ISALY SAMUEL D

Row 1 · 2017-07-24 · Grant · Acquired 3,298,516 · Balance 3,298,516

F1: Pursuant to that certain Agreement and Plan of Merger and Reorganization (the "Merger Agreement"), dated as of April 18, 2017, by and among the Issuer, Nautilus Merger Sub, Inc. and the corporation then known as Alpine Immune Sciences, Inc. ("Old Alpine"), each share of Old Alpine common stock was converted into 0.4969 shares of the Issuer's common stock (the "Exchange Ratio").

F2: These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP VI. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP VI, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities.

F3: This report on Form 4 is jointly filed by GP VI, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Peter A. Thompson, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 1 · 2017-03-27 · Purchase · Acquired 1,190,476 · Balance 6,149,377

F1: Each American Depositary Share ("ADS") represents six ordinary shares, nominal value GBP 0.001 per share, of the Issuer. OrbiMed Private Investments V, LP ("OPI V") is the holder of record of the securities reported on this Form 4. OPI V's holdings consist of 25,408,300 ordinary shares held directly, and, 1,914,660 ADSs representing 11,487,960 ordinary shares. Column 5 reports such holdings on an aggregate basis in terms of the corresponding number of ADSs.

F2: These securities are held of record by 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. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly 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").

F3: This report on Form 4 is jointly filed by GP V, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Peter A. Thompson, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 1 · 2017-09-29 · Sale · Disposed 672,000 · Balance 4,129,638

F1: These shares of the Issuer's common stock ("Shares") were sold in a block order at a price of $28.25.

F2: These Shares are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the general partner of OPI IV and OrbiMed Advisors LLC ("Advisors") is the managing member of GP IV. Samuel D. Isaly ("Isaly") is the managing member of, and owner of a controlling interest in, Advisors. By virtue of such relationships, GP IV, Advisors and Isaly may be deemed to have voting and investment power with respect to the Shares held by OPI IV and as a result may be deemed to have beneficial ownership over such Shares.

F3: This report on Form 4 is being jointly filed by GP IV, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report on Form 4 shall not be deemed an admission that the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 1 · 2017-06-13 · Conversion · Acquired 5,000,000 · Balance 5,000,000

F1: The reportable securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP VI. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP VI, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI VI 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").

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

Row 2 · 2017-06-13 · Conversion · Disposed 7,500 · Balance 0

F2: Each share of the Issuer's Series N-3 Preferred Stock ("Preferred Stock") beneficially owned by the Reporting Persons converted into a number of shares of the Issuer's common stock, no par value per share, determined by dividing the stated value of each share of Preferred Stock (which is $2,000) by $3.00. Such conversion is reflected in the number of Shares of common stock reported in column 7 as underlying the security. The Preferred Stock has no expiration date.

F3: The purchase price for the Preferred Stock was $2,000 per share.

F1: The reportable securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP VI. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP VI, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI VI 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").

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

Row 1 · 2017-08-31 · Sale · Disposed 44,498 · Balance 1,358,833

F1: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were sold in multiple transactions at prices ranging from $37.75 to $37.83 inclusive. Upon request, the Reporting Persons undertake to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F6: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III"). OrbiMed Capital GP III LLC ("GP III") is the general partner of OPI III, and OrbiMed Advisors LLC ("Advisors") is the managing member of GP III. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, GP III, Advisors and Isaly may be deemed to have voting and investment power over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F8: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 2 · 2017-08-31 · Sale · Disposed 424 · Balance 12,945

F1: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were sold in multiple transactions at prices ranging from $37.75 to $37.83 inclusive. Upon request, the Reporting Persons undertake to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F7: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power over the securities held by Associates III and as a result may be deemed to have beneficial ownership over such securities.

F8: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 3 · 2017-09-01 · Sale · Disposed 109,040 · Balance 1,249,793

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

F6: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III"). OrbiMed Capital GP III LLC ("GP III") is the general partner of OPI III, and OrbiMed Advisors LLC ("Advisors") is the managing member of GP III. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, GP III, Advisors and Isaly may be deemed to have voting and investment power over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F8: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 4 · 2017-09-01 · Sale · Disposed 1,038 · Balance 11,907

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

F7: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power over the securities held by Associates III and as a result may be deemed to have beneficial ownership over such securities.

F8: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 5 · 2017-09-05 · Sale · Disposed 173,349 · Balance 1,076,444

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

F6: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III"). OrbiMed Capital GP III LLC ("GP III") is the general partner of OPI III, and OrbiMed Advisors LLC ("Advisors") is the managing member of GP III. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, GP III, Advisors and Isaly may be deemed to have voting and investment power over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F8: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 6 · 2017-09-05 · Sale · Disposed 1,651 · Balance 10,256

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

F7: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power over the securities held by Associates III and as a result may be deemed to have beneficial ownership over such securities.

