GYRE

SEC source: 0001193805-18-000436 · e617828_4a-catalyst.xml · nonDerivative · entry 8

Flynn James E · CIK 0001352546 · 10% owner · Possible Member of 10% Group

Deerfield Mgmt L.P. · CIK 0001010823 · 10% owner · Possible Member of 10% Group

DEERFIELD MANAGEMENT COMPANY, L.P. (SERIES C) · CIK 0001009258 · 10% owner · Possible Member of 10% Group

Deerfield Special Situations Fund, L.P. · CIK 0001354395 · 10% owner · Possible Member of 10% Group

DEERFIELD PARTNERS, L.P. · CIK 0001301041 · 10% owner · Possible Member of 10% Group

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

10b5-1 filing: Not disclosed

Ownership: Indirect · Through Deerfield Special Situations Fund, L.P.

Disclosed balance after: 308,198

F4 · ownership.nature: This Form 4 is being filed by the undersigned as well as the entities listed on the Joint Filer Information Statement attached as an exhibit hereto (the "Reporting Persons"). Deerfield Mgmt, L.P. is the general partner of Deerfield Special Situations Fund, L.P. and Deerfield Partners, L.P. (the "Funds"). Deerfield Management Company, L.P. is the investment manager of the Funds. James E. Flynn is the sole member of the general partner of each of Deerfield Mgmt, L.P. and Deerfield Management Company, L.P.

F5 · ownership.nature: In accordance with Instruction 4 (b)(iv) to Form 4, the entire amount of the Issuer's securities held by the Funds is reported herein. For purposes of Section 16 of the Securities Exchange Act of 1934, as amended, each Reporting Person disclaims beneficial ownership of any such securities, except to the extent of his/its indirect pecuniary interest therein, if any, and this report shall not be deemed an admission that such Reporting Person is the beneficial owner of such securities for purposes of Section 16 or otherwise.

F6 · ownership.nature: This Amendment to the Form 4 filed with the Commission on March 8, 2018 (the "Original Filing") is being filed to correctly report the identity of the direct beneficial owners of shares sold on March 6, 2018, March 7, 2018 and March 8, 2018 (as well as the direct holder of shares beneficially owned by the applicable Reporting Persons following such sales) which were incorrectly reported on the March 8, 2018 Form 4 report. The aggregate number of shares sold by the Funds and the aggregate number of shares beneficially owned by the Reporting Persons, as reported in the Original Filing, remains unchanged.

SEC source: 0001193805-18-000436 · e617828_4a-catalyst.xml · nonDerivative · entry 7

Flynn James E · CIK 0001352546 · 10% owner · Possible Member of 10% Group

Deerfield Mgmt L.P. · CIK 0001010823 · 10% owner · Possible Member of 10% Group

DEERFIELD MANAGEMENT COMPANY, L.P. (SERIES C) · CIK 0001009258 · 10% owner · Possible Member of 10% Group

Deerfield Special Situations Fund, L.P. · CIK 0001354395 · 10% owner · Possible Member of 10% Group

DEERFIELD PARTNERS, L.P. · CIK 0001301041 · 10% owner · Possible Member of 10% Group

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

10b5-1 filing: Not disclosed

Ownership: Indirect · Through Deerfield Partners, L.P.

Disclosed balance after: 813,147

F4 · ownership.nature: This Form 4 is being filed by the undersigned as well as the entities listed on the Joint Filer Information Statement attached as an exhibit hereto (the "Reporting Persons"). Deerfield Mgmt, L.P. is the general partner of Deerfield Special Situations Fund, L.P. and Deerfield Partners, L.P. (the "Funds"). Deerfield Management Company, L.P. is the investment manager of the Funds. James E. Flynn is the sole member of the general partner of each of Deerfield Mgmt, L.P. and Deerfield Management Company, L.P.

F5 · ownership.nature: In accordance with Instruction 4 (b)(iv) to Form 4, the entire amount of the Issuer's securities held by the Funds is reported herein. For purposes of Section 16 of the Securities Exchange Act of 1934, as amended, each Reporting Person disclaims beneficial ownership of any such securities, except to the extent of his/its indirect pecuniary interest therein, if any, and this report shall not be deemed an admission that such Reporting Person is the beneficial owner of such securities for purposes of Section 16 or otherwise.

F6 · ownership.nature: This Amendment to the Form 4 filed with the Commission on March 8, 2018 (the "Original Filing") is being filed to correctly report the identity of the direct beneficial owners of shares sold on March 6, 2018, March 7, 2018 and March 8, 2018 (as well as the direct holder of shares beneficially owned by the applicable Reporting Persons following such sales) which were incorrectly reported on the March 8, 2018 Form 4 report. The aggregate number of shares sold by the Funds and the aggregate number of shares beneficially owned by the Reporting Persons, as reported in the Original Filing, remains unchanged.

