SILVERSTEIN JONATHAN

SEC source: 0000947871-20-000781 · ownership.xml · nonDerivative · entry 2

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 902,286

F1 · shares: These shares of the Issuer's common stock ("Shares") were purchased in a private placement exempt from the registration requirements of the Securities Act of 1933, as amended.

F3 · ownership.nature: The Reporting Person is the designated representative of OrbiMed Advisors, OrbiMed GP VII, and OrbiMed Capital LLC ("OrbiMed Capital") on the Issuer's board of directors. Each of OrbiMed GP VII, OrbiMed Advisors, OrbiMed Capital LLC, and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report on Form 4 shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

F4 · ownership.nature: The Shares are held of record by OrbiMed Partners Master Fund Limited ("OPM"). OrbiMed Capital is the investment manager of OPM and is a relying adviser of OrbiMed Advisors. OrbiMed Advisors and OrbiMed Capital exercise voting and investment power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and the Reporting Person, each of whom disclaims beneficial ownership of the Shares held by OPM.

SEC source: 0000947871-20-000781 · ownership.xml · nonDerivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 4,267,564

F1 · shares: These shares of the Issuer's common stock ("Shares") were purchased in a private placement exempt from the registration requirements of the Securities Act of 1933, as amended.

F2 · ownership.nature: The Shares are held of record by OrbiMed Private Investments VII, LP ("OPI VII"). OrbiMed Capital GP VII LLC ("OrbiMed GP VII"), is the general partner of OPI VII and OrbiMed Advisors LLC ("OrbiMed Advisors") is the managing member of OrbiMed GP VII. OrbiMed GP VII and OrbiMed Advisors may be deemed to have voting and investment power over the securities held by OPI VII and may be deemed to have beneficial ownership over such securities. OrbiMed Advisors exercises voting and investment power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and the Reporting Person, each of whom disclaims beneficial ownership of the Shares held by OPI VII.

F3 · ownership.nature: The Reporting Person is the designated representative of OrbiMed Advisors, OrbiMed GP VII, and OrbiMed Capital LLC ("OrbiMed Capital") on the Issuer's board of directors. Each of OrbiMed GP VII, OrbiMed Advisors, OrbiMed Capital LLC, and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report on Form 4 shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-20-015455 · doc4.xml · derivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 14,414

Underlying: Common Stock · 14,414 shares

Expires 2030-06-02

F1 · derivative.exercise_date: This option was granted on June 3, 2020 with respect to 14,414 shares of Common Stock and vests in full on the earlier to occur of (a) the first anniversary of the grant date or (b) the date of the next annual meeting of stockholders following the date of grant.

SEC source: 0001567619-20-005549 · doc1.xml · derivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 24,000

Underlying: Common Stock · 24,000 shares

Expires 2030-02-27

F1 · derivative.exercise_date: The option vests and becomes exercisable 100% on the earlier of the date of the next annual meeting of the Issuer's stockholders or February 27, 2021.

SEC source: 0000947871-20-000078 · ownership.xml · derivative · entry 8

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 429,786 shares

Expires not disclosed

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.

F6 · derivative.exercise_price: The Series C Preferred Stock automatically converted into shares of the Issuer's common stock on a one-for-one immediately upon the closing of the Issuer's initial public offering and had no expiration date.

F6 · derivative.exercise_date: The Series C Preferred Stock automatically converted into shares of the Issuer's common stock on a one-for-one immediately upon the closing of the Issuer's initial public offering and had no expiration date.

F6 · derivative.expiration_date: The Series C Preferred Stock automatically converted into shares of the Issuer's common stock on a one-for-one immediately upon the closing of the Issuer's initial public offering and had no expiration date.

F3 · ownership.nature: Each of OrbiMed GP VII, OrbiMed Capital, OrbiMed Advisors and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its pecuniary interest therein, if any. This report on Form 4 shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

F4 · ownership.nature: The Shares are held of record by OrbiMed Partners Master Fund Limited ("OPMF"). OrbiMed Capital is the investment manager of OPMF and is a relying adviser of OrbiMed Advisors. OrbiMed Advisors and OrbiMed Capital exercise voting and investment power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and the Reporting Person, each of whom disclaims beneficial ownership of the Shares held by OPMF.

SEC source: 0000947871-20-000078 · ownership.xml · derivative · entry 7

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 859,573 shares

Expires not disclosed

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.

F6 · derivative.exercise_price: The Series C Preferred Stock automatically converted into shares of the Issuer's common stock on a one-for-one immediately upon the closing of the Issuer's initial public offering and had no expiration date.

F6 · derivative.exercise_date: The Series C Preferred Stock automatically converted into shares of the Issuer's common stock on a one-for-one immediately upon the closing of the Issuer's initial public offering and had no expiration date.