F8: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 7 · 2017-09-05 · Sale · Disposed 189,792 · Balance 886,652

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

F6: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III"). OrbiMed Capital GP III LLC ("GP III") is the general partner of OPI III, and OrbiMed Advisors LLC ("Advisors") is the managing member of GP III. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, GP III, Advisors and Isaly may be deemed to have voting and investment power over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F8: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 8 · 2017-09-05 · Sale · Disposed 1,808 · Balance 8,448

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

F7: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power over the securities held by Associates III and as a result may be deemed to have beneficial ownership over such securities.

F8: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 9 · 2017-09-05 · Sale · Disposed 58,047 · Balance 828,605

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

F6: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III"). OrbiMed Capital GP III LLC ("GP III") is the general partner of OPI III, and OrbiMed Advisors LLC ("Advisors") is the managing member of GP III. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, GP III, Advisors and Isaly may be deemed to have voting and investment power over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F8: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 10 · 2017-09-05 · Sale · Disposed 553 · Balance 7,895

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

F7: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power over the securities held by Associates III and as a result may be deemed to have beneficial ownership over such securities.

F8: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Jonathan T. Silverstein, a member of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 1 · 2018-01-10 · Purchase · Acquired 170,338 · Balance 2,622,569

F1: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were purchased in multiple transactions at prices ranging from $12.30 to $13.15 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.

F4: These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP VI. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP VI, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI VI 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").

F5: This report on Form 4 is jointly filed by GP VI, Advisors and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

Row 2 · 2018-01-11 · Purchase · Acquired 41,700 · Balance 2,664,269

F2: The price reported in Column 4 is a weighted average price. These Shares were purchased in multiple transactions at prices ranging from $13.09 to $13.95 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.

F4: These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP VI. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP VI, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI VI 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").

F5: This report on Form 4 is jointly filed by GP VI, Advisors and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

Row 3 · 2018-01-12 · Purchase · Acquired 28,446 · Balance 2,692,715

F3: The price reported in Column 4 is a weighted average price. These Shares were purchased in multiple transactions at prices ranging from $14.85 to $15.60 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.

F4: These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP VI. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP VI, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI VI 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").

F5: This report on Form 4 is jointly filed by GP VI, Advisors and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

Row 1 · 2017-12-08 · Sale · Disposed 250,000 · Balance 941,000

F1: These shares of the Issuer's common stock ("Shares") were sold in a block order at a price of $82.50.

F2: These Shares 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. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly 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").

F3: This report on Form 4 is jointly filed by GP V, Advisors and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently, David P. Bonita, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 1 · Balance 167,794

F1: Represented by 1,677,940 American Depositary Shares ("ADSs").

F2: These shares are held of record by OrbiMed Private Investments V, LP ("OPI V"). OrbiMed Advisors LLC ("Advisors"), a registered investment adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of OrbiMed Capital GP V LLC ("GP V"), which is the sole general partner of OPI V, which is the majority member of OrbiMed Private Investments V Cooperatief U.A. ("OPI V Cooperatief"), which is the sole shareholder of OrbiMed Private Investments V-NB B.V. ("OPI V-NB"). OPI V and OPI V-NB hold ADSs and Common Shares, respectively, as described herein. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of Advisors and owns a controlling interest in Advisors.

F3: This report on Form 3 is jointly filed by Advisors, GP V, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Chau Quang Khuong, an employee of Advisors, to serve on the issuer's board of directors. This report on Form 3 shall not be deemed an admission that any such entity or person, including 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.

Row 2 · Balance 224,166

F3: This report on Form 3 is jointly filed by Advisors, GP V, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Chau Quang Khuong, an employee of Advisors, to serve on the issuer's board of directors. This report on Form 3 shall not be deemed an admission that any such entity or person, including 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.

F4: These shares are held of record by OPI V-NB.

Row 1 · 2018-01-03 · Sale · Disposed 1,693,492 · Balance 5,500,730

F1: These shares of the Issuer's common stock ("Shares") were sold in a block order at a price of $7.35.

F2: These Shares are held of record by OrbiMed Private Investments III, LP ("OPI III"). OrbiMed Capital GP III LLC ("GP III") is the general partner of OPI III, and OrbiMed Advisors LLC ("Advisors") is the managing member of GP III. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, GP III, Advisors and Isaly may be deemed to have voting and investment power over the securities held by OPI III and as a result may be deemed to have beneficial ownership over such securities.

F4: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 2 · 2018-01-03 · Sale · Disposed 16,128 · Balance 49,270

F1: These shares of the Issuer's common stock ("Shares") were sold in a block order at a price of $7.35.

F3: These Shares are held of record by OrbiMed Associates III, LP ("Associates III"). Advisors is the general partner of Associates III. Isaly is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power over the securities held by Associates III and as a result may be deemed to have beneficial ownership over such securities.

