted Stock are fully vested. Felix J. Baker and Julian C. Baker serve on the Issuer's Board of Directors as representatives of the Funds (as defined below).

F3 · ownership.nature: Pursuant to the policies of the Adviser (as defined below), Felix J. Baker and Julian C. Baker do 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.

F4 · ownership.nature: Baker/Tisch Investments, L.P. ("Baker Tisch"), Baker Bros. Investments, L.P. ("Baker Bros. Investments"), Baker Bros. Investments II, L.P. ("Baker Bros. Investments II"), 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with Baker Tisch, Baker Bros. Investments, Baker Bros. Investments II, 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Restricted 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 Restricted 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 Bros. Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 194,044 shares of Common Stock of the Issuer beneficially owned by Baker Bros. Investments, a limited partnership of which the sole general partner is Baker Bros. Capital, L.P., a limited partnership of which the sole general partner is Baker Bros. Capital (GP), LLC, due to Baker Bros. Capital, L.P.'s right to receive an allocation of a portion of the profits from Baker Bros. Investments. Includes beneficial ownership of 11,897 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 8,250 shares which were received from exercise of 8,250 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.

F11 · 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 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.

F12 · ownership.nature: The disclosure of the grant of Restricted Stock reported on this form is the sum of two grants totaling 680 shares. The 680 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000029 · doc4_4448.xml · nonDerivative · entry 2

BAKER FELIX · CIK 0001087940 · Director · 10% owner

14159, L.P. · CIK 0001551138 · 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 BROS. ADVISORS LP · CIK 0001263508 · Director · 10% owner

Baker Bros. Investments II, L.P. · CIK 0001551132 · Director · 10% owner

Baker Bros. Investments, L.P. · CIK 0001551136 · Director · 10% owner

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

Baker/Tisch Investments, LP · CIK 0001551137 · Director · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 214,308

F2 · ownership.nature: 340 shares of restricted stock (the "Restricted Stock") issued to Felix J. Baker and 340 shares of Restricted Stock issued to Julian C. Baker pursuant to the Issuer's 2005 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $10,000, respectively. The shares of Restricted Stock are fully vested. Felix J. Baker and Julian C. Baker serve on the Issuer's Board of Directors as representatives of the Funds (as defined below).

F3 · ownership.nature: Pursuant to the policies of the Adviser (as defined below), Felix J. Baker and Julian C. Baker do 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.

F4 · ownership.nature: Baker/Tisch Investments, L.P. ("Baker Tisch"), Baker Bros. Investments, L.P. ("Baker Bros. Investments"), Baker Bros. Investments II, L.P. ("Baker Bros. Investments II"), 667, L.P. ("667"), Baker Brothers Life Sciences, L.P. ("Life Sciences") and 14159, L.P. ("14159", and together with Baker Tisch, Baker Bros. Investments, Baker Bros. Investments II, 667, and Life Sciences, the "Funds") each owns an indirect proportionate pecuniary interest in the shares of Restricted 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 Restricted Stock issued in lieu of director retainer fees (ie. no direct pecuniary interest).

F5 · ownership.nature: As a result of Felix J. Baker's and Julian C. Baker's ownership interest in Baker/Tisch Capital (GP), LLC, Felix J. Baker and Julian C. Baker may be deemed to have an indirect pecuniary interest in 214,308 shares of Common Stock of the Issuer beneficially owned by Baker Tisch, a limited partnership of which the sole general partner is Baker/Tisch Capital, L.P., a limited partnership of which the sole general partner is Baker/Tisch Capital (GP), LLC, due to Baker/Tisch Capital, L.P.'s right to receive an allocation of a portion of the profits from Baker Tisch. Includes beneficial ownership of 11,897 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 8,250 shares which were received from exercise of 8,250 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.

F11 · 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 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.

