OWNERSHIP PROFILE

Shareholder Breakdown

Shareholder Holders Value ($MM) % O/S Shares
Institution 79 96.21 71.69 74,524,865
Mutual Fund 43 19.82 18.23 18,953,568
Insider 8 2.44 2.53 2,632,180

Institutional Shareholder Rotation

Shareholder Holders Value Chg ($MM) % O/S Share Change
Buyers 36 51.40 39.52 41,082,027
Sellers 34 -2.29 1.80 -1,872,256
Net -- 49.11 37.72 39,209,771

Institutional Shareholder Concentration

Value ($MM) % O/S Shares
Total Inst. 96.21 71.69 74,524,865
Top 10 Inst. 84.06 62.05 64,505,308
Top 20 Inst. 91.76 68.40 71,104,823
Top 50 Inst. 96.00 71.54 74,371,418

Institutional Shareholder Style

Holders Value ($MM) % Inst Shares Shares
Growth 10 2.72 2.09 2,171,826
Core Growth 8 2.71 2.08 2,164,991
Growth 2 0.01 0.01 6,835
Income 1 0.04 0.03 34,188
Income Value 1 0.04 0.03 34,188
Index 7 5.64 4.34 4,511,147
Other 27 66.15 51.01 53,030,549
Broker Dealer 8 1.04 0.80 831,942
GARP 5 21.31 16.51 17,157,851
Hedge Fund 13 30.06 23.14 24,050,846
VC/Private Equi 1 13.74 10.57 10,989,910
Value 10 0.77 0.59 612,355
Core Value 7 0.73 0.57 589,683
Deep Value 3 0.04 0.02 22,672

Top Holders: Institutional Investor

Holder Shares Held % O/S Share Change Filing Date
Fidelity Management & Research Company 15,567,859 14.98 7,590,510 9/30/17
BVF Partners L.P. 12,949,229 12.46 9,670,329 9/30/17
New Enterprise Associates (NEA) 10,989,910 10.57 10,989,910 9/30/17
EcoR1 Capital, LLC 5,239,225 5.04 1,530,081 9/30/17
Sanofi SA 5,053,779 4.86 -- 3/31/17
Broadfin Capital, L.L.C. 4,294,505 4.13 4,294,505 9/30/17
AstraZeneca Plc 3,522,000 3.39 -- 3/31/17
The Vanguard Group, Inc. 2,870,972 2.76 1,400,608 9/30/17
Boxer Capital, L.L.C. 2,197,802 2.11 2,197,802 9/30/17
South Dakota Investment Council 1,820,027 1.75 492,969 9/30/17
Papadopoulos (Stelios B) 1,797,306 1.73 96,629 12/4/17
BlackRock Institutional Trust Company, N.A. 762,055 0.73 243,477 9/30/17
Candriam Luxembourg S.A. 600,000 0.58 600,000 9/30/17
Rhenman & Partners Asset Management AB 580,000 0.56 -13,629 9/30/17
Oppenheim Asset Management Services S.à r.l. 514,892 0.50 514,892 9/30/17
Candriam Belgium S.A. 500,000 0.48 -100,000 11/30/17
Wells Fargo Advisors 492,191 0.47 -206,199 9/30/17
Geode Capital Management, L.L.C. 483,951 0.47 272,411 9/30/17
Medical Strategy GmbH 471,392 0.45 471,392 9/30/17
Millennium Management LLC 397,728 0.38 -72,532 9/30/17
Rastetter (William H) 350,000 0.34 250,000 3/31/17
Victory Capital Management Inc. 277,240 0.27 277,240 9/30/17
Wright (Timothy Michael) 274,725 0.26 274,725 7/25/17
Hagan (Joseph P) 233,434 0.22 219,780 7/25/17
GSA Capital Partners LLP 203,815 0.20 63,100 9/30/17
Northern Trust Investments, Inc. 183,271 0.18 109,068 9/30/17
Wedbush Securities, Inc. 179,321 0.17 -20,200 9/30/17
Quantitative Investment Management LLC 178,000 0.17 73,000 9/30/17
California Public Employees' Retirement System 177,600 0.17 -- 9/30/17
SELECTRA Management Company S.A. 177,000 0.17 -- 12/31/16
RBC Capital Markets Wealth Management 146,500 0.14 -37,000 9/30/17
Apo Asset Management GmbH 112,000 0.11 -- 10/31/17
Foletta Mark G Iii 81,910 0.08 71,910 12/4/17
Squarepoint Capital LLP 74,000 0.07 29,636 9/30/17
Baltimore (David) 60,674 0.06 60,674 12/4/17
Witz (Pascale) 60,674 0.06 60,674 12/4/17
Element Capital Management, LLC 60,473 0.06 -103,134 9/30/17
Chevallard (Daniel R) 59,415 0.06 54,945 7/25/17
Rosen (Hugh M.D., Ph.D.) 56,179 0.05 56,179 12/4/17
Renaissance Technologies LLC 43,589 0.04 43,589 9/30/17
Bourgeon Capital Management, LLC 40,804 0.04 40,804 9/30/17
BNY Mellon Asset Management 34,188 0.03 9,732 9/30/17
BlackRock Financial Management, Inc. 33,260 0.03 28,892 9/30/17
D. E. Shaw & Co., L.P. 29,728 0.03 29,728 9/30/17
Guggenheim Investments 29,097 0.03 29,097 9/30/17
State Street Global Advisors (US) 26,000 0.03 -6,500 9/30/17
A.R.T. Advisors, LLC 24,850 0.02 -234,619 9/30/17
Hightower Advisors, LLC 20,248 0.02 10,000 9/30/17
Macquarie Investment Management 20,000 0.02 -- 9/30/17
ClariVest Asset Management LLC 18,600 0.02 18,600 6/30/16

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