F6 · derivative.expiration_date: The Series C Preferred Stock automatically converted into shares of the Issuer's common stock on a one-for-one immediately upon the closing of the Issuer's initial public offering and had no expiration date.

F2 · ownership.nature: The Shares are held of record by OrbiMed Private Investments VII, LP ("OPI VII"). OrbiMed Capital GP VII LLC ("OrbiMed GP VII"), is the general partner of OPI VII and OrbiMed Advisors LLC is the managing member of OPI VII. OrbiMed GP VII and OrbiMed Advisors may be deemed to have voting and investment power over the securities held by OPI VII and may be deemed to have beneficial ownership over such securities. OrbiMed Captial LLC ("OrbiMed Capital") is a relying adviser of OrbiMed Advisors. OrbiMed Advisors and OrbiMed Capital exercise voting and investment power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and the Reporting Person, each of whom disclaims beneficial ownership of the Shares held by OPI VII.

F3 · ownership.nature: Each of OrbiMed GP VII, OrbiMed Capital, OrbiMed Advisors and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its pecuniary interest therein, if any. This report on Form 4 shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-20-000078 · ownership.xml · derivative · entry 6

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 2,825,603 shares

Expires not disclosed

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

F5 · derivative.exercise_price: The Series B Preferred Stock automatically converted into shares of the Issuer's common stock on a one-for-one basis immediately upon the closing of the Issuer's initial public offering and had no expiration date.

F5 · derivative.exercise_date: The Series B Preferred Stock automatically converted into shares of the Issuer's common stock on a one-for-one basis immediately upon the closing of the Issuer's initial public offering and had no expiration date.

F5 · derivative.expiration_date: The Series B Preferred Stock automatically converted into shares of the Issuer's common stock on a one-for-one basis immediately upon the closing of the Issuer's initial public offering and had no expiration date.

F2 · ownership.nature: The Shares are held of record by OrbiMed Private Investments VII, LP ("OPI VII"). OrbiMed Capital GP VII LLC ("OrbiMed GP VII"), is the general partner of OPI VII and OrbiMed Advisors LLC is the managing member of OPI VII. OrbiMed GP VII and OrbiMed Advisors may be deemed to have voting and investment power over the securities held by OPI VII and may be deemed to have beneficial ownership over such securities. OrbiMed Captial LLC ("OrbiMed Capital") is a relying adviser of OrbiMed Advisors. OrbiMed Advisors and OrbiMed Capital exercise voting and investment power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and the Reporting Person, each of whom disclaims beneficial ownership of the Shares held by OPI VII.

F3 · ownership.nature: Each of OrbiMed GP VII, OrbiMed Capital, OrbiMed Advisors and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its pecuniary interest therein, if any. This report on Form 4 shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-20-000078 · ownership.xml · nonDerivative · entry 5

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 606,286

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.

F6 · price: The Series C Preferred Stock automatically converted into shares of the Issuer's common stock on a one-for-one immediately upon the closing of the Issuer's initial public offering and had no expiration date.

F3 · ownership.nature: Each of OrbiMed GP VII, OrbiMed Capital, OrbiMed Advisors and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its pecuniary interest therein, if any. This report on Form 4 shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

F4 · ownership.nature: The Shares are held of record by OrbiMed Partners Master Fund Limited ("OPMF"). OrbiMed Capital is the investment manager of OPMF and is a relying adviser of OrbiMed Advisors. OrbiMed Advisors and OrbiMed Capital exercise voting and investment power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and the Reporting Person, each of whom disclaims beneficial ownership of the Shares held by OPMF.

SEC source: 0000947871-20-000078 · ownership.xml · nonDerivative · entry 4

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 4,067,564

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.

F6 · price: The Series C Preferred Stock automatically converted into shares of the Issuer's common stock on a one-for-one immediately upon the closing of the Issuer's initial public offering and had no expiration date.

F2 · ownership.nature: The Shares are held of record by OrbiMed Private Investments VII, LP ("OPI VII"). OrbiMed Capital GP VII LLC ("OrbiMed GP VII"), is the general partner of OPI VII and OrbiMed Advisors LLC is the managing member of OPI VII. OrbiMed GP VII and OrbiMed Advisors may be deemed to have voting and investment power over the securities held by OPI VII and may be deemed to have beneficial ownership over such securities. OrbiMed Captial LLC ("OrbiMed Capital") is a relying adviser of OrbiMed Advisors. OrbiMed Advisors and OrbiMed Capital exercise voting and investment power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and the Reporting Person, each of whom disclaims beneficial ownership of the Shares held by OPI VII.

