RYTM

SEC source: 0001104659-19-009039 · a4.xml · derivative · entry 1

Kelner Simon · CIK 0001742917 · Chief Human Resources Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 55,000

Underlying: Common Stock · 55,000 shares

Expires 2029-02-12

F1 · derivative.exercise_date: This option was granted on February 13, 2019 and the shares underlying this option vest in sixteen equal quarterly installments beginning on May 13, 2019.

SEC source: 0001104659-19-005511 · a4.xml · derivative · entry 2

Smith Hunter C · CIK 0001636385 · Chief Financial Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 195,744

Underlying: Common Stock · 3,000 shares

Expires 2027-08-08

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

F1 · derivative.exercise_date: The stock options were granted on August 9, 2017. 25% of the stock options vested and became exercisable on July 31, 2018. 75% of the stock options shall vest in 36 successive, equal monthly installments with the first such installment vesting and becoming exercisable on August 31, 2018.

SEC source: 0001104659-19-005511 · a4.xml · nonDerivative · entry 1

Smith Hunter C · CIK 0001636385 · Chief Financial Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 6,000

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

SEC source: 0001104659-19-003144 · a4.xml · nonDerivative · entry 2

Gottesdiener Keith Michael · CIK 0001615856 · Director · CEO and President

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 544,920

F3 · kind: On January 23, 2019, Mr. Gottesdiener sold 105 shares pursuant to a plan of disposition adopted in accordance with Rule 10b5-1 of the Securities Exchange Act of 1934, as amended.

SEC source: 0001104659-19-003144 · a4.xml · nonDerivative · entry 1

Gottesdiener Keith Michael · CIK 0001615856 · Director · CEO and President

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 545,025

F1 · kind: On January 22, 2019, Mr. Gottesdiener sold 15,674 shares pursuant to a plan of disposition adopted in accordance with Rule 10b5-1 of the Securities Exchange Act of 1934, as amended.

F2 · price: This transaction was executed in multiple trades at prices ranging from $30.00 to $30.63, inclusive; the price reported above reflects the weighted average sale price. Mr. Gottesdiener hereby undertakes to provide to the Securities and Exchange Commission staff, the issuer or any security holder of the issuer, upon request, full information regarding the number of shares and prices at which the transaction was effected.

SEC source: 0001104659-19-002735 · a4.xml · nonDerivative · entry 1

Gottesdiener Keith Michael · CIK 0001615856 · Director · CEO & President

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 560,699

F1 · kind: On January 18, 2019, Mr. Gottesdiener sold 10,115 shares pursuant to a plan of disposition adopted in accordance with Rule 10b5-1 of the Securities Exchange Act of 1934, as amended.

F2 · price: This transaction was executed in multiple trades at prices ranging from $30.00 to $30.25, inclusive; the price reported above reflects the weighted average sale price. Mr. Gottesdiener hereby undertakes to provide to the Securities and Exchange Commission staff, the issuer or any security holder of the issuer, upon request, full information regarding the number of shares and prices at which the transaction was effected.

SEC source: 0001104659-19-002328 · a4.xml · nonDerivative · entry 1

Gottesdiener Keith Michael · CIK 0001615856 · Director · CEO & President

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 570,814

F1 · kind: On January 16, 2019, Mr. Gottesdiener sold 662 shares pursuant to a plan of disposition adopted in accordance with Rule 10b5-1 of the Securities Exchange Act of 1934, as amended.

F2 · price: This transaction was executed in multiple trades at prices ranging from $30.00 to $30.02, inclusive; the price reported above reflects the weighted average sale price. Mr. Gottesdiener hereby undertakes to provide to the Securities and Exchange Commission staff, the issuer or any security holder of the issuer, upon request, full information regarding the number of shares and prices at which the transaction was effected.

