PBYI

SEC source: 0001209191-18-003948 · doc4.xml · derivative · entry 1

HUNT DOUGLAS M · CIK 0001727172 · See Remarks

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 90,000

Underlying: Common Stock · 90,000 shares

Expires 2028-01-15

F1 · derivative.exercise_date: The vesting commencement date ("Vesting Commencement Date") of the option is January 2, 2018. The option vests (i) with respect to one-third (1/3) of the shares underlying the option on the first anniversary of the Vesting Commencement Date and (ii) with respect to 1/36th of the shares underlying the option, on each monthly anniversary of the Vesting Commencement Date thereafter, subject to the Reporting Person's continued employment with the Issuer through the applicable vesting date.

SEC source: 0001209191-17-063874 · doc4.xml · nonDerivative · entry 1

EYLER CHARLES R · CIK 0001358246 · SEE REMARKS

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 28,696

F1 · kind: The sales reported in this Form 4 were effected pursuant to a 10b5-1 trading plan adopted by the Reporting Person on September 13, 2017 to satisfy tax obligations in connection with the vesting of restricted stock units.

F2 · shares: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $105.3696 to $105.7000, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares sold at each separate price within the ranges set forth in this footnote.

SEC source: 0001209191-17-054619 · doc4.xml · derivative · entry 3

BRYCE RICHARD PAUL · CIK 0001553037 · SR VP, CLINICAL RESEARCH & DEV

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 67,000

Underlying: COMMON STOCK · 15,000 shares

Expires 2022-06-26

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

F2 · derivative.exercise_date: The option is fully vested and is exercisable.

SEC source: 0001209191-17-054619 · doc4.xml · nonDerivative · entry 2

BRYCE RICHARD PAUL · CIK 0001553037 · SR VP, CLINICAL RESEARCH & DEV

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 27,239

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

SEC source: 0001209191-17-054619 · doc4.xml · nonDerivative · entry 1

BRYCE RICHARD PAUL · CIK 0001553037 · SR VP, CLINICAL RESEARCH & DEV

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 42,239

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

SEC source: 0001209191-17-052039 · doc4.xml · derivative · entry 6

BRYCE RICHARD PAUL · CIK 0001553037 · SR VP, CLINICAL RESEARCH & DEV

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 82,000

Underlying: COMMON STOCK · 14,000 shares

Expires 2022-06-26

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

F2 · derivative.exercise_date: The option is fully vested and is exercisable.

SEC source: 0001209191-17-052039 · doc4.xml · nonDerivative · entry 4

BRYCE RICHARD PAUL · CIK 0001553037 · SR VP, CLINICAL RESEARCH & DEV

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 27,239

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

SEC source: 0001209191-17-052039 · doc4.xml · nonDerivative · entry 3

BRYCE RICHARD PAUL · CIK 0001553037 · SR VP, CLINICAL RESEARCH & DEV

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 41,239

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

SEC source: 0001209191-17-052039 · doc4.xml · derivative · entry 5

BRYCE RICHARD PAUL · CIK 0001553037 · SR VP, CLINICAL RESEARCH & DEV

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 96,000

Underlying: COMMON STOCK · 1,000 shares

Expires 2022-06-26

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

F2 · derivative.exercise_date: The option is fully vested and is exercisable.

SEC source: 0001209191-17-052039 · doc4.xml · nonDerivative · entry 2

BRYCE RICHARD PAUL · CIK 0001553037 · SR VP, CLINICAL RESEARCH & DEV

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 27,239

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

SEC source: 0001209191-17-052039 · doc4.xml · nonDerivative · entry 1

BRYCE RICHARD PAUL · CIK 0001553037 · SR VP, CLINICAL RESEARCH & DEV

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 28,239

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

SEC source: 0001209191-17-046092 · doc4.xml · nonDerivative · entry 1

Lo Steven · CIK 0001501959 · Chief Commercial Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 27,220

F1 · kind: The sales reported in this Form 4 were effected pursuant to a 10b5-1 trading plan adopted by the Reporting Person on December 22, 2016 to satisfy tax obligations in connection with the vesting of restricted stock units.

SEC source: 0001209191-17-046090 · doc4.xml · nonDerivative · entry 1

EYLER CHARLES R · CIK 0001358246 · SEE REMARKS

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 30,018

F1 · kind: The sales reported in this Form 4 were effected pursuant to a 10b5-1 trading plan adopted by the Reporting Person on December 16, 2016 to satisfy tax obligations in connection with the vesting of restricted stock units.

F2 · price: The price reported in Column 4 is a weighted average price. The shares were sold in two transactions with one transaction pricing at $95.151 and the other transaction pricing at $95.701. The Reporting Person undertakes to provide to the Issuer, any security holder, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares sold at each separate price set forth in this footnote.

