PVLA

SEC source: 0001562180-19-000566 · primarydocument.xml · derivative · entry 1

GERAGHTY JAMES A · CIK 0001239746 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 25,000

Underlying: Common Stock · 25,000 shares

Expires 2029-01-25

F1 · derivative.exercise_date: The stock option will vest as to 100% of the underlying shares on January 25, 2020, subject to the Reporting Person's continued service as a director through the vesting date.

SEC source: 0001562180-19-000578 · primarydocument.xml · derivative · entry 1

Prelack Steven · CIK 0001302315 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 20,000

Underlying: Common Stock · 20,000 shares

Expires 2029-01-25

F1 · derivative.exercise_date: The stock option will vest as to 100% of the underlying shares on January 25, 2020, subject to the Reporting Person's continued service as a director through the vesting date.

SEC source: 0001562180-19-000572 · primarydocument.xml · derivative · entry 1

Kiener Peter A · CIK 0001328146 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 20,000

Underlying: Common Stock · 20,000 shares

Expires 2029-01-25

F1 · derivative.exercise_date: The stock option will vest as to 100% of the underlying shares on January 25, 2020, subject to the Reporting Person's continued service as a director through the vesting date.

SEC source: 0001562180-19-000579 · primarydocument.xml · derivative · entry 2

Richman Michael · CIK 0001366265 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 20,000

Underlying: Common Stock · 20,000 shares

Expires 2029-01-25

F2 · derivative.exercise_date: The stock option will vest as to 100% of the underlying shares on January 25, 2020, subject to the Reporting Person's continued service as a director through the vesting date.

SEC source: 0001562180-19-000579 · primarydocument.xml · derivative · entry 1

Richman Michael · CIK 0001366265 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 6,096

Underlying: Common Stock · 6,096 shares

Expires 2029-01-25

F1 · price: The stock option was issued to the Reporting Person, who elected to take stock options in lieu of $10,937.50 in cash compensation for services as a director and committee member, which compensation is payable to the Reporting Person quarterly in arrears, pursuant to the Issuer's non-employee director compensation policy.

SEC source: 0001562180-19-000571 · primarydocument.xml · derivative · entry 1

BIZZARI JEAN-PIERRE · CIK 0001630914 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 20,000

Underlying: Common Stock · 20,000 shares

Expires 2029-01-25

F1 · derivative.exercise_date: The stock option will vest as to 100% of the underlying shares on January 25, 2020, subject to the Reporting Person's continued service as a director through the vesting date.

SEC source: 0001562180-18-004310 · primarydocument.xml · derivative · entry 1

Richman Michael · CIK 0001366265 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 3,829

Underlying: Common Stock · 3,829 shares

Expires 2028-10-25

F1 · price: The stock option was issued to the Reporting Person, who elected to take stock options in lieu of $10,937.50 in cash compensation for services as a director and committee member, pursuant to the Issuer's non-employee director compensation policy.

SEC source: 0001562180-18-004281 · primarydocument.xml · derivative · entry 1

Sherman Matthew L · CIK 0001325710 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 30,000

Underlying: Common Stock · 30,000 shares

Expires 2028-10-24

F1 · derivative.exercise_date: The stock option will vest as to 100% of the underlying shares on October 24, 2019, subject to the Reporting Person's continued service as a director through the vesting date.

SEC source: 0001562180-18-004280 · primarydocument.xml · derivative · entry 1

Kiener Peter A · CIK 0001328146 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 30,000

Underlying: Common Stock · 30,000 shares

Expires 2028-10-24

F1 · derivative.exercise_date: The stock option will vest as to 100% of the underlying shares on October 24, 2019, subject to the Reporting Person's continued service as a director through the vesting date.

SEC source: 0001562180-18-003953 · primarydocument.xml · nonDerivative · entry 1

KIRITSY CHRISTOPHER P · CIK 0001261156 · 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 $5.05 to $5.15, 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 range set forth in this footnote.

SEC source: 0001562180-18-003419 · primarydocument.xml · derivative · entry 1

Richman Michael · CIK 0001366265 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 2,837

Underlying: Common Stock · 2,837 shares

Expires 2028-07-25

F1 · price: The stock option was issued to the Reporting Person, who elected to take stock options in lieu of $10,937.50 in cash compensation for services as a director and committee member, pursuant to the Issuer's non-employee director compensation policy.

SEC source: 0001562180-18-002509 · primarydocument.xml · nonDerivative · entry 1

GERAGHTY JAMES A · CIK 0001239746 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 20,000

F1 · price: The price reported in Column 4 is a weighted average price. These shares were purchased in multiple transactions at prices ranging from $5.719 to $5.77, 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: 0000947871-18-000372 · ss90746_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner · See Remarks

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 38,870

F1 · price: These shares of the Issuer's common stock ("Shares") were sold in a block order at a price of $6.35.

