OrbiMed Capital GP III LLC

SEC source: 0000947871-17-000672 · ss56657_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: 7,708

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 $1.48 to $1.53 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F5 · ownership.nature: These securities are held of record by OrbiMed Associates III, LP ("Associates III") and may be deemed to be indirectly beneficially owned by Advisors and Isaly. Advisors is the sole general partner of Associates III. Isaly is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationship, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by Associates III noted above. As a result, each of Advisors and Isaly may be deemed to have beneficial ownership of the securities held by Associates III.

F6 · 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 the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000672 · ss56657_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: 809,386

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 $1.48 to $1.53 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F3 · ownership.nature: These securities are held of record by OrbiMed Private Investments III, LP ("OPI III") and may be deemed to be indirectly beneficially owned by OrbiMed Capital GP III LLC ("GP III"), OrbiMed Advisors LLC ("Advisors") and Samuel D. Isaly ("Isaly"). GP III is the sole general partner of OPI III. Advisors, a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI III noted above.

F4 · ownership.nature: Isaly, a natural person, may also be deemed to have voting and investment power with respect to the securities held by OPI III noted above in his capacity as the managing member of, and holder of a controlling interest, in Advisors. As a result, each of GP III, Advisors and Isaly may be deemed to have beneficial ownership of the securities held by OPI III.

F6 · 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 the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000664 · ss56118_4.xml · nonDerivative · entry 6

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

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

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,718

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $1.51 to $1.54 inclusive. Upon request, the Reporting Person undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F6 · ownership.nature: These securities are held of record by OrbiMed Associates III, LP ("Associates III") and may be deemed to be indirectly beneficially owned by Advisors and Isaly. Advisors is the sole general partner of Associates III. Isaly is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationship, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by Associates III noted above. As a result, each of Advisors and Isaly may be deemed to have beneficial ownership of the securities held by Associates III.

F7 · 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 the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000664 · ss56118_4.xml · nonDerivative · entry 5

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

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

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 810,476

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $1.51 to $1.54 inclusive. Upon request, the Reporting Person undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F4 · ownership.nature: These securities are held of record by OrbiMed Private Investments III, LP ("OPI III") and may be deemed to be indirectly beneficially owned by OrbiMed Capital GP III LLC ("GP III"), OrbiMed Advisors LLC ("Advisors") and Samuel D. Isaly ("Isaly"). GP III is the sole general partner of OPI III. Advisors, a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI III noted above.

F5 · ownership.nature: Isaly, a natural person, may also be deemed to have voting and investment power with respect to the securities held by OPI III noted above in his capacity as the managing member of, and holder of a controlling interest, in Advisors. As a result, each of GP III, Advisors and Isaly may be deemed to have beneficial ownership of the securities held by OPI III.

F7 · 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 the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000664 · ss56118_4.xml · nonDerivative · entry 4

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

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

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 7,770

F2 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $1.49 to $1.51 inclusive. Upon request, the Reporting Person undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F6 · ownership.nature: These securities are held of record by OrbiMed Associates III, LP ("Associates III") and may be deemed to be indirectly beneficially owned by Advisors and Isaly. Advisors is the sole general partner of Associates III. Isaly is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationship, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by Associates III noted above. As a result, each of Advisors and Isaly may be deemed to have beneficial ownership of the securities held by Associates III.

F7 · 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 the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000664 · ss56118_4.xml · nonDerivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

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

ISALY SAMUEL D · CIK 0001055949 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 815,924

F2 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $1.49 to $1.51 inclusive. Upon request, the Reporting Person undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F4 · ownership.nature: These securities are held of record by OrbiMed Private Investments III, LP ("OPI III") and may be deemed to be indirectly beneficially owned by OrbiMed Capital GP III LLC ("GP III"), OrbiMed Advisors LLC ("Advisors") and Samuel D. Isaly ("Isaly"). GP III is the sole general partner of OPI III. Advisors, a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI III noted above.

F5 · ownership.nature: Isaly, a natural person, may also be deemed to have voting and investment power with respect to the securities held by OPI III noted above in his capacity as the managing member of, and holder of a controlling interest, in Advisors. As a result, each of GP III, Advisors and Isaly may be deemed to have beneficial ownership of the securities held by OPI III.