SEC source: 0001193805-18-000371 · e617783_4-catalyst.xml · nonDerivative · entry 3

Flynn James E · CIK 0001352546 · 10% owner · Possible Member of 10% Group

Deerfield Mgmt L.P. · CIK 0001010823 · 10% owner · Possible Member of 10% Group

DEERFIELD MANAGEMENT COMPANY, L.P. (SERIES C) · CIK 0001009258 · 10% owner · Possible Member of 10% Group

Deerfield Special Situations Fund, L.P. · CIK 0001354395 · 10% owner · Possible Member of 10% Group

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

10b5-1 filing: Not disclosed

Ownership: Indirect · Through Deerfield Special Situations Fund, L.P.

Disclosed balance after: 1,122,539

F4 · ownership.nature: This Form 4 is being filed by the undersigned as well as the entities listed on the Joint Filer Information Statement attached as an exhibit hereto (the "Reporting Persons"). Deerfield Mgmt, L.P. is the general partner of Deerfield Special Situations Fund, L.P. (the "Fund"). Deerfield Management Company, L.P. is the investment manager of the Fund. James E. Flynn is the sole member of the general partner of each of Deerfield Mgmt, L.P. and Deerfield Management Company, L.P.

F5 · ownership.nature: In accordance with Instruction 4 (b)(iv) to Form 4, the entire amount of the Issuer's securities held by the Fund is reported herein. For purposes of Section 16 of the Securities Exchange Act of 1934, as amended, each Reporting Person disclaims beneficial ownership of any such securities, except to the extent of his/its indirect pecuniary interest therein, if any, and this report shall not be deemed an admission that such Reporting Person is the beneficial owner of such securities for purposes of Section 16 or otherwise.

SEC source: 0001193805-18-000436 · e617828_4a-catalyst.xml · nonDerivative · entry 6

Flynn James E · CIK 0001352546 · 10% owner · Possible Member of 10% Group

Deerfield Mgmt L.P. · CIK 0001010823 · 10% owner · Possible Member of 10% Group

DEERFIELD MANAGEMENT COMPANY, L.P. (SERIES C) · CIK 0001009258 · 10% owner · Possible Member of 10% Group

Deerfield Special Situations Fund, L.P. · CIK 0001354395 · 10% owner · Possible Member of 10% Group

DEERFIELD PARTNERS, L.P. · CIK 0001301041 · 10% owner · Possible Member of 10% Group

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

10b5-1 filing: Not disclosed

Ownership: Indirect · Through Deerfield Special Situations Fund, L.P.

Disclosed balance after: 308,526

F4 · ownership.nature: This Form 4 is being filed by the undersigned as well as the entities listed on the Joint Filer Information Statement attached as an exhibit hereto (the "Reporting Persons"). Deerfield Mgmt, L.P. is the general partner of Deerfield Special Situations Fund, L.P. and Deerfield Partners, L.P. (the "Funds"). Deerfield Management Company, L.P. is the investment manager of the Funds. James E. Flynn is the sole member of the general partner of each of Deerfield Mgmt, L.P. and Deerfield Management Company, L.P.

F5 · ownership.nature: In accordance with Instruction 4 (b)(iv) to Form 4, the entire amount of the Issuer's securities held by the Funds is reported herein. For purposes of Section 16 of the Securities Exchange Act of 1934, as amended, each Reporting Person disclaims beneficial ownership of any such securities, except to the extent of his/its indirect pecuniary interest therein, if any, and this report shall not be deemed an admission that such Reporting Person is the beneficial owner of such securities for purposes of Section 16 or otherwise.

F6 · ownership.nature: This Amendment to the Form 4 filed with the Commission on March 8, 2018 (the "Original Filing") is being filed to correctly report the identity of the direct beneficial owners of shares sold on March 6, 2018, March 7, 2018 and March 8, 2018 (as well as the direct holder of shares beneficially owned by the applicable Reporting Persons following such sales) which were incorrectly reported on the March 8, 2018 Form 4 report. The aggregate number of shares sold by the Funds and the aggregate number of shares beneficially owned by the Reporting Persons, as reported in the Original Filing, remains unchanged.

SEC source: 0001193805-18-000436 · e617828_4a-catalyst.xml · nonDerivative · entry 5

Flynn James E · CIK 0001352546 · 10% owner · Possible Member of 10% Group

Deerfield Mgmt L.P. · CIK 0001010823 · 10% owner · Possible Member of 10% Group

DEERFIELD MANAGEMENT COMPANY, L.P. (SERIES C) · CIK 0001009258 · 10% owner · Possible Member of 10% Group

Deerfield Special Situations Fund, L.P. · CIK 0001354395 · 10% owner · Possible Member of 10% Group

DEERFIELD PARTNERS, L.P. · CIK 0001301041 · 10% owner · Possible Member of 10% Group

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

10b5-1 filing: Not disclosed

Ownership: Indirect · Through Deerfield Partners, L.P.