SEC source: 0001104659-19-002494 · a4.xml · nonDerivative · entry 1

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 42,339

F1 · kind: On January 16, 2019, Mr. Van der Ploeg sold 200 shares pursuant to a plan of disposition adopted in accordance with Rule 10b5-1 of the Securities Exchange Act of 1934, as amended.

SEC source: 0001104659-18-071680 · a4.xml · nonDerivative · entry 1

Gottesdiener Keith Michael · CIK 0001615856 · Director · CEO and President

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 571,476

F1 · kind: On December 3, 2018, Mr. Gottesdiener sold 563 shares pursuant to a plan of disposition adopted in accordance with Rule 10b5-1 of the Securities Exchange Act of 1934.

SEC source: 0001104659-18-066381 · a4.xml · derivative · entry 7

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 30,894

Underlying: Common Stock · 10,000 shares

Expires 2025-12-30

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.

F5 · derivative.exercise_date: The stock options vest and become exercisable in 48 successive, equal monthly installments measured from August 3, 2015.

SEC source: 0001104659-18-066381 · a4.xml · derivative · entry 6

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 55,430

Underlying: Common Stock · 10,000 shares

Expires 2027-04-04

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

F4 · derivative.exercise_date: The stock options vest and become exercisable in 48 successive, equal monthly installments measured from January 6, 2017.

SEC source: 0001104659-18-066381 · a4.xml · derivative · entry 5

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 33,471

Underlying: Common Stock · 8,200 shares

Expires 2025-11-16

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.

F3 · derivative.exercise_date: The stock options vest and become exercisable in 48 successive, equal monthly installments measured from August 3, 2015.

SEC source: 0001104659-18-066381 · a4.xml · nonDerivative · entry 4

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 42,539

F1 · kind: On November 2, 2018, Mr. Van der Ploeg sold 38,000 shares pursuant to a plan of disposition adopted in accordance with Rule 10b5-1 of the Securities Exchange Act of 1934, as amended.

F2 · price: This transaction was executed in multiple trades at prices ranging from $30.00 to $30.31, inclusive; the price reported above reflects the weighted average sale price. Mr. Van der Ploeg hereby undertakes to provide to the Securities and Exchange Commission staff, the issuer or any security holder of the issuer, upon request, full information regarding the number of shares and prices at which the transaction was effected.

SEC source: 0001104659-18-066381 · a4.xml · nonDerivative · entry 3

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 80,539

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

SEC source: 0001104659-18-066381 · a4.xml · nonDerivative · entry 2

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 70,539

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

SEC source: 0001104659-18-066381 · a4.xml · nonDerivative · entry 1

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 60,539

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

SEC source: 0001104659-18-066382 · a4.xml · nonDerivative · entry 1

Gottesdiener Keith Michael · CIK 0001615856 · Director · CEO and President

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 572,039

F1 · kind: On November 2, 2018, Mr. Gottesdiener sold 16,500 shares pursuant to a plan of disposition adopted in accordance with Rule 10b5-1 of the Securities Exchange Act of 1934.

F2 · price: This transaction was executed in multiple trades at prices ranging from $30.00 to $30.28, inclusive; the price reported above reflects the weighted average sale price. Mr. Gottesdiener hereby undertakes to provide to the Securities and Exchange Commission staff, the issuer or any security holder of the issuer, upon request, full information regarding the number of shares and prices at which the transaction was effected.

SEC source: 0001104659-18-062553 · a4.xml · derivative · entry 1

Stewart Murray · CIK 0001723450 · Chief Medical Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 100,000

Underlying: Common Stock · 100,000 shares

Expires 2028-10-14

F1 · derivative.exercise_date: The option vests as follows: (1) 25% on October 15, 2019, and (2) the remaining 75% in 12 equal quarterly installments.

SEC source: 0001104659-18-059105 · a4.xml · derivative · entry 8

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 41,671

Underlying: Common Stock · 21,800 shares

Expires 2025-11-16

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.

F8 · derivative.exercise_date: The stock options vest and become exercisable in 48 successive, equal monthly installments measured from August 3, 2015.

