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cash flows from operating activities:
net income	251,084,000	-66,277,000	-57,479,000	-83,763,000	-111,570,000	-16,889,000	-65,935,000	-137,870,000	147,753,000	-276,024,000	-174,101,000	-207,493,000	-405,920,000	-277,402,000	-240,341,000	-258,460,000	-204,514,000	-189,559,000	-200,291,000	-243,540,000	-253,291,000	-179,229,000	-182,221,000	-276,185,000	-208,535,000	-219,481,000	-181,915,000	-211,441,000	-245,282,000	-163,560,000	-141,214,000	-142,227,000	-122,937,000	-118,420,000	-107,290,000	-112,934,000	-104,071,000	-90,129,000	-102,974,000	-90,721,000	-76,792,000	-71,783,000	-50,777,000	-21,389,000	-43,989,000	-44,074,000	-250,943,000	-32,357,000	-29,686,000	-18,169,000	-9,013,000	-62,188,000	-19,502,000	-12,956,000	-11,368,000	-14,303,000	-13,237,000	-13,824,000	-16,285,000	-6,930,000	-9,630,000	-14,632,000	-12,323,000	-7,791,000	-9,208,000	-22,702,000	-7,889,000	-9,392,000	-2,858,000	-12,760,000	-1,239,000	1,662,000	-52,792,000	-12,691,000	-21,645,000	-8,438,000	-7,400,000	-9,910,000	-8,860,000	-14,491,000	-10,678,000	-11,145,000	-6,600,000	-6,416,000
adjustments to reconcile net income to net cash from operating activities:
depreciation and amortization	13,803,000	13,944,000	14,405,000	14,168,000	13,982,000	15,003,000	13,517,000	13,482,000	13,328,000	13,179,000	14,065,000	14,311,000	10,600,000	10,097,000	9,460,000	11,375,000	11,786,000	11,805,000	12,601,000	10,386,000	8,573,000	8,200,000	7,613,000	5,442,000							3,178,000	3,714,000	3,587,000	3,066,000	3,000,000	3,018,000	3,500,000	4,011,000	4,601,000	5,069,000	5,270,000	5,021,000	3,690,000	3,341,000	3,117,000	2,868,000	2,600,000	2,627,000	2,764,000	2,711,000	2,127,000	2,024,000	2,285,000	2,605,000	2,121,000	1,237,000	1,262,000	1,287,000	1,339,000	1,291,000	1,266,000	1,223,000	1,161,000	1,136,000	1,111,000	1,943,000	1,802,000	1,798,000	1,631,000	1,346,000	951,000	902,000	1,048,000	937,000	1,195,000	1,087,000	992,000	947,000	789,000	752,000	740,000	952,000	675,000	728,000
non-cash interest expense on liability related to the sale of future royalties	40,864,000	36,472,000	34,962,000	35,299,000	30,731,000	29,538,000	31,565,000	27,636,000	27,271,000	26,372,000	25,275,000	24,579,000	24,917,000	27,002,000	27,702,000	29,365,000	30,177,000	28,836,000	28,184,000	28,517,000
stock-based compensation expense	108,211,000				45,804,000	89,288,000	45,347,000
realized and unrealized loss on marketable equity securities	0				1,567,000				16,844,000	-1,400,000	2,267,000
loss on extinguishment of debt												0
change in fair value of development derivative liability	64,663,000	15,259,000	58,891,000	70,271,000	36,271,000	55,642,000	8,586,000	23,102,000	31,209,000	30,215,000	6,471,000	23,883,000
deferred income taxes	5,598,000	9,735,000	9,639,000																																																									10,875,000	11,000	-13,000	-131,000	-5,194,000	281,000	-13,000	-237,000
other	6,400,000	-18,510,000	-19,354,000	-6,760,000	-16,863,000	-10,177,000	-5,188,000	-14,655,000	23,340,000	-1,976,000	-6,276,000	-20,128,000	-42,915,000	42,345,000	21,177,000	22,454,000	2,870,000	1,575,000	30,777,000	9,631,000	-2,744,000	3,712,000	660,000	1,224,000	-5,201,000							0	0	0	608,000
changes in operating assets and liabilities:
accounts receivable	-399,863,000	-136,913,000	-7,434,000	-59,508,000	-37,092,000	9,640,000	410,000	3,869,000	-107,991,000	-2,970,000	19,153,000	-53,269,000	-38,423,000	6,399,000	39,696,000	-59,449,000	3,670,000	-35,311,000	-10,709,000	-21,166,000	-8,971,000	6,783,000	-32,882,000	5,479,000	-17,783,000	3,107,000	-15,041,000	-15,398,000
inventory	4,976,000	11,144,000	6,215,000	849,000	5,925,000	6,794,000	22,000	11,990,000	4,795,000	1,985,000	-403,000	-18,978,000	-7,884,000	-9,200,000	1,926,000	-10,760,000	-13,634,000	-3,955,000	1,934,000	-8,464,000	-2,784,000	-12,226,000	-11,952,000	-4,316,000	-13,055,000	-7,906,000	-7,134,000	-12,291,000