Disclosed balance after: 814,013

F4 · ownership.nature: This Form 4 is being filed by the undersigned as well as the entities listed on the Joint Filer Information Statement attached as an exhibit hereto (the "Reporting Persons"). Deerfield Mgmt, L.P. is the general partner of Deerfield Special Situations Fund, L.P. and Deerfield Partners, L.P. (the "Funds"). Deerfield Management Company, L.P. is the investment manager of the Funds. James E. Flynn is the sole member of the general partner of each of Deerfield Mgmt, L.P. and Deerfield Management Company, L.P.

F5 · ownership.nature: In accordance with Instruction 4 (b)(iv) to Form 4, the entire amount of the Issuer's securities held by the Funds is reported herein. For purposes of Section 16 of the Securities Exchange Act of 1934, as amended, each Reporting Person disclaims beneficial ownership of any such securities, except to the extent of his/its indirect pecuniary interest therein, if any, and this report shall not be deemed an admission that such Reporting Person is the beneficial owner of such securities for purposes of Section 16 or otherwise.

F6 · ownership.nature: This Amendment to the Form 4 filed with the Commission on March 8, 2018 (the "Original Filing") is being filed to correctly report the identity of the direct beneficial owners of shares sold on March 6, 2018, March 7, 2018 and March 8, 2018 (as well as the direct holder of shares beneficially owned by the applicable Reporting Persons following such sales) which were incorrectly reported on the March 8, 2018 Form 4 report. The aggregate number of shares sold by the Funds and the aggregate number of shares beneficially owned by the Reporting Persons, as reported in the Original Filing, remains unchanged.

SEC source: 0001193805-18-000371 · e617783_4-catalyst.xml · nonDerivative · entry 2

Flynn James E · CIK 0001352546 · 10% owner · Possible Member of 10% Group

Deerfield Mgmt L.P. · CIK 0001010823 · 10% owner · Possible Member of 10% Group

DEERFIELD MANAGEMENT COMPANY, L.P. (SERIES C) · CIK 0001009258 · 10% owner · Possible Member of 10% Group

Deerfield Special Situations Fund, L.P. · CIK 0001354395 · 10% owner · Possible Member of 10% Group

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

10b5-1 filing: Not disclosed

Ownership: Indirect · Through Deerfield Special Situations Fund, L.P.

Disclosed balance after: 1,132,539

F2 · price: The price reported in Column 4 is a weighted average price. The shares were sold in multiple transactions at prices ranging from $31.00 to $31.21, inclusive.

F4 · ownership.nature: This Form 4 is being filed by the undersigned as well as the entities listed on the Joint Filer Information Statement attached as an exhibit hereto (the "Reporting Persons"). Deerfield Mgmt, L.P. is the general partner of Deerfield Special Situations Fund, L.P. (the "Fund"). Deerfield Management Company, L.P. is the investment manager of the Fund. James E. Flynn is the sole member of the general partner of each of Deerfield Mgmt, L.P. and Deerfield Management Company, L.P.

F5 · ownership.nature: In accordance with Instruction 4 (b)(iv) to Form 4, the entire amount of the Issuer's securities held by the Fund is reported herein. For purposes of Section 16 of the Securities Exchange Act of 1934, as amended, each Reporting Person disclaims beneficial ownership of any such securities, except to the extent of his/its indirect pecuniary interest therein, if any, and this report shall not be deemed an admission that such Reporting Person is the beneficial owner of such securities for purposes of Section 16 or otherwise.

SEC source: 0001193805-18-000371 · e617783_4-catalyst.xml · nonDerivative · entry 1

Flynn James E · CIK 0001352546 · 10% owner · Possible Member of 10% Group

Deerfield Mgmt L.P. · CIK 0001010823 · 10% owner · Possible Member of 10% Group

DEERFIELD MANAGEMENT COMPANY, L.P. (SERIES C) · CIK 0001009258 · 10% owner · Possible Member of 10% Group

Deerfield Special Situations Fund, L.P. · CIK 0001354395 · 10% owner · Possible Member of 10% Group

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

10b5-1 filing: Not disclosed

Ownership: Indirect · Through Deerfield Special Situations Fund, L.P.

Disclosed balance after: 1,171,839

F1 · price: The price reported in Column 4 is a weighted average price. The shares were sold in multiple transactions at prices ranging from $29.75 to $30.50, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares sold at each separate price within the ranges set forth in footnotes (1), (2) and (3) of this Form 4.

F4 · ownership.nature: This Form 4 is being filed by the undersigned as well as the entities listed on the Joint Filer Information Statement attached as an exhibit hereto (the "Reporting Persons"). Deerfield Mgmt, L.P. is the general partner of Deerfield Special Situations Fund, L.P. (the "Fund"). Deerfield Management Company, L.P. is the investment manager of the Fund. James E. Flynn is the sole member of the general partner of each of Deerfield Mgmt, L.P. and Deerfield Management Company, L.P.

