XENE

SEC source: 0001209191-19-049538 · doc4.xml · nonDerivative · entry 2

ROBIN SHERRINGTON · CIK 0001619962 · EVP, Strategy & Innovation

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,196

F2 · price: Represents the closing price of the Company's common shares on September 11, 2019, which was converted to a Canadian dollar amount for purposes of net settlement calculations.

SEC source: 0001209191-19-049538 · doc4.xml · nonDerivative · entry 1

ROBIN SHERRINGTON · CIK 0001619962 · EVP, Strategy & Innovation

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,064

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

F1 · price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange on the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the day of exercise.

SEC source: 0000899243-19-014470 · doc4.xml · derivative · entry 2

TARNOW MICHAEL M · CIK 0001263647 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Shares · 2,057 shares

Expires 2019-06-30

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

F1 · derivative.exercise_price: The exercise price was converted from $3.74 CAD using the closing rate of exchange of the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the date of exercise.

F2 · derivative.exercise_date: The shares subject to the option fully vested on December 31, 2011.

SEC source: 0000899243-19-014470 · doc4.xml · nonDerivative · entry 1

TARNOW MICHAEL M · CIK 0001263647 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 64,569

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

F1 · price: The exercise price was converted from $3.74 CAD using the closing rate of exchange of the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the date of exercise.

SEC source: 0000899243-19-008569 · doc4.xml · derivative · entry 4

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · By Genworks Inc.

Disclosed balance after: 0

Underlying: Common Shares · 20,576 shares

Expires 2019-08-31

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

F1 · derivative.exercise_price: The exercise price was converted from $3.74 CAD using the closing rate of exchange of the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the date of exercise.

F2 · derivative.exercise_date: The shares subject to the option fully vested on September 1, 2013.

F3 · ownership.nature: Michael Hayden is the president and principal beneficial shareholder of Genworks Inc.

SEC source: 0000899243-19-008569 · doc4.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · By Genworks Inc.

Disclosed balance after: 50,924

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

F1 · price: The exercise price was converted from $3.74 CAD using the closing rate of exchange of the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the date of exercise.

F3 · ownership.nature: Michael Hayden is the president and principal beneficial shareholder of Genworks Inc.

SEC source: 0000899243-19-007264 · doc4.xml · nonDerivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · By Spouse

Disclosed balance after: 114,403

SEC source: 0000899243-19-007264 · doc4.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 107,562

F1 · kind: 6,708 of the shares were gifted to family members that do not share the reporting person's household.

SEC source: 0001171843-18-008556 · ownership.xml · nonDerivative · entry 1

TARNOW MICHAEL M · CIK 0001263647 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 62,512

F1 · kind: The shares were gifted to family members that do not share the reporting person's household.

SEC source: 0001171843-18-008471 · ownership.xml · derivative · entry 3

PATOU GARY · CIK 0001283535 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Shares · 2,057 shares

Expires 2018-12-31

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

F2 · derivative.exercise_price: By Gary & Karen Barbara Patou TTEE Patou Family Trust FBO Gary Patou Karen Barbara Patou.

F3 · derivative.exercise_date: The shares subject to the option fully vested on December 31, 2011.

SEC source: 0001171843-18-008471 · ownership.xml · nonDerivative · entry 1

PATOU GARY · CIK 0001283535 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 19,459

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

F1 · price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange on the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the day of exercise.

SEC source: 0001171843-18-008430 · ownership.xml · derivative · entry 3

COHEN CHARLES J. · CIK 0001619967 · VP, Biology

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Shares · 4,115 shares

Expires 2018-12-31

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

F1 · derivative.exercise_price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange on the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the day of exercise.

F3 · derivative.exercise_date: The shares subject to the option fully vested on December 31, 2012.

SEC source: 0001171843-18-008430 · ownership.xml · nonDerivative · entry 2

COHEN CHARLES J. · CIK 0001619967 · VP, Biology

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 6,550

F4 · shares: The Company withheld the number of shares set forth above pursuant to a net settlement permitted under the terms of a lock-up agreement executed by the Reporting Person in favor of the underwriters of the Company's public offering in September 2018. No shares were sold by the Reporting Person in connection with the exercise and the common shares issued as a result of the exercise are subject to the terms of the lock-up agreement.

F2 · price: Represents the closing price of the Company's common shares in U.S. dollars on December 10, 2018, converted to a Canadian dollar amount for purposes of net settlementment calculations.