SEC source: 0001104659-18-059105 · a4.xml · nonDerivative · entry 7

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 52,339

F2 · kind: On September 25, 2018, Mr. Van der Ploeg sold 31,800 shares in multiple trades at prices ranging from $27.12 to $32.36 pursuant to a plan of disposition adopted in accordance with Rule 10b5-1 of the Securities Exchange Act of 1934 (the "10b5-1 Plan").

F7 · price: This transaction was executed in multiple trades at prices ranging from $31.36 to $32.05, inclusive; the price reported above reflects the weighted average sale price. Mr. Van der Ploeg hereby undertakes to provide to the Staff, the issuer or any security holder of the issuer, upon request, full information regarding the number of shares and prices at which the transaction was effected.

SEC source: 0001104659-18-059105 · a4.xml · nonDerivative · entry 6

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 58,441

F2 · kind: On September 25, 2018, Mr. Van der Ploeg sold 31,800 shares in multiple trades at prices ranging from $27.12 to $32.36 pursuant to a plan of disposition adopted in accordance with Rule 10b5-1 of the Securities Exchange Act of 1934 (the "10b5-1 Plan").

F6 · price: This transaction was executed in multiple trades at prices ranging from $30.21 to $31.20, inclusive; the price reported above reflects the weighted average sale price. Mr. Van der Ploeg hereby undertakes to provide to the Staff, the issuer or any security holder of the issuer, upon request, full information regarding the number of shares and prices at which the transaction was effected.

SEC source: 0001104659-18-059105 · a4.xml · nonDerivative · entry 5

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 63,745

F2 · kind: On September 25, 2018, Mr. Van der Ploeg sold 31,800 shares in multiple trades at prices ranging from $27.12 to $32.36 pursuant to a plan of disposition adopted in accordance with Rule 10b5-1 of the Securities Exchange Act of 1934 (the "10b5-1 Plan").

F5 · price: This transaction was executed in multiple trades at prices ranging from $29.21 to $30.20, inclusive; the price reported above reflects the weighted average sale price. Mr. Van der Ploeg hereby undertakes to provide to the Staff, the issuer or any security holder of the issuer, upon request, full information regarding the number of shares and prices at which the transaction was effected.

SEC source: 0001104659-18-059105 · a4.xml · nonDerivative · entry 4

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 71,401

F2 · kind: On September 25, 2018, Mr. Van der Ploeg sold 31,800 shares in multiple trades at prices ranging from $27.12 to $32.36 pursuant to a plan of disposition adopted in accordance with Rule 10b5-1 of the Securities Exchange Act of 1934 (the "10b5-1 Plan").

F4 · price: This transaction was executed in multiple trades at prices ranging from $28.20 to $29.19, inclusive; the price reported above reflects the weighted average sale price. Mr. Van der Ploeg hereby undertakes to provide to the Staff, the issuer or any security holder of the issuer, upon request, full information regarding the number of shares and prices at which the transaction was effected.

SEC source: 0001104659-18-059105 · a4.xml · nonDerivative · entry 3

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 80,453

F2 · kind: On September 25, 2018, Mr. Van der Ploeg sold 31,800 shares in multiple trades at prices ranging from $27.12 to $32.36 pursuant to a plan of disposition adopted in accordance with Rule 10b5-1 of the Securities Exchange Act of 1934 (the "10b5-1 Plan").

F3 · price: This transaction was executed in multiple trades at prices ranging from $27.12 to $27.88, inclusive; the price reported above reflects the weighted average sale price. Mr. Van der Ploeg hereby undertakes to provide to the Securities and Exchange Commission staff (the "Staff"), the issuer or any security holder of the issuer, upon request, full information regarding the number of shares and prices at which the transaction was effected.