F7 · 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 the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000664 · ss56118_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: 7,798

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 $1.45 to $1.64 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F6 · ownership.nature: These securities are held of record by OrbiMed Associates III, LP ("Associates III") and may be deemed to be indirectly beneficially owned by Advisors and Isaly. Advisors is the sole general partner of Associates III. Isaly is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationship, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by Associates III noted above. As a result, each of Advisors and Isaly may be deemed to have beneficial ownership of the securities held by Associates III.

F7 · 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 the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000664 · ss56118_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: 818,876

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 $1.45 to $1.64 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F4 · ownership.nature: These securities are held of record by OrbiMed Private Investments III, LP ("OPI III") and may be deemed to be indirectly beneficially owned by OrbiMed Capital GP III LLC ("GP III"), OrbiMed Advisors LLC ("Advisors") and Samuel D. Isaly ("Isaly"). GP III is the sole general partner of OPI III. Advisors, a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI III noted above.

F5 · ownership.nature: Isaly, a natural person, may also be deemed to have voting and investment power with respect to the securities held by OPI III noted above in his capacity as the managing member of, and holder of a controlling interest, in Advisors. As a result, each of GP III, Advisors and Isaly may be deemed to have beneficial ownership of the securities held by OPI III.

F7 · 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 the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000653 · ss55687_4.xml · nonDerivative · entry 6

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 13,369

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $37.52 to $38.26 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.

F5 · 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.

F6 · 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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000653 · ss55687_4.xml · nonDerivative · entry 5

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 1,403,331

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $37.52 to $38.26 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.

F4 · 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.

F6 · 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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000653 · ss55687_4.xml · nonDerivative · entry 4

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 15,509

F2 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $38.00 to $38.28 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.

F5 · 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.

F6 · 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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000653 · ss55687_4.xml · nonDerivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 1,628,111

F2 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $38.00 to $38.28 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.

F4 · 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.

F6 · 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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000653 · ss55687_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 16,128

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 $37.96 to $38.48 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 purchased at each separate price within the range set forth in this footnote.

F5 · 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.

F6 · 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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000653 · ss55687_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 1,693,072

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 $37.96 to $38.48 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 purchased at each separate price within the range set forth in this footnote.

F4 · 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.

F6 · 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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000210 · ss34861_4.xml · nonDerivative · entry 8

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 16,435

F4 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $44.31 to $44.69 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.

F6 · 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.

F7 · 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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000210 · ss34861_4.xml · nonDerivative · entry 7

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 1,725,265

F4 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $44.31 to $44.69 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.

F5 · 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.

F7 · 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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000210 · ss34861_4.xml · nonDerivative · entry 6

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 17,134

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $46.04 to $46.23 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.

F6 · 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.

F7 · 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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000210 · ss34861_4.xml · nonDerivative · entry 5

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 1,798,666

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $46.04 to $46.23 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.

F5 · 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.

F7 · 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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000210 · ss34861_4.xml · nonDerivative · entry 4

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 17,141

F2 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $45.00 to $45.87 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.

F6 · 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.

F7 · 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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000210 · ss34861_4.xml · nonDerivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 1,799,359

F2 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $45.00 to $45.87 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.

F5 · 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.

F7 · 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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000210 · ss34861_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 19,129

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 $45.80 to $46.31 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 purchased at each separate price within the range set forth in this footnote.

F6 · 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.

F7 · 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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000210 · ss34861_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 2,008,071

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 $45.80 to $46.31 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 purchased at each separate price within the range set forth in this footnote.

F5 · 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.

F7 · 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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000198 · ss33905_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 20,044

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 $47.00 to $47.13 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.

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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000198 · ss33905_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director

OrbiMed Capital GP III LLC · CIK 0001432241 · Director

ISALY SAMUEL D · CIK 0001055949 · 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: 2,104,184

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 $47.00 to $47.13 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.

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. 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 for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000057 · ss27693_4.xml · derivative · entry 4

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

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

ISALY SAMUEL D · CIK 0001055949 · Director · 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: 3,843

Underlying: Common Stock · 623 shares

Expires 2024-01-18

F2 · ownership.nature: These securities are held of record by OrbiMed Associates III, LP ("Associates III") and may be deemed to be indirectly beneficially owned by Advisors and Isaly. Advisors is the sole general partner of Associates III. Isaly is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationship, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by Associates III noted above. As a result, each of Advisors and Isaly may be deemed to have beneficial ownership of the securities held by Associates III.

