| RA CAPITAL MANAGEMENT, L.P. |
| 6.43% | 6.14% | #3 | $740.2M | 6.7M | $579.8M | 6.7M | 00.00% | Unchanged |
| BlackRock, Inc. |
| 0.01% | 0.01% | #123 | $683.6M | 6.2M | $542.4M | 6.2M | -80,249-1.29% | Reduce |
| BAKER BROS. ADVISORS LP |
| 3.12% | 2.8% | #8 | $622.3M | 5.6M | $487.4M | 5.6M | 00.00% | Unchanged |
| PRIMECAP MANAGEMENT CO/CA/ |
| 0.21% | 0.23% | #43 | $351.8M | 3.2M | $297.2M | 3.4M | -248,656-7.28% | Reduce |
| VANGUARD PORTFOLIO MANAGEMENT LLC |
| 0.02% | 0.01% | #100 | $348.3M | 3.1M | $264.5M | 3.0M | +96,177+3.16% | Add |
| VANGUARD CAPITAL MANAGEMENT LLC |
| 0.01% | 0.01% | #141 | $333.8M | 3.0M | $258.1M | 3.0M | +38,152+1.29% | Add |
| JPMORGAN CHASE & CO |
| 0.02% | 0.01% | #99 | $292.2M | 2.7M | $120.0M | 1.6M | +1.1M+70.74% | Add |
| PERCEPTIVE ADVISORS LLC |
| 4.31% | 4.03% | #4 | $287.2M | 2.6M | $206.4M | 2.4M | +212,500+8.95% | Add |
| STATE STREET CORP |
| 0.01% | 0.01% | #130 | $285.7M | 2.6M | $197.6M | 2.3M | +301,678+13.28% | Add |
| PRICE T ROWE ASSOCIATES INC /MD/ |
| 0.03% | 0.02% | #86 | $284.9M | 2.6M | $143.9M | 1.7M | +911,295+55.07% | Add |
| WESTFIELD CAPITAL MANAGEMENT CO LP |
| 0.8% | 0.7% | #21 | $245.2M | 2.2M | $167.8M | 1.9M | +279,472+14.49% | Add |
| GOLDMAN SACHS GROUP INC |
| 0.02% | 0.02% | #93 | $236.1M | 2.1M | $170.9M | 2.0M | +161,070+8.20% | Add |
| FEDERATED HERMES, INC. |
| 0.29% | 0.18% | #37 | $198.3M | 1.8M | $111.9M | 1.3M | +499,413+38.83% | Add |
| Polar Capital Holdings Plc |
| 0.44% | 0.5% | #27 | $184.7M | 1.7M | $140.5M | 1.6M | +48,046+2.97% | Add |
| GEODE CAPITAL MANAGEMENT, LLC |
| 0.01% | 0.01% | #125 | $170.3M | 1.5M | $123.2M | 1.4M | +117,429+8.29% | Add |
| Capital Research Global Investors |
| 0.02% | 0.02% | #91 | $170.1M | 1.5M | $97.0M | 1.1M | +416,843+37.37% | Add |
| CITADEL ADVISORS LLC |
| 0.02% | 0.02% | #96 | $145.4M | 1.3M | $126.4M | 1.5M | -143,867-9.90% | Reduce |
| Checkpoint Capital L.P. |
| 33.79% | 38.3% | #1 | $131.7M | 1.2M | $106.7M | 1.2M | -41,200-3.36% | Reduce |
| Siren, L.L.C. |
| 2.55% | 1.75% | #9 | $126.2M | 1.1M | $63.1M | 725,511 | +410,764+56.62% | Add |
| MORGAN STANLEY |
| 0.01% | <0.01% | #145 | $123.5M | 1.1M | $47.0M | 465,190 | +647,050+139.09% | Add |
| FMR LLC |
| <0.01% | 0.01% | #156 | $113.9M | 1.0M | $147.0M | 1.7M | -663,831-39.29% | Reduce |
| Pictet Asset Management Holding SA |
| 0.1% | 0.06% | #52 | $106.3M | 957,785 | $57.3M | 667,046 | +290,739+43.59% | Add |
| Jupiter Topco LLC |
| 0.04% | — | #79 | $102.8M | 925,490 | $0 | 0 | +925,490 | New Buy |
| Woodline Partners LP |
| 0.26% | 0.25% | #39 | $84.3M | 758,891 | $66.0M | 758,891 | 00.00% | Unchanged |
| ALLIANCEBERNSTEIN L.P. |
| 0.03% | 0.03% | #87 | $77.8M | 894,723 | $97.5M | 910,413 | -15,690-1.72% | Reduce |
| Clearbridge Investments, LLC |
| 0.06% | 0.05% | #64 | $77.3M | 696,473 | $53.0M | 609,437 | +87,036+14.28% | Add |