SEC source: 0001104659-18-059105 · a4.xml · nonDerivative · entry 2

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 84,139

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

SEC source: 0001104659-18-055584 · a4.xml · derivative · entry 2

Smith Hunter C · CIK 0001636385 · Chief Financial Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 198,744

Underlying: Common Stock · 3,000 shares

Expires 2027-08-08

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

F1 · derivative.exercise_date: The stock options were granted on August 9, 2017. 25% of the stock options vested and became exercisable on July 31, 2018. 75% of the stock options shall vest in 36 successive, equal monthly installments with the first such installment vesting and becoming exercisable on August 31, 2018.

SEC source: 0001104659-18-055584 · a4.xml · nonDerivative · entry 1

Smith Hunter C · CIK 0001636385 · Chief Financial Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 3,000

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

SEC source: 0000899243-18-023708 · doc4.xml · nonDerivative · entry 1

THIRD ROCK VENTURES LP · CIK 0001408591 · 10% owner

Third Rock Ventures GP, L.P. · CIK 0001578976 · 10% owner

TRV GP, LLC · CIK 0001578973 · 10% owner

STARR KEVIN P · CIK 0001192603 · 10% owner

TEPPER ROBERT I · CIK 0001192595 · 10% owner

LEVIN MARK J · CIK 0001180428 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 2,981,437

F1 · kind: Pursuant to a Rule 10b5-1 trading plan adopted by Third Rock Ventures, L.P. ("TRV"), Third Rock Ventures GP, L.P. ("TRV GP") and TRV GP, LLC ("TRV GP LLC"), TRV distributed on August 30, 2018, for no consideration, 1,000,000 shares of Common Stock of the Issuer (the "Shares") to its limited partners and to TRV GP, the general partner of TRV, representing each such partner's pro rata interest in such Shares. On the same date, TRV GP distributed, for no consideration, the Shares it received in the distribution by TRV to its partners, representing each such partner's pro rata interest in such Shares. All of the aforementioned distributions were made in accordance with the exemptions afforded by Rules 16a-13 and 16a-9 of the Securities Exchange Act of 1934, as amended.

F1 · price: Pursuant to a Rule 10b5-1 trading plan adopted by Third Rock Ventures, L.P. ("TRV"), Third Rock Ventures GP, L.P. ("TRV GP") and TRV GP, LLC ("TRV GP LLC"), TRV distributed on August 30, 2018, for no consideration, 1,000,000 shares of Common Stock of the Issuer (the "Shares") to its limited partners and to TRV GP, the general partner of TRV, representing each such partner's pro rata interest in such Shares. On the same date, TRV GP distributed, for no consideration, the Shares it received in the distribution by TRV to its partners, representing each such partner's pro rata interest in such Shares. All of the aforementioned distributions were made in accordance with the exemptions afforded by Rules 16a-13 and 16a-9 of the Securities Exchange Act of 1934, as amended.

F2 · ownership.direct: These shares are directly held by TRV. The general partner of TRV is TRV GP. The general partner of TRV GP is TRV GP LLC. The individual managers of TRV GP LLC are Mark Levin ("Levin"), Kevin Starr ("Starr") and Dr. Robert Tepper ("Tepper"). Each of TRV GP, TRV GP LLC, Levin, Starr and Tepper disclaims beneficial ownership of the shares except to the extent of its or his pecuniary interest therein, if any, and this report shall not be deemed an admission that it or he is the beneficial owner of such shares.

SEC source: 0001104659-18-051945 · a4.xml · derivative · entry 2

Desikan Nithya · CIK 0001714105 · Chief Commercial Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 187,210

Underlying: Common Stock · 14,534 shares

Expires 2027-08-08

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

F1 · derivative.exercise_date: The stock options were granted on August 9, 2017. 32,715 of the total shares vested and became exercisable immediately upon grant. 25% of the remaining stock options vested and became exercisable on July 23, 2018. 75% of the remaining stock options shall vest in 36 successive, equal monthly installments with the first such installment vesting and becoming exercisable on August 23, 2018.