SEC source: 0001171843-18-008430 · ownership.xml · nonDerivative · entry 1

COHEN CHARLES J. · CIK 0001619967 · VP, Biology

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 8,194

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

F1 · price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange on the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the day of exercise.

SEC source: 0000899243-18-030608 · doc4.xml · derivative · entry 2

AZAB MOHAMMAD · CIK 0001309653 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Shares · 3,086 shares

Expires 2018-12-31

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

F1 · derivative.exercise_price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange on the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the day of exercise.

F2 · derivative.exercise_date: The shares subject to the option fully vested on December 31, 2011.

SEC source: 0000899243-18-030608 · doc4.xml · nonDerivative · entry 1

AZAB MOHAMMAD · CIK 0001309653 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 57,584

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 · shares: No shares were sold by the Reporting Person in connection with the exercise and the common shares issued as a result of the exercise are subject to the terms of a lock-up agreement executed by the Reporting Person in favor of the underwriters of the Company's public offering in September 2018.

F1 · price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange on the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the day of exercise.

SEC source: 0001171843-18-004796 · formfour.xml · derivative · entry 6

TARNOW MICHAEL M · CIK 0001263647 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Shares · 5,144 shares

Expires 2018-12-31

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

F1 · derivative.exercise_price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange of the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the date of exercise.

F4 · derivative.exercise_date: The shares subject to the option fully vested on December 31, 2011.

SEC source: 0001171843-18-004796 · formfour.xml · derivative · entry 5

TARNOW MICHAEL M · CIK 0001263647 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Shares · 2,057 shares

Expires 2018-06-30

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

F1 · derivative.exercise_price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange of the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the date of exercise.

F3 · derivative.exercise_date: The shares subject to the option fully vested on June 30, 2011.

SEC source: 0001171843-18-004796 · formfour.xml · derivative · entry 4

TARNOW MICHAEL M · CIK 0001263647 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Shares · 5,144 shares

Expires 2018-06-26

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.

F1 · derivative.exercise_price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange of the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the date of exercise.

F2 · derivative.exercise_date: The shares subject to the option fully vested on May 31, 2011.

SEC source: 0001171843-18-004796 · formfour.xml · nonDerivative · entry 3

TARNOW MICHAEL M · CIK 0001263647 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 67,512

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

F1 · price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange of the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the date of exercise.

SEC source: 0001171843-18-004796 · formfour.xml · nonDerivative · entry 2

TARNOW MICHAEL M · CIK 0001263647 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 62,368

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

F1 · price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange of the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the date of exercise.

SEC source: 0001171843-18-004796 · formfour.xml · nonDerivative · entry 1

TARNOW MICHAEL M · CIK 0001263647 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 60,311

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

F1 · price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange of the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the date of exercise.

SEC source: 0001171843-18-004795 · formfour.xml · derivative · entry 2

AZAB MOHAMMAD · CIK 0001309653 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Shares · 10,288 shares

Expires 2018-06-26

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.

F1 · derivative.exercise_price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange on the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the day of exercise.

F2 · derivative.exercise_date: The shares subject to the option fully vested on May 31, 2011.

SEC source: 0001171843-18-004795 · formfour.xml · nonDerivative · entry 1

AZAB MOHAMMAD · CIK 0001309653 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 54,498

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

F1 · price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange on the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the day of exercise.

SEC source: 0001171843-18-004695 · formfour.xml · derivative · entry 4

PATOU GARY · CIK 0001283535 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Shares · 8,230 shares

Expires 2018-06-26

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.

F1 · derivative.exercise_price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange on the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the day of exercise.

F4 · derivative.exercise_date: The shares subject to the option fully vested on May 31, 2011.

SEC source: 0001171843-18-004695 · formfour.xml · nonDerivative · entry 2

PATOU GARY · CIK 0001283535 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 17,402

F2 · price: Represents the closing price of the Company's common shares in U.S. dollars on June 13, 2018, which was converted to a Canadian dollar amount for purposes of net settlement calculations.

SEC source: 0001171843-18-004695 · formfour.xml · nonDerivative · entry 1

PATOU GARY · CIK 0001283535 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 20,258

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

F1 · price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange on the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the day of exercise.