F3 · ownership.nature: Each of OrbiMed GP VII, OrbiMed Capital, OrbiMed Advisors and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its pecuniary interest therein, if any. This report on Form 4 shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-20-000078 · ownership.xml · nonDerivative · entry 3

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 3,207,991

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 · price: The Series B Preferred Stock automatically converted into shares of the Issuer's common stock on a one-for-one basis immediately upon the closing of the Issuer's initial public offering and had no expiration date.

F2 · ownership.nature: The Shares are held of record by OrbiMed Private Investments VII, LP ("OPI VII"). OrbiMed Capital GP VII LLC ("OrbiMed GP VII"), is the general partner of OPI VII and OrbiMed Advisors LLC is the managing member of OPI VII. OrbiMed GP VII and OrbiMed Advisors may be deemed to have voting and investment power over the securities held by OPI VII and may be deemed to have beneficial ownership over such securities. OrbiMed Captial LLC ("OrbiMed Capital") is a relying adviser of OrbiMed Advisors. OrbiMed Advisors and OrbiMed Capital exercise voting and investment power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and the Reporting Person, each of whom disclaims beneficial ownership of the Shares held by OPI VII.

F3 · ownership.nature: Each of OrbiMed GP VII, OrbiMed Capital, OrbiMed Advisors and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its pecuniary interest therein, if any. This report on Form 4 shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-20-000078 · ownership.xml · nonDerivative · entry 2

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 176,500

F1 · price: These shares of the Issuer's common stock ("Shares") were purchased in the Issuer's initial public offering.

F3 · ownership.nature: Each of OrbiMed GP VII, OrbiMed Capital, OrbiMed Advisors and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its pecuniary interest therein, if any. This report on Form 4 shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

F4 · ownership.nature: The Shares are held of record by OrbiMed Partners Master Fund Limited ("OPMF"). OrbiMed Capital is the investment manager of OPMF and is a relying adviser of OrbiMed Advisors. OrbiMed Advisors and OrbiMed Capital exercise voting and investment power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and the Reporting Person, each of whom disclaims beneficial ownership of the Shares held by OPMF.

SEC source: 0000947871-20-000078 · ownership.xml · nonDerivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 382,388

F1 · price: These shares of the Issuer's common stock ("Shares") were purchased in the Issuer's initial public offering.

F2 · ownership.nature: The Shares are held of record by OrbiMed Private Investments VII, LP ("OPI VII"). OrbiMed Capital GP VII LLC ("OrbiMed GP VII"), is the general partner of OPI VII and OrbiMed Advisors LLC is the managing member of OPI VII. OrbiMed GP VII and OrbiMed Advisors may be deemed to have voting and investment power over the securities held by OPI VII and may be deemed to have beneficial ownership over such securities. OrbiMed Captial LLC ("OrbiMed Capital") is a relying adviser of OrbiMed Advisors. OrbiMed Advisors and OrbiMed Capital exercise voting and investment power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and the Reporting Person, each of whom disclaims beneficial ownership of the Shares held by OPI VII.

F3 · ownership.nature: Each of OrbiMed GP VII, OrbiMed Capital, OrbiMed Advisors and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its pecuniary interest therein, if any. This report on Form 4 shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001209191-19-057945 · doc4.xml · derivative · entry 3

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 3,005 shares

Expires not disclosed

F5 · derivative.exercise_price: Each restricted stock unit ("RSU") represents a contingent right to receive one share of the Issuer's common stock.

F6 · price: At the Effective Time, each outstanding restricted stock unit ("Issuer RSU") (excluding any Issuer RSU that vested prior to or as a result of the consummation of the Merger and which settled in shares of Issuer Common Stock that were converted into the right to receive shares of Parent Common Stock as a result of the Merger) was assumed by Parent and converted into the right to receive shares of Parent Common Stock (rounded down to the nearest whole share) using a conversion ratio designed to preserve the intrinsic value of such Issuer RSU.

F6 · derivative.exercise_date: At the Effective Time, each outstanding restricted stock unit ("Issuer RSU") (excluding any Issuer RSU that vested prior to or as a result of the consummation of the Merger and which settled in shares of Issuer Common Stock that were converted into the right to receive shares of Parent Common Stock as a result of the Merger) was assumed by Parent and converted into the right to receive shares of Parent Common Stock (rounded down to the nearest whole share) using a conversion ratio designed to preserve the intrinsic value of such Issuer RSU.

F6 · derivative.expiration_date: At the Effective Time, each outstanding restricted stock unit ("Issuer RSU") (excluding any Issuer RSU that vested prior to or as a result of the consummation of the Merger and which settled in shares of Issuer Common Stock that were converted into the right to receive shares of Parent Common Stock as a result of the Merger) was assumed by Parent and converted into the right to receive shares of Parent Common Stock (rounded down to the nearest whole share) using a conversion ratio designed to preserve the intrinsic value of such Issuer RSU.