F12 · ownership.nature: The disclosure of the grant of Restricted Stock reported on this form is the sum of two grants totaling 680 shares. The 680 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000024 · doc4_4439.xml · nonDerivative · entry 6

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

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

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

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 533,909

F4 · ownership.nature: 189 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 533,909 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 1,418 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 75,000 shares received previously from exercise of 75,000 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 189 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000024 · doc4_4439.xml · nonDerivative · entry 5

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

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

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

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 19,758,174

F4 · ownership.nature: 189 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 19,758,174 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 1,418 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 75,000 shares received previously from exercise of 75,000 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 189 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-17-000024 · doc4_4439.xml · nonDerivative · entry 4

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

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

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

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 3,359,840

F4 · ownership.nature: 189 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 3,359,840 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 1,418 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 75,000 shares received previously from exercise of 75,000 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 189 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-16-001591 · doc4_4343.xml · nonDerivative · entry 5

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

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

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

14159, L.P. · CIK 0001551138 · 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: 3,317,977

F3 · 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 Ordinary Shares reported in column 5 of Table I directly 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.

F5 · ownership.nature: On November 18, 2016, 667 and Life Sciences purchased 165,824 and 1,594,671 American Depositary Shares of the Issuer, respectively, each representing 13 Ordinary Shares (the "ADS") for $32.00 per ADS, pursuant to an underwritten public offering.

F6 · 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 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: 0001638599-16-001591 · doc4_4343.xml · nonDerivative · entry 4

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

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

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

14159, L.P. · CIK 0001551138 · 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: 355,198

F2 · 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 Ordinary Shares reported in column 5 of Table I directly 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.

F5 · ownership.nature: On November 18, 2016, 667 and Life Sciences purchased 165,824 and 1,594,671 American Depositary Shares of the Issuer, respectively, each representing 13 Ordinary Shares (the "ADS") for $32.00 per ADS, pursuant to an underwritten public offering.

F6 · 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 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: 0001638599-16-001463 · doc4_4264.xml · nonDerivative · entry 3

BAKER JULIAN · CIK 0001087939 · Director

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

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director

Baker Brothers Life Sciences LP · CIK 0001363364 · Director

14159, L.P. · CIK 0001551138 · Director

BAKER FELIX · CIK 0001087940 · Director

667, L.P. · CIK 0001551139 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 9,309,333

F2 · ownership.nature: On October 7, 2016, 667, L.P. ("667") and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667 and 14159 the "Funds") purchased 321,404 and 2,928,596 shares of the Common Stock, respectively of the Issuer, pursuant to an underwritten public offering.

F4 · ownership.nature: After giving effect to the transactions reported herein and 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 9,309,333 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 75,905 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees, of which the fund may be deemed to own a portion.

F5 · 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 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.

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.

SEC source: 0001638599-16-001463 · doc4_4264.xml · nonDerivative · entry 2

BAKER JULIAN · CIK 0001087939 · Director

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

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director

Baker Brothers Life Sciences LP · CIK 0001363364 · Director

14159, L.P. · CIK 0001551138 · Director

BAKER FELIX · CIK 0001087940 · Director

667, L.P. · CIK 0001551139 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 1,003,781

F2 · ownership.nature: On October 7, 2016, 667, L.P. ("667") and Baker Brothers Life Sciences, L.P. ("Life Sciences", and together with 667 and 14159 the "Funds") purchased 321,404 and 2,928,596 shares of the Common Stock, respectively of the Issuer, pursuant to an underwritten public offering.

F3 · ownership.nature: After giving effect to the transactions reported herein and 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 1,003,781 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 75,905 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees,of which the fund may be deemed to own a portion.

F5 · 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 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.

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.

SEC source: 0001638599-16-001444 · doc4_4255.xml · nonDerivative · entry 3

BAKER JULIAN · CIK 0001087939 · Director

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

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director

Baker Brothers Life Sciences LP · CIK 0001363364 · Director

14159, L.P. · CIK 0001551138 · Director

BAKER FELIX · CIK 0001087940 · Director

667, L.P. · CIK 0001551139 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 111,010

F1 · ownership.nature: 3,417 shares of common stock (the "Common Stock") issued to Julian C. Baker and 4,882 shares of Common Stock issued to Dr. Kelvin M. Neu, respectively, a principal and an employee of Baker Bros. Advisors LP (the "Adviser") pursuant to the Issuer's 2013 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $8,750 and $12,500, respectively. The shares of Common Stock are fully vested. Julian C. Baker and Dr. Neu serve on the Issuer's Board of Directors (the "Board") as representatives of the Funds (as defined below). Dr. Neu also serves on the Compensation Committee of the Board for which he receives additional director retainer fees.

