| ORBIMED ADVISORS LLC |
| 1.38% | 0.74% | #1 | $73.2M | 13.7M | $37.3M | 10.9M | +2.8M+25.81% | Add |
| BAKER BROS. ADVISORS LP |
| 0.27% | 0.2% | #6 | $54.0M | 10.1M | $34.6M | 10.1M | 00.00% | Unchanged |
| RA CAPITAL MANAGEMENT, L.P. |
| 0.3% | — | #5 | $34.5M | 6.5M | $0 | 0 | +6.5M | New Buy |
| Soleus Capital Management, L.P. |
| 0.62% | — | #4 | $18.0M | 3.4M | $0 | 0 | +3.4M | New Buy |
| Kynam Capital Management, LP |
| 0.71% | 0.34% | #2 | $12.9M | 2.4M | $5.4M | 1.6M | +822,536+51.65% | Add |
| VANGUARD CAPITAL MANAGEMENT LLC |
| <0.01% | <0.01% | #33 | $10.7M | 2.0M | $4.2M | 1.2M | +779,039+63.32% | Add |
| BlackRock, Inc. |
| <0.01% | <0.01% | #38 | $9.6M | 1.8M | $1.1M | 321,886 | +1.5M+458.43% | Add |
| SPHERA FUNDS MANAGEMENT LTD. |
| 0.71% | 0.3% | #3 | $5.4M | 1.0M | $1.9M | 558,339 | +461,493+82.65% | Add |
| TWO SIGMA INVESTMENTS, LP |
| <0.01% | <0.01% | #16 | $5.3M | 993,369 | $3.2M | 923,626 | +69,743+7.55% | Add |
| ADAR1 Capital Management, LLC |
| 0.22% | 0.03% | #7 | $4.8M | 900,900 | $522,662 | 152,825 | +748,075+489.50% | Add |
| MILLENNIUM MANAGEMENT LLC |
| <0.01% | <0.01% | #19 | $4.5M | 844,993 | $1.3M | 382,737 | +462,256+120.78% | Add |
| GEODE CAPITAL MANAGEMENT, LLC |
| <0.01% | <0.01% | #31 | $4.5M | 841,862 | $1.0M | 302,458 | +539,404+178.34% | Add |
| ADAGE CAPITAL PARTNERS GP, L.L.C. |
| 0.01% | — | #12 | $4.1M | 766,095 | $0 | 0 | +766,095 | New Buy |
| ACADIAN ASSET MANAGEMENT LLC |
| <0.01% | <0.01% | #15 | $3.3M | 611,359 | $1.7M | 511,519 | +99,840+19.52% | Add |
| MORGAN STANLEY |
| <0.01% | <0.01% | #37 | $2.7M | 503,860 | $409,252 | 284,203 | +219,657+77.29% | Add |
| STATE STREET CORP |
| <0.01% | <0.01% | #46 | $2.3M | 428,787 | $472,750 | 138,231 | +290,556+210.20% | Add |
| UBS Group AG |
| <0.01% | <0.01% | #34 | $1.7M | 318,797 | $220,607 | 64,505 | +254,292+394.22% | Add |
| VANGUARD FIDUCIARY TRUST CO |
| <0.01% | <0.01% | #28 | $1.5M | 284,886 | $538,240 | 157,380 | +127,506+81.02% | Add |
| RENAISSANCE TECHNOLOGIES LLC |
| <0.01% | <0.01% | #18 | $1.5M | 281,200 | $941,184 | 275,200 | +6,000+2.18% | Add |
| NORTHERN TRUST CORP |
| <0.01% | <0.01% | #36 | $1.3M | 240,599 | $171,410 | 50,120 | +190,479+380.05% | Add |
| VANGUARD PORTFOLIO MANAGEMENT LLC |
| <0.01% | — | #52 | $1.0M | 193,920 | $0 | 0 | +193,920 | New Buy |
| MARSHALL WACE, LLP |
| <0.01% | <0.01% | #21 | $1.0M | 190,692 | $1.2M | 358,906 | -168,214-46.87% | Reduce |
| SUSQUEHANNA INTERNATIONAL GROUP, LLP |
| <0.01% | <0.01% | #45 | $931,151 | 174,700 | $987,655 | 288,788 | -114,088-39.51% | Reduce |
| Connor, Clark & Lunn Investment Management Ltd. |
| <0.01% | <0.01% | #20 | $669,480 | 125,606 | $373,071 | 109,085 | +16,521+15.15% | Add |
| GOLDMAN SACHS GROUP INC |