SEC source: 0001104659-18-051945 · a4.xml · nonDerivative · entry 1

Desikan Nithya · CIK 0001714105 · Chief Commercial Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 14,534

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

SEC source: 0001104659-18-059105 · a4.xml · nonDerivative · entry 1

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 62,339

F1 · kind: Mr. Van der Ploeg is voluntarily reporting a gift transfer of shares of common stock.

SEC source: 0001209191-19-008847 · doc5.xml · nonDerivative · entry 1

Foley Todd · CIK 0001473930 · Director

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnote

Disclosed balance after: 3,074,893

F1 · shares: The shares are were purchased as follows: 364,347 by MPM BioVentures V, L.P. ("BV V") and 14,154 by MPM Asset Management Investors BV5 LLC ("AM BV5"). MPM BioVentures V GP LLC and MPM BioVentures V LLC ("BV LLC") are the direct and indirect general partners of BV V. Ansbert Gadicke, Luke Evnin and Todd Foley are the members of BV LLC. The Reporting Person disclaims beneficial ownership of the securities except to the extent of his pecuniary interest therein.

F2 · ownership.nature: Shares are held as follows: 2,959,906 by BV V and 114,987 by AM BV5. The Reporting Person disclaims beneficial ownership of the securities except to the extent of his pecuniary interest therein.

SEC source: 0001104659-18-039180 · a4.xml · derivative · entry 1

Exter Neil · CIK 0001620014 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 10,000 shares

Expires 2028-06-05

F1 · derivative.exercise_date: The options fully vest upon the earlier of (i) 1 year from the date of grant or (ii) the date of the Issuer's next annual meeting of the stockholders.

SEC source: 0001104659-18-039177 · a4.xml · derivative · entry 1

Foley Todd · CIK 0001473930 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 10,000 shares

Expires 2028-06-05

F1 · derivative.exercise_date: The options fully vest upon the earlier of (i) 1 year from the date of grant or (ii) the date of the Issuer's next annual meeting of the stockholders.

SEC source: 0001104659-18-039178 · a4.xml · derivative · entry 1

MCGIRR DAVID W J · CIK 0001219023 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 10,000 shares

Expires 2028-06-05

F1 · derivative.exercise_date: The options fully vest upon the earlier of (i) 1 year from the date of grant or (ii) the date of the Issuer's next annual meeting of the stockholders.

SEC source: 0001209191-18-036724 · doc4.xml · derivative · entry 1

Mathers Edward T · CIK 0001328625 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 10,000 shares

Expires 2028-06-05

F1 · derivative.exercise_date: The options fully vest upon the earlier of (i) 1 year from the date of grant or (ii) the date of the Issuer's next annual meeting of the stockholders.

SEC source: 0001104659-18-039181 · a4.xml · derivative · entry 1

JEAN CHRISTOPHE · CIK 0001378435 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 10,000 shares

Expires 2028-06-05

F1 · derivative.exercise_date: The options fully vest upon the earlier of (i) 1 year from the date of grant or (ii) the date of the Issuer's next annual meeting of the stockholders.

SEC source: 0001104659-18-039179 · a4.xml · derivative · entry 1

Meeker David P · CIK 0001385155 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 10,000 shares

Expires 2028-06-05

F1 · derivative.exercise_date: The options fully vest upon the earlier of (i) 1 year from the date of grant or (ii) the date of the Issuer's next annual meeting of the stockholders.

SEC source: 0001104659-18-039182 · a4.xml · derivative · entry 1

Kelner Simon · CIK 0001742917 · Chief Human Resources Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 60,000

Underlying: Common Stock · 60,000 shares

Expires 2028-06-05

F1 · derivative.exercise_date: The option vests as follows: (1) 25% on June 4, 2019, and (2) the remaining 75% in 12 equal quarterly installments.