F5 · ownership.nature: In accordance with Instruction 4 (b)(iv) to Form 4, the entire amount of the Issuer's securities held by the Fund is reported herein. For purposes of Section 16 of the Securities Exchange Act of 1934, as amended, each Reporting Person disclaims beneficial ownership of any such securities, except to the extent of his/its indirect pecuniary interest therein, if any, and this report shall not be deemed an admission that such Reporting Person is the beneficial owner of such securities for purposes of Section 16 or otherwise.

SEC source: 0001193805-18-000436 · e617828_4a-catalyst.xml · nonDerivative · entry 4

Flynn James E · CIK 0001352546 · 10% owner · Possible Member of 10% Group

Deerfield Mgmt L.P. · CIK 0001010823 · 10% owner · Possible Member of 10% Group

DEERFIELD MANAGEMENT COMPANY, L.P. (SERIES C) · CIK 0001009258 · 10% owner · Possible Member of 10% Group

Deerfield Special Situations Fund, L.P. · CIK 0001354395 · 10% owner · Possible Member of 10% Group

DEERFIELD PARTNERS, L.P. · CIK 0001301041 · 10% owner · Possible Member of 10% Group

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

10b5-1 filing: Not disclosed

Ownership: Indirect · Through Deerfield Special Situations Fund, L.P.

Disclosed balance after: 311,274

F2 · price: The price reported in Column 4 is a weighted average price. The shares were sold in multiple transactions at prices ranging from $31.00 to $31.21, inclusive.

F4 · ownership.nature: This Form 4 is being filed by the undersigned as well as the entities listed on the Joint Filer Information Statement attached as an exhibit hereto (the "Reporting Persons"). Deerfield Mgmt, L.P. is the general partner of Deerfield Special Situations Fund, L.P. and Deerfield Partners, L.P. (the "Funds"). Deerfield Management Company, L.P. is the investment manager of the Funds. James E. Flynn is the sole member of the general partner of each of Deerfield Mgmt, L.P. and Deerfield Management Company, L.P.

F5 · ownership.nature: In accordance with Instruction 4 (b)(iv) to Form 4, the entire amount of the Issuer's securities held by the Funds is reported herein. For purposes of Section 16 of the Securities Exchange Act of 1934, as amended, each Reporting Person disclaims beneficial ownership of any such securities, except to the extent of his/its indirect pecuniary interest therein, if any, and this report shall not be deemed an admission that such Reporting Person is the beneficial owner of such securities for purposes of Section 16 or otherwise.

F6 · ownership.nature: This Amendment to the Form 4 filed with the Commission on March 8, 2018 (the "Original Filing") is being filed to correctly report the identity of the direct beneficial owners of shares sold on March 6, 2018, March 7, 2018 and March 8, 2018 (as well as the direct holder of shares beneficially owned by the applicable Reporting Persons following such sales) which were incorrectly reported on the March 8, 2018 Form 4 report. The aggregate number of shares sold by the Funds and the aggregate number of shares beneficially owned by the Reporting Persons, as reported in the Original Filing, remains unchanged.

SEC source: 0001193805-18-000436 · e617828_4a-catalyst.xml · nonDerivative · entry 3

Flynn James E · CIK 0001352546 · 10% owner · Possible Member of 10% Group

Deerfield Mgmt L.P. · CIK 0001010823 · 10% owner · Possible Member of 10% Group

DEERFIELD MANAGEMENT COMPANY, L.P. (SERIES C) · CIK 0001009258 · 10% owner · Possible Member of 10% Group

Deerfield Special Situations Fund, L.P. · CIK 0001354395 · 10% owner · Possible Member of 10% Group

DEERFIELD PARTNERS, L.P. · CIK 0001301041 · 10% owner · Possible Member of 10% Group

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

10b5-1 filing: Not disclosed

Ownership: Indirect · Through Deerfield Partners, L.P.

Disclosed balance after: 821,265

F2 · price: The price reported in Column 4 is a weighted average price. The shares were sold in multiple transactions at prices ranging from $31.00 to $31.21, inclusive.

F4 · ownership.nature: This Form 4 is being filed by the undersigned as well as the entities listed on the Joint Filer Information Statement attached as an exhibit hereto (the "Reporting Persons"). Deerfield Mgmt, L.P. is the general partner of Deerfield Special Situations Fund, L.P. and Deerfield Partners, L.P. (the "Funds"). Deerfield Management Company, L.P. is the investment manager of the Funds. James E. Flynn is the sole member of the general partner of each of Deerfield Mgmt, L.P. and Deerfield Management Company, L.P.

F5 · ownership.nature: In accordance with Instruction 4 (b)(iv) to Form 4, the entire amount of the Issuer's securities held by the Funds is reported herein. For purposes of Section 16 of the Securities Exchange Act of 1934, as amended, each Reporting Person disclaims beneficial ownership of any such securities, except to the extent of his/its indirect pecuniary interest therein, if any, and this report shall not be deemed an admission that such Reporting Person is the beneficial owner of such securities for purposes of Section 16 or otherwise.