F3 · 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.

F4 · ownership.nature: This report on Form 4 is jointly filed by GP III and Advisors. 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: 0000947871-18-000372 · ss90746_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner · See Remarks

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

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 4,511,130

F1 · price: These shares of the Issuer's common stock ("Shares") were sold in a block order at a price of $6.35.

F2 · 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.

F4 · ownership.nature: This report on Form 4 is jointly filed by GP III and Advisors. 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: 0001562180-18-002004 · primarydocument.xml · derivative · entry 1

Barbier Ann · CIK 0001737596 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 30,000

Underlying: Common Stock · 30,000 shares

Expires 2028-04-25

F1 · derivative.exercise_date: The stock option will vest in four equal quarterly installments on each of June 30, 2018, September 30, 2018, December 31, 2018 and March 31, 2019, subject to the Reporting Person's continued service as a director.

SEC source: 0001562180-18-002005 · primarydocument.xml · derivative · entry 1

Richman Michael · CIK 0001366265 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 2,665

Underlying: Common Stock · 2,665 shares

Expires 2028-04-25

F1 · price: The stock option was issued to the Reporting Person, who elected to take stock options in lieu of $10,937.50 in cash compensation for services as a director and committee member, pursuant to the Issuer's non-employee director compensation policy.

SEC source: 0001562180-18-001253 · primarydocument.xml · derivative · entry 1

Matis Louis · CIK 0001650991 · Chief Development Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 100,000

Underlying: Common Stock · 100,000 shares

Expires 2028-02-20

F1 · derivative.exercise_date: The option vests as to 25% of the option shares on January 1, 2019 and vests as to an additional 6.25% of the option shares at the end of each successive three-month period thereafter.

SEC source: 0001562180-18-001252 · primarydocument.xml · derivative · entry 2

Reine Allan · CIK 0001714023 · Chief Financial Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 50,000

Underlying: Common Stock · 50,000 shares

Expires 2027-08-08

F2 · derivative.exercise_date: On August 9, 2017, the reporting person was granted an option to purchase up to a maximum of 50,000 shares of common stock of which 50,000 shares were earned based on the reporting person's achievement of his 2017 personal goals as certified by the Compensation Committee of the Board of Directors on February 20, 2018. The earned shares vest as to 25% on February 20, 2019 and the remainder vests as to an additional 6.25% quarterly thereafter beginning on the last day of the next calendar quarter.

SEC source: 0001562180-18-001252 · primarydocument.xml · derivative · entry 1

Reine Allan · CIK 0001714023 · Chief Financial Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 53,833

Underlying: Common Stock · 53,833 shares

Expires 2028-02-20

F1 · derivative.exercise_date: The option vests as to 25% of the option shares on January 1, 2019 and vests as to an additional 6.25% of the option shares at the end of each successive three-month period thereafter.

SEC source: 0001562180-18-001251 · primarydocument.xml · derivative · entry 1

Yoder Stephen S. · CIK 0001645577 · Director · Chief Executive Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 325,000

Underlying: Common Stock · 325,000 shares

Expires 2028-02-20

F1 · derivative.exercise_date: The option vests as to 25% of the option shares on January 1, 2019 and vests as to an additional 6.25% of the option shares at the end of each successive three-month period thereafter.

SEC source: 0000947871-18-000156 · ss80152_4.xml · derivative · entry 10

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 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 · 17 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 January 25, 2018 for services as a director of the Issuer. The award included stock options relating to a total of 1,782 shares of the Issuer's Common Stock and was vested and exercisable on January 25, 2018. Mr. Khuong is no longer a director of the Issuer.

F4 · 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.

F5 · ownership.nature: Samuel D. Isaly, who was included as a Reporting Person on previous reports under Section 16 of the Exchange Act filed by GP III and Advisors, is no longer subject to Section 16 with respect to securities of the Issuer.

F6 · ownership.nature: This report on Form 4 is jointly filed by GP III and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under 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: 0000947871-18-000156 · ss80152_4.xml · derivative · entry 9

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 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 · 1,765 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 January 25, 2018 for services as a director of the Issuer. The award included stock options relating to a total of 1,782 shares of the Issuer's Common Stock and was vested and exercisable on January 25, 2018. Mr. Khuong is no longer a director of the Issuer.

F3 · 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.

F5 · ownership.nature: Samuel D. Isaly, who was included as a Reporting Person on previous reports under Section 16 of the Exchange Act filed by GP III and Advisors, is no longer subject to Section 16 with respect to securities of the Issuer.

