| STATE STREET CORPORATION |
MA |
0 |
4719748 |
0 |
0 |
5148293 |
5.1 % |
17/10/2024 |
| 52-0556948 |
Maryland |
1568056 |
0 |
4359645 |
0 |
4359645 |
4.5 % |
14/02/2022 |
| EIN #00-0000000 |
Jersey, Channel Islands |
0 |
7445839 |
0 |
7445839 |
7445839 |
7.8 % |
10/02/2022 |
| The Vanguard Group - 23-1945930 |
Pennsylvania For |
0 |
77127 |
8644767 |
143224 |
8787991 |
9.26 % |
10/02/2022 |
| (1) BlackRock, Inc. |
Delaware |
10973740 |
0 |
11476545 |
0 |
11476545 |
12.1 % |
27/01/2022 |
| (1) BlackRock, Inc. |
Delaware |
10984281 |
0 |
11476545 |
0 |
11476545 |
12.1 % |
25/01/2022 |
| FMR LLC |
Delaware |
189423 |
0 |
3780076 |
0 |
3780076 |
3.994 % |
10/08/2021 |
| EIN #00-0000000 |
Jersey, Channel Islands |
0 |
9444121 |
0 |
9444121 |
9444121 |
10 % |
12/04/2021 |
| (1) BlackRock, Inc. |
Delaware |
10506344 |
0 |
10989646 |
0 |
10989646 |
11.7 % |
09/04/2021 |
| 95-1411037 |
Delaware |
3781423 |
0 |
4049442 |
0 |
13 |
4.3 % |
16/02/2021 |
| 52-0556948 |
Maryland |
1786530 |
0 |
6271730 |
0 |
6271730 |
6.7 % |
16/02/2021 |
| EIN #00-0000000 |
|
0 |
9307920 |
0 |
9307920 |
9307920 |
9.9 % |
11/02/2021 |
| The Vanguard Group - 23-1945930 |
Pennsylvania |
0 |
96343 |
8170398 |
166867 |
8337265 |
8.92 % |
10/02/2021 |
| (1) BlackRock, Inc. |
Delaware |
6487970 |
0 |
6997795 |
0 |
6997795 |
7.5 % |
29/01/2021 |
| Perceptive Advisors LLC |
Delaware |
0 |
3612554 |
0 |
3612554 |
3612554 |
3.9 % |
14/02/2020 |
| Ltd. |
Delaware |
0 |
3412504 |
0 |
3412504 |
3412504 |
3.7 % |
14/02/2020 |
| Joseph Edelman |
Delaware |
0 |
3612554 |
0 |
3612554 |
3612554 |
3.9 % |
14/02/2020 |
| 52-0556948 |
Maryland |
1886323 |
0 |
7291297 |
0 |
7291297 |
7.9 % |
14/02/2020 |
| Capital International Investors ** |
|
6362060 |
0 |
6740419 |
0 |
6740419 |
7.3 % |
14/02/2020 |
| The Vanguard Group - 23-1945930 |
Pennsylvania |
71392 |
22416 |
8232423 |
84474 |
8316897 |
9.03 % |
12/02/2020 |
| (1) BlackRock, Inc. |
Delaware |
6095205 |
0 |
6591552 |
0 |
6591552 |
7.2 % |
10/02/2020 |
| FMR LLC |
United States of America |
0 |
0 |
7431373 |
0 |
7431373 |
8.058 % |
07/02/2020 |
| FMR LLC |
Delaware |
1039938 |
0 |
8470788 |
0 |
8470788 |
9.186 % |
10/12/2019 |
| 52-0556948 |
Maryland |
728136 |
0 |
4009363 |
0 |
4009363 |
4.4 % |
14/02/2019 |
| Abigail P. Johnson |
Delaware |
0 |
0 |
13097329 |
0 |
13097329 |
14.43 % |
13/02/2019 |
| FMR LLC |
Delaware |
1805400 |
0 |
13097329 |
0 |
13097329 |
14.43 % |
13/02/2019 |
| (1) BlackRock, Inc. |
Delaware |
4617444 |
0 |
4978917 |
0 |
4978917 |
5.5 % |
11/02/2019 |
| 2 |
Delaware |
0 |
5151589 |
0 |
5151589 |
5151589 |
5.6 % |
14/02/2018 |
| 52-0556948 |
Maryland |
1023752 |
0 |
6231030 |
0 |
6231030 |
7 % |
14/02/2018 |