SEC source: 0001171843-18-004457 · formfour.xml · derivative · entry 1

HOLLER FRANK A · CIK 0000938801 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Shares · 15,000 shares

Expires 2028-06-03

F1 · derivative.exercise_date: One-third of the total shares subject to the Option shall vest on the one year anniversary of the grant date, one-third of the total shares subject to the Option shall vest on the two year anniversary of the grant date, and the balance of the total shares subject to the Option shall vest on the three year anniversary of the grant date.

SEC source: 0001171843-18-004455 · formfour.xml · derivative · entry 1

GANNON STEVEN · CIK 0001643085 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Shares · 15,000 shares

Expires 2028-06-03

F1 · derivative.exercise_date: One-third of the total shares subject to the Option shall vest on the one year anniversary of the grant date, one-third of the total shares subject to the Option shall vest on the two year anniversary of the grant date, and the balance of the total shares subject to the Option shall vest on the three year anniversary of the grant date.

SEC source: 0001171843-18-004456 · form4.xml · derivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Shares · 15,000 shares

Expires 2028-06-03

F1 · derivative.exercise_date: One-third of the total shares subject to the Option shall vest on the one year anniversary of the grant date, one-third of the total shares subject to the Option shall vest on the two year anniversary of the grant date, and the balance of the total shares subject to the Option shall vest on the three year anniversary of the grant date.

SEC source: 0001171843-18-004458 · form4.xml · derivative · entry 1

PATOU GARY · CIK 0001283535 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Shares · 15,000 shares

Expires 2028-06-03

F1 · derivative.exercise_date: One-third of the total shares subject to the Option shall vest on the one year anniversary of the grant date, one-third of the total shares subject to the Option shall vest on the two year anniversary of the grant date, and the balance of the total shares subject to the Option shall vest on the three year anniversary of the grant date.

SEC source: 0001171843-18-004461 · form4.xml · derivative · entry 1

TARNOW MICHAEL M · CIK 0001263647 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Shares · 15,000 shares

Expires 2028-06-03

F1 · derivative.exercise_date: One-third of the total shares subject to the Option shall vest on the one year anniversary of the grant date, one-third of the total shares subject to the Option shall vest on the two year anniversary of the grant date, and the balance of the total shares subject to the Option shall vest on the three year anniversary of the grant date.

SEC source: 0001171843-18-004459 · formfour.xml · derivative · entry 1

SCHELLER RICHARD H · CIK 0001214133 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Shares · 15,000 shares

Expires 2028-06-03

F1 · derivative.exercise_date: One-third of the total shares subject to the Option shall vest on the one year anniversary of the grant date, one-third of the total shares subject to the Option shall vest on the two year anniversary of the grant date, and the balance of the total shares subject to the Option shall vest on the three year anniversary of the grant date.

SEC source: 0001171843-18-004454 · form4.xml · derivative · entry 1

AZAB MOHAMMAD · CIK 0001309653 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Shares · 15,000 shares

Expires 2028-06-03

F1 · derivative.exercise_date: One-third of the total shares subject to the Option shall vest on the one year anniversary of the grant date, one-third of the total shares subject to the Option shall vest on the two year anniversary of the grant date, and the balance of the total shares subject to the Option shall vest on the three year anniversary of the grant date.

SEC source: 0001171843-18-004460 · formfour.xml · derivative · entry 1

Svoronos Dawn · CIK 0001574579 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,000

Underlying: Common Shares · 15,000 shares

Expires 2028-06-03

F1 · derivative.exercise_date: One-third of the total shares subject to the Option shall vest on the one year anniversary of the grant date, one-third of the total shares subject to the Option shall vest on the two year anniversary of the grant date, and the balance of the total shares subject to the Option shall vest on the three year anniversary of the grant date.

SEC source: 0000921895-18-001107 · form407422010xen_03292018.xml · derivative · entry 6

BVF PARTNERS L P/IL · CIK 0001055947 · 10% owner

BIOTECHNOLOGY VALUE FUND L P · CIK 0000918923 · See Explanation of Responses

BIOTECHNOLOGY VALUE FUND II LP · CIK 0001102444 · See Explanation of Responses

Biotechnology Value Trading Fund OS LP · CIK 0001660683 · See Explanation of Responses

BVF Partners OS Ltd. · CIK 0001660684 · See Explanation of Responses

BVF INC/IL · CIK 0001056807 · 10% owner

LAMPERT MARK N · CIK 0001233840 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 238,000