F4: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 1 · 2016-11-29 · Other · Disposed 3,604,266 · Balance 0

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

F2: This report on Form 4 is jointly filed by OrbiMed Capital GP III LLC ("OrbiMed Capital"), OrbiMed Advisors LLC ("OrbiMed Advisors"), Samuel D. Isaly ("Isaly"), OrbiMed Advisors Limited ("OrbiMed Limited") and OrbiMed Asia GP, L.P. ("OrbiMed Asia"). Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that the reporting persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

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

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

Row 2 · 2016-11-29 · Other · Disposed 34,291 · Balance 0

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

F2: This report on Form 4 is jointly filed by OrbiMed Capital GP III LLC ("OrbiMed Capital"), OrbiMed Advisors LLC ("OrbiMed Advisors"), Samuel D. Isaly ("Isaly"), OrbiMed Advisors Limited ("OrbiMed Limited") and OrbiMed Asia GP, L.P. ("OrbiMed Asia"). Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that the reporting persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

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

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

Row 3 · 2016-11-29 · Other · Disposed 2,149,902 · Balance 0

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

F2: This report on Form 4 is jointly filed by OrbiMed Capital GP III LLC ("OrbiMed Capital"), OrbiMed Advisors LLC ("OrbiMed Advisors"), Samuel D. Isaly ("Isaly"), OrbiMed Advisors Limited ("OrbiMed Limited") and OrbiMed Asia GP, L.P. ("OrbiMed Asia"). Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that the reporting persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

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

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

Row 4 · Balance 2,085,383

F7: Price shown is denominated in Canadian Dollars.

F8: In connection with the Arrangement, all outstanding Warrants will remain exercisable in accordance with their terms.

F2: This report on Form 4 is jointly filed by OrbiMed Capital GP III LLC ("OrbiMed Capital"), OrbiMed Advisors LLC ("OrbiMed Advisors"), Samuel D. Isaly ("Isaly"), OrbiMed Advisors Limited ("OrbiMed Limited") and OrbiMed Asia GP, L.P. ("OrbiMed Asia"). Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that the reporting persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

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

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

Row 5 · Balance 19,858

F7: Price shown is denominated in Canadian Dollars.

F8: In connection with the Arrangement, all outstanding Warrants will remain exercisable in accordance with their terms.

F2: This report on Form 4 is jointly filed by OrbiMed Capital GP III LLC ("OrbiMed Capital"), OrbiMed Advisors LLC ("OrbiMed Advisors"), Samuel D. Isaly ("Isaly"), OrbiMed Advisors Limited ("OrbiMed Limited") and OrbiMed Asia GP, L.P. ("OrbiMed Asia"). Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that the reporting persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

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

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

Row 6 · Balance 1,245,964

F7: Price shown is denominated in Canadian Dollars.

F8: In connection with the Arrangement, all outstanding Warrants will remain exercisable in accordance with their terms.

F2: This report on Form 4 is jointly filed by OrbiMed Capital GP III LLC ("OrbiMed Capital"), OrbiMed Advisors LLC ("OrbiMed Advisors"), Samuel D. Isaly ("Isaly"), OrbiMed Advisors Limited ("OrbiMed Limited") and OrbiMed Asia GP, L.P. ("OrbiMed Asia"). Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that the reporting persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

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

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

Row 1 · 2017-10-10 · Conversion · Acquired 2,546,295 · Balance 2,546,295

F1: In connection with the closing of the Issuer's initial public offering, each share of the Issuer's series A convertible preferred stock (the "Series A Preferred") converted into the Issuer's common stock on a 9.17-for-one basis without payment or consideration. The Series A Preferred had no expiration date.

F2: The reportable 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 Advisers Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly") a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V and as a result, may be deemed to have beneficial ownership over such shares.

F3: This report on Form 4 is jointly filed by GP V, Advisors and Isaly. Each of OPI V, GP V, Advisors and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 2 · 2017-10-10 · Purchase · Acquired 355,000 · Balance 2,901,295

F2: The reportable 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 Advisers Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly") a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V and as a result, may be deemed to have beneficial ownership over such shares.

F3: This report on Form 4 is jointly filed by GP V, Advisors and Isaly. Each of OPI V, GP V, Advisors and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 3 · 2017-10-10 · Conversion · Disposed 2,546,295 · Balance 0

F1: In connection with the closing of the Issuer's initial public offering, each share of the Issuer's series A convertible preferred stock (the "Series A Preferred") converted into the Issuer's common stock on a 9.17-for-one basis without payment or consideration. The Series A Preferred had no expiration date.

F4: Reflects the number of shares of Series A Preferred held by the Reporting Person on an as-converted to common stock basis.

F2: The reportable 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 Advisers Act of 1940, as amended, is the sole managing member of GP V. Samuel D. Isaly ("Isaly") a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI V and as a result, may be deemed to have beneficial ownership over such shares.