F3 · 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. The Reporting Persons have designated a representative, currently David Bonita, an employee 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: 0000947871-17-000057 · ss27693_4.xml · derivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

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

ISALY SAMUEL D · CIK 0001055949 · Director · 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: 403,692

Underlying: Common Stock · 65,491 shares

Expires 2024-01-18

F1 · ownership.nature: These securities are held of record by OrbiMed Private Investments III, LP ("OPI III") and may be deemed to be indirectly beneficially owned by OrbiMed Capital GP III LLC ("GP III"), OrbiMed Advisors LLC ("Advisors") and Samuel D. Isaly ("Isaly"). GP III is the sole general partner of OPI III. Advisors, a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI III noted above.

F3 · 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. The Reporting Persons have designated a representative, currently David Bonita, an employee 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: 0000947871-17-000057 · ss27693_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

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

ISALY SAMUEL D · CIK 0001055949 · Director · 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: 89,225

F2 · ownership.nature: These securities are held of record by OrbiMed Associates III, LP ("Associates III") and may be deemed to be indirectly beneficially owned by Advisors and Isaly. Advisors is the sole general partner of Associates III. Isaly is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationship, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by Associates III noted above. As a result, each of Advisors and Isaly may be deemed to have beneficial ownership of the securities held by Associates III.

F3 · 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. The Reporting Persons have designated a representative, currently David Bonita, an employee 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: 0000947871-17-000057 · ss27693_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

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

ISALY SAMUEL D · CIK 0001055949 · Director · 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: 9,369,342

F1 · ownership.nature: These securities are held of record by OrbiMed Private Investments III, LP ("OPI III") and may be deemed to be indirectly beneficially owned by OrbiMed Capital GP III LLC ("GP III"), OrbiMed Advisors LLC ("Advisors") and Samuel D. Isaly ("Isaly"). GP III is the sole general partner of OPI III. Advisors, a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI III noted above.

F3 · 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. The Reporting Persons have designated a representative, currently David Bonita, an employee 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: 0001437749-16-042830 · rdgdoc.xml · nonDerivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Advisors Ltd · CIK 0001491569 · Director · 10% owner

ISALY SAMUEL D · CIK 0001055949 · Director · 10% owner

ORBIMED ASIA GP, LP · CIK 0001491520 · Director · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · Director · 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

F1 · price: In connection with the consummation of the transactions contemplated by the Agreement and Plan of Arrangement by and between the issuer and 1077801 B.C. Ltd., dated June 16, 2016 (the "Arrangement"), the reporting person rolled over their shares of common stock of the issuer into shares of common stock of 1077801 B.C. Ltd on a one-to-one basis.

F2 · ownership.nature: This report on Form 4 is jointly filed by OrbiMed Capital GP III LLC ("OrbiMed Capital"), OrbiMed Advisors LLC ("OrbiMed Advisors"), Samuel D. Isaly ("Isaly"), OrbiMed Advisors Limited ("OrbiMed Limited") and OrbiMed Asia GP, L.P. ("OrbiMed Asia"). 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 the reporting persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

F4 · ownership.nature: The reporting persons have designated two representatives to serve on the Issuer's board of directors which, as of immediately prior to the closing of the Arrangement, are Jonathan Wang and Peter Thompson, both of whom are employees of OrbiMed Advisors. Each such representative disclaims beneficial ownership of the securities reported herein, except to the extent of his pecuniary interest therein, if any. This report shall not be deemed an admission that any of them are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

F6 · ownership.nature: These Shares and Warrants are held of record by OrbiMed Asia Partners, L.P. ("OAP") and may be deemed to be indirectly beneficially owned by OrbiMed Asia and OrbiMed Limited. OrbiMed Asia is the sole general partner of OAP and OrbiMed Limited is the sole general partner of OrbiMed Asia. As a result, OrbiMed Asia has the power to direct the vote and to direct the disposition of the securities held by OAP and such power is exercised through OrbiMed Limited.

