PVLA

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 43

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 9,642 shares

Expires 2018-02-15

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

F8 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on July 25, 2016 for services as a director of the Issuer. The award included stock options relating to a total of 9,734 shares of the Issuer's Common Stock and was vested and exercisable on July 25, 2016. Mr. Khuong is no longer a director of the Issuer.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 42

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 77 shares

Expires 2018-02-15

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.

F7 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on April 27, 2016 for services as a director of the Issuer. The award included stock options relating to a total of 8,174 shares of the Issuer's Common Stock and was vested and exercisable on April 27, 2016. Mr. Khuong is no longer a director of the Issuer.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 41

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 8,097 shares

Expires 2018-02-15

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.

F7 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on April 27, 2016 for services as a director of the Issuer. The award included stock options relating to a total of 8,174 shares of the Issuer's Common Stock and was vested and exercisable on April 27, 2016. Mr. Khuong is no longer a director of the Issuer.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 40

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 189 shares

Expires 2018-02-15

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_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on February 16, 2016 for services as a director of the Issuer. The award included stock options relating to a total of 20,000 shares of the Issuer's Common Stock and was scheduled to vest in four equal installments on each of March 31, 2016, June 30, 2016, September 30, 2016 and December 31, 2016 with 100% of the total shares vested and exercisable on December 31, 2016, subject to the director's provision of service to the issuer on each vesting date. Mr. Khuong is no longer a director of the Issuer.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 39

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 19,811 shares

Expires 2018-02-15

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_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on February 16, 2016 for services as a director of the Issuer. The award included stock options relating to a total of 20,000 shares of the Issuer's Common Stock and was scheduled to vest in four equal installments on each of March 31, 2016, June 30, 2016, September 30, 2016 and December 31, 2016 with 100% of the total shares vested and exercisable on December 31, 2016, subject to the director's provision of service to the issuer on each vesting date. Mr. Khuong is no longer a director of the Issuer.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 38

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 97 shares

Expires 2018-02-15

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

F5 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on January 15, 2016 for services as a director of the Issuer. The award included stock options relating to a total of 10,277 shares of the Issuer's Common Stock and was vested and exercisable on January 15, 2016. Mr. Khuong is no longer a director of the Issuer.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 37

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 10,180 shares

Expires 2018-02-15

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

F5 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on January 15, 2016 for services as a director of the Issuer. The award included stock options relating to a total of 10,277 shares of the Issuer's Common Stock and was vested and exercisable on January 15, 2016. Mr. Khuong is no longer a director of the Issuer.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 36

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 83 shares

Expires 2018-02-15

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

F4 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on October 15, 2015 for services as a director of the Issuer. The award included stock options relating to a total of 8,800 shares of the Issuer's Common Stock and was vested and exercisable on October 15, 2015. Mr. Khuong is no longer a director of the Issuer.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 35

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 8,717 shares

Expires 2018-02-15

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

F4 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on October 15, 2015 for services as a director of the Issuer. The award included stock options relating to a total of 8,800 shares of the Issuer's Common Stock and was vested and exercisable on October 15, 2015. Mr. Khuong is no longer a director of the Issuer.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 34

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 63 shares

Expires 2018-02-15

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

F3 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on July 15, 2015 for services as a director of the Issuer. The award included stock options relating to a total of 6,717 shares of the Issuer's Common Stock and was vested and exercisable on July 15, 2015. Mr. Khuong is no longer a director of the Issuer.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 33

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 6,654 shares

Expires 2018-02-15

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

F3 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on July 15, 2015 for services as a director of the Issuer. The award included stock options relating to a total of 6,717 shares of the Issuer's Common Stock and was vested and exercisable on July 15, 2015. Mr. Khuong is no longer a director of the Issuer.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 32

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 50 shares

Expires 2018-02-15

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 stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on April 30, 2015 for services as a director of the Issuer. The award included stock options relating to a total of 5,277 shares of the Issuer's Common Stock and was vested and exercisable on April 30, 2015. Mr. Khuong is no longer a director of the Issuer.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 31

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 5,227 shares

Expires 2018-02-15

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 stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on April 30, 2015 for services as a director of the Issuer. The award included stock options relating to a total of 5,277 shares of the Issuer's Common Stock and was vested and exercisable on April 30, 2015. Mr. Khuong is no longer a director of the Issuer.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 30