SEC source: 0000947871-18-000450 · ss93582_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner · See Remarks

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner · See Remarks

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 2,750,079

F2 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $30.90 to $31.10 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F3 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F4 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000450 · ss93582_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner · See Remarks

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner · See Remarks

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 2,751,679

F1 · price: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were sold in multiple transactions at prices ranging from $29.90 to $30.89 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F3 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F4 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000439 · ss93205_4.xml · nonDerivative · entry 2

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 2,769,659

F2 · price: The price reported in Column 4 is a weighted average price. These Shares were sold in multiple transactions at prices ranging from $30.75 to $31.27 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F3 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F4 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0000947871-18-000439 · ss93205_4.xml · nonDerivative · entry 1

ORBIMED ADVISORS LLC · CIK 0001055951 · 10% owner

OrbiMed Capital GP V LLC · CIK 0001615374 · 10% owner

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

10b5-1 filing: Not disclosed

Ownership: Indirect · See Footnotes

Disclosed balance after: 2,832,159

F1 · price: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were sold in multiple transactions at prices ranging from $30.44 to $31.35 inclusive. Upon request, the Reporting Persons undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F3 · ownership.nature: These securities are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Capital GP V LLC ("GP V") is the sole general partner of OPI V, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP V. By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to beneficially own such securities for purposes of Rule 13d-3 under the Securities Exchange Act of 1934, as amended (the "Exchange Act"). Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.

F4 · ownership.nature: This report on Form 4 is jointly filed by GP V and Advisors. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

SEC source: 0001104659-18-032155 · a4.xml · derivative · entry 2

Gottesdiener Keith Michael · CIK 0001615856 · Director · C.E.O. and President

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 124,780

Underlying: Common Stock · 3,000 shares

Expires 2025-11-16

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_date: The stock options vest and become exercisable in 48 successive, equal monthly installments measured from August 3, 2015.

SEC source: 0001104659-18-032155 · a4.xml · nonDerivative · entry 1

Gottesdiener Keith Michael · CIK 0001615856 · Director · C.E.O. and President

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 588,539

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

SEC source: 0001104659-18-010366 · a4.xml · derivative · entry 1

Van der Ploeg Leonardus H.T. · CIK 0001615726 · Chief Scientific Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 55,000

Underlying: Common Stock · 55,000 shares

Expires 2028-02-13

F1 · derivative.exercise_date: This option was granted on February 14, 2018 and the shares underlying this option vest in sixteen equal quarterly installments.

SEC source: 0001104659-18-010369 · a4.xml · derivative · entry 1

Gottesdiener Keith Michael · CIK 0001615856 · Director · CEO & President

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 175,000

Underlying: Common Stock · 175,000 shares

Expires 2028-02-13

F1 · derivative.exercise_date: This option was granted on February 14, 2018 and the shares underlying this option vest in sixteen equal quarterly installments.

SEC source: 0001104659-18-010370 · a4.xml · derivative · entry 1

Smith Hunter C · CIK 0001636385 · CFO and Treasurer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 61,000

Underlying: Common Stock · 61,000 shares

Expires 2028-02-13

F1 · derivative.exercise_date: This option was granted on February 14, 2018 and the shares underlying this option vest in sixteen equal quarterly installments.

SEC source: 0001104659-18-010368 · a4.xml · derivative · entry 2

Fiedorek Fred T. · CIK 0001657185 · Chief Medical Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 25,000

Underlying: Common Stock · 25,000 shares

Expires 2028-02-13

F2 · derivative.exercise_date: This option was granted on February 14, 2018 and the shares underlying this option shall vest upon completion of a milestone.

SEC source: 0001104659-18-010368 · a4.xml · derivative · entry 1

Fiedorek Fred T. · CIK 0001657185 · Chief Medical Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 25,000

Underlying: Common Stock · 25,000 shares

Expires 2028-02-13

F1 · derivative.exercise_date: This option was granted on February 14, 2018 and the shares underlying this option vest in sixteen equal quarterly installments.