SEC source: 0001437749-16-042830 · rdgdoc.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Advisors Ltd · CIK 0001491569 · Director · 10% owner

ISALY SAMUEL D · CIK 0001055949 · Director · 10% owner

ORBIMED ASIA GP, LP · CIK 0001491520 · Director · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · Director · 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

F1 · price: In connection with the consummation of the transactions contemplated by the Agreement and Plan of Arrangement by and between the issuer and 1077801 B.C. Ltd., dated June 16, 2016 (the "Arrangement"), the reporting person rolled over their shares of common stock of the issuer into shares of common stock of 1077801 B.C. Ltd on a one-to-one basis.

F2 · ownership.nature: This report on Form 4 is jointly filed by OrbiMed Capital GP III LLC ("OrbiMed Capital"), OrbiMed Advisors LLC ("OrbiMed Advisors"), Samuel D. Isaly ("Isaly"), OrbiMed Advisors Limited ("OrbiMed Limited") and OrbiMed Asia GP, L.P. ("OrbiMed Asia"). 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 the reporting persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

F4 · ownership.nature: The reporting persons have designated two representatives to serve on the Issuer's board of directors which, as of immediately prior to the closing of the Arrangement, are Jonathan Wang and Peter Thompson, both of whom are employees of OrbiMed Advisors. Each such representative disclaims beneficial ownership of the securities reported herein, except to the extent of his pecuniary interest therein, if any. This report shall not be deemed an admission that any of them are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

F5 · ownership.nature: These Shares and Warrants are held of record by OrbiMed Associates III, LP ("OA III") and may be deemed to be indirectly beneficially owned by OrbiMed Advisors and Isaly. OrbiMed Advisors is the sole general partner of OA III, and Isaly is the managing member of, and holder of a controlling interest in, OrbiMed Advisors. As a result, Isaly and OrbiMed Advisors share power to direct the vote and to direct the disposition of the securities held by OA III.

SEC source: 0001437749-16-042830 · rdgdoc.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

OrbiMed Advisors Ltd · CIK 0001491569 · Director · 10% owner

ISALY SAMUEL D · CIK 0001055949 · Director · 10% owner

ORBIMED ASIA GP, LP · CIK 0001491520 · Director · 10% owner

OrbiMed Capital GP III LLC · CIK 0001432241 · Director · 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

F1 · price: In connection with the consummation of the transactions contemplated by the Agreement and Plan of Arrangement by and between the issuer and 1077801 B.C. Ltd., dated June 16, 2016 (the "Arrangement"), the reporting person rolled over their shares of common stock of the issuer into shares of common stock of 1077801 B.C. Ltd on a one-to-one basis.

F2 · ownership.nature: This report on Form 4 is jointly filed by OrbiMed Capital GP III LLC ("OrbiMed Capital"), OrbiMed Advisors LLC ("OrbiMed Advisors"), Samuel D. Isaly ("Isaly"), OrbiMed Advisors Limited ("OrbiMed Limited") and OrbiMed Asia GP, L.P. ("OrbiMed Asia"). 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 the reporting persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

F3 · ownership.nature: These Shares and warrants to purchase Shares ("Warrants") are held of record by OrbiMed Private Investments III, LP ("OPI III") and may be deemed to be indirectly beneficially owned by OrbiMed Capital, OrbiMed Advisors and Isaly. OrbiMed Capital is the sole general partner of OPI III. OrbiMed Advisors, a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of OrbiMed Capital. Pursuant to those relationships, OrbiMed Capital and OrbiMed Advisors have discretionary investment management authority with respect to the assets of OPI III. Such authority includes the power to vote and otherwise dispose of the securities held by OPI III. Isaly, a natural person, is the managing member of, and holder of a controlling interest in, OrbiMed Advisors. As a result, Isaly, OrbiMed Advisors and OrbiMed Capital share power to direct the vote and to direct the disposition of the securities held by OPI III.