| <0.01% | <0.01% | #49 | $644,045 | 120,834 | $808,724 | 236,469 | -115,635-48.90% | Reduce |
| JANE STREET GROUP, LLC |
| <0.01% | <0.01% | #56 | $448,786 | 84,200 | $659,933 | 192,963 | -108,763-56.36% | Reduce |
| Hillsdale Investment Management Inc. |
| 0.01% | — | #10 | $433,862 | 81,400 | $0 | 0 | +81,400 | New Buy |
| CITADEL ADVISORS LLC |
| <0.01% | <0.01% | #54 | $372,855 | 69,954 | $425,373 | 124,378 | -54,424-43.76% | Reduce |
| Bank of New York Mellon Corp |
| <0.01% | — | #48 | $363,436 | 68,187 | $0 | 0 | +68,187 | New Buy |
| CHARLES SCHWAB INVESTMENT MANAGEMENT INC |
| <0.01% | — | #50 | $360,425 | 67,622 | $0 | 0 | +67,622 | New Buy |
| BRIDGEWAY CAPITAL MANAGEMENT, LLC |
| 0.01% | <0.01% | #11 | $343,785 | 64,500 | $182,970 | 53,500 | +11,000+20.56% | Add |
| Squarepoint Ops LLC |
| <0.01% | — | #26 | $317,348 | 59,540 | $0 | 0 | +59,540 | New Buy |
| PANAGORA ASSET MANAGEMENT INC |
| <0.01% | — | #22 | $253,569 | 47,574 | $0 | 0 | +47,574 | New Buy |
| Mariner, LLC |
| <0.01% | — | #30 | $241,241 | 45,261 | $0 | 0 | +45,261 | New Buy |
| Nuveen, LLC |
| <0.01% | — | #51 | $197,333 | 37,023 | $0 | 0 | +37,023 | New Buy |
| DIMENSIONAL FUND ADVISORS LP |
| <0.01% | <0.01% | #57 | $186,839 | 35,210 | $119,690 | 35,210 | 00.00% | Unchanged |
| Invesco Ltd. |
| <0.01% | — | #63 | $185,175 | 34,742 | $0 | 0 | +34,742 | New Buy |
| Cerity Partners LLC |
| <0.01% | <0.01% | #35 | $175,224 | 32,875 | $112,433 | 32,875 | 00.00% | Unchanged |
| State of Wyoming |
| 0.02% | — | #9 | $175,154 | 32,862 | $0 | 0 | +32,862 | New Buy |
| Graham Capital Management, L.P. |
| <0.01% | <0.01% | #17 | $158,674 | 29,770 | $38,793 | 11,343 | +18,427+162.45% | Add |
| DEUTSCHE BANK AG\ |
| <0.01% | — | #53 | $148,302 | 27,824 | $0 | 0 | +27,824 | New Buy |
| WELLS FARGO & COMPANY/MN |
| <0.01% | — | #62 | $134,982 | 25,325 | $0 | 0 | +25,325 | New Buy |
| SIMPLEX TRADING, LLC |
| <0.01% | <0.01% | #44 | $132,184 | 24,800 | $2,394 | 700 | +24,100+3,442.86% | Add |
| BANK OF AMERICA CORP /DE/ |
| <0.01% | <0.01% | #71 | $127,254 | 23,875 | $193,316 | 56,525 | -32,650-57.76% | Reduce |
| PRICE T ROWE ASSOCIATES INC /MD/ |
| <0.01% | — | #67 | $121,300 | 22,758 | $0 | 0 | +22,758 | New Buy |
| RHUMBLINE ADVISERS |
| <0.01% | — | #42 | $117,649 | 22,074 | $0 | 0 | +22,074 | New Buy |
| Vanguard Global Advisers, LLC |
| <0.01% | <0.01% | #55 | $86,399 | 16,210 | $15,855 | 4,636 | +11,574+249.65% | Add |
| ExodusPoint Capital Management, LP |
| <0.01% | — | #23 | $82,482 | 15,475 | $0 | 0 | +15,475 | New Buy |
| BARCLAYS PLC |
| <0.01% | <0.01% | #64 | $77,439 | 14,529 | $29,412 | 8,600 | +5,929+68.94% | Add |
| NEW YORK STATE COMMON RETIREMENT FUND |
| <0.01% | — | #41 | $75,686 | 14,200 | $0 | 0 | +14,200 | New Buy |
