GKOS

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

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 828,605

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

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

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

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

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 8,448

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

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

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

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

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 886,652

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

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

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

SEC source: 0000947871-17-000697 · ss57835_4.xml · nonDerivative · entry 6

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 10,256

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $37.75 to $38.04 inclusive. Upon request, the Reporting Person undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

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

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

SEC source: 0000947871-17-000697 · ss57835_4.xml · nonDerivative · entry 5

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 1,076,444

F3 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $37.75 to $38.04 inclusive. Upon request, the Reporting Person undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares sold at each separate price within the range set forth in this footnote.

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

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

SEC source: 0001562180-17-002857 · primarydocument.xml · derivative · entry 7

Burns Thomas William · CIK 0001644557 · Director · Chief Executive Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 169,428

Underlying: Common Stock · 1,212 shares

Expires 2020-01-26

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: This option was granted on January 26, 2010, has a four-year vesting schedule in which 25% vests on the first year anniversary date of the grant and the remainder vests equally for 36 months thereafter, such that the stock option vests in full on the four-year anniversary of the grant date.

SEC source: 0001562180-17-002857 · primarydocument.xml · nonDerivative · entry 2

Burns Thomas William · CIK 0001644557 · Director · Chief Executive Officer

10b5-1 filing: Not disclosed

Ownership: Indirect · Through the Burns Family Trust

Disclosed balance after: 210,240

F1 · kind: These trades were made pursuant to a Rule 10b5-1 trading plan with pre-determined share amounts and prices.

F2 · price: This transaction was executed in multiple trades at prices ranging from $41.25 to $41.26. The price reported above reflects the weighted average price. The reporting person hereby undertakes to provide upon request to the SEC staff, the issuer or a security holder of the issuer full information regarding the number of shares and prices at which the transaction was effected.

SEC source: 0001562180-17-002857 · primarydocument.xml · nonDerivative · entry 1

Burns Thomas William · CIK 0001644557 · Director · Chief Executive Officer

10b5-1 filing: Not disclosed

Ownership: Indirect · Through the Burns Family Trust

Disclosed balance after: 211,452

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.

SEC source: 0000947871-17-000698 · ss57834_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: 11,907

F2 · price: These Shares were sold in a block order at a price of $37.72.

F7 · 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.

F8 · 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 of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000698 · ss57834_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: 1,249,793

F2 · price: These Shares were sold in a block order at a price of $37.72.

F6 · 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.

F8 · 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 of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000697 · ss57835_4.xml · nonDerivative · entry 4

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 11,907

F2 · price: These Shares were sold in a block order at a price of $37.72.

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

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

SEC source: 0000947871-17-000697 · ss57835_4.xml · nonDerivative · entry 3

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 1,249,793

F2 · price: These Shares were sold in a block order at a price of $37.72.

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

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

SEC source: 0000947871-17-000698 · ss57834_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: 12,945

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 $37.75 to $37.83 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.

F7 · 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.

F8 · 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 of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000698 · ss57834_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: 1,358,833

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 $37.75 to $37.83 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.

F6 · 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.

F8 · 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 of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000697 · ss57835_4.xml · nonDerivative · entry 2

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 12,945

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 $37.75 to $37.83 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.

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

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

SEC source: 0000947871-17-000697 · ss57835_4.xml · nonDerivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 1,358,833

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 $37.75 to $37.83 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 Shares are held of record by OrbiMed Private Investments III, LP ("OPI III") and may be deemed to be indirectly beneficially owned by OrbiMed Capital GP III LLC ("GP III"), OrbiMed Advisors LLC ("Advisors") and Samuel D. Isaly ("Isaly"). GP III is the sole general partner of OPI III. Advisors, a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP III. Isaly, a natural person, is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, GP III, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI III noted above. The Reporting Person is a member of Advisors.

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

SEC source: 0000947871-17-000653 · 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: 0000947871-17-000654 · ss55689_4.xml · nonDerivative · entry 6

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

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 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.

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

SEC source: 0000947871-17-000654 · ss55689_4.xml · nonDerivative · entry 5

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

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 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. The Reporting Person is a member of Advisors.

F6 · ownership.nature: Each of the Reporting Person, GP III, Advisors, and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000653 · 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: 0000947871-17-000654 · ss55689_4.xml · nonDerivative · entry 4

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

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 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.

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

SEC source: 0000947871-17-000654 · ss55689_4.xml · nonDerivative · entry 3

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

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 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. The Reporting Person is a member of Advisors.

F6 · ownership.nature: Each of the Reporting Person, GP III, Advisors, and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000653 · 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: 0000947871-17-000654 · ss55689_4.xml · nonDerivative · entry 2

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

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

SEC source: 0000947871-17-000654 · ss55689_4.xml · nonDerivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

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 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. The Reporting Person is a member of Advisors.