F4 · ownership.nature: The reporting persons have designated two representatives to serve on the Issuer's board of directors which, as of immediately prior to the closing of the Arrangement, are Jonathan Wang and Peter Thompson, both of whom are employees of OrbiMed Advisors. Each such representative disclaims beneficial ownership of the securities reported herein, except to the extent of his pecuniary interest therein, if any. This report shall not be deemed an admission that any of them are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-16-001509 · ss11703_4.xml · derivative · entry 4

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

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

ISALY SAMUEL D · CIK 0001055949 · Director · 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: 53,909

Underlying: Common Stock · 53,909 shares

Expires not disclosed

F2 · derivative.exercise_price: Represents warrants ("Warrants") to purchase Common Shares. The Warrants are immediately exercisable when issued, are exercisable for five years from the date of issuance and have an exercise price of $0.70 per Common Share.

F3 · price: The purchase price for Preferred Shares and associated Warrants was $1,000 per share.

F2 · derivative.exercise_date: Represents warrants ("Warrants") to purchase Common Shares. The Warrants are immediately exercisable when issued, are exercisable for five years from the date of issuance and have an exercise price of $0.70 per Common Share.

F2 · derivative.expiration_date: Represents warrants ("Warrants") to purchase Common Shares. The Warrants are immediately exercisable when issued, are exercisable for five years from the date of issuance and have an exercise price of $0.70 per Common Share.

F6 · ownership.nature: These securities are held of record by OrbiMed Associates III, LP ("Associates III") and may be deemed to be indirectly beneficially owned by Advisors and Isaly. Advisors is the sole general partner of Associates III. Isaly is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationship, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by Associates III noted above. As a result, each of Advisors and Isaly may be deemed to have beneficial ownership of the securities held by Associates III.

F7 · 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. The Reporting Persons have designated a representative, currently Jonathan Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-16-001509 · ss11703_4.xml · derivative · entry 3

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

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

ISALY SAMUEL D · CIK 0001055949 · Director · 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: 5,660,377

Underlying: Common Stock · 5,660,377 shares

Expires not disclosed

F2 · derivative.exercise_price: Represents warrants ("Warrants") to purchase Common Shares. The Warrants are immediately exercisable when issued, are exercisable for five years from the date of issuance and have an exercise price of $0.70 per Common Share.

F3 · price: The purchase price for Preferred Shares and associated Warrants was $1,000 per share.

F2 · derivative.exercise_date: Represents warrants ("Warrants") to purchase Common Shares. The Warrants are immediately exercisable when issued, are exercisable for five years from the date of issuance and have an exercise price of $0.70 per Common Share.

F2 · derivative.expiration_date: Represents warrants ("Warrants") to purchase Common Shares. The Warrants are immediately exercisable when issued, are exercisable for five years from the date of issuance and have an exercise price of $0.70 per Common Share.

F4 · ownership.nature: These securities are held of record by OrbiMed Private Investments III, LP ("OPI III") and may be deemed to be indirectly beneficially owned by OrbiMed Capital GP III LLC ("GP III"), OrbiMed Advisors LLC ("Advisors") and Samuel D. Isaly ("Isaly"). GP III is the sole general partner of OPI III. Advisors, a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI III noted above.

F5 · ownership.nature: Isaly, a natural person, may also be deemed to have voting and investment power with respect to the securities held by OPI III noted above in his capacity as the managing member of, and holder of a controlling interest, in Advisors. As a result, each of GP III, Advisors and Isaly may be deemed to have beneficial ownership of the securities held by OPI III.

F7 · 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. The Reporting Persons have designated a representative, currently Jonathan Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-16-001509 · ss11703_4.xml · derivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

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

ISALY SAMUEL D · CIK 0001055949 · Director · 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: 37.74

Underlying: Common Stock · 53,909 shares

Expires not disclosed

F1 · derivative.exercise_price: Represents shares of Series A Convertible Preferred Stock, par value $0.001 per share ("Preferred Shares"). Upon receipt by the Issuer of shareholder approval as specified in the Certificate of Designation of Preferences, Rights and Limitations for the Preferred Shares, each Preferred Share will automatically convert into a number of shares of the Issuer's common stock, par value $0.001 per share ("Common Shares"), determined by dividing the stated value of each Preferred Share (which is $1,000) by $0.70. Such conversion is reflected in the amount of Common Shares reported in column 7 as underlying the security.

F3 · price: The purchase price for Preferred Shares and associated Warrants was $1,000 per share.