F6 · ownership.nature: This report on Form 4 is jointly filed by GP III and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under 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: 0000947871-18-000156 · ss80152_4.xml · derivative · entry 8

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 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 · 58 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 October 25, 2017 for services as a director of the Issuer. The award included stock options relating to a total of 6,115 shares of the Issuer's Common Stock and was vested and exercisable on October 25, 2017. Mr. Khuong is no longer a director of the Issuer.

F4 · 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.

F5 · ownership.nature: Samuel D. Isaly, who was included as a Reporting Person on previous reports under Section 16 of the Exchange Act filed by GP III and Advisors, is no longer subject to Section 16 with respect to securities of the Issuer.

F6 · ownership.nature: This report on Form 4 is jointly filed by GP III and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under 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: 0000947871-18-000156 · ss80152_4.xml · derivative · entry 7

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 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 · 6,057 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 October 25, 2017 for services as a director of the Issuer. The award included stock options relating to a total of 6,115 shares of the Issuer's Common Stock and was vested and exercisable on October 25, 2017. Mr. Khuong is no longer a director of the Issuer.

F3 · 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.

F5 · ownership.nature: Samuel D. Isaly, who was included as a Reporting Person on previous reports under Section 16 of the Exchange Act filed by GP III and Advisors, is no longer subject to Section 16 with respect to securities of the Issuer.

F6 · ownership.nature: This report on Form 4 is jointly filed by GP III and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under 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: 0000947871-18-000156 · ss80152_4.xml · nonDerivative · entry 6

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 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: 49,270

F4 · 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.

F5 · ownership.nature: Samuel D. Isaly, who was included as a Reporting Person on previous reports under Section 16 of the Exchange Act filed by GP III and Advisors, is no longer subject to Section 16 with respect to securities of the Issuer.

F6 · ownership.nature: This report on Form 4 is jointly filed by GP III and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under 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: 0000947871-18-000156 · ss80152_4.xml · nonDerivative · entry 5

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 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: 5,500,730

F3 · 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.

F5 · ownership.nature: Samuel D. Isaly, who was included as a Reporting Person on previous reports under Section 16 of the Exchange Act filed by GP III and Advisors, is no longer subject to Section 16 with respect to securities of the Issuer.

F6 · ownership.nature: This report on Form 4 is jointly filed by GP III and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under 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: 0000947871-18-000156 · ss80152_4.xml · nonDerivative · entry 4

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 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: 49,345

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

F4 · ownership.nature: 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.

F5 · ownership.nature: Samuel D. Isaly, who was included as a Reporting Person on previous reports under Section 16 of the Exchange Act filed by GP III and Advisors, is no longer subject to Section 16 with respect to securities of the Issuer.

F6 · ownership.nature: This report on Form 4 is jointly filed by GP III and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under 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: 0000947871-18-000156 · ss80152_4.xml · nonDerivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 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: 5,508,552

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 · 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.

F5 · ownership.nature: Samuel D. Isaly, who was included as a Reporting Person on previous reports under Section 16 of the Exchange Act filed by GP III and Advisors, is no longer subject to Section 16 with respect to securities of the Issuer.

F6 · ownership.nature: This report on Form 4 is jointly filed by GP III and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under 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: 0000947871-18-000156 · ss80152_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 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: 49,328

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

F4 · ownership.nature: 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.

F5 · ownership.nature: Samuel D. Isaly, who was included as a Reporting Person on previous reports under Section 16 of the Exchange Act filed by GP III and Advisors, is no longer subject to Section 16 with respect to securities of the Issuer.

F6 · ownership.nature: This report on Form 4 is jointly filed by GP III and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under 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: 0000947871-18-000156 · ss80152_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · 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: 5,506,787

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 · 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.

F5 · ownership.nature: Samuel D. Isaly, who was included as a Reporting Person on previous reports under Section 16 of the Exchange Act filed by GP III and Advisors, is no longer subject to Section 16 with respect to securities of the Issuer.

F6 · ownership.nature: This report on Form 4 is jointly filed by GP III and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under 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: 0001562180-18-000484 · primarydocument.xml · derivative · entry 1

KIRITSY CHRISTOPHER P · CIK 0001261156 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 20,000

Underlying: Common Stock · 20,000 shares

Expires 2028-01-25

F1 · derivative.exercise_date: The stock option will vest in four equal installments on each of March 31, June 30, September 30 and December 31, 2018.

SEC source: 0001562180-18-000479 · primarydocument.xml · derivative · entry 1

GERAGHTY JAMES A · CIK 0001239746 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 25,000

Underlying: Common Stock · 25,000 shares

Expires 2028-01-25

F1 · derivative.exercise_date: The stock option will vest in four equal installments on each of March 31, June 30, September 30 and December 31, 2018.