SEC source: 0001209191-19-057945 · doc4.xml · derivative · entry 2

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 8,314 shares

Expires 2029-01-08

F4 · price: At the Effective Time, each outstanding and unexercised option to purchase Issuer Common Stock (whether vested or unvested) immediately prior to the Effective Time, was assumed by Parent and converted into an option to purchase shares of Parent Common Shares (rounded down to the nearest whole share) using a conversion ratio designed to preserve the intrinsic value of such option of Issuer.

F4 · derivative.exercise_date: At the Effective Time, each outstanding and unexercised option to purchase Issuer Common Stock (whether vested or unvested) immediately prior to the Effective Time, was assumed by Parent and converted into an option to purchase shares of Parent Common Shares (rounded down to the nearest whole share) using a conversion ratio designed to preserve the intrinsic value of such option of Issuer.

SEC source: 0001209191-19-057945 · doc4.xml · nonDerivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 0

F1 · price: Pursuant to the Agreement and Plan of Merger (the "Merger Agreement") dated as of August 7, 2019, by and among Avedro, Inc. (the "Issuer"), Glaukos Corporation ("Parent") and Atlantic Merger Sub, Inc., a Delaware corporation and wholly owned subsidiary of Parent ("Merger Sub"), on November 21, 2019, Merger Sub merged with and into the Issuer (the "Merger") with the Issuer continuing as the surviving corporation. Pursuant to the terms of the Merger Agreement, at the effective time of the Merger (the "Effective Time"), each share of common stock of the Issuer ("Issuer Common Stock") that was issued and outstanding immediately prior to the Effective Time was automatically cancelled and converted into the right to receive 0.365 of a share of Parent's common stock ("Parent Common Stock"). The closing price of shares of the Parent Common Stock on November 21, 2019 was $63.07 per share.

F2 · ownership.nature: These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. By virtue of such relationships, GP VI and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities. The Reporting Person is a member of Advisors.

F3 · ownership.nature: Each of GP VI, Advisors, and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001209191-19-037850 · doc4.xml · derivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 3,005

Underlying: Common Stock · 3,005 shares

Expires not disclosed

F1 · derivative.exercise_price: Each restricted stock unit ("RSU") represents a contingent right to receive one share of the Issuer's common stock.

F2 · derivative.exercise_date: The RSUs vest on June 1, 2020, subject to Reporting Person's continuous service through such date.

F2 · derivative.expiration_date: The RSUs vest on June 1, 2020, subject to Reporting Person's continuous service through such date.

SEC source: 0000899243-19-012924 · doc4.xml · derivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 14,414

Underlying: Common Stock · 14,414 shares

Expires 2029-05-07

F1 · derivative.exercise_date: This option was granted on May 8, 2019 with respect to 14,414 shares of Common Stock and vests in full on the earlier to occur of (a) the first anniversary of the grant date or (b) the date of the next annual meeting of stockholders following the date of grant.

SEC source: 0001209191-19-011346 · doc4.xml · derivative · entry 7

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 8,314

Underlying: Common Stock · 8,314 shares

Expires 2029-01-08

F4 · derivative.exercise_date: One hundred percent (100%) of the shares subject to the option shall vest on the earlier of (x) June 1, 2020 and (y) the first anniversary of the first annual meeting of the Issuer's stockholders following the Issuer's initial public offering, subject to the Reporting Person continuing to provide service through such date.

SEC source: 0001209191-19-011346 · doc4.xml · derivative · entry 6

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 0

Underlying: Common Stock · 383,746 shares

Expires not disclosed

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

F1 · derivative.exercise_price: Each share of Series AA Convertible Preferred Stock, Series BB Convertible Preferred Stock and Series CC Convertible Preferred Stock was convertible at any time, at the option of the holder, into Common Stock, on a one-for-one basis, had no expiration date and converted into shares of Common Stock upon the closing of the Issuer's initial public offering.

F1 · derivative.exercise_date: Each share of Series AA Convertible Preferred Stock, Series BB Convertible Preferred Stock and Series CC Convertible Preferred Stock was convertible at any time, at the option of the holder, into Common Stock, on a one-for-one basis, had no expiration date and converted into shares of Common Stock upon the closing of the Issuer's initial public offering.

F1 · derivative.expiration_date: Each share of Series AA Convertible Preferred Stock, Series BB Convertible Preferred Stock and Series CC Convertible Preferred Stock was convertible at any time, at the option of the holder, into Common Stock, on a one-for-one basis, had no expiration date and converted into shares of Common Stock upon the closing of the Issuer's initial public offering.