F6 · ownership.nature: This Amendment to the Form 4 filed with the Commission on March 8, 2018 (the "Original Filing") is being filed to correctly report the identity of the direct beneficial owners of shares sold on March 6, 2018, March 7, 2018 and March 8, 2018 (as well as the direct holder of shares beneficially owned by the applicable Reporting Persons following such sales) which were incorrectly reported on the March 8, 2018 Form 4 report. The aggregate number of shares sold by the Funds and the aggregate number of shares beneficially owned by the Reporting Persons, as reported in the Original Filing, remains unchanged.

SEC source: 0001193805-18-000436 · e617828_4a-catalyst.xml · nonDerivative · entry 2

Flynn James E · CIK 0001352546 · 10% owner · Possible Member of 10% Group

Deerfield Mgmt L.P. · CIK 0001010823 · 10% owner · Possible Member of 10% Group

DEERFIELD MANAGEMENT COMPANY, L.P. (SERIES C) · CIK 0001009258 · 10% owner · Possible Member of 10% Group

Deerfield Special Situations Fund, L.P. · CIK 0001354395 · 10% owner · Possible Member of 10% Group

DEERFIELD PARTNERS, L.P. · CIK 0001301041 · 10% owner · Possible Member of 10% Group

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

10b5-1 filing: Not disclosed

Ownership: Indirect · Through Deerfield Special Situations Fund, L.P.

Disclosed balance after: 322,076

F1 · price: The price reported in Column 4 is a weighted average price. The shares were sold in multiple transactions at prices ranging from $29.75 to $30.50, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer or the staff of the Securities and Exchange Commission (the "Commission"), upon request, full information regarding the number of shares sold at each separate price within the ranges set forth in footnotes (1), (2) and (3) of this Form 4.

F4 · ownership.nature: This Form 4 is being filed by the undersigned as well as the entities listed on the Joint Filer Information Statement attached as an exhibit hereto (the "Reporting Persons"). Deerfield Mgmt, L.P. is the general partner of Deerfield Special Situations Fund, L.P. and Deerfield Partners, L.P. (the "Funds"). Deerfield Management Company, L.P. is the investment manager of the Funds. James E. Flynn is the sole member of the general partner of each of Deerfield Mgmt, L.P. and Deerfield Management Company, L.P.

F5 · ownership.nature: In accordance with Instruction 4 (b)(iv) to Form 4, the entire amount of the Issuer's securities held by the Funds is reported herein. For purposes of Section 16 of the Securities Exchange Act of 1934, as amended, each Reporting Person disclaims beneficial ownership of any such securities, except to the extent of his/its indirect pecuniary interest therein, if any, and this report shall not be deemed an admission that such Reporting Person is the beneficial owner of such securities for purposes of Section 16 or otherwise.

F6 · ownership.nature: This Amendment to the Form 4 filed with the Commission on March 8, 2018 (the "Original Filing") is being filed to correctly report the identity of the direct beneficial owners of shares sold on March 6, 2018, March 7, 2018 and March 8, 2018 (as well as the direct holder of shares beneficially owned by the applicable Reporting Persons following such sales) which were incorrectly reported on the March 8, 2018 Form 4 report. The aggregate number of shares sold by the Funds and the aggregate number of shares beneficially owned by the Reporting Persons, as reported in the Original Filing, remains unchanged.

SEC source: 0001193805-18-000436 · e617828_4a-catalyst.xml · nonDerivative · entry 1

Flynn James E · CIK 0001352546 · 10% owner · Possible Member of 10% Group

Deerfield Mgmt L.P. · CIK 0001010823 · 10% owner · Possible Member of 10% Group

DEERFIELD MANAGEMENT COMPANY, L.P. (SERIES C) · CIK 0001009258 · 10% owner · Possible Member of 10% Group

Deerfield Special Situations Fund, L.P. · CIK 0001354395 · 10% owner · Possible Member of 10% Group

DEERFIELD PARTNERS, L.P. · CIK 0001301041 · 10% owner · Possible Member of 10% Group

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

10b5-1 filing: Not disclosed

Ownership: Indirect · Through Deerfield Partners, L.P.

Disclosed balance after: 849,763

F1 · price: The price reported in Column 4 is a weighted average price. The shares were sold in multiple transactions at prices ranging from $29.75 to $30.50, inclusive. The reporting persons undertake to provide to the Issuer, any security holder of the Issuer or the staff of the Securities and Exchange Commission (the "Commission"), upon request, full information regarding the number of shares sold at each separate price within the ranges set forth in footnotes (1), (2) and (3) of this Form 4.

