| BAKER BROS. ADVISORS LP | 42,896,690 | $1,145,771 |
| BlackRock, Inc. | 20,755,452 | $554,378 |
| VANGUARD GROUP INC | 15,153,957 | $404,762 |
| STATE STREET CORP | 7,910,733 | $211,296 |
| RTW INVESTMENTS, LP | 7,144,524 | $190,830 |
| Point72 Asset Management, L.P. | 3,377,311 | $90,208 |
| GEODE CAPITAL MANAGEMENT, LLC | 3,239,451 | $86,539 |
| DIMENSIONAL FUND ADVISORS LP | 2,920,974 | $78,019 |
| Palo Alto Investors LP | 2,484,031 | $66,348 |
| FIRST TRUST ADVISORS LP | 2,270,034 | $60,633 |
| BRAIDWELL LP | 2,032,021 | $54,275 |
| GOLDMAN SACHS GROUP INC | 1,570,051 | $41,936 |
| FRED ALGER MANAGEMENT, LLC | 1,559,962 | $41,667 |
| Pictet Asset Management Holding SA | 1,547,103 | $41,493 |
| RENAISSANCE TECHNOLOGIES LLC | 1,532,596 | $40,936 |
| NORGES BANK | 1,507,527 | $40,266 |
| ARROWSTREET CAPITAL, LIMITED PARTNERSHIP | 1,502,617 | $40,135 |
| Trails Edge Capital Partners, LP | 1,419,406 | $37,912 |
| CITADEL ADVISORS LLC | 1,367,459 | $36,525 |
| Frazier Life Sciences Management, L.P. | 1,297,198 | $34,648 |
| NORTHERN TRUST CORP | 1,235,829 | $33,009 |
| BANK OF AMERICA CORP /DE/ | 1,221,445 | $32,625 |
| Qube Research & Technologies Ltd | 1,202,601 | $32,121 |
| CHARLES SCHWAB INVESTMENT MANAGEMENT INC | 1,172,317 | $31,313 |
| MORGAN STANLEY | 1,141,974 | $30,502 |
| TWO SIGMA INVESTMENTS, LP | 1,119,117 | $29,892 |
| Rockefeller Capital Management L.P. | 1,113,040 | $29,729 |
| MASSACHUSETTS FINANCIAL SERVICES CO /MA/ | 1,072,483 | $28,646 |
| Nuveen, LLC | 1,057,527 | $28,247 |
| D. E. Shaw & Co., Inc. | 1,026,785 | $27,425 |
| Logos Global Management LP | 850,000 | $22,704 |
| Invesco Ltd. | 847,961 | $22,649 |
| DEUTSCHE BANK AG\ | 828,594 | $22,132 |
| EMERALD ADVISERS, LLC | 811,197 | $21,667 |
| UBS Group AG | 769,392 | $20,550 |
| Bank of New York Mellon Corp | 751,985 | $20,086 |
| PRINCIPAL FINANCIAL GROUP INC | 745,356 | $19,908 |
| FMR LLC | 726,963 | $19,417 |
| PANAGORA ASSET MANAGEMENT INC | 681,102 | $18,192 |
| Fisher Asset Management, LLC | 665,087 | $17,764 |
| AMERIPRISE FINANCIAL INC | 662,241 | $17,678 |
| Allspring Global Investments Holdings, LLC | 658,813 | $17,320 |
| Voya Investment Management LLC | 641,511 | $17,135 |
| JUPITER ASSET MANAGEMENT LTD | 621,049 | $16,588 |
| PRICE T ROWE ASSOCIATES INC /MD/ | 615,169 | $16 |
| ALGERT GLOBAL LLC | 614,410 | $16 |
| AQR CAPITAL MANAGEMENT LLC | 604,748 | $16,153 |
| RICE HALL JAMES & ASSOCIATES, LLC | 603,740 | $16,126 |
| Connor, Clark & Lunn Investment Management Ltd. | 580,969 | $15,518 |
| MILLENNIUM MANAGEMENT LLC | 553,674 | $14,789 |