F2 · ownership.nature: These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. By virtue of such relationships, GP VI and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities. The Reporting Person is a member of Advisors.

F3 · ownership.nature: Each of GP VI, Advisors, and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001209191-19-011346 · doc4.xml · derivative · entry 5

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 0

Underlying: Common Stock · 333,178 shares

Expires not disclosed

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

F1 · derivative.exercise_price: Each share of Series AA Convertible Preferred Stock, Series BB Convertible Preferred Stock and Series CC Convertible Preferred Stock was convertible at any time, at the option of the holder, into Common Stock, on a one-for-one basis, had no expiration date and converted into shares of Common Stock upon the closing of the Issuer's initial public offering.

F1 · derivative.exercise_date: Each share of Series AA Convertible Preferred Stock, Series BB Convertible Preferred Stock and Series CC Convertible Preferred Stock was convertible at any time, at the option of the holder, into Common Stock, on a one-for-one basis, had no expiration date and converted into shares of Common Stock upon the closing of the Issuer's initial public offering.

F1 · derivative.expiration_date: Each share of Series AA Convertible Preferred Stock, Series BB Convertible Preferred Stock and Series CC Convertible Preferred Stock was convertible at any time, at the option of the holder, into Common Stock, on a one-for-one basis, had no expiration date and converted into shares of Common Stock upon the closing of the Issuer's initial public offering.

F2 · ownership.nature: These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. By virtue of such relationships, GP VI and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities. The Reporting Person is a member of Advisors.

F3 · ownership.nature: Each of GP VI, Advisors, and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001209191-19-011346 · doc4.xml · derivative · entry 4

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 0

Underlying: Common Stock · 3,370,786 shares

Expires not disclosed

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

F1 · derivative.exercise_price: Each share of Series AA Convertible Preferred Stock, Series BB Convertible Preferred Stock and Series CC Convertible Preferred Stock was convertible at any time, at the option of the holder, into Common Stock, on a one-for-one basis, had no expiration date and converted into shares of Common Stock upon the closing of the Issuer's initial public offering.

F1 · derivative.exercise_date: Each share of Series AA Convertible Preferred Stock, Series BB Convertible Preferred Stock and Series CC Convertible Preferred Stock was convertible at any time, at the option of the holder, into Common Stock, on a one-for-one basis, had no expiration date and converted into shares of Common Stock upon the closing of the Issuer's initial public offering.

F1 · derivative.expiration_date: Each share of Series AA Convertible Preferred Stock, Series BB Convertible Preferred Stock and Series CC Convertible Preferred Stock was convertible at any time, at the option of the holder, into Common Stock, on a one-for-one basis, had no expiration date and converted into shares of Common Stock upon the closing of the Issuer's initial public offering.

F2 · ownership.nature: These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. By virtue of such relationships, GP VI and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities. The Reporting Person is a member of Advisors.

F3 · ownership.nature: Each of GP VI, Advisors, and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001209191-19-011346 · doc4.xml · nonDerivative · entry 3

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 4,240,128

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

F1 · price: Each share of Series AA Convertible Preferred Stock, Series BB Convertible Preferred Stock and Series CC Convertible Preferred Stock was convertible at any time, at the option of the holder, into Common Stock, on a one-for-one basis, had no expiration date and converted into shares of Common Stock upon the closing of the Issuer's initial public offering.

F2 · ownership.nature: These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. By virtue of such relationships, GP VI and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities. The Reporting Person is a member of Advisors.

F3 · ownership.nature: Each of GP VI, Advisors, and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001209191-19-011346 · doc4.xml · nonDerivative · entry 2

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 3,856,382

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

F1 · price: Each share of Series AA Convertible Preferred Stock, Series BB Convertible Preferred Stock and Series CC Convertible Preferred Stock was convertible at any time, at the option of the holder, into Common Stock, on a one-for-one basis, had no expiration date and converted into shares of Common Stock upon the closing of the Issuer's initial public offering.

F2 · ownership.nature: These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. By virtue of such relationships, GP VI and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities. The Reporting Person is a member of Advisors.

F3 · ownership.nature: Each of GP VI, Advisors, and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001209191-19-011346 · doc4.xml · nonDerivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 3,523,204

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

F1 · price: Each share of Series AA Convertible Preferred Stock, Series BB Convertible Preferred Stock and Series CC Convertible Preferred Stock was convertible at any time, at the option of the holder, into Common Stock, on a one-for-one basis, had no expiration date and converted into shares of Common Stock upon the closing of the Issuer's initial public offering.

F2 · ownership.nature: These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. By virtue of such relationships, GP VI and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities. The Reporting Person is a member of Advisors.