F3: This report on Form 4 is jointly filed by GP V, Advisors and Isaly. Each of OPI V, GP V, Advisors and Isaly disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 1 · 2017-10-03 · Sale · Disposed 199,718 · Balance 0

F1: 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 $0.66 to $0.71 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F2: These securities are held of record by OrbiMed Private Investments III, LP ("OPI III") and may be deemed to be indirectly beneficially owned by OrbiMed Capital GP III LLC ("GP III"), OrbiMed Advisors LLC ("Advisors") and Samuel D. Isaly ("Isaly"). GP III is the sole general partner of OPI III. Advisors, a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP III. By virtue of such relationships, GP III and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI III noted above.

F3: Isaly, a natural person, may also be deemed to have voting and investment power with respect to the securities held by OPI III noted above in his capacity as the managing member of, and holder of a controlling interest, in Advisors. As a result, each of GP III, Advisors and Isaly may be deemed to have beneficial ownership of the securities held by OPI III.

F5: This report on Form 4 is jointly filed by GP III, Advisors and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 2 · 2017-10-03 · Sale · Disposed 1,899 · Balance 0

F1: 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 $0.66 to $0.71 inclusive. Upon request, the Reporting Person undertakes to provide the Issuer, any security holder of the Issuer, or the Securities and Exchange Commission (the "SEC") full information regarding the Shares sold at each separate price within the range set forth in this footnote.

F4: These securities are held of record by OrbiMed Associates III, LP ("Associates III") and may be deemed to be indirectly beneficially owned by Advisors and Isaly. Advisors is the sole general partner of Associates III. Isaly is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationship, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by Associates III noted above. As a result, each of Advisors and Isaly may be deemed to have beneficial ownership of the securities held by Associates III.

F5: This report on Form 4 is jointly filed by GP III, Advisors and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that the Reporting Persons are beneficial owners for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 1 · Balance 1,314,996

F1: These shares are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP VI, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities. The Reporting Persons have designated a representative, currently Chau Khuong, a Private Equity Partner of Advisors, to serve on the Issuer's board of directors.

F2: This report on Form 3 is jointly filed by OPI VI, GP VI, Advisors and Isaly. Each of GP VI, Advisors, Isaly and the Reporting Person disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 1 · 2017-02-16 · Purchase · Acquired 30,500 · Balance 1,390,724

F1: The price reported in Column 4 is a weighted average price. These shares of the Issuer's common stock ("Shares") were purchased in multiple transactions at prices ranging from $4.97 to $5.10 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.

F4: 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. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly 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").

F5: This report on Form 4 is jointly filed by GP V, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any 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.

Row 2 · 2017-02-17 · Purchase · Acquired 71,800 · Balance 1,462,524

F2: The price reported in Column 4 is a weighted average price. These Shares were purchased in multiple transactions at prices ranging from $5.10 to $5.25 inclusive. Upon request, the Reporting Persons undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F4: 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. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly 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").

F5: This report on Form 4 is jointly filed by GP V, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any 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.

Row 3 · 2017-02-21 · Purchase · Acquired 7,000 · Balance 1,469,524

F3: The price reported in Column 4 is a weighted average price. These Shares were purchased in multiple transactions at prices ranging from $5.25 to $5.50 inclusive. Upon request, the Reporting Persons undertake to provide the Issuer, any security holder of the Issuer, or the SEC full information regarding the Shares purchased at each separate price within the range set forth in this footnote.

F4: 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. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly 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").

F5: This report on Form 4 is jointly filed by GP V, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any 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.

Row 1 · 2017-04-25 · Purchase · Acquired 587,000 · Balance 2,123,098

F1: These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP VI. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, GP VI, Advisors and Isaly may be deemed to have voting and investment power over the securities held by OPI VI and as a result may be deemed to have beneficial ownership over such securities.

F4: This report on Form 4 is jointly filed by GP VI, OrbiMed Limited, OIP GP, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 2 · 2017-04-25 · Purchase · Acquired 587,000 · Balance 2,123,098

F2: These securities are held of record by OrbiMed Israel Partners II, L.P. ("OIP II"). OrbiMed Israel GP II, L.P. ("OIP GP") is the general partner of OIP II, and OrbiMed Advisors Israel II Limited ("OrbiMed Limited") is the managing member of OIP GP. By virtue of such relationships, OIP GP and OrbiMed Limited may be deemed to have voting and investment power over the securities held by OIP II and as a result may be deemed to have beneficial ownership over such securities.

F4: This report on Form 4 is jointly filed by GP VI, OrbiMed Limited, OIP GP, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 3 · 2017-04-25 · Purchase · Acquired 293,500 · Balance 293,500

F3: Warrants ("Warrants") to purchase Ordinary Shares. The Warrants are immediately exercisable when issued, are exercisable for five years from the date of issuance and have an exercise price of $6.875 per Ordinary Share.