SEC source: 0001562180-18-000483 · primarydocument.xml · derivative · entry 1

ADAMS JULIAN · CIK 0001230486 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 20,000

Underlying: Common Stock · 20,000 shares

Expires 2028-01-25

F1 · derivative.exercise_date: The stock option will vest in four equal installments on each of March 31, June 30, September 30 and December 31, 2018.

SEC source: 0001562180-18-000480 · primarydocument.xml · derivative · entry 1

Prelack Steven · CIK 0001302315 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 20,000

Underlying: Common Stock · 20,000 shares

Expires 2028-01-25

F1 · derivative.exercise_date: The stock option will vest in four equal installments on each of March 31, June 30, September 30 and December 31, 2018.

SEC source: 0001562180-18-000481 · primarydocument.xml · derivative · entry 2

Richman Michael · CIK 0001366265 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 20,000

Underlying: Common Stock · 20,000 shares

Expires 2028-01-25

F2 · derivative.exercise_date: The stock option will vest in four equal installments on each of March 31, June 30, September 30 and December 31, 2018.

SEC source: 0001562180-18-000481 · primarydocument.xml · derivative · entry 1

Richman Michael · CIK 0001366265 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 2,243

Underlying: Common Stock · 2,243 shares

Expires 2028-01-25

F1 · price: The stock option was issued to the Reporting Person, who elected to take stock options in lieu of $11,406.25 in cash compensation for services as a director and committee member, pursuant to the Issuer's non-employee director compensation policy.

SEC source: 0001562180-18-000482 · primarydocument.xml · derivative · entry 1

BIZZARI JEAN-PIERRE · CIK 0001630914 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 20,000

Underlying: Common Stock · 20,000 shares

Expires 2028-01-25

F1 · derivative.exercise_date: The stock option will vest in four equal installments on each of March 31, June 30, September 30 and December 31, 2018.

SEC source: 0000947871-18-000012 · ss74180_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: 49,270

F1 · price: These shares of the Issuer's common stock ("Shares") were sold in a block order at a price of $7.35.

F3 · 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.

F4 · 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: 0000947871-18-000012 · ss74180_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: 5,500,730

F1 · price: These shares of the Issuer's common stock ("Shares") were sold in a block order at a price of $7.35.

F2 · 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.

F4 · 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 54

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 · 47 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.

F13 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on July 25, 2017 for services as a director of the Issuer. The award included stock options relating to a total of 5,018 shares of the Issuer's Common Stock and was vested and exercisable on July 25, 2017. 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 53

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 · 4,971 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.

F13 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on July 25, 2017 for services as a director of the Issuer. The award included stock options relating to a total of 5,018 shares of the Issuer's Common Stock and was vested and exercisable on July 25, 2017. 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 52

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 · 99 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.

F12 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on April 25, 2017 for services as a director of the Issuer. The award included stock options relating to a total of 10,546 shares of the Issuer's Common Stock and was vested and exercisable on April 25, 2017. 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 51

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 · 10,447 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.

F12 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on April 25, 2017 for services as a director of the Issuer. The award included stock options relating to a total of 10,546 shares of the Issuer's Common Stock and was vested and exercisable on April 25, 2017. 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 50

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.

F11 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on January 25, 2017 for services as a director of the Issuer. The award included stock options relating to a total of 10,313 shares of the Issuer's Common Stock and was vested and exercisable on January 25, 2017. 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 49

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 · 10,216 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.

F11 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on January 25, 2017 for services as a director of the Issuer. The award included stock options relating to a total of 10,313 shares of the Issuer's Common Stock and was vested and exercisable on January 25, 2017. 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 48

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 · 142 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.

F10 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on January 25, 2017 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, 2017, June 30, 2017, September 30, 2017 and December 31, 2017 with 100% of the total shares vested and exercisable on December 31, 2017, 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 47

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 · 14,858 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.

F10 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on January 25, 2017 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, 2017, June 30, 2017, September 30, 2017 and December 31, 2017 with 100% of the total shares vested and exercisable on December 31, 2017, 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 46

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.

F9 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on October 25, 2016 for services as a director of the Issuer. The award included stock options relating to a total of 10,279 shares of the Issuer's Common Stock and was vested and exercisable on October 25, 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 45

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 · 10,182 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.

F9 · derivative.exercise_date: The stock options were included in an award to Chau Khuong, an employee of the Reporting Persons, made on October 25, 2016 for services as a director of the Issuer. The award included stock options relating to a total of 10,279 shares of the Issuer's Common Stock and was vested and exercisable on October 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 44

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 · 92 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.

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.