| Rock Springs Capital Management LP |
| 3.75% | 3.54% | #6 | $76.9M | 692,598 | $60.0M | 689,748 | +2,850+0.41% | Add |
| NORGES BANK |
| 0.01% | <0.01% | #137 | $76.1M | 685,844 | $11.8M | 223,484 | +462,360+206.89% | Add |
| FRANKLIN RESOURCES INC |
| 0.01% | 0.01% | #108 | $64.1M | 577,033 | $54.5M | 626,845 | -49,812-7.95% | Reduce |
| CHARLES SCHWAB INVESTMENT MANAGEMENT INC |
| 0.01% | 0.01% | #133 | $61.4M | 552,738 | $45.8M | 526,459 | +26,279+4.99% | Add |
| Integral Health Asset Management, LLC |
| 2.41% | 2.5% | #10 | $61.1M | 550,000 | $52.2M | 600,000 | -50,000-8.33% | Reduce |
| Invesco Ltd. |
| <0.01% | <0.01% | #159 | $60.3M | 543,271 | $31.7M | 364,306 | +178,965+49.12% | Add |
| NORTHERN TRUST CORP |
| 0.01% | 0.01% | #142 | $60.0M | 540,332 | $43.4M | 498,514 | +41,818+8.39% | Add |
| UBS AM, a distinct business unit of UBS ASSET MANAGEMENT AMERICAS LLC |
| 0.01% | 0.01% | #122 | $57.2M | 514,850 | $47.1M | 541,450 | -26,600-4.91% | Reduce |
| WELLINGTON MANAGEMENT GROUP LLP |
| 0.01% | <0.01% | #124 | $54.3M | 488,747 | $23.8M | 273,757 | +214,990+78.53% | Add |
| VANGUARD FIDUCIARY TRUST CO |
| 0.01% | 0.01% | #116 | $49.5M | 445,723 | $36.7M | 421,911 | +23,812+5.64% | Add |
| LOOMIS SAYLES & CO L P |
| 0.06% | 0.05% | #67 | $48.2M | 434,102 | $40.4M | 465,102 | -31,000-6.67% | Reduce |
| Candriam S.C.A. |
| 0.22% | 0.15% | #42 | $48.0M | 433,025 | $30.8M | 287,907 | +145,118+50.40% | Add |
| Squarepoint Ops LLC |
| 0.05% | 0.03% | #73 | $47.0M | 422,921 | $22.9M | 262,968 | +159,953+60.83% | Add |
| Point72 Asset Management, L.P. |
| 0.05% | 0.09% | #76 | $46.0M | 414,210 | $73.6M | 846,801 | -432,591-51.09% | Reduce |
| Sofinnova Investments, Inc. |
| 2.34% | 1.49% | #11 | $45.3M | 408,027 | $39.1M | 450,096 | -42,069-9.35% | Reduce |
| AMERIPRISE FINANCIAL INC |
| 0.01% | 0.01% | #126 | $44.6M | 401,634 | $33.4M | 383,957 | +17,677+4.60% | Add |
| ADAGE CAPITAL PARTNERS GP, L.L.C. |
| 0.06% | 0.1% | #66 | $44.1M | 397,000 | $63.1M | 725,744 | -328,744-45.30% | Reduce |
| Bank of New York Mellon Corp |
| 0.01% | <0.01% | #140 | $43.8M | 394,044 | $25.5M | 293,298 | +100,746+34.35% | Add |
| BRAIDWELL LP |
| 1.57% | 0.9% | #14 | $42.3M | 381,128 | $27.0M | 310,628 | +70,500+22.70% | Add |
| Artisan Partners Limited Partnership |
| 0.06% | 0.05% | #65 | $39.4M | 354,816 | $34.0M | 390,669 | -35,853-9.18% | Reduce |
| BANK OF AMERICA CORP /DE/ |
| <0.01% | <0.01% | #189 | $36.1M | 325,470 | $54.7M | 628,667 | -303,197-48.23% | Reduce |
| ORBIMED ADVISORS LLC |
| 0.68% | 0.54% | #24 | $35.9M | 322,900 | $27.3M | 314,100 | +8,800+2.80% | Add |
| MILLENNIUM MANAGEMENT LLC |
| 0.01% | 0.02% | #111 | $35.2M | 316,719 | $39.3M | 451,825 | -135,106-29.90% | Reduce |
| SILVERARC CAPITAL MANAGEMENT, LLC |
| 3.59% | 2.72% | #7 | $34.6M | 311,461 | $26.6M | 306,000 | +5,461+1.78% | Add |