F4 · ownership.nature: This Form 4 is being filed by the undersigned as well as the entities listed on the Joint Filer Information Statement attached as an exhibit hereto (the "Reporting Persons"). Deerfield Mgmt, L.P. is the general partner of Deerfield Special Situations Fund, L.P. and Deerfield Partners, L.P. (the "Funds"). Deerfield Management Company, L.P. is the investment manager of the Funds. James E. Flynn is the sole member of the general partner of each of Deerfield Mgmt, L.P. and Deerfield Management Company, L.P.

F5 · ownership.nature: In accordance with Instruction 4 (b)(iv) to Form 4, the entire amount of the Issuer's securities held by the Funds is reported herein. For purposes of Section 16 of the Securities Exchange Act of 1934, as amended, each Reporting Person disclaims beneficial ownership of any such securities, except to the extent of his/its indirect pecuniary interest therein, if any, and this report shall not be deemed an admission that such Reporting Person is the beneficial owner of such securities for purposes of Section 16 or otherwise.

F6 · ownership.nature: This Amendment to the Form 4 filed with the Commission on March 8, 2018 (the "Original Filing") is being filed to correctly report the identity of the direct beneficial owners of shares sold on March 6, 2018, March 7, 2018 and March 8, 2018 (as well as the direct holder of shares beneficially owned by the applicable Reporting Persons following such sales) which were incorrectly reported on the March 8, 2018 Form 4 report. The aggregate number of shares sold by the Funds and the aggregate number of shares beneficially owned by the Reporting Persons, as reported in the Original Filing, remains unchanged.

SEC source: 0001209191-18-012450 · doc4.xml · derivative · entry 1

Richard John P · CIK 0001296528 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: Not disclosed

Underlying: Common Stock · 120 shares

Expires not disclosed

F1 · derivative.exercise_price: Reflects a 1:15 reverse stock split effected on February 10, 2017.

F2 · kind: Reflects a redeemable convertible note of the Issuer (the "Note") that matured, with the face value of the Note repaid to the Reporting Person.

F3 · derivative.exercise_date: At the option of the Reporting Person, at any time on or before February 19, 2018, the Note was redeemable into cash at a rate of $1 for each $1 principal amount of the Note or convertible into shares of common stock of the Issuer at a conversion rate of $137.85 per share, respectively.

F4 · derivative.expiration_date: The Note matured on February 19, 2018.

SEC source: 0001209191-18-012438 · doc4.xml · derivative · entry 2

HILL STEPHEN A · CIK 0001237404 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 156 shares

Expires not disclosed

F1 · derivative.exercise_price: Reflects a 1:15 reverse stock split effected on February 10, 2017.

F2 · kind: Reflects a redeemable convertible note of the Issuer (the "Note") that matured, with the face value of the Note repaid to the Reporting Person.

F3 · derivative.exercise_date: At the option of the Reporting Person, at any time on or before February 19, 2018, the Note was redeemable into cash at a rate of $1 for each $1 principal amount of the Note or convertible into shares of common stock of the Issuer at a conversion rate of $137.85 per share, respectively.

F4 · derivative.expiration_date: The Note matured on February 19, 2018.

SEC source: 0001209191-18-012438 · doc4.xml · derivative · entry 1

HILL STEPHEN A · CIK 0001237404 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: Not disclosed

Underlying: Common Stock · 1,371 shares

Expires not disclosed

F1 · derivative.exercise_price: Reflects a 1:15 reverse stock split effected on February 10, 2017.

F2 · kind: Reflects a redeemable convertible note of the Issuer (the "Note") that matured, with the face value of the Note repaid to the Reporting Person.

F3 · derivative.exercise_date: At the option of the Reporting Person, at any time on or before February 19, 2018, the Note was redeemable into cash at a rate of $1 for each $1 principal amount of the Note or convertible into shares of common stock of the Issuer at a conversion rate of $137.85 per share, respectively.

F4 · derivative.expiration_date: The Note matured on February 19, 2018.

SEC source: 0001209191-18-012430 · doc4.xml · derivative · entry 2

DESOUZA ERROL B · CIK 0001213895 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 33 shares

Expires not disclosed

F1 · derivative.exercise_price: Reflects a 1:15 reverse stock split effected on February 10, 2017.

F2 · kind: Reflects a redeemable convertible note of the Issuer (the "Note") that matured, with the face value of the Note repaid to the Reporting Person.

F3 · derivative.exercise_date: At the option of the Reporting Person, at any time on or before February 19, 2018, the Note was redeemable into cash at a rate of $1 for each $1 principal amount of the Note or convertible into shares of common stock of the Issuer at a conversion rate of $137.85 per share, respectively.

F4 · derivative.expiration_date: The Note matured on February 19, 2018.

SEC source: 0001209191-18-012430 · doc4.xml · derivative · entry 1

DESOUZA ERROL B · CIK 0001213895 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: Not disclosed

Underlying: Common Stock · 78 shares

Expires not disclosed

F1 · derivative.exercise_price: Reflects a 1:15 reverse stock split effected on February 10, 2017.