Underlying: Common Shares, no par value per share · 238,000 shares

Expires not disclosed

F5 · derivative.exercise_price: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · kind: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · price: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · derivative.exercise_date: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · derivative.expiration_date: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F4 · ownership.direct: Securities owned directly by Trading Fund OS. As the general partner of Trading Fund OS, Partners OS may be deemed to beneficially own the securities owned directly by Trading Fund OS. As the investment manager of Trading Fund OS and the sole member of Partners OS, Partners may be deemed to beneficially own the securities owned directly by Trading Fund OS. As the investment adviser and general partner of Partners, BVF Inc. may be deemed to beneficially own the securities owned directly by Trading Fund OS. As a director and officer of BVF Inc., Mr. Lampert may be deemed to beneficially own the securities owned directly by Trading Fund OS.

SEC source: 0000921895-18-001107 · form407422010xen_03292018.xml · derivative · entry 5

BVF PARTNERS L P/IL · CIK 0001055947 · 10% owner

BIOTECHNOLOGY VALUE FUND L P · CIK 0000918923 · See Explanation of Responses

BIOTECHNOLOGY VALUE FUND II LP · CIK 0001102444 · See Explanation of Responses

Biotechnology Value Trading Fund OS LP · CIK 0001660683 · See Explanation of Responses

BVF Partners OS Ltd. · CIK 0001660684 · See Explanation of Responses

BVF INC/IL · CIK 0001056807 · 10% owner

LAMPERT MARK N · CIK 0001233840 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 861,000

Underlying: Common Shares, no par value per share · 861,000 shares

Expires not disclosed

F5 · derivative.exercise_price: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · kind: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · price: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · derivative.exercise_date: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · derivative.expiration_date: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F3 · ownership.direct: Securities owned directly by BVF2. As the general partner of BVF2, Partners may be deemed to beneficially own the securities owned directly by BVF2. As the investment adviser and general partner of Partners, BVF Inc. may be deemed to beneficially own the securities owned directly by BVF2. As a director and officer of BVF Inc., Mr. Lampert may be deemed to beneficially own the securities owned directly by BVF2.

SEC source: 0000921895-18-001107 · form407422010xen_03292018.xml · derivative · entry 4

BVF PARTNERS L P/IL · CIK 0001055947 · 10% owner

BIOTECHNOLOGY VALUE FUND L P · CIK 0000918923 · See Explanation of Responses

BIOTECHNOLOGY VALUE FUND II LP · CIK 0001102444 · See Explanation of Responses

Biotechnology Value Trading Fund OS LP · CIK 0001660683 · See Explanation of Responses

BVF Partners OS Ltd. · CIK 0001660684 · See Explanation of Responses

BVF INC/IL · CIK 0001056807 · 10% owner

LAMPERT MARK N · CIK 0001233840 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 1,338,000

Underlying: Common Shares, no par value per share · 1,338,000 shares

Expires not disclosed

F5 · derivative.exercise_price: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · kind: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · price: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · derivative.exercise_date: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · derivative.expiration_date: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F2 · ownership.direct: Securities owned directly by BVF. As the general partner of BVF, Partners may be deemed to beneficially own the securities owned directly by BVF. As the investment adviser and general partner of Partners, BVF Inc. may be deemed to beneficially own the securities owned directly by BVF. As a director and officer of BVF Inc., Mr. Lampert may be deemed to beneficially own the securities owned directly by BVF.

SEC source: 0000921895-18-001107 · form407422010xen_03292018.xml · nonDerivative · entry 3

BVF PARTNERS L P/IL · CIK 0001055947 · 10% owner

BIOTECHNOLOGY VALUE FUND L P · CIK 0000918923 · See Explanation of Responses

BIOTECHNOLOGY VALUE FUND II LP · CIK 0001102444 · See Explanation of Responses

Biotechnology Value Trading Fund OS LP · CIK 0001660683 · See Explanation of Responses

BVF Partners OS Ltd. · CIK 0001660684 · See Explanation of Responses

BVF INC/IL · CIK 0001056807 · 10% owner

LAMPERT MARK N · CIK 0001233840 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 59,464

F1 · security: This Form 4 is filed jointly by Biotechnology Value Fund, L.P. ("BVF"), Biotechnology Value Fund II, L.P. ("BVF2"), Biotechnology Value Trading Fund OS LP ("Trading Fund OS"), BVF Partners OS Ltd. ("Partners OS"), BVF Partners L.P. ("Partners"), BVF Inc. and Mark N. Lampert (collectively, the "Reporting Persons"). Each of the Reporting Persons is a member of a Section 13(d) group that collectively owned more than 10% of the Issuer's outstanding Common Shares. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein except to the extent of his or its pecuniary interest therein.