F1: These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the managing member of GP VI. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, GP VI, Advisors and Isaly may be deemed to have voting and investment power over the securities held by OPI VI and as a result may be deemed to have beneficial ownership over such securities.

F4: This report on Form 4 is jointly filed by GP VI, OrbiMed Limited, OIP GP, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 4 · 2017-04-25 · Purchase · Acquired 293,500 · Balance 293,500

F3: Warrants ("Warrants") to purchase Ordinary Shares. The Warrants are immediately exercisable when issued, are exercisable for five years from the date of issuance and have an exercise price of $6.875 per Ordinary Share.

F2: These securities are held of record by OrbiMed Israel Partners II, L.P. ("OIP II"). OrbiMed Israel GP II, L.P. ("OIP GP") is the general partner of OIP II, and OrbiMed Advisors Israel II Limited ("OrbiMed Limited") is the managing member of OIP GP. By virtue of such relationships, OIP GP and OrbiMed Limited may be deemed to have voting and investment power over the securities held by OIP II and as a result may be deemed to have beneficial ownership over such securities.

F4: This report on Form 4 is jointly filed by GP VI, OrbiMed Limited, OIP GP, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 1 · 2017-01-18 · Purchase · Acquired 327,459 · Balance 9,369,342

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

F3: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently David Bonita, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 2 · 2017-01-18 · Purchase · Acquired 3,118 · Balance 89,225

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

F3: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently David Bonita, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 3 · 2017-01-18 · Purchase · Acquired 65,491 · Balance 403,692

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

F3: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently David Bonita, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 4 · 2017-01-18 · Purchase · Acquired 623 · Balance 3,843

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

F3: This report on Form 4 is jointly filed by GP III, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently David Bonita, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 1 · 2017-03-15 · Purchase · Acquired 762,995 · Balance 4,416,446

F1: 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. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP V, Advisors and Isaly 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 have beneficial ownership over such securities.

F2: This report on Form 4 is jointly filed by GP V, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Chau Khuong, an employee of Advisors, to serve on the Company's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Row 1 · 2017-11-20 · Conversion · Acquired 19,533 · Balance 19,533

F1: The Series A-1 Convertible Preferred Stock converted into Common Stock on a 0.29300-for-one basis upon the closing of the Issuer's initial public offering without payment of consideration. The Series A-1 Convertible Preferred Stock was convertible at any time at the holder's election and automatically upon the closing at the Issuer's initial public offering. The shares had no expiration date.

F6: The reported securities are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the sole general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP IV. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and owner of a controlling interest in, Advisors. By virtue of such relationships, GP IV, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI IV. The Reporting Persons have designated a representative, currently Carl Gordon, a member of Advisors, to serve on the Issuer's board of directors.

F7: This report on Form 4 is jointly filed by GP IV, Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report on Form 4 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.

Row 2 · 2017-11-20 · Conversion · Acquired 252,230 · Balance 271,763

F2: The Series A-2 Convertible Preferred Stock converted into Common Stock on a 0.35785-for-one basis upon the closing of the Issuer's initial public offering without payment of consideration. The Series A-2 Convertible Preferred Stock was convertible at any time at the holder's election and automatically upon the closing at the Issuer's initial public offering. The shares had no expiration date.

F6: The reported securities are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the sole general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP IV. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and owner of a controlling interest in, Advisors. By virtue of such relationships, GP IV, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI IV. The Reporting Persons have designated a representative, currently Carl Gordon, a member of Advisors, to serve on the Issuer's board of directors.

F7: This report on Form 4 is jointly filed by GP IV, Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report on Form 4 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.

Row 3 · 2017-11-20 · Conversion · Acquired 328,909 · Balance 600,672

F3: The Series B Convertible Preferred Stock converted into Common Stock on a 0.44650-for-one basis upon the closing of the Issuer's initial public offering without payment of consideration. The Series B Convertible Preferred Stock was convertible at any time at the holder's election and automatically upon the closing at the Issuer's initial public offering. The shares had no expiration date.

F6: The reported securities are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the sole general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP IV. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and owner of a controlling interest in, Advisors. By virtue of such relationships, GP IV, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI IV. The Reporting Persons have designated a representative, currently Carl Gordon, a member of Advisors, to serve on the Issuer's board of directors.

F7: This report on Form 4 is jointly filed by GP IV, Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report on Form 4 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.

Row 4 · 2017-11-20 · Conversion · Acquired 114,320 · Balance 714,992

F4: The Series C Convertible Preferred Stock converted into Common Stock on a 0.49832-for-one basis upon the closing of the Issuer's initial public offering without payment of consideration. The Series C Convertible Preferred Stock was convertible at any time at the holder's election and automatically upon the closing at the Issuer's initial public offering. The shares had no expiration date.

F6: The reported securities are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the sole general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP IV. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and owner of a controlling interest in, Advisors. By virtue of such relationships, GP IV, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI IV. The Reporting Persons have designated a representative, currently Carl Gordon, a member of Advisors, to serve on the Issuer's board of directors.

