OrbiMed Capital GP III LLC

SEC source: 0000947871-18-000220 · ss82779_4.xml · nonDerivative · entry 12

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 445

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

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

F10 · ownership.nature: 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.

F11 · 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) of the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000220 · ss82779_4.xml · nonDerivative · entry 11

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 46,676

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

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

F10 · 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.

F11 · 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) of the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000220 · ss82779_4.xml · nonDerivative · entry 10

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 637

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

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

F10 · ownership.nature: 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.

F11 · 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) of the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000220 · ss82779_4.xml · nonDerivative · entry 9

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

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

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

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

F10 · 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.

F11 · 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) of the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000220 · ss82779_4.xml · nonDerivative · entry 8

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 1,523

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

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

F10 · ownership.nature: 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.

F11 · 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) of the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000220 · ss82779_4.xml · nonDerivative · entry 7

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 159,798

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

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

F10 · 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.

F11 · 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) of the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000220 · ss82779_4.xml · nonDerivative · entry 6

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 2,291

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

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

F10 · ownership.nature: 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.

F11 · 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) of the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000220 · ss82779_4.xml · nonDerivative · entry 5

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 240,314

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

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

F10 · 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.

F11 · 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) of the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000220 · ss82779_4.xml · nonDerivative · entry 4

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 3,511

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

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

F10 · ownership.nature: 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.

F11 · 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) of the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000220 · ss82779_4.xml · nonDerivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 368,406

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

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

F10 · 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.

F11 · 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) of the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000220 · ss82779_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 5,362

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

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

F10 · ownership.nature: 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.

F11 · 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) of the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000220 · ss82779_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 562,839

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

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

F10 · 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.

F11 · 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) of the Exchange Act, except to the extent of its pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000156 · 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: 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.

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.