F1 · derivative.exercise_date: Represents shares of Series A Convertible Preferred Stock, par value $0.001 per share ("Preferred Shares"). Upon receipt by the Issuer of shareholder approval as specified in the Certificate of Designation of Preferences, Rights and Limitations for the Preferred Shares, each Preferred Share will automatically convert into a number of shares of the Issuer's common stock, par value $0.001 per share ("Common Shares"), determined by dividing the stated value of each Preferred Share (which is $1,000) by $0.70. Such conversion is reflected in the amount of Common Shares reported in column 7 as underlying the security.

F1 · derivative.expiration_date: Represents shares of Series A Convertible Preferred Stock, par value $0.001 per share ("Preferred Shares"). Upon receipt by the Issuer of shareholder approval as specified in the Certificate of Designation of Preferences, Rights and Limitations for the Preferred Shares, each Preferred Share will automatically convert into a number of shares of the Issuer's common stock, par value $0.001 per share ("Common Shares"), determined by dividing the stated value of each Preferred Share (which is $1,000) by $0.70. Such conversion is reflected in the amount of Common Shares reported in column 7 as underlying the security.

F6 · ownership.nature: These securities are held of record by OrbiMed Associates III, LP ("Associates III") and may be deemed to be indirectly beneficially owned by Advisors and Isaly. Advisors is the sole general partner of Associates III. Isaly is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationship, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by Associates III noted above. As a result, each of Advisors and Isaly may be deemed to have beneficial ownership of the securities held by Associates III.

F7 · 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. The Reporting Persons have designated a representative, currently Jonathan Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-16-001509 · ss11703_4.xml · derivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · Director · 10% owner

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

ISALY SAMUEL D · CIK 0001055949 · Director · 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: 3,962.26

Underlying: Common Stock · 5,660,377 shares

Expires not disclosed

F1 · derivative.exercise_price: Represents shares of Series A Convertible Preferred Stock, par value $0.001 per share ("Preferred Shares"). Upon receipt by the Issuer of shareholder approval as specified in the Certificate of Designation of Preferences, Rights and Limitations for the Preferred Shares, each Preferred Share will automatically convert into a number of shares of the Issuer's common stock, par value $0.001 per share ("Common Shares"), determined by dividing the stated value of each Preferred Share (which is $1,000) by $0.70. Such conversion is reflected in the amount of Common Shares reported in column 7 as underlying the security.

F3 · price: The purchase price for Preferred Shares and associated Warrants was $1,000 per share.

F1 · derivative.exercise_date: Represents shares of Series A Convertible Preferred Stock, par value $0.001 per share ("Preferred Shares"). Upon receipt by the Issuer of shareholder approval as specified in the Certificate of Designation of Preferences, Rights and Limitations for the Preferred Shares, each Preferred Share will automatically convert into a number of shares of the Issuer's common stock, par value $0.001 per share ("Common Shares"), determined by dividing the stated value of each Preferred Share (which is $1,000) by $0.70. Such conversion is reflected in the amount of Common Shares reported in column 7 as underlying the security.

F1 · derivative.expiration_date: Represents shares of Series A Convertible Preferred Stock, par value $0.001 per share ("Preferred Shares"). Upon receipt by the Issuer of shareholder approval as specified in the Certificate of Designation of Preferences, Rights and Limitations for the Preferred Shares, each Preferred Share will automatically convert into a number of shares of the Issuer's common stock, par value $0.001 per share ("Common Shares"), determined by dividing the stated value of each Preferred Share (which is $1,000) by $0.70. Such conversion is reflected in the amount of Common Shares reported in column 7 as underlying the security.

F4 · ownership.nature: These securities are held of record by OrbiMed Private Investments III, LP ("OPI III") and may be deemed to be indirectly beneficially owned by OrbiMed Capital GP III LLC ("GP III"), OrbiMed Advisors LLC ("Advisors") and Samuel D. Isaly ("Isaly"). GP III is the sole general partner of OPI III. Advisors, a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI III noted above.

F5 · ownership.nature: Isaly, a natural person, may also be deemed to have voting and investment power with respect to the securities held by OPI III noted above in his capacity as the managing member of, and holder of a controlling interest, in Advisors. As a result, each of GP III, Advisors and Isaly may be deemed to have beneficial ownership of the securities held by OPI III.

F7 · 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. The Reporting Persons have designated a representative, currently Jonathan Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.