F7: This report on Form 4 is jointly filed by GP IV, Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report on Form 4 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.

Row 5 · 2017-11-20 · Conversion · Acquired 653,974 · Balance 1,368,966

F5: The Series D Convertible Preferred Stock converted into Common Stock on a 0.29300-for-one basis upon the closing of the Issuer's initial public offering without payment of consideration. The Series D Convertible Preferred Stock was convertible at any time at the holder's election and automatically upon the closing at the Issuer's initial public offering. The shares had no expiration date.

F6: The reported securities are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the sole general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP IV. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and owner of a controlling interest in, Advisors. By virtue of such relationships, GP IV, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI IV. The Reporting Persons have designated a representative, currently Carl Gordon, a member of Advisors, to serve on the Issuer's board of directors.

F7: This report on Form 4 is jointly filed by GP IV, Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report on Form 4 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.

Row 6 · 2017-11-20 · Conversion · Acquired 500,000 · Balance 1,868,966

F6: The reported securities are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the sole general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP IV. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and owner of a controlling interest in, Advisors. By virtue of such relationships, GP IV, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI IV. The Reporting Persons have designated a representative, currently Carl Gordon, a member of Advisors, to serve on the Issuer's board of directors.

F7: This report on Form 4 is jointly filed by GP IV, Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report on Form 4 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.

Row 7 · 2017-11-20 · Conversion · Disposed 66,667 · Balance 0

F1: The Series A-1 Convertible Preferred Stock converted into Common Stock on a 0.29300-for-one basis upon the closing of the Issuer's initial public offering without payment of consideration. The Series A-1 Convertible Preferred Stock was convertible at any time at the holder's election and automatically upon the closing at the Issuer's initial public offering. The shares had no expiration date.

F6: The reported securities are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the sole general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP IV. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and owner of a controlling interest in, Advisors. By virtue of such relationships, GP IV, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI IV. The Reporting Persons have designated a representative, currently Carl Gordon, a member of Advisors, to serve on the Issuer's board of directors.

F7: This report on Form 4 is jointly filed by GP IV, Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report on Form 4 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.

Row 8 · 2017-11-20 · Conversion · Disposed 704,846 · Balance 0

F2: The Series A-2 Convertible Preferred Stock converted into Common Stock on a 0.35785-for-one basis upon the closing of the Issuer's initial public offering without payment of consideration. The Series A-2 Convertible Preferred Stock was convertible at any time at the holder's election and automatically upon the closing at the Issuer's initial public offering. The shares had no expiration date.

F6: The reported securities are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the sole general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP IV. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and owner of a controlling interest in, Advisors. By virtue of such relationships, GP IV, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI IV. The Reporting Persons have designated a representative, currently Carl Gordon, a member of Advisors, to serve on the Issuer's board of directors.

F7: This report on Form 4 is jointly filed by GP IV, Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report on Form 4 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.

Row 9 · 2017-11-20 · Conversion · Disposed 736,648 · Balance 0

F3: The Series B Convertible Preferred Stock converted into Common Stock on a 0.44650-for-one basis upon the closing of the Issuer's initial public offering without payment of consideration. The Series B Convertible Preferred Stock was convertible at any time at the holder's election and automatically upon the closing at the Issuer's initial public offering. The shares had no expiration date.

F6: The reported securities are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the sole general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP IV. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and owner of a controlling interest in, Advisors. By virtue of such relationships, GP IV, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI IV. The Reporting Persons have designated a representative, currently Carl Gordon, a member of Advisors, to serve on the Issuer's board of directors.

F7: This report on Form 4 is jointly filed by GP IV, Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report on Form 4 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.

Row 10 · 2017-11-20 · Conversion · Disposed 229,412 · Balance 0

F4: The Series C Convertible Preferred Stock converted into Common Stock on a 0.49832-for-one basis upon the closing of the Issuer's initial public offering without payment of consideration. The Series C Convertible Preferred Stock was convertible at any time at the holder's election and automatically upon the closing at the Issuer's initial public offering. The shares had no expiration date.

F6: The reported securities are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the sole general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP IV. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and owner of a controlling interest in, Advisors. By virtue of such relationships, GP IV, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI IV. The Reporting Persons have designated a representative, currently Carl Gordon, a member of Advisors, to serve on the Issuer's board of directors.

F7: This report on Form 4 is jointly filed by GP IV, Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report on Form 4 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.

Row 11 · 2017-11-20 · Conversion · Disposed 2,232,014 · Balance 0

F5: The Series D Convertible Preferred Stock converted into Common Stock on a 0.29300-for-one basis upon the closing of the Issuer's initial public offering without payment of consideration. The Series D Convertible Preferred Stock was convertible at any time at the holder's election and automatically upon the closing at the Issuer's initial public offering. The shares had no expiration date.