F3 · ownership.nature: Each of GP VI, Advisors, and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000221 · ss82780_4.xml · nonDerivative · entry 14

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

F7 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $31.49 to $32.46 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F9 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. By virtue of such relationships, Advisors may be deemed to have voting and investment power over the securities held by Associates III and as a result may be deemed to have beneficial ownership over such securities. Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by Associates III.

F10 · ownership.nature: Each of the Reporting Person, GP III and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000221 · ss82780_4.xml · nonDerivative · entry 13

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

F7 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $31.49 to $32.46 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F8 · ownership.nature: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III"). OrbiMed Capital GP III LLC ("GP III") is the general partner of OPI III, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power over the securities held by OPI III and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI III. The Reporting Person is a member of Advisors.

F10 · ownership.nature: Each of the Reporting Person, GP III and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000221 · ss82780_4.xml · nonDerivative · entry 12

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 445

F6 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $30.48 to $31.47 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F9 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. By virtue of such relationships, Advisors may be deemed to have voting and investment power over the securities held by Associates III and as a result may be deemed to have beneficial ownership over such securities. Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by Associates III.

F10 · ownership.nature: Each of the Reporting Person, GP III and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000221 · ss82780_4.xml · nonDerivative · entry 11

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 46,676

F6 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $30.48 to $31.47 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F8 · ownership.nature: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III"). OrbiMed Capital GP III LLC ("GP III") is the general partner of OPI III, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power over the securities held by OPI III and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI III. The Reporting Person is a member of Advisors.

F10 · ownership.nature: Each of the Reporting Person, GP III and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000221 · ss82780_4.xml · nonDerivative · entry 10

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 637

F5 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $29.48 to $30.47 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F9 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. By virtue of such relationships, Advisors may be deemed to have voting and investment power over the securities held by Associates III and as a result may be deemed to have beneficial ownership over such securities. Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by Associates III.

F10 · ownership.nature: Each of the Reporting Person, GP III and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000221 · ss82780_4.xml · nonDerivative · entry 9

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 66,790

F5 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $29.48 to $30.47 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F8 · ownership.nature: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III"). OrbiMed Capital GP III LLC ("GP III") is the general partner of OPI III, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power over the securities held by OPI III and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI III. The Reporting Person is a member of Advisors.

F10 · ownership.nature: Each of the Reporting Person, GP III and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000221 · ss82780_4.xml · nonDerivative · entry 8

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 1,523

F4 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $32.64 to $33.39 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F9 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. By virtue of such relationships, Advisors may be deemed to have voting and investment power over the securities held by Associates III and as a result may be deemed to have beneficial ownership over such securities. Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by Associates III.

F10 · ownership.nature: Each of the Reporting Person, GP III and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000221 · ss82780_4.xml · nonDerivative · entry 7

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 159,798

F4 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $32.64 to $33.39 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F8 · ownership.nature: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III"). OrbiMed Capital GP III LLC ("GP III") is the general partner of OPI III, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power over the securities held by OPI III and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI III. The Reporting Person is a member of Advisors.

F10 · ownership.nature: Each of the Reporting Person, GP III and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000221 · ss82780_4.xml · nonDerivative · entry 6

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 2,291

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $31.64 to $32.62 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F9 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. By virtue of such relationships, Advisors may be deemed to have voting and investment power over the securities held by Associates III and as a result may be deemed to have beneficial ownership over such securities. Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by Associates III.

F10 · ownership.nature: Each of the Reporting Person, GP III and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000221 · ss82780_4.xml · nonDerivative · entry 5

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 240,314

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $31.64 to $32.62 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F8 · ownership.nature: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III"). OrbiMed Capital GP III LLC ("GP III") is the general partner of OPI III, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power over the securities held by OPI III and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI III. The Reporting Person is a member of Advisors.

F10 · ownership.nature: Each of the Reporting Person, GP III and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000221 · ss82780_4.xml · nonDerivative · entry 4

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 3,511

F2 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $32.42 to $33.40 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F9 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. By virtue of such relationships, Advisors may be deemed to have voting and investment power over the securities held by Associates III and as a result may be deemed to have beneficial ownership over such securities. Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by Associates III.

F10 · ownership.nature: Each of the Reporting Person, GP III and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000221 · ss82780_4.xml · nonDerivative · entry 3

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 368,406

F2 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $32.42 to $33.40 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F8 · ownership.nature: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III"). OrbiMed Capital GP III LLC ("GP III") is the general partner of OPI III, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power over the securities held by OPI III and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI III. The Reporting Person is a member of Advisors.