| Abigail P. Johnson |
United States of America |
0 |
0 |
13273956 |
0 |
13273956 |
14.999 % |
13/02/2018 |
| FMR LLC |
Delaware |
1879529 |
0 |
13273956 |
0 |
13273956 |
14.999 % |
13/02/2018 |
| (1) BlackRock, Inc. |
Delaware |
4473636 |
0 |
4775746 |
0 |
4775746 |
5.4 % |
08/02/2018 |
| 2 |
Delaware |
0 |
4657589 |
0 |
4657589 |
4657589 |
5.3 % |
08/09/2017 |
| 52-0556948 |
Maryland |
1141064 |
0 |
5980163 |
0 |
5980163 |
6.8 % |
07/02/2017 |
| (1) BlackRock, Inc. |
Delaware |
4963323 |
0 |
5255737 |
0 |
5255737 |
6.1 % |
25/01/2017 |
| (1) BlackRock, Inc. |
Delaware |
6850293 |
0 |
7046711 |
0 |
7046711 |
8.2 % |
27/01/2016 |
| Abigail P. Johnson |
United States of America |
0 |
0 |
11400773 |
0 |
11400773 |
14.999 % |
13/02/2015 |
| FMR LLC |
Delaware |
849588 |
0 |
11400773 |
0 |
11400773 |
14.999 % |
13/02/2015 |
| Edward C. Johnson 3d |
United States of America |
0 |
0 |
11400773 |
0 |
11400773 |
14.999 % |
13/02/2015 |
| (1) BlackRock, Inc. |
Delaware |
6180716 |
0 |
6347260 |
0 |
6347260 |
8.4 % |
23/01/2015 |
| (1) BlackRock, Inc. |
Delaware |
4423455 |
0 |
4601027 |
0 |
4601027 |
6.8 % |
29/01/2014 |
| BVF Investments, L.L.C. |
Illinois |
0 |
0 |
0 |
0 |
0 |
0 % |
14/02/2013 |
| Biotechnology Value Fund II, L.P. |
Illinois |
0 |
0 |
0 |
0 |
0 |
0 % |
14/02/2013 |
| Biotechnology Value Fund, L.P. |
Illinois |
0 |
0 |
0 |
0 |
0 |
0 % |
14/02/2013 |
| Investment 10, L.L.C. |
Illinois |
0 |
0 |
0 |
0 |
0 |
0 % |
14/02/2013 |
| BVF Partners L.P. |
Illinois |
0 |
0 |
0 |
0 |
0 |
0 % |
14/02/2013 |
| BVF Inc. |
Illinois |
0 |
0 |
0 |
0 |
0 |
0 % |
14/02/2013 |
| Mark N. Lampert |
Illinois |
0 |
0 |
0 |
0 |
0 |
0 % |
14/02/2013 |
| FMR LLC |
Delaware |
903180 |
0 |
9957703 |
0 |
9957703 |
15 % |
14/02/2013 |
| Edward C. Johnson 3d |
United States of America |
0 |
0 |
9957703 |
0 |
9957703 |
15 % |
14/02/2013 |
| Perceptive Advisors LLC |
Delaware, United States of America |
0 |
4212137 |
0 |
|
4212137 |
6.33 % |
14/02/2013 |
| (1) BlackRock, Inc. |
Delaware |
3845485 |
0 |
3845485 |
0 |
3845485 |
5.79 % |
30/01/2013 |
| (1) BlackRock, Inc. |
Delaware |
3259381 |
0 |
3259381 |
0 |
3259381 |
4.92 % |
08/06/2012 |
| Edward C. Johnson 3d |
Delaware |
0 |
0 |
8287661 |
0 |
8287661 |
14.998 % |
14/02/2012 |
| FMR LLC |
Delaware |
1159550 |
0 |
8287661 |
0 |
8287661 |
14.998 % |
14/02/2012 |
| Mark N. Lampert |
Delaware |
0 |
5895965 |
0 |
0 |
5895965 |
10.7 % |
12/10/2011 |
| Biotechnology Value Fund, L.P. |
Delaware |
0 |
1230465 |
0 |
0 |
1230465 |
2.2 % |
12/10/2011 |
| BVF Investments, L.L.C. |
Delaware |
0 |
3505400 |
0 |
0 |
3505400 |
6.4 % |
12/10/2011 |
| BVF Partners L.P. |
Delaware |
0 |
5895965 |
0 |
0 |
5895965 |
10.7 % |