F6: The reported securities are held of record by OrbiMed Private Investments IV, LP ("OPI IV"). OrbiMed Capital GP IV LLC ("GP IV") is the sole general partner of OPI IV, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP IV. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and owner of a controlling interest in, Advisors. By virtue of such relationships, GP IV, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI IV. The Reporting Persons have designated a representative, currently Carl Gordon, a member of Advisors, to serve on the Issuer's board of directors.

F7: This report on Form 4 is jointly filed by GP IV, Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report on Form 4 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.

Row 1 · Balance 1,927,977

F1: These securities are held of record by ROS Acquisition Offshore LP ("ROS Acquisition"). OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the investment manager of ROS Acquisition. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. Advisors is also the investment manager of Royalty Opportunities S.a r.l., of which ROS Acquisition is a wholly-owned subsidiary. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by ROS Acquisition noted above and as a result may be deemed to have beneficial ownership over such securities.

F3: This report on Form 3 is jointly filed by Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

Row 2 · Balance 823,207

F2: These securities are held of record by OrbiMed Royalty Opportunities II, LP ("ORO II"). OrbiMed ROF II LLC ("ROF II") is the sole general partner of ORO II, and Advisors is the sole managing member of ROF II. Isaly, a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by ORO II noted above and as a result may be deemed to have beneficial ownership over such securities.

F3: This report on Form 3 is jointly filed by Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

Row 3 · Balance Not disclosed

F1: These securities are held of record by ROS Acquisition Offshore LP ("ROS Acquisition"). OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the investment manager of ROS Acquisition. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. Advisors is also the investment manager of Royalty Opportunities S.a r.l., of which ROS Acquisition is a wholly-owned subsidiary. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by ROS Acquisition noted above and as a result may be deemed to have beneficial ownership over such securities.

F3: This report on Form 3 is jointly filed by Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

Row 4 · Balance Not disclosed

F4: These convertible notes (collectively, the "Notes") may be converted into shares of common stock ("Shares") of the Issuer at any time prior to the close of business on the second business day immediately preceding July 15, 2021. However, the Notes will not be convertible to the extent that such conversion would result in the holder of each Note or any of its affiliates being deemed to beneficially own in excess of 9.99% of the then-outstanding Shares.

F5: Pursuant to the Restructuring and Exchange Agreement entered into on January 11, 2018 among the Issuer, ORO II, ROS Acquisition and certain other parties, which agreement is filed as an exhibit to the Issuer's Form 8-K filed with the Securities and Exchange Commission on January 12, 2018 (the "Form 8-K"), the Issuer, ORO II and ROS Acquisition have agreed to amend the Notes to clarify that the restriction that prevents any holder or any of its affiliates from effecting a conversion thereof if such conversion would result in the holder or any of its affiliates beneficially owning in excess of 9.99% of the then-outstanding Shares shall not be applicable to the Tier 2 Transaction (as described in the Form 8-K).

F1: These securities are held of record by ROS Acquisition Offshore LP ("ROS Acquisition"). OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the investment manager of ROS Acquisition. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. Advisors is also the investment manager of Royalty Opportunities S.a r.l., of which ROS Acquisition is a wholly-owned subsidiary. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by ROS Acquisition noted above and as a result may be deemed to have beneficial ownership over such securities.

F3: This report on Form 3 is jointly filed by Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

Row 5 · Balance Not disclosed

F4: These convertible notes (collectively, the "Notes") may be converted into shares of common stock ("Shares") of the Issuer at any time prior to the close of business on the second business day immediately preceding July 15, 2021. However, the Notes will not be convertible to the extent that such conversion would result in the holder of each Note or any of its affiliates being deemed to beneficially own in excess of 9.99% of the then-outstanding Shares.

F5: Pursuant to the Restructuring and Exchange Agreement entered into on January 11, 2018 among the Issuer, ORO II, ROS Acquisition and certain other parties, which agreement is filed as an exhibit to the Issuer's Form 8-K filed with the Securities and Exchange Commission on January 12, 2018 (the "Form 8-K"), the Issuer, ORO II and ROS Acquisition have agreed to amend the Notes to clarify that the restriction that prevents any holder or any of its affiliates from effecting a conversion thereof if such conversion would result in the holder or any of its affiliates beneficially owning in excess of 9.99% of the then-outstanding Shares shall not be applicable to the Tier 2 Transaction (as described in the Form 8-K).

F2: These securities are held of record by OrbiMed Royalty Opportunities II, LP ("ORO II"). OrbiMed ROF II LLC ("ROF II") is the sole general partner of ORO II, and Advisors is the sole managing member of ROF II. Isaly, a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by ORO II noted above and as a result may be deemed to have beneficial ownership over such securities.