F2 · kind: Reflects a redeemable convertible note of the Issuer (the "Note") that matured, with the face value of the Note repaid to the Reporting Person.

F3 · derivative.exercise_date: At the option of the Reporting Person, at any time on or before February 19, 2018, the Note was redeemable into cash at a rate of $1 for each $1 principal amount of the Note or convertible into shares of common stock of the Issuer at a conversion rate of $137.85 per share, respectively.

F4 · derivative.expiration_date: The Note matured on February 19, 2018.

SEC source: 0001209191-18-004356 · doc4.xml · derivative · entry 10

SELICK HAROLD E · CIK 0001287233 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 10,000 shares

Expires 2020-07-11

F3 · derivative.expiration_date: The reported transactions involved an amendment to the post-termination exercise period of outstanding options, resulting in the deemed cancellation of the vested options and the grant of replacement fully vested options.

SEC source: 0001209191-18-004356 · doc4.xml · derivative · entry 9

SELICK HAROLD E · CIK 0001287233 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 10,000 shares

Expires 2027-07-13

F2 · derivative.exercise_date: The option is fully vested and exercisable.

SEC source: 0001209191-18-004356 · doc4.xml · derivative · entry 8

SELICK HAROLD E · CIK 0001287233 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 500

Underlying: Common Stock · 500 shares

Expires 2020-07-11

F3 · derivative.expiration_date: The reported transactions involved an amendment to the post-termination exercise period of outstanding options, resulting in the deemed cancellation of the vested options and the grant of replacement fully vested options.

SEC source: 0001209191-18-004356 · doc4.xml · derivative · entry 7

SELICK HAROLD E · CIK 0001287233 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 500 shares

Expires 2026-06-09

F1 · derivative.exercise_price: Reflects a fifteen-for-one reverse stock split on February 10, 2017.

F1 · shares: Reflects a fifteen-for-one reverse stock split on February 10, 2017.

F2 · derivative.exercise_date: The option is fully vested and exercisable.

F1 · derivative.underlying_shares: Reflects a fifteen-for-one reverse stock split on February 10, 2017.

SEC source: 0001209191-18-004356 · doc4.xml · derivative · entry 6

SELICK HAROLD E · CIK 0001287233 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 450

Underlying: Common Stock · 450 shares

Expires 2020-07-11

F3 · derivative.expiration_date: The reported transactions involved an amendment to the post-termination exercise period of outstanding options, resulting in the deemed cancellation of the vested options and the grant of replacement fully vested options.

SEC source: 0001209191-18-004356 · doc4.xml · derivative · entry 5

SELICK HAROLD E · CIK 0001287233 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 450 shares

Expires 2025-10-22

F1 · derivative.exercise_price: Reflects a fifteen-for-one reverse stock split on February 10, 2017.

F1 · shares: Reflects a fifteen-for-one reverse stock split on February 10, 2017.

F2 · derivative.exercise_date: The option is fully vested and exercisable.

F1 · derivative.underlying_shares: Reflects a fifteen-for-one reverse stock split on February 10, 2017.

SEC source: 0001209191-18-004356 · doc4.xml · derivative · entry 4

SELICK HAROLD E · CIK 0001287233 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 550

Underlying: Common Stock · 550 shares

Expires 2020-07-11

F3 · derivative.expiration_date: The reported transactions involved an amendment to the post-termination exercise period of outstanding options, resulting in the deemed cancellation of the vested options and the grant of replacement fully vested options.

SEC source: 0001209191-18-004356 · doc4.xml · derivative · entry 3

SELICK HAROLD E · CIK 0001287233 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 550 shares

Expires 2025-10-22

F1 · derivative.exercise_price: Reflects a fifteen-for-one reverse stock split on February 10, 2017.

F1 · shares: Reflects a fifteen-for-one reverse stock split on February 10, 2017.

F2 · derivative.exercise_date: The option is fully vested and exercisable.

F1 · derivative.underlying_shares: Reflects a fifteen-for-one reverse stock split on February 10, 2017.

SEC source: 0001209191-18-004356 · doc4.xml · derivative · entry 2

SELICK HAROLD E · CIK 0001287233 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 197

Underlying: Common Stock · 197 shares

Expires 2020-07-11

F3 · derivative.expiration_date: The reported transactions involved an amendment to the post-termination exercise period of outstanding options, resulting in the deemed cancellation of the vested options and the grant of replacement fully vested options.

SEC source: 0001209191-18-004356 · doc4.xml · derivative · entry 1

SELICK HAROLD E · CIK 0001287233 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 197 shares

Expires 2020-05-13

F1 · derivative.exercise_price: Reflects a fifteen-for-one reverse stock split on February 10, 2017.

F1 · shares: Reflects a fifteen-for-one reverse stock split on February 10, 2017.

F2 · derivative.exercise_date: The option is fully vested and exercisable.