12/10/2011 |
| Investment 10, L.L.C. |
Delaware |
0 |
403500 |
0 |
0 |
403500 |
1 % |
12/10/2011 |
| BVF Inc. |
Delaware |
0 |
5895965 |
0 |
0 |
5895965 |
10.7 % |
12/10/2011 |
| Biotechnology Value Fund II, L.P. |
Delaware |
0 |
756600 |
0 |
0 |
756600 |
1.4 % |
12/10/2011 |
| 04-2683227 |
Massachusetts |
0 |
2122668 |
0 |
0 |
2171668 |
3.96 % |
14/02/2011 |
| (1) BlackRock, Inc. |
Delaware |
3093603 |
0 |
3093603 |
0 |
3093603 |
5.64 % |
07/02/2011 |
| Edward C. Johnson 3d |
Delaware |
0 |
0 |
6438318 |
0 |
6438318 |
11.742 % |
10/05/2010 |
| FMR LLC |
Delaware |
263307 |
0 |
6438318 |
0 |
6438318 |
11.742 % |
10/05/2010 |
| Biotechnology Value Fund II, L.P. |
Delaware |
0 |
845000 |
0 |
0 |
845000 |
1.6 % |
14/04/2010 |
| Investment 10, L.L.C. |
Delaware |
0 |
363500 |
0 |
0 |
363500 |
1 % |
14/04/2010 |
| BVF Investments, L.L.C. |
Delaware |
0 |
2963000 |
0 |
0 |
2963000 |
5.4 % |
14/04/2010 |
| BVF Inc. |
Delaware |
0 |
5404947 |
0 |
0 |
5404947 |
9.9 % |
14/04/2010 |
| Biotechnology Value Fund, L.P. |
Delaware |
0 |
1233447 |
0 |
0 |
1233447 |
2.3 % |
14/04/2010 |
| Mark N. Lampert |
Delaware |
0 |
5404947 |
0 |
0 |
5404947 |
9.9 % |
14/04/2010 |
| BVF Partners L.P. |
Delaware |
0 |
5404947 |
0 |
0 |
5404947 |
9.9 % |
14/04/2010 |
| 04-2683227 |
Massachusetts |
0 |
2140163 |
0 |
0 |
2201263 |
5.61 % |
12/02/2010 |
| (. |
Delaware Limited Partnership |
2006677 |
0 |
2029853 |
0 |
2029853 |
5.18 % |
08/02/2010 |
| Hove, Anders |
United States |
0 |
0 |
0 |
4784689 |
4784689 |
10.9 % |
05/01/2010 |
| VHCP Management, LLC |
United States |
0 |
0 |
0 |
4784689 |
4784689 |
10.9 % |
05/01/2010 |
| Venrock Co-Investment Holdings, LLC |
United States |
0 |
0 |
0 |
0 |
739900 |
1.7 % |
05/01/2010 |
| Roberts, Bryan |
United States |
0 |
0 |
0 |
4784689 |
4784689 |
10.9 % |
05/01/2010 |
| Venrock Healthcare Capital Partners, L.P. |
United States |
0 |
0 |
0 |
0 |
4044789 |
9.2 % |
05/01/2010 |
| 52-0556948 |
MARYLAND |
112400 |
0 |
529461 |
0 |
529461 |
1.3 % |
12/02/2009 |
| (. |
Delaware Limited Partnership |
2385394 |
0 |
2435859 |
0 |
2435859 |
6.31 % |
09/02/2009 |
| EIN #75-3019302 |
Delaware |
0 |
0 |
0 |
0 |
0 |
0 % |
14/02/2008 |
| 52-0556948 |
MARYLAND |
255700 |
0 |
2212961 |
0 |
2212961 |
5.7 % |
12/02/2008 |
| (. |
Delaware Limited Partnership |
2932456 |
0 |
2932456 |
0 |
2932456 |
7.72 % |
06/02/2008 |
| Biotechnology Value Fund II, L.P. |
Delaware |
0 |
0 |
0 |
460000 |
460000 |
1.2 % |
22/01/2008 |
| Investment 10, L.L.C. |
Delaware |
0 |
0 |
0 |
196000 |
196000 |
0.5 % |
22/01/2008 |
| BVF Partners L.P. |
Delaware |
0 |
0 |
0 |
2927100 |
2927100 |
7.7 % |
22/01/2008 |
| BVF Inc. |
Delaware |
0 |
0 |
0 |
2927100 |
2927100 |
7.7 % |