F3: This report on Form 3 is jointly filed by Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

Row 6 · Balance Not disclosed

F4: These convertible notes (collectively, the "Notes") may be converted into shares of common stock ("Shares") of the Issuer at any time prior to the close of business on the second business day immediately preceding July 15, 2021. However, the Notes will not be convertible to the extent that such conversion would result in the holder of each Note or any of its affiliates being deemed to beneficially own in excess of 9.99% of the then-outstanding Shares.

F5: Pursuant to the Restructuring and Exchange Agreement entered into on January 11, 2018 among the Issuer, ORO II, ROS Acquisition and certain other parties, which agreement is filed as an exhibit to the Issuer's Form 8-K filed with the Securities and Exchange Commission on January 12, 2018 (the "Form 8-K"), the Issuer, ORO II and ROS Acquisition have agreed to amend the Notes to clarify that the restriction that prevents any holder or any of its affiliates from effecting a conversion thereof if such conversion would result in the holder or any of its affiliates beneficially owning in excess of 9.99% of the then-outstanding Shares shall not be applicable to the Tier 2 Transaction (as described in the Form 8-K).

F1: These securities are held of record by ROS Acquisition Offshore LP ("ROS Acquisition"). OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the investment manager of ROS Acquisition. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. Advisors is also the investment manager of Royalty Opportunities S.a r.l., of which ROS Acquisition is a wholly-owned subsidiary. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by ROS Acquisition noted above and as a result may be deemed to have beneficial ownership over such securities.

F3: This report on Form 3 is jointly filed by Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

Row 7 · Balance Not disclosed

F4: These convertible notes (collectively, the "Notes") may be converted into shares of common stock ("Shares") of the Issuer at any time prior to the close of business on the second business day immediately preceding July 15, 2021. However, the Notes will not be convertible to the extent that such conversion would result in the holder of each Note or any of its affiliates being deemed to beneficially own in excess of 9.99% of the then-outstanding Shares.

F5: Pursuant to the Restructuring and Exchange Agreement entered into on January 11, 2018 among the Issuer, ORO II, ROS Acquisition and certain other parties, which agreement is filed as an exhibit to the Issuer's Form 8-K filed with the Securities and Exchange Commission on January 12, 2018 (the "Form 8-K"), the Issuer, ORO II and ROS Acquisition have agreed to amend the Notes to clarify that the restriction that prevents any holder or any of its affiliates from effecting a conversion thereof if such conversion would result in the holder or any of its affiliates beneficially owning in excess of 9.99% of the then-outstanding Shares shall not be applicable to the Tier 2 Transaction (as described in the Form 8-K).

F2: These securities are held of record by OrbiMed Royalty Opportunities II, LP ("ORO II"). OrbiMed ROF II LLC ("ROF II") is the sole general partner of ORO II, and Advisors is the sole managing member of ROF II. Isaly, a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by ORO II noted above and as a result may be deemed to have beneficial ownership over such securities.

F3: This report on Form 3 is jointly filed by Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

Row 1 · 2017-11-21 · Conversion · Acquired 2,576,532 · Balance 2,576,532

F1: Represents the total number of shares of Common Stock received by OrbiMed Private Investments VI, L.P. ("OPI VI"), upon conversion of the Issuer's Series B Preferred Stock in connection with the closing of the Issuer's initial public offering.

F2: These securities are held of record by OPI VI. OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors") is the managing member of GP VI. Samuel D. Isaly, a natural person, is a managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, GP VI, Advisors and Mr. Isaly may be deemed to have voting and investment power over the securities held by OPI VI and as a result may be deemed to have beneficial ownership over such securities.

F3: This report on Form 4 is jointly filed by GP VI, Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

Row 2 · 2017-11-21 · Purchase · Acquired 833,333 · Balance 3,409,865

F2: These securities are held of record by OPI VI. OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors") is the managing member of GP VI. Samuel D. Isaly, a natural person, is a managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, GP VI, Advisors and Mr. Isaly may be deemed to have voting and investment power over the securities held by OPI VI and as a result may be deemed to have beneficial ownership over such securities.

F3: This report on Form 4 is jointly filed by GP VI, Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.

Row 3 · 2017-11-21 · Conversion · Disposed 18,500,000 · Balance 0

F4: All series of Convertible Preferred Stock automatically converted into the Issuer's Common Stock on a 7.180193-for-1 basis on November 21, 2017 and had no expiration date.

F2: These securities are held of record by OPI VI. OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors") is the managing member of GP VI. Samuel D. Isaly, a natural person, is a managing member of and owner of a controlling interest in Advisors. By virtue of such relationships, GP VI, Advisors and Mr. Isaly may be deemed to have voting and investment power over the securities held by OPI VI and as a result may be deemed to have beneficial ownership over such securities.

F3: This report on Form 4 is jointly filed by GP VI, Advisors and Isaly. Each of the reporting persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any of the reporting persons is a beneficial owner of such securities for the purposes of Section 16 of the Exchange Act, or for any other purposes.