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 259 shares

Expires 2018-02-15

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_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on December 17, 2014 for services as a director of the Issuer. The award included stock options relating to a total of 30,000 shares of the Issuer's Common Stock and was scheduled to vest quarterly over three years beginning March 31, 2015, with 100% of the total shares vested and exercisable on March 31, 2018, subject to the director's provision of service to the issuer on each vesting date. Mr. Khuong is no longer a director of the Issuer.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · derivative · entry 29

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 0

Underlying: Common Stock · 27,241 shares

Expires 2018-02-15

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_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on December 17, 2014 for services as a director of the Issuer. The award included stock options relating to a total of 30,000 shares of the Issuer's Common Stock and was scheduled to vest quarterly over three years beginning March 31, 2015, with 100% of the total shares vested and exercisable on March 31, 2018, subject to the director's provision of service to the issuer on each vesting date. Mr. Khuong is no longer a director of the Issuer.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 28

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 65,398

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 27

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,194,222

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 26

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 66,790

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.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 25

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,340,465

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.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 24

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 66,743

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.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 23

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,335,494

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.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 22

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 66,644

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.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 21

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,325,047

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.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 20

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 66,547

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.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 19

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,314,831

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.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 18

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 66,405

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.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 17

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,299,973

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.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 16

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 66,308

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.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 15

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,289,791

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.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 14

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 66,216

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.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 13

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,280,149

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.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 12

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 66,139

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.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 11

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,272,052

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.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 10

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 65,950

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.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 9

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,252,241

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.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 8

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 65,853

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.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 7

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,242,061

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.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 6

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 65,770

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.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 5

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,233,344

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.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 4

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 65,707

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.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,226,690

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.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 65,657

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.

F15 · ownership.nature: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly 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.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-001023 · ss72777_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 10% owner

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,221,463

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.

F14 · 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") is the managing member of GP III. Samuel D. Isaly ("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 over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F16 · ownership.nature: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons 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 of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001562180-17-003871 · primarydocument.xml · derivative · entry 1

GERAGHTY JAMES A · CIK 0001239746 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 40,000

Underlying: Common Stock · 40,000 shares

Expires 2028-12-12

F1 · derivative.exercise_date: The option vests as to 25% of the option shares on November 15, 2018 and vests as to an additional 6.25% of the option shares at the end of each full fiscal quarter thereafter.

SEC source: 0001562180-17-003340 · primarydocument.xml · derivative · entry 1

Richman Michael · CIK 0001366265 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 4,006

Underlying: Common Stock · 4,006 shares

Expires 2027-10-25

SEC source: 0001562180-17-003339 · primarydocument.xml · derivative · entry 1

Khuong Chau Quang · CIK 0001609405 · Director · 10% owner

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 6,115

Underlying: Common Stock · 6,115 shares

Expires 2027-10-25

F1 · security: The Reporting Person is an employee of OrbiMed Advisors LLC ("Advisors") and is obligated to transfer any shares issued under equity grants made to him by the Issuer, or the economic benefits thereof, to Advisors for the ultimate benefit of OrbiMed Private Investments III, LP and OrbiMed Associates III, LP.

SEC source: 0000899243-17-020636 · doc4.xml · nonDerivative · entry 1

GERAGHTY JAMES A · CIK 0001239746 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

F1 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $4.71 to $4.89, inclusive. The Reporting Person undertakes to provide 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 sent forth in this footnote.

SEC source: 0000899243-17-020635 · doc4.xml · nonDerivative · entry 2

Reine Allan · CIK 0001714023 · See Remarks

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 65,000

SEC source: 0000899243-17-020635 · doc4.xml · nonDerivative · entry 1

Reine Allan · CIK 0001714023 · See Remarks

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 45,000

F1 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $4.69 to $4.90, inclusive. The Reporting Person undertakes to provide 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 sent forth in this footnote.

SEC source: 0000899243-17-020179 · doc4.xml · derivative · entry 1

Reine Allan · CIK 0001714023 · See Remarks

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 450,000

Underlying: Common Stock · 450,000 shares

Expires 2027-08-09

F1 · derivative.exercise_date: The option vests as to 25% of the option shares on August 9, 2018 and vests as to an additional 6.25% of the option shares at the end of each successive three-month period thereafter until August 9, 2021.