F10 · ownership.nature: Each of the Reporting Person, GP III and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000221 · ss82780_4.xml · nonDerivative · entry 2

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 5,362

F1 · price: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were sold in multiple transactions at prices ranging from $31.41 to $32.39 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F9 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. By virtue of such relationships, Advisors may be deemed to have voting and investment power over the securities held by Associates III and as a result may be deemed to have beneficial ownership over such securities. Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by Associates III.

F10 · ownership.nature: Each of the Reporting Person, GP III and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000221 · ss82780_4.xml · nonDerivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 562,839

F1 · price: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were sold in multiple transactions at prices ranging from $31.41 to $32.39 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F8 · ownership.nature: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III"). OrbiMed Capital GP III LLC ("GP III") is the general partner of OPI III, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power over the securities held by OPI III and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI III. The Reporting Person is a member of Advisors.

F10 · ownership.nature: Each of the Reporting Person, GP III and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-002320 · doc4.xml · derivative · entry 5

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 1,871,569 shares

Expires not disclosed

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

F5 · derivative.exercise_price: All series of Convertible Preferred Stock automatically converted into the Issuer's Common Stock on a 1.2804-for-1 basis on January 30, 2018 and had no expiration date.

F5 · derivative.exercise_date: All series of Convertible Preferred Stock automatically converted into the Issuer's Common Stock on a 1.2804-for-1 basis on January 30, 2018 and had no expiration date.

F5 · derivative.expiration_date: All series of Convertible Preferred Stock automatically converted into the Issuer's Common Stock on a 1.2804-for-1 basis on January 30, 2018 and had no expiration date.

F5 · derivative.underlying_shares: All series of Convertible Preferred Stock automatically converted into the Issuer's Common Stock on a 1.2804-for-1 basis on January 30, 2018 and had no expiration date.

F2 · ownership.nature: The shares are held of record by OrbiMed Private Investments VI, LP("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. By virtue of such relationships, GP VI, and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities. The Reporting Person is a member of Advisors.

F3 · ownership.nature: Each of GP VI, Advisors, and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-002320 · doc4.xml · derivative · entry 4

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 2,425,485 shares

Expires not disclosed

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

F5 · derivative.exercise_price: All series of Convertible Preferred Stock automatically converted into the Issuer's Common Stock on a 1.2804-for-1 basis on January 30, 2018 and had no expiration date.

F5 · derivative.exercise_date: All series of Convertible Preferred Stock automatically converted into the Issuer's Common Stock on a 1.2804-for-1 basis on January 30, 2018 and had no expiration date.

F5 · derivative.expiration_date: All series of Convertible Preferred Stock automatically converted into the Issuer's Common Stock on a 1.2804-for-1 basis on January 30, 2018 and had no expiration date.

F5 · derivative.underlying_shares: All series of Convertible Preferred Stock automatically converted into the Issuer's Common Stock on a 1.2804-for-1 basis on January 30, 2018 and had no expiration date.

F2 · ownership.nature: The shares are held of record by OrbiMed Private Investments VI, LP("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. By virtue of such relationships, GP VI, and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities. The Reporting Person is a member of Advisors.

F3 · ownership.nature: Each of GP VI, Advisors, and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-002320 · doc4.xml · nonDerivative · entry 3

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 4,830,387

F2 · ownership.nature: The shares are held of record by OrbiMed Private Investments VI, LP("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. By virtue of such relationships, GP VI, and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities. The Reporting Person is a member of Advisors.

F3 · ownership.nature: Each of GP VI, Advisors, and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-002320 · doc4.xml · nonDerivative · entry 2

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 4,297,054

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 · price: Represents the total number of shares of Common Stock received by the Reporting Person upon conversion of the Issuer's Series B Preferred Stock in connection with the closing of the Issuer's initial public offering.

F2 · ownership.nature: The shares are held of record by OrbiMed Private Investments VI, LP("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. By virtue of such relationships, GP VI, and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities. The Reporting Person is a member of Advisors.

F3 · ownership.nature: Each of GP VI, Advisors, and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000899243-18-002320 · doc4.xml · nonDerivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 2,425,485

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

F1 · price: Represents the total number of shares of Common Stock received by the Reporting Person upon conversion of the Issuer's Series A Preferred Stock in connection with the closing of the Issuer's initial public offering.

F2 · ownership.nature: The shares are held of record by OrbiMed Private Investments VI, LP("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. By virtue of such relationships, GP VI, and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities. The Reporting Person is a member of Advisors.

F3 · ownership.nature: Each of GP VI, Advisors, and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001562180-17-003884 · primarydocument.xml · derivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Stock · 15,000 shares

Expires 2027-12-13

F1 · derivative.exercise_date: Granted pursuant to the Issuer's 2015 Omnibus Incentive Compensation Plan. Vests in full on May 31, 2018.