F1 · derivative.underlying_shares: Reflects a fifteen-for-one reverse stock split on February 10, 2017.

SEC source: 0000899243-18-001064 · doc4.xml · derivative · entry 1

USMAN NASSIM · CIK 0001206872 · Director · President and CEO

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 95,000

Underlying: Common Stock · 95,000 shares

Expires 2028-01-12

F1 · derivative.exercise_date: The Option vests monthly over a period of four years commencing January 12, 2018.

SEC source: 0000899243-18-001063 · doc4.xml · derivative · entry 1

Payne Fletcher · CIK 0001650476 · Chief Financial Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 26,000

Underlying: Common Stock · 26,000 shares

Expires 2028-01-12

F1 · derivative.exercise_date: The Option vests monthly over a period of four years commencing January 12, 2018.

SEC source: 0000899243-18-001062 · doc4.xml · derivative · entry 1

Levy Howard · CIK 0001672333 · Chief Medical Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 33,000

Underlying: Common Stock · 33,000 shares

Expires 2028-01-12

F1 · derivative.exercise_date: The Option vests monthly over a period of four years commencing January 12, 2018.

SEC source: 0001209191-18-000364 · doc4.xml · derivative · entry 1

Williams Eddie · CIK 0001725276 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 10,000 shares

Expires 2028-01-02

F1 · derivative.exercise_date: The Option shall vest monthly over a period of three years commencing January 2, 2018.

SEC source: 0001209191-17-067088 · doc4.xml · derivative · entry 1

Richard John P · CIK 0001296528 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: Not disclosed

Underlying: Common Stock · 58 shares

Expires not disclosed

F1 · kind: Reflects a redeemable convertible note of the Issuer (the "Note") that was called for redemption by the Reporting Person at a price equal to its face value.

F2 · derivative.exercise_date: At the option of the Reporting Person, at any time on or before February 19, 2018, the Note shall be redeemable into cash at a rate of $1 for each $1 principal amount of the Note or convertible into shares of common stock of the Issuer at a conversion rate of $137.85 per share, respectively.

F3 · derivative.expiration_date: The Note will mature on February 19, 2018.

SEC source: 0001209191-17-058099 · doc4.xml · derivative · entry 1

Hunt Andrea · CIK 0001720487 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 10,000 shares

Expires 2027-10-25

F1 · derivative.exercise_date: The Option shall vest monthly over a period of three years commencing October 25, 2017.

SEC source: 0001209191-17-045216 · doc4.xml · derivative · entry 1

SELICK HAROLD E · CIK 0001287233 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 10,000 shares

Expires 2027-07-13

F1 · derivative.exercise_date: The option shall vest monthly over a period of 12 months commencing June 15, 2017.

SEC source: 0001209191-17-045214 · doc4.xml · derivative · entry 1

LAWLOR AUGUSTINE · CIK 0001262327 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 10,000 shares

Expires 2027-07-13

F1 · derivative.exercise_date: The option shall vest monthly over a period of 12 months commencing June 15, 2017.

SEC source: 0001209191-17-045213 · doc4.xml · derivative · entry 1

HILL STEPHEN A · CIK 0001237404 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 10,000 shares

Expires 2027-07-13

F1 · derivative.exercise_date: The option shall vest monthly over a period of 12 months commencing June 15, 2017.

SEC source: 0001209191-17-045212 · doc4.xml · derivative · entry 1

DESOUZA ERROL B · CIK 0001213895 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 10,000 shares

Expires 2027-07-13

F1 · derivative.exercise_date: The option shall vest monthly over a period of 12 months commencing June 15, 2017.

SEC source: 0001209191-17-045311 · doc4.xml · derivative · entry 1

Richard John P · CIK 0001296528 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 10,000 shares

Expires 2027-07-13

F1 · derivative.exercise_date: The option shall vest monthly over a period of 12 months commencing June 15, 2017.

SEC source: 0001209191-17-044902 · doc4.xml · derivative · entry 1

Levy Howard · CIK 0001672333 · Chief Medical Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 95,000

Underlying: Common Stock · 95,000 shares

Expires 2017-07-11

F1 · derivative.exercise_date: The Option vests monthly over a period of four years commencing June 15, 2017.

SEC source: 0001209191-17-044901 · doc4.xml · derivative · entry 1

Payne Fletcher · CIK 0001650476 · Chief Financial Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 75,000

Underlying: Common Stock · 75,000 shares

Expires 2027-07-11

F1 · derivative.exercise_date: The Option vests monthly over a period of four years commencing June 15, 2017.

SEC source: 0001209191-17-044899 · doc4.xml · derivative · entry 1

USMAN NASSIM · CIK 0001206872 · Director · President & CEO

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 275,000

Underlying: Common Stock · 275,000 shares

Expires 2027-07-11

F1 · derivative.exercise_date: The Option vests monthly over a period of four years commencing June 15, 2017.