SEC source: 0001209191-17-046089 · doc4.xml · nonDerivative · entry 2

BRYCE RICHARD PAUL · CIK 0001553037 · SR VP, CLINICAL RESEARCH & DEV

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 27,239

F1 · kind: The sales reported in this Form 4 were effected pursuant to a 10b5-1 trading plan adopted by the Reporting Person on December 19, 2016 to satisfy tax obligations in connection with the vesting of restricted stock units.

SEC source: 0001209191-17-046089 · doc4.xml · nonDerivative · entry 1

BRYCE RICHARD PAUL · CIK 0001553037 · SR VP, CLINICAL RESEARCH & DEV

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 27,246

F1 · kind: The sales reported in this Form 4 were effected pursuant to a 10b5-1 trading plan adopted by the Reporting Person on December 19, 2016 to satisfy tax obligations in connection with the vesting of restricted stock units.

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $94.1589 to $94.8500, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares sold at each separate price within the ranges set forth in this footnote.

SEC source: 0001209191-17-046087 · doc4.xml · nonDerivative · entry 2

AUERBACH ALAN H · CIK 0001358285 · Director · PRESIDENT AND CEO · 10% owner

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 4,166,623

F1 · kind: The sales reported in this Form 4 were effected pursuant to a 10b5-1 trading plan adopted by the Reporting Person on December 16, 2016 to satisfy tax obligations in connection with the vesting of restricted stock units.

SEC source: 0001209191-17-046087 · doc4.xml · nonDerivative · entry 1

AUERBACH ALAN H · CIK 0001358285 · Director · PRESIDENT AND CEO · 10% owner

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 4,170,623

F1 · kind: The sales reported in this Form 4 were effected pursuant to a 10b5-1 trading plan adopted by the Reporting Person on December 16, 2016 to satisfy tax obligations in connection with the vesting of restricted stock units.

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in two transactions with one transaction pricing at $94.10 and the other transaction pricing at $94.35. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares sold at each separate price set forth in this footnote.

SEC source: 0001209191-17-045240 · doc4.xml · derivative · entry 3

BRYCE RICHARD PAUL · CIK 0001553037 · SR VP, CLINICAL RESEARCH & DEV

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 97,000

Underlying: COMMON STOCK · 5,000 shares

Expires 2022-06-26

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

F2 · derivative.exercise_date: The option is fully vested and is exercisable.

SEC source: 0001209191-17-045240 · doc4.xml · nonDerivative · entry 2

BRYCE RICHARD PAUL · CIK 0001553037 · SR VP, CLINICAL RESEARCH & DEV

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 29,237

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

SEC source: 0001209191-17-045240 · doc4.xml · nonDerivative · entry 1

BRYCE RICHARD PAUL · CIK 0001553037 · SR VP, CLINICAL RESEARCH & DEV

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 34,237

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.

SEC source: 0000902664-17-002616 · p17-1335form4.xml · nonDerivative · entry 6

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 3,696,580

F7 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $79.7 to $80.4, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002616 · p17-1335form4.xml · nonDerivative · entry 5

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 3,708,277

F6 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $78.7 to $79.65, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0001209191-17-039915 · doc4.xml · derivative · entry 1

ZAVRL FRANK · CIK 0001652169 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 7,604

Underlying: Common Stock · 7,604 shares

Expires 2027-06-11

F1 · derivative.exercise_date: The option vests in full on the earlier of the one-year anniversary of the date of grant and the date of the annual shareholder meeting following the date of grant, subject to the Reporting Person's continued service with the Issuer.

SEC source: 0001209191-17-040003 · doc4.xml · derivative · entry 1

Senderowicz Adrian · CIK 0001616230 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 7,604

Underlying: Common Stock · 7,604 shares

Expires 2027-06-11

F1 · derivative.exercise_date: The option vests in full on the earlier of the one-year anniversary of the date of grant and the date of the annual shareholder meeting following the date of grant, subject to the Reporting Person's continued service with the Issuer.

SEC source: 0001209191-17-039914 · doc4.xml · derivative · entry 1

WILSON TROY EDWARD · CIK 0001589597 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 7,604

Underlying: Common Stock · 7,604 shares

Expires 2027-06-11

F1 · derivative.exercise_date: The option vests in full on the earlier of the one-year anniversary of the date of grant and the date of the annual shareholder meeting following the date of grant, subject to the Reporting Person's continued service with the Issuer.