F6 · ownership.nature: Each of the Reporting Person, GP III, Advisors, and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001510192-17-000040 · primary_doc.xml · derivative · entry 2

Gilliam Joseph E · CIK 0001705850 · CFO, SVP Corporate Development

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 300,000

Underlying: Common Stock · 300,000 shares

Expires 2027-05-05

F3 · derivative.exercise_date: Granted pursuant to the Issuer's 2015 Omnibus Incentive Compensation Plan. Vests over a four-year period, with 25% to vest on the 1st anniversary of the grant date and 1/36th of the total remaining number to vest on the last day of each month thereafter.

SEC source: 0001510192-17-000040 · primary_doc.xml · nonDerivative · entry 1

Gilliam Joseph E · CIK 0001705850 · CFO, SVP Corporate Development

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 100,000

F1 · security: Granted by the Issuer in the form of restricted stock units which vest over a four-year period, with 25% to vest on each anniversary of the grant date.

F2 · balance_after: Consists of 100,000 restricted stock units that have not yet vested or been delivered to the Reporting Person.

SEC source: 0001562180-18-000714 · primarydocument.xml · derivative · entry 1

Burns Thomas William · CIK 0001644557 · Director · Chief Executive Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 180,000

Underlying: Common Stock · 180,000 shares

Expires 2027-03-15

F1 · derivative.exercise_date: This option has a four-year vesting schedule in which 25% will vest on the first year anniversary date of the grant and then will vest equally for 36 months thereafter, such that the stock option is vested in full on the four-year anniversary of the grant date.

SEC source: 0001562180-18-000713 · primarydocument.xml · derivative · entry 1

Calcaterra Chris M. · CIK 0001640771 · Chief Operating Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 80,000

Underlying: Common Stock · 80,000 shares

Expires 2027-03-15

F1 · derivative.exercise_date: This option has a four-year vesting schedule in which 25% will vest on the first year anniversary date of the grant and then will vest equally for 36 months thereafter, such that the stock option is vested in full on the four-year anniversary of the grant date.

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: 0000947871-17-000211 · ss34862_4.xml · nonDerivative · entry 8

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

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

SEC source: 0000947871-17-000211 · ss34862_4.xml · nonDerivative · entry 7

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

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 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.

F5 · 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. The Reporting Person is a member of Advisors.

F7 · ownership.nature: Each of the Reporting Person, GP III, Advisors, and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000210 · 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: 0000947871-17-000211 · ss34862_4.xml · nonDerivative · entry 6

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

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

SEC source: 0000947871-17-000211 · ss34862_4.xml · nonDerivative · entry 5

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

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 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.

F5 · 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. The Reporting Person is a member of Advisors.

F7 · ownership.nature: Each of the Reporting Person, GP III, Advisors, and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000211 · ss34862_4.xml · nonDerivative · entry 4

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

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

SEC source: 0000947871-17-000211 · ss34862_4.xml · nonDerivative · entry 3

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

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 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.

F5 · 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. The Reporting Person is a member of Advisors.

F7 · ownership.nature: Each of the Reporting Person, GP III, Advisors, and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-17-000210 · 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: 0000947871-17-000211 · ss34862_4.xml · nonDerivative · entry 2

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

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

SEC source: 0000947871-17-000211 · ss34862_4.xml · nonDerivative · entry 1

SILVERSTEIN JONATHAN · CIK 0001171005 · Director

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 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 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. The Reporting Person is a member of Advisors.

F7 · ownership.nature: Each of the Reporting Person, GP III, Advisors, and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001209191-17-019379 · doc4.xml · nonDerivative · entry 2

LINK WILLIAM J PHD · CIK 0001228684 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · see footnote

Disclosed balance after: 90,479

F3 · kind: Represents a change in the form of ownership by virtue of the receipt of shares in the pro-rata in-kind distribution of Common Stock of the Issuer by Versant Ventures I, LLC without consideration to its members.

F2 · ownership.nature: The shares are held by The Link Family Trust (the "Link Trust") for the benefit of William J. Link. William J. Link is a trustee of the Link Trust. The Reporting Person disclaims beneficial ownership of the shares except to the extent of his proportionate pecuniary interest therein.

SEC source: 0001209191-17-019379 · doc4.xml · nonDerivative · entry 1

LINK WILLIAM J PHD · CIK 0001228684 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · see footnote

Disclosed balance after: 87,824

F1 · kind: Represents a change in the form of ownership by virtue of the receipt of shares in the pro-rata in-kind distribution of Common Stock of the Issuer for no consideration by Versant Side Fund I, L.P.

F2 · ownership.nature: The shares are held by The Link Family Trust (the "Link Trust") for the benefit of William J. Link. William J. Link is a trustee of the Link Trust. The Reporting Person disclaims beneficial ownership of the shares except to the extent of his proportionate pecuniary interest therein.