| MANUFACTURERS LIFE INSURANCE COMPANY, THE | 532,533 | $14,224 |
| MARSHALL WACE, LLP | 493,379 | $13,178 |
| PRUDENTIAL FINANCIAL INC | 485,880 | $12,978 |
| EMERALD MUTUAL FUND ADVISERS TRUST | 484,506 | $12,941 |
| GLENMEDE TRUST CO NA | 453,643 | $12,117 |
| Public Sector Pension Investment Board | 433,247 | $11,572 |
| JACOBS LEVY EQUITY MANAGEMENT, INC | 371,047 | $9,911 |
| TWO SIGMA ADVISERS, LP | 370,200 | $9,888 |
| BARCLAYS PLC | 368,304 | $9,837 |
| RHUMBLINE ADVISERS | 361,086 | $9,645 |
| Man Group plc | 348,160 | $9,299 |
| Edgestream Partners, L.P. | 316,239 | $8,447 |
| Legal & General Group Plc | 314,351 | $8,396 |
| GREAT LAKES ADVISORS, LLC | 313,536 | $8,375 |
| TANG CAPITAL MANAGEMENT LLC | 300,000 | $8,013 |
| Trexquant Investment LP | 297,802 | $7,954 |
| Allianz Asset Management GmbH | 295,476 | $7,892 |
| ROYAL BANK OF CANADA | 290,854 | $7,770 |
| JANUS HENDERSON GROUP PLC | 290,111 | $7,749 |
| JPMORGAN CHASE & CO | 270,826 | $7,234 |
| NORDEA INVESTMENT MANAGEMENT AB | 237,645 | $6,347 |
| Swiss National Bank | 232,904 | $6,221 |
| LAZARD ASSET MANAGEMENT LLC | 226,222 | $6,042 |
| F/M Investments LLC | 224,005 | $5,983 |
| SPHERA FUNDS MANAGEMENT LTD. | 212,202 | $5,668 |
| WELLS FARGO & COMPANY/MN | 209,188 | $5,587 |
| UBS ASSET MANAGEMENT AMERICAS INC | 205,433 | $5,487 |
| Rafferty Asset Management, LLC | 198,263 | $5,296 |
| DZ BANK AG Deutsche Zentral Genossenschafts Bank, Frankfurt | 194,146 | $5,186 |
| VICTORY CAPITAL MANAGEMENT INC | 177,605 | $4,744 |
| Eversept Partners, LP | 176,594 | $4,717 |
| FRANKLIN RESOURCES INC | 171,483 | $4,580 |
| Birchview Capital, LP | 171,000 | $4,567 |
| Ishara Investments LP | 160,000 | $4,274 |
| ALPS ADVISORS INC | 158,197 | $4,225 |
| ALLIANCEBERNSTEIN L.P. | 156,243 | $4,173 |
| SEI INVESTMENTS CO | 154,130 | $4,117 |
| ENVESTNET ASSET MANAGEMENT INC | 152,163 | $4,064 |
| STATE OF WISCONSIN INVESTMENT BOARD | 150,386 | $4,017 |
| HUSSMAN STRATEGIC ADVISORS, INC. | 147,000 | $3,926 |
| Russell Investments Group, Ltd. | 138,296 | $3,694 |
| Bridgewater Associates, LP | 138,179 | $3,691 |
| Axecap Investments, LLC | 136,676 | $3,651 |
| Erste Asset Management GmbH | 133,700 | $3,645 |
| AMERICAN CENTURY COMPANIES INC | 128,998 | $3,446 |
| STATE BOARD OF ADMINISTRATION OF FLORIDA RETIREMENT SYSTEM | 128,689 | $3,437 |
| CALIFORNIA STATE TEACHERS RETIREMENT SYSTEM | 126,807 | $3,387 |
| SEGALL BRYANT & HAMILL, LLC | 126,066 | $3,367 |
| ACADIAN ASSET MANAGEMENT LLC | 119,742 | $3 |
| MARTINGALE ASSET MANAGEMENT L P | 109,319 | $2,920 |
| 231 other institutions | 5,256,323 | $118,208 |