22/01/2008 |
| BVF Investments, L.L.C. |
Delaware |
0 |
0 |
0 |
1606000 |
1606000 |
4.2 % |
22/01/2008 |
| Biotechnology Value Fund, L.P. |
Delaware |
0 |
0 |
0 |
665100 |
665100 |
1.8 % |
22/01/2008 |
| FMR LLC |
Delaware |
0 |
0 |
100 |
0 |
100 |
0 % |
10/01/2008 |
| Edward C. Johnson 3d |
United States of America |
0 |
0 |
100 |
0 |
100 |
0 % |
10/01/2008 |
| Peter Kolchinsky |
USA |
0 |
0 |
0 |
1955000 |
1955000 |
5.1 % |
20/12/2007 |
| RA Capital Biotech Fund II, L.P. |
USA |
0 |
0 |
0 |
0 |
25415 |
0.1 % |
20/12/2007 |
| RA Capital Biotech Fund, L.P. |
USA |
0 |
0 |
0 |
0 |
1929585 |
5 % |
20/12/2007 |
| Richard H. Aldrich |
USA |
0 |
0 |
0 |
1955000 |
1955000 |
5.1 % |
20/12/2007 |
| RA Capital Management, LLC |
USA |
0 |
0 |
0 |
0 |
1955000 |
5.1 % |
20/12/2007 |
| FMR LLC |
Delaware |
672750 |
0 |
3182865 |
0 |
3182865 |
8.378 % |
10/10/2007 |
| Edward C. Johnson 3d |
United States of America |
0 |
0 |
3182865 |
0 |
3182865 |
8.378 % |
10/10/2007 |
| Edward C. Johnson 3d |
United States of America |
0 |
0 |
5242965 |
0 |
5242965 |
13.84 % |
14/02/2007 |
| FMR Corp. |
Delaware |
1346686 |
0 |
5242965 |
0 |
5242965 |
13.84 % |
14/02/2007 |
| EIN #75-3019302 |
Delaware |
2119810 |
0 |
2119810 |
0 |
2119810 |
5.6 % |
14/02/2007 |
| 52-0556948 |
MARYLAND |
365600 |
0 |
1847361 |
0 |
1847361 |
4.8 % |
13/02/2007 |
| 52-0556948 |
MARYLAND |
545400 |
0 |
1983861 |
0 |
1983861 |
5.2 % |
08/12/2006 |
| EIN #75-3019302 |
Delaware |
1231095 |
0 |
1231095 |
0 |
1231095 |
3.3 % |
12/06/2006 |
| EIN #75-3019302 |
Delaware |
4740237 |
0 |
4740237 |
0 |
4740237 |
12.8 % |
14/02/2006 |
| Massachusetts Financial Services Company ("MFS") |
Delaware |
804120 |
0 |
804120 |
0 |
804120 |
2.2 % |
14/02/2006 |
| Edward C. Johnson 3d |
United States of America |
0 |
0 |
3761400 |
0 |
3761400 |
10.186 % |
14/02/2006 |
| FMR Corp. |
Delaware |
837400 |
0 |
3761400 |
0 |
3761400 |
10.186 % |
14/02/2006 |
| 52-0556948 |
MARYLAND |
947860 |
0 |
4420221 |
0 |
4420221 |
11.9 % |
14/02/2006 |
| EIN #75-3019302 |
Delaware |
4029736 |
0 |
4029736 |
0 |
4029736 |
11.1 % |
14/02/2005 |
| FMR Corp. |
Delaware |
328900 |
0 |
4402598 |
0 |
4402598 |
12.073 % |
14/02/2005 |
| Abigail P. Johnson |
United States of America |
0 |
0 |
4402598 |
0 |
4402598 |
12.073 % |
14/02/2005 |
| Edward C. Johnson 3d |
United States of America |
0 |
0 |
4402598 |
0 |
4402598 |
12.073 % |
14/02/2005 |
| 52-0556948 |
MARYLAND |
1066360 |
0 |
4579921 |
0 |
4579921 |
12.5 % |
11/02/2005 |
| Massachusetts Financial Services Company ("MFS") |
Delaware |
1890570 |
0 |
1918150 |
0 |
1918150 |
5.26 % |
08/02/2005 |
| EIN #75-3019302 |
Delaware |
4207902 |
0 |
4207902 |
0 |
4207902 |
11.6 % |
