| Beutel, Goodman & Co Ltd. |
| 0.18% | 0.18% | #13 | $24.0M | 3.6M | $26.4M | 3.7M | -38,601-1.05% | Reduce |
| Affinity Asset Advisors, LLC |
| 0.49% | 0.59% | #8 | $10.9M | 1.7M | $11.5M | 1.6M | +60,995+3.84% | Add |
| BALYASNY ASSET MANAGEMENT L.P. |
| 0.01% | 0.01% | #27 | $8.9M | 1.4M | $9.8M | 1.4M | +15+0.00% | Add |
| Vivo Capital, LLC |
| 0.81% | 0.81% | #4 | $8.9M | 1.4M | $9.8M | 1.4M | 00.00% | Unchanged |
| SCOTIA CAPITAL INC. |
| 0.03% | 0.03% | #20 | $8.8M | 1.3M | $7.2M | 1.3M | +1,548+0.12% | Add |
| PFM Health Sciences, LP |
| 0.69% | 0.36% | #5 | $8.0M | 1.2M | $3.9M | 540,871 | +669,790+123.84% | Add |
| GREAT POINT PARTNERS LLC |
| 1.5% | 2% | #1 | $7.9M | 1.2M | $8.7M | 1.2M | 00.00% | Unchanged |
| Jupiter Topco LLC |
| <0.01% | — | #36 | $6.9M | 1.0M | $0 | 0 | +1.0M | New Buy |
| Rubric Capital Management LP |
| 0.05% | 0.05% | #17 | $5.7M | 867,424 | $5.0M | 691,170 | +176,254+25.50% | Add |
| Ikarian Capital, LLC |
| 0.57% | 0.71% | #7 | $5.4M | 809,741 | $8.8M | 1.2M | -405,000-33.34% | Reduce |
| Woodline Partners LP |
| 0.02% | 0.01% | #23 | $4.9M | 746,864 | $3.2M | 440,551 | +306,313+69.53% | Add |
| Point72 Asset Management, L.P. |
| 0.01% | 0.01% | #31 | $4.8M | 730,284 | $7.0M | 967,575 | -237,291-24.52% | Reduce |
| AMERIPRISE FINANCIAL INC |
| <0.01% | <0.01% | #44 | $4.7M | 711,024 | $3.8M | 524,257 | +186,767+35.63% | Add |
| Redmile Group, LLC |
| 0.27% | 0.34% | #11 | $4.0M | 611,400 | $5.1M | 700,000 | -88,600-12.66% | Reduce |
| Seven Fleet Capital Management LP |
| 0.67% | 1% | #6 | $4.0M | 610,785 | $3.1M | 433,515 | +177,270+40.89% | Add |
| UBS Group AG |
| <0.01% | <0.01% | #48 | $3.4M | 519,211 | $5.5M | 762,635 | -243,424-31.92% | Reduce |
| CITADEL ADVISORS LLC |
| <0.01% | <0.01% | #49 | $3.3M | 502,011 | $1.7M | 230,176 | +271,835+118.10% | Add |
| MILLENNIUM MANAGEMENT LLC |
| <0.01% | — | #42 | $2.9M | 441,586 | $0 | 0 | +441,586 | New Buy |
| Alyeska Investment Group, L.P. |
| 0.01% | 0.01% | #29 | $2.5M | 375,000 | $2.7M | 375,000 | 00.00% | Unchanged |
| PICTON MAHONEY ASSET MANAGEMENT |
| 0.02% | — | #22 | $2.4M | 360,878 | $0 | 0 | +360,878 | New Buy |
| Velan Capital Investment Management LP |
| 1.42% | 1.6% | #3 | $2.3M | 352,000 | $2.5M | 352,000 | 00.00% | Unchanged |
| JANE STREET GROUP, LLC |
| <0.01% | <0.01% | #55 | $2.2M | 329,053 | $254,030 | 35,210 | +293,843+834.54% | Add |
| Aisling Capital Management LP |
| 0.46% | 0.49% | #9 | $2.1M | 325,000 | $2.4M | 325,000 | 00.00% | Unchanged |
| SummitTX Capital, L.P. |
| 0.05% | 0.07% | #16 | $2.1M | 318,784 | $2.4M | 327,997 | -9,213-2.81% | Reduce |
| ROYAL BANK OF CANADA |
| <0.01% | <0.01% | #51 | $2.1M | 311,435 | $1.9M | 261,376 | +50,059+19.15% | Add |
| DV EQUITIES, LLC |