SEC source: 0000899243-17-027190 · doc4.xml · derivative · entry 2

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · By: OrbiMed Private Investments VI, L.P.

Disclosed balance after: 0

Underlying: Common Stock · 2,576,532 shares

Expires not disclosed

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

F3 · derivative.exercise_price: All series of Convertible Preferred Stock automatically converted into the Issuer's Common Stock on a 7.180193-for-1 basis on November 21, 2017 and had no expiration date.

F3 · derivative.exercise_date: All series of Convertible Preferred Stock automatically converted into the Issuer's Common Stock on a 7.180193-for-1 basis on November 21, 2017 and had no expiration date.

F3 · derivative.expiration_date: All series of Convertible Preferred Stock automatically converted into the Issuer's Common Stock on a 7.180193-for-1 basis on November 21, 2017 and had no expiration date.

F3 · derivative.underlying_shares: All series of Convertible Preferred Stock automatically converted into the Issuer's Common Stock on a 7.180193-for-1 basis on November 21, 2017 and had no expiration date.

F2 · ownership.nature: The shares of Series B Preferred Stock are held of record by OPI VI. OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. Jonathan Silverstein, a natural person, is a managing member of, and holder of a controlling interest in Advisors. The reporting person disclaims beneficial ownership of such shares except to the extent of his pecuniary interest, if any, and this report shall not be deemed an admission that the reporting person is the beneficial owner of all of the reported shares for purposes of Section 16 or any other purpose.

SEC source: 0000899243-17-027190 · doc4.xml · nonDerivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · By: OrbiMed Private Investments VI, L.P.

Disclosed balance after: 2,576,532

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

F1 · price: Represents the total number of shares of Common Stock received by OrbiMed Private Investments VI, L.P. ("OPI VI"), upon conversion of the Issuer's Series B Preferred Stock in connection with the closing of the Issuer's initial public offering.

F2 · ownership.nature: The shares of Series B Preferred Stock are held of record by OPI VI. OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. Jonathan Silverstein, a natural person, is a managing member of, and holder of a controlling interest in Advisors. The reporting person disclaims beneficial ownership of such shares except to the extent of his pecuniary interest, if any, and this report shall not be deemed an admission that the reporting person is the beneficial owner of all of the reported shares for purposes of Section 16 or any other purpose.

SEC source: 0000947871-17-000697 · ss57835_4.xml · nonDerivative · entry 10

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,895

F5 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $40.33 to $41.22 inclusive. Upon request, the Reporting Person undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F7 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III") and may be deemed to be indirectly beneficially owned by Advisors and Isaly. Advisors is the sole general partner of Associates III. Isaly is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by Associates III noted above. As a result, each of Advisors and Isaly may be deemed to have beneficial ownership of the securities held by Associates III.

F8 · ownership.nature: Each of the Reporting Person, GP III, Advisors, and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000697 · ss57835_4.xml · nonDerivative · entry 9

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 828,605

F5 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $40.33 to $41.22 inclusive. Upon request, the Reporting Person undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F6 · ownership.nature: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III") and may be deemed to be indirectly beneficially owned by OrbiMed Capital GP III LLC ("GP III"), OrbiMed Advisors LLC ("Advisors") and Samuel D. Isaly ("Isaly"). GP III is the sole general partner of OPI III. Advisors, a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP III. Isaly, a natural person, is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, GP III, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI III noted above. The Reporting Person is a member of Advisors.

F8 · ownership.nature: Each of the Reporting Person, GP III, Advisors, and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000697 · ss57835_4.xml · nonDerivative · entry 8

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 8,448

F4 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $39.33 to $40.30 inclusive. Upon request, the Reporting Person undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F7 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III") and may be deemed to be indirectly beneficially owned by Advisors and Isaly. Advisors is the sole general partner of Associates III. Isaly is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by Associates III noted above. As a result, each of Advisors and Isaly may be deemed to have beneficial ownership of the securities held by Associates III.

F8 · ownership.nature: Each of the Reporting Person, GP III, Advisors, and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000697 · ss57835_4.xml · nonDerivative · entry 7

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 886,652

F4 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $39.33 to $40.30 inclusive. Upon request, the Reporting Person undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F6 · ownership.nature: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III") and may be deemed to be indirectly beneficially owned by OrbiMed Capital GP III LLC ("GP III"), OrbiMed Advisors LLC ("Advisors") and Samuel D. Isaly ("Isaly"). GP III is the sole general partner of OPI III. Advisors, a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP III. Isaly, a natural person, is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, GP III, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI III noted above. The Reporting Person is a member of Advisors.

F8 · ownership.nature: Each of the Reporting Person, GP III, Advisors, and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.