F2 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker and Dr. Neu do 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 (i.e., no direct pecuniary interest).

F5 · 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 111,010 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 75,905 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees, of which the fund may be deemed to own a portion.

F6 · 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.

F7 · ownership.nature: The disclosure of the grant of Common Stock reported on this form is the sum of two grants totaling 8,299 shares. The 8,299 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-16-001444 · doc4_4255.xml · nonDerivative · entry 2

BAKER JULIAN · CIK 0001087939 · Director

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

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director

Baker Brothers Life Sciences LP · CIK 0001363364 · Director

14159, L.P. · CIK 0001551138 · Director

BAKER FELIX · CIK 0001087940 · Director

667, L.P. · CIK 0001551139 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 6,380,737

F1 · ownership.nature: 3,417 shares of common stock (the "Common Stock") issued to Julian C. Baker and 4,882 shares of Common Stock issued to Dr. Kelvin M. Neu, respectively, a principal and an employee of Baker Bros. Advisors LP (the "Adviser") pursuant to the Issuer's 2013 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $8,750 and $12,500, respectively. The shares of Common Stock are fully vested. Julian C. Baker and Dr. Neu serve on the Issuer's Board of Directors (the "Board") as representatives of the Funds (as defined below). Dr. Neu also serves on the Compensation Committee of the Board for which he receives additional director retainer fees.

F2 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker and Dr. Neu do 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 (i.e., no direct pecuniary interest).

F4 · 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 6,380,737 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 75,905 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees, of which the fund may be deemed to own a portion.

F6 · 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.

F7 · ownership.nature: The disclosure of the grant of Common Stock reported on this form is the sum of two grants totaling 8,299 shares. The 8,299 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-16-001444 · doc4_4255.xml · nonDerivative · entry 1

BAKER JULIAN · CIK 0001087939 · Director

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

BAKER BROS. ADVISORS LP · CIK 0001263508 · Director

Baker Brothers Life Sciences LP · CIK 0001363364 · Director

14159, L.P. · CIK 0001551138 · Director

BAKER FELIX · CIK 0001087940 · Director

667, L.P. · CIK 0001551139 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See footnote

Disclosed balance after: 682,377

F1 · ownership.nature: 3,417 shares of common stock (the "Common Stock") issued to Julian C. Baker and 4,882 shares of Common Stock issued to Dr. Kelvin M. Neu, respectively, a principal and an employee of Baker Bros. Advisors LP (the "Adviser") pursuant to the Issuer's 2013 Stock Incentive Plan (the "Stock Incentive Plan") in lieu of director retainer fees of $8,750 and $12,500, respectively. The shares of Common Stock are fully vested. Julian C. Baker and Dr. Neu serve on the Issuer's Board of Directors (the "Board") as representatives of the Funds (as defined below). Dr. Neu also serves on the Compensation Committee of the Board for which he receives additional director retainer fees.

F2 · ownership.nature: Pursuant to the policies of the Adviser, Julian C. Baker and Dr. Neu do 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 (i.e., no direct pecuniary interest).

F3 · 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 682,377 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 75,905 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees,of which the fund may be deemed to own a portion.

F6 · 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.

F7 · ownership.nature: The disclosure of the grant of Common Stock reported on this form is the sum of two grants totaling 8,299 shares. The 8,299 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-16-001442 · doc4_4251.xml · nonDerivative · entry 6

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 533,720

F4 · ownership.nature: 201 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 533,720 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 1,229 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 75,000 shares received previously from exercise of 75,000 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 201 shares are reported for each of the Funds as each has an indirect pecuniary interest.

SEC source: 0001638599-16-001442 · doc4_4251.xml · nonDerivative · entry 5

BAKER JULIAN · CIK 0001087939 · Director · 10% owner

BAKER FELIX · CIK 0001087940 · Director · 10% owner

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

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

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

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

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 19,757,985

F4 · ownership.nature: 201 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 19,757,985 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 1,229 shares issued pursuant to the Stock Incentive Plan in lieu of director retainer fees and 75,000 shares received previously from exercise of 75,000 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 201 shares are reported for each of the Funds as each has an indirect pecuniary interest.