F5 · kind: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · price: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F4 · ownership.direct: Securities owned directly by Trading Fund OS. As the general partner of Trading Fund OS, Partners OS may be deemed to beneficially own the securities owned directly by Trading Fund OS. As the investment manager of Trading Fund OS and the sole member of Partners OS, Partners may be deemed to beneficially own the securities owned directly by Trading Fund OS. As the investment adviser and general partner of Partners, BVF Inc. may be deemed to beneficially own the securities owned directly by Trading Fund OS. As a director and officer of BVF Inc., Mr. Lampert may be deemed to beneficially own the securities owned directly by Trading Fund OS.

SEC source: 0000921895-18-001107 · form407422010xen_03292018.xml · nonDerivative · entry 2

BVF PARTNERS L P/IL · CIK 0001055947 · 10% owner

BIOTECHNOLOGY VALUE FUND L P · CIK 0000918923 · See Explanation of Responses

BIOTECHNOLOGY VALUE FUND II LP · CIK 0001102444 · See Explanation of Responses

Biotechnology Value Trading Fund OS LP · CIK 0001660683 · See Explanation of Responses

BVF Partners OS Ltd. · CIK 0001660684 · See Explanation of Responses

BVF INC/IL · CIK 0001056807 · 10% owner

LAMPERT MARK N · CIK 0001233840 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 216,694

F1 · security: This Form 4 is filed jointly by Biotechnology Value Fund, L.P. ("BVF"), Biotechnology Value Fund II, L.P. ("BVF2"), Biotechnology Value Trading Fund OS LP ("Trading Fund OS"), BVF Partners OS Ltd. ("Partners OS"), BVF Partners L.P. ("Partners"), BVF Inc. and Mark N. Lampert (collectively, the "Reporting Persons"). Each of the Reporting Persons is a member of a Section 13(d) group that collectively owned more than 10% of the Issuer's outstanding Common Shares. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein except to the extent of his or its pecuniary interest therein.

F5 · kind: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · price: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F3 · ownership.direct: Securities owned directly by BVF2. As the general partner of BVF2, Partners may be deemed to beneficially own the securities owned directly by BVF2. As the investment adviser and general partner of Partners, BVF Inc. may be deemed to beneficially own the securities owned directly by BVF2. As a director and officer of BVF Inc., Mr. Lampert may be deemed to beneficially own the securities owned directly by BVF2.

SEC source: 0000921895-18-001107 · form407422010xen_03292018.xml · nonDerivative · entry 1

BVF PARTNERS L P/IL · CIK 0001055947 · 10% owner

BIOTECHNOLOGY VALUE FUND L P · CIK 0000918923 · See Explanation of Responses

BIOTECHNOLOGY VALUE FUND II LP · CIK 0001102444 · See Explanation of Responses

Biotechnology Value Trading Fund OS LP · CIK 0001660683 · See Explanation of Responses

BVF Partners OS Ltd. · CIK 0001660684 · See Explanation of Responses

BVF INC/IL · CIK 0001056807 · 10% owner

LAMPERT MARK N · CIK 0001233840 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 336,468

F1 · security: This Form 4 is filed jointly by Biotechnology Value Fund, L.P. ("BVF"), Biotechnology Value Fund II, L.P. ("BVF2"), Biotechnology Value Trading Fund OS LP ("Trading Fund OS"), BVF Partners OS Ltd. ("Partners OS"), BVF Partners L.P. ("Partners"), BVF Inc. and Mark N. Lampert (collectively, the "Reporting Persons"). Each of the Reporting Persons is a member of a Section 13(d) group that collectively owned more than 10% of the Issuer's outstanding Common Shares. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein except to the extent of his or its pecuniary interest therein.

F5 · kind: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F5 · price: Pursuant to an agreement between the Issuer and the Reporting Persons, the Reporting Persons agreed to exchange in the aggregate 2,868,000 Common Shares for 2,868,000 shares of Series 1 Preferred Shares ("Series 1 Preferred"). Each share of Series 1 Preferred is convertible into one Common Share without payment of any additional consideration. The Series 1 Preferred may not be converted if, after such conversion, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934 (the "Exchange Act"), in excess of 9.99% of the number of Common Shares then issued and outstanding (the "Beneficial Ownership Limitation"). As the date hereof, the Beneficial Ownership Limitation limits the aggregate conversion of Series 1 Preferred by the Reporting Persons to 772,006 Common Shares underlying certain shares of the Series 1 Preferred owned by the Reporting Persons in the aggregate.