10/08/2004 |
| EIN #75-3019302 |
Delaware |
2489785 |
0 |
2489785 |
0 |
2489785 |
7.1 % |
17/02/2004 |
| FMR Corp. |
Delaware |
125228 |
0 |
3658498 |
0 |
3658498 |
10.373 % |
17/02/2004 |
| Abigail P. Johnson |
United States of America |
0 |
0 |
3658498 |
0 |
3658498 |
10.373 % |
17/02/2004 |
| Edward C. Johnson 3d |
United States of America |
0 |
0 |
3658498 |
0 |
3658498 |
10.373 % |
17/02/2004 |
| 52-0556948 |
MARYLAND |
936560 |
0 |
3774821 |
0 |
3774821 |
10.7 % |
10/02/2004 |
| FMR Corp. |
Delaware |
334098 |
0 |
3978006 |
0 |
3978006 |
13 % |
13/02/2003 |
| Abigail P. Johnson |
United States of America |
0 |
0 |
3978006 |
0 |
3978006 |
13 % |
13/02/2003 |
| Edward C. Johnson 3d |
United States of America |
0 |
0 |
3978006 |
0 |
3978006 |
13 % |
13/02/2003 |
| 52-0556948 |
MARYLAND |
682360 |
0 |
3096821 |
0 |
3096821 |
10.1 % |
11/02/2003 |
| 52-0556948 |
MARYLAND |
665460 |
0 |
3001221 |
0 |
3001221 |
9.8 % |
10/02/2003 |
| 52-0556948 |
MARYLAND |
665460 |
0 |
3001221 |
0 |
3001221 |
9.8 % |
05/02/2003 |
| 52-0556948 |
MARYLAND |
460750 |
0 |
2276450 |
0 |
2276450 |
7.6 % |
22/02/2002 |
| Abigail P. Johnson |
United States of America |
0 |
0 |
2790400 |
0 |
2790400 |
9.471 % |
14/02/2002 |
| FMR Corp. |
Commonwealth of Massachusetts |
334400 |
0 |
2790400 |
0 |
2790400 |
9.471 % |
14/02/2002 |
| Edward C. Johnson 3d |
United States of America |
0 |
0 |
2790400 |
0 |
2790400 |
9.471 % |
14/02/2002 |
| Edward C. Johnson 3d |
United States of America |
0 |
0 |
3864308 |
0 |
3864308 |
13 % |
11/02/2002 |
| 52-0556948 |
MARYLAND |
480750 |
0 |
2276450 |
0 |
2276450 |
7.6 % |
11/02/2002 |
| FMR Corp. |
Commonwealth of Massachusetts |
340700 |
0 |
3864308 |
0 |
3864308 |
13 % |
11/02/2002 |
| Abigail P. Johnson |
United States of America |
0 |
0 |
3864308 |
0 |
3864308 |
13 % |
11/02/2002 |
| Deutsche Bank AG |
Federal Republic of Germany |
0 |
0 |
0 |
1344400 |
1344400 |
5.3 % |
19/04/2001 |
| 52-0556948 |
MARYLAND |
582500 |
0 |
2646600 |
0 |
2646600 |
10.5 % |
10/04/2001 |
| Wells Fargo & Company |
Delaware |
622838 |
0 |
325993 |
840600 |
1173218 |
5.4 % |
13/02/2001 |
| 52-0556948 |
MARYLAND |
314300 |
0 |
2116200 |
0 |
2116200 |
8.4 % |
09/02/2001 |
| 52-0791372 |
Maryland |
1150700 |
0 |
0 |
0 |
1150700 |
4.5 % |
09/02/2001 |
| 52-0556948 |
MARYLAND |
69900 |
0 |
1687800 |
0 |
1687800 |
8.8 % |
07/02/2000 |
| 52-0791372 |
Maryland |
1005700 |
0 |
0 |
0 |
1005700 |
5.2 % |
07/02/2000 |
| 52-0556948 |
MARYLAND |
331543 |
0 |
2211643 |
0 |
2211643 |
12.1 % |
09/02/1999 |
| 52-0791372 |
Maryland |
985000 |
0 |
0 |
0 |
985000 |
5.4 % |
09/02/1999 |
| 52-0556948 |
MARYLAND |
250143 |
0 |
1767643 |
0 |
1767643 |
10.3 % |
07/05/1998 |