| 0.26% | — | #12 | $1.8M | 276,000 | $0 | 0 | +276,000 | New Buy |
| ORBIMED ADVISORS LLC |
| 0.03% | — | #19 | $1.8M | 269,000 | $0 | 0 | +269,000 | New Buy |
| BANK OF AMERICA CORP /DE/ |
| <0.01% | <0.01% | #58 | $1.7M | 264,721 | $1.9M | 268,221 | -3,500-1.30% | Reduce |
| Ally Bridge Group (NY) LLC |
| 1.47% | 3.86% | #2 | $1.7M | 252,175 | $4.8M | 660,375 | -408,200-61.81% | Reduce |
| CIBC WORLD MARKET INC. |
| <0.01% | <0.01% | #37 | $1.5M | 234,673 | $1.1M | 150,950 | +83,723+55.46% | Add |
| DAFNA Capital Management LLC |
| 0.28% | — | #10 | $1.5M | 225,600 | $0 | 0 | +225,600 | New Buy |
| TWO SIGMA INVESTMENTS, LP |
| <0.01% | <0.01% | #40 | $1.5M | 221,084 | $78,192 | 10,800 | +210,284+1,947.07% | Add |
| BOOTHBAY FUND MANAGEMENT, LLC |
| 0.02% | 0.03% | #21 | $1.4M | 212,653 | $2.3M | 323,843 | -111,190-34.33% | Reduce |
| MARSHALL WACE, LLP |
| <0.01% | <0.01% | #45 | $1.0M | 158,133 | $1.1M | 158,133 | 00.00% | Unchanged |
| Delaney Capital Management Ltd. |
| 0.12% | — | #14 | $767,862 | 117,200 | $0 | 0 | +117,200 | New Buy |
| TD Waterhouse Canada Inc. |
| <0.01% | <0.01% | #38 | $534,915 | 79,607 | $589,804 | 81,725 | -2,118-2.59% | Reduce |
| XTX Topco Ltd |
| 0.01% | — | #30 | $464,452 | 70,265 | $0 | 0 | +70,265 | New Buy |
| INGALLS & SNYDER LLC |
| 0.01% | 0.02% | #26 | $452,454 | 68,450 | $548,000 | 75,650 | -7,200-9.52% | Reduce |
| Annis Gardner Whiting Capital Advisors, LLC |
| 0.06% | — | #15 | $396,600 | 60,000 | $0 | 0 | +60,000 | New Buy |
| GOLDMAN SACHS GROUP INC |
| <0.01% | <0.01% | #62 | $383,763 | 58,058 | $384,299 | 53,080 | +4,978+9.38% | Add |
| RAYMOND JAMES FINANCIAL INC |
| <0.01% | <0.01% | #59 | $353,655 | 53,503 | $366,055 | 50,560 | +2,943+5.82% | Add |
| 1832 Asset Management L.P. |
| <0.01% | <0.01% | #56 | $333,356 | 50,432 | $434,400 | 60,000 | -9,568-15.95% | Reduce |
| BNP PARIBAS FINANCIAL MARKETS |
| <0.01% | <0.01% | #57 | $305,018 | 46,145 | $46,546 | 6,429 | +39,716+617.76% | Add |
| Stonepine Capital Management, LLC |
| 0.04% | — | #18 | $287,476 | 43,491 | $0 | 0 | +43,491 | New Buy |
| BANK OF MONTREAL /CAN/ |
| <0.01% | <0.01% | #60 | $252,195 | 38,457 | $276,115 | 38,250 | +207+0.54% | Add |
| GEODE CAPITAL MANAGEMENT, LLC |
| <0.01% | <0.01% | #64 | $239,354 | 36,211 | $185,438 | 25,613 | +10,598+41.38% | Add |
| Brevan Howard Capital Management LP |
| <0.01% | — | #39 | $229,810 | 34,767 | $0 | 0 | +34,767 | New Buy |
| Qube Research & Technologies Ltd |
| <0.01% | — | #53 | $226,307 | 34,237 | $0 | 0 | +34,237 | New Buy |
| TORONTO DOMINION BANK |
| <0.01% | <0.01% | #52 | $202,769 | 30,920 | $237,481 | 32,898 | -1,978-6.01% | Reduce |
| AXQ CAPITAL, LP |
| 0.02% | 0.01% | #24 | $139,802 | 21,150 | $114,102 | 15,760 | +5,390+34.20% | Add |