SEC source: 0001209191-17-039912 · doc4.xml · derivative · entry 1

MOYES JAY M · CIK 0001191062 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 7,604

Underlying: Common Stock · 7,604 shares

Expires 2027-06-11

F1 · derivative.exercise_date: The option vests in full on the earlier of the one-year anniversary of the date of grant and the date of the annual shareholder meeting following the date of grant, subject to the Reporting Person's continued service with the Issuer.

SEC source: 0000902664-17-002616 · p17-1335form4.xml · nonDerivative · entry 4

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 3,785,524

F5 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $81 to $81.5, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002616 · p17-1335form4.xml · nonDerivative · entry 3

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 3,809,634

F4 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $80 to $80.95, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002616 · p17-1335form4.xml · nonDerivative · entry 2

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 3,843,840

F3 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $81.4 to $81.7, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002616 · p17-1335form4.xml · nonDerivative · entry 1

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 3,854,302

F1 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $80.4 to $81.375, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002551 · p17-1315form4.xml · nonDerivative · entry 10

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 3,943,840

F10 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $99 to $99.45, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002551 · p17-1315form4.xml · nonDerivative · entry 9

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 3,955,508

F9 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $96.5 to $97, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002551 · p17-1315form4.xml · nonDerivative · entry 8

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 4,007,524

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002551 · p17-1315form4.xml · nonDerivative · entry 7

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 4,010,607

F8 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $91 to $91.65, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002551 · p17-1315form4.xml · nonDerivative · entry 6

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 4,033,879

F7 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $90 to $90.75, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002551 · p17-1315form4.xml · nonDerivative · entry 5

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 4,186,641

F6 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $87.625 to $88.6, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002551 · p17-1315form4.xml · nonDerivative · entry 4

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 4,249,868

F5 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $85.25 to $85.45, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002551 · p17-1315form4.xml · nonDerivative · entry 3

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 4,250,968

F4 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $83 to $83.45, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002551 · p17-1315form4.xml · nonDerivative · entry 2

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 4,281,443

F3 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $83.2 to $84, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002551 · p17-1315form4.xml · nonDerivative · entry 1

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 4,286,643

F1 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $81.75 to $82.625, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0001209191-17-036835 · doc4.xml · nonDerivative · entry 1

EYLER CHARLES R · CIK 0001358246 · SEE REMARKS

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 30,680

F1 · shares: Represents Restricted Stock Units which vest in six substantially equal installments on each six-month anniversary of the Vesting Commencement Date of May 31, 2017, subject to the Reporting Person's continued service with the Issuer through the applicable vesting date.

SEC source: 0000902664-17-002486 · p17-1283form4.xml · nonDerivative · entry 14

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 4,450,968

F13 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $78.35 to $78.4, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002486 · p17-1283form4.xml · nonDerivative · entry 13

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 4,451,298

F12 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $77.275 to $78.25, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002486 · p17-1283form4.xml · nonDerivative · entry 12

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 4,563,121

F11 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $76.275 to $77.25, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002486 · p17-1283form4.xml · nonDerivative · entry 11

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 4,750,968

F10 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $79.5 to $80, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002486 · p17-1283form4.xml · nonDerivative · entry 10

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 4,826,004

F9 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $78.1 to $78.4, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002486 · p17-1283form4.xml · nonDerivative · entry 9

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 4,833,252

F8 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $77.1 to $78, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002486 · p17-1283form4.xml · nonDerivative · entry 8

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 5,065,442

F7 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $76.1 to $77.075, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002486 · p17-1283form4.xml · nonDerivative · entry 7

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 5,150,968

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.

SEC source: 0000902664-17-002486 · p17-1283form4.xml · nonDerivative · entry 6

ADAGE CAPITAL PARTNERS GP, L.L.C. · CIK 0001165408 · 10% owner

Adage Capital Partners, L.P. · CIK 0001163846 · 10% owner

Adage Capital Advisors, L.L.C. · CIK 0001403403 · 10% owner

Atchinson Robert · CIK 0001403404 · 10% owner

Gross Phillip · CIK 0001403413 · 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: 5,267,101

F6 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $74 to $74.9875, inclusive. The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the ranges set forth herein.

F2 · ownership.nature: The securities to which this filing relates are held directly by Adage Capital Partners, L.P., a Delaware limited partnership (the "Fund"). Adage Capital Partners GP, L.L.C., a Delaware limited liability company ("ACPGP"), serves as the general partner of the Fund and as such has discretion over the portfolio securities beneficially owned by the Fund. Adage Capital Advisors, L.L.C., a Delaware limited liability company ("ACA"), is the managing member of ACPGP and directs ACPGP's operations. Robert Atchinson and Phillip Gross are the managing members of ACPGP and ACA and general partners of the Fund. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Section 16 of the Securities and Exchange Act of 1934, as amended, except as to such extent of the reporting person's pecuniary interest in the securities.