F2 · ownership.direct: Securities owned directly by BVF. As the general partner of BVF, Partners may be deemed to beneficially own the securities owned directly by BVF. As the investment adviser and general partner of Partners, BVF Inc. may be deemed to beneficially own the securities owned directly by BVF. As a director and officer of BVF Inc., Mr. Lampert may be deemed to beneficially own the securities owned directly by BVF.

SEC source: 0001171843-18-002118 · formfour.xml · derivative · entry 1

AYCARDI-FONSECA ERNESTO · CIK 0001734218 · Chief Medical Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 50,000

Underlying: Common Shares · 50,000 shares

Expires 2028-03-18

F1 · derivative.exercise_date: Vesting 25% on March 19, 2019, and 75% vesting thereafter over the course of the next 3 years, in equal amounts, on the last day of each month.

SEC source: 0001171843-18-002049 · formfoursherrington.xml · derivative · entry 3

ROBIN SHERRINGTON · CIK 0001619962 · EVP Bus. & Corp. Development

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Shares · 3,086 shares

Expires 2018-03-16

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

F1 · derivative.exercise_price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange on the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the day of exercise.

F3 · derivative.exercise_date: The shares subject to the option fully vested on December 31, 2011. The date the options became fully vested was incorrectly reflected on the Reporting Person's Form 3.

SEC source: 0001171843-18-002049 · formfoursherrington.xml · nonDerivative · entry 2

ROBIN SHERRINGTON · CIK 0001619962 · EVP Bus. & Corp. Development

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 5,892

F2 · price: Represents the closing price of the Company's common shares on March 14, 2018, which was converted to a Canadian dollar amount for purposes of net settlement calculations.

SEC source: 0001171843-18-002049 · formfoursherrington.xml · nonDerivative · entry 1

ROBIN SHERRINGTON · CIK 0001619962 · EVP Bus. & Corp. Development

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 7,820

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

F1 · price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange on the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the day of exercise.

SEC source: 0001171843-18-002044 · formfourholler.xml · derivative · entry 3

HOLLER FRANK A · CIK 0000938801 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Shares · 3,086 shares

Expires 2018-03-16

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

F1 · derivative.exercise_price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange on the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the day of exercise.

F2 · derivative.exercise_date: The shares subject to the option fully vested on December 31, 2011. The date the options became fully vested was incorrectly reflected on the Reporting Person's Form 3.

SEC source: 0001171843-18-002044 · formfourholler.xml · nonDerivative · entry 1

HOLLER FRANK A · CIK 0000938801 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 118,955

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

F1 · price: The exercise price was converted to U.S. dollars from $3.74 CAD using the closing rate of exchange on the Bank of Canada on the date of grant. The actual exercise price is the Canadian dollar amount regardless of the exchange rate on the day of exercise.

SEC source: 0001171843-18-001913 · formfour.xml · derivative · entry 1

PIMSTONE SIMON N. · CIK 0001620084 · Director · CEO

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 140,000

Underlying: Common Shares · 140,000 shares

Expires 2028-03-11

F1 · derivative.exercise_date: Vesting 25% on January 1, 2019, and 75% vesting thereafter over the course of the next 3 years, in equal amounts, on the last day of each month.

SEC source: 0001171843-18-001918 · formfour.xml · derivative · entry 1

COHEN CHARLES J. · CIK 0001619967 · VP, Biology

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 40,000

Underlying: Common Shares · 40,000 shares

Expires 2028-03-11

F1 · derivative.exercise_date: Vesting 25% on January 1, 2019, and 75% vesting thereafter over the course of the next 3 years, in equal amounts, on the last day of each month.

SEC source: 0001171843-18-001917 · form4.xml · derivative · entry 1

EMPFIELD JAMES R. · CIK 0001665430 · SVP, Drug Discovery

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 45,000

Underlying: Common Shares · 45,000 shares

Expires 2028-03-11

F1 · derivative.exercise_date: Vesting 25% on January 1, 2019, and 75% vesting thereafter over the course of the next 3 years, in equal amounts, on the last day of each month.