prepaid expenses and other assets	-20,742,000	6,777,000	-32,769,000	25,281,000	-8,277,000	61,687,000	-75,462,000	23,398,000	-3,318,000	-27,874,000	-1,235,000	8,687,000	3,965,000	-21,307,000	-29,852,000	16,672,000	-18,144,000	-16,967,000	-13,654,000	11,465,000	17,325,000	6,398,000	-19,958,000	-8,380,000	-18,525,000	14,281,000	-9,418,000	-942,000	-12,864,000	6,279,000	-27,540,000	-18,659,000	-1,854,000	-3,906,000	3,708,000	-2,463,000	2,780,000	-3,583,000	-2,010,000	606,000	-2,336,000	-1,911,000	-3,179,000	960,000	-429,000	-1,861,000	-4,499,000	866,000	-572,000	-706,000	-944,000	3,139,000	1,254,000	319,000	-2,932,000	751,000	168,000	-158,000	1,970,000	-457,000	-411,000	-912,000	-958,000	1,022,000	154,000	127,000	-780,000	-151,000	-341,000	-2,260,000	1,004,000	1,198,000	-5,732,000	-480,000	666,000	-438,000	490,000	-467,000	79,000
accounts payable, accrued expenses and other liabilities	223,509,000	182,148,000	-155,737,000	-62,107,000	83,595,000	74,470,000	-4,865,000	-38,666,000	118,740,000	82,741,000	-81,975,000	102,617,000	69,745,000	68,143,000	-48,736,000	39,502,000	46,364,000	68,947,000	-66,573,000	68,168,000	73,528,000	16,251,000	-14,215,000
deferred revenue	-12,540,000	-13,079,000	-27,321,000	-16,564,000	624,000	-190,943,000	-28,563,000	17,689,000	24,467,000	21,716,000	-8,850,000	-41,279,000	-12,465,000	158,000	-12,325,000	9,690,000	-8,352,000	-23,938,000	-27,804,000	-28,041,000	-8,834,000	-3,060,000	-4,030,000	-7,333,000	411,000	400,007,000	-834,000	-1,113,000	-8,616,000	-29,848,000	26,961,000	7,892,000	-4,985,000	-931,000	-128,000	5,951,000	3,286,000	2,799,000	2,579,000	2,668,000	3,374,000	2,051,000	-6,189,000	16,556,000	-9,252,000	-7,245,000	-7,845,000	753,000	-5,859,000	-8,332,000	7,237,000	16,106,000	12,732,000	-17,331,000	-20,069,000	-19,684,000	-20,306,000	-20,367,000	-9,898,000	-19,828,000	-22,122,000	-19,083,000	328,000	-20,284,000	-20,142,000	-19,259,000	1,513,000	-19,504,000	-185,000	99,412,000	-13,054,000	-15,122,000	265,102,000	-2,608,000	-2,376,000	-1,469,000	3,113,000	-2,172,000	-2,376,000	15,748,000	112,000	-373,000	270,000	567,000
net cash from operating activities	325,109,000	153,730,000	-118,314,000	-94,662,000	43,707,000	124,158,000	-81,515,000	-29,795,000	359,412,000	-58,986,000	-166,475,000	-131,978,000	-115,284,000	-122,819,000	-171,193,000	-150,141,000	-134,036,000	-121,856,000	-235,660,000	-123,144,000	-110,326,000	-135,330,000	-246,161,000	-195,980,000	-182,632,000	288,695,000	-188,510,000	-150,457,000	-153,808,000	-102,687,000	-155,664,000	-103,044,000	-98,363,000	-81,049,000	-100,330,000	-78,337,000	-75,536,000	-70,205,000	-83,623,000	-53,064,000	-54,365,000	-55,456,000	-26,255,000	-36,635,000	-40,706,000	-46,625,000	-41,675,000	-22,369,000	-21,715,000	-23,602,000	-971,000	-68,912,000	5,212,000	-21,694,000	-30,215,000	-25,159,000	-29,025,000	-26,579,000	-6,305,000	-20,388,000	-24,038,000	-24,314,000	-15,601,000	-16,869,000	-20,588,000	-35,919,000	1,231,000	-4,849,000	-16,010,000	95,008,000	-8,658,000	-8,438,000	224,309,000	-8,391,000	-10,961,000	-4,613,000	-2,932,000	-8,382,000	-8,703,000	3,616,000	-6,212,000	-6,250,000	-7,639,000	-3,612,000
capex	-12,142,000	-14,293,000	-8,970,000	-9,094,000	-4,192,000	-8,018,000	-12,973,000	-15,309,000	-17,092,000	-15,919,000	-13,891,000	-21,635,000	-16,510,000	-16,055,000	-17,859,000	-21,886,000	-26,062,000	-11,246,000	-17,178,000	-21,668,000	-12,418,000	-16,658,000	-19,617,000	-38,805,000	-36,058,000	-21,244,000	-44,049,000	-37,513,000	-45,409,000	-22,708,000	-21,257,000	-20,728,000	-25,678,000	-21,651,000	-36,152,000	0	-20,298,000	-21,621,000	-2,759,000	-3,099,000	-6,477,000	-1,264,000	-2,110,000	-3,526,000	-3,195,000	-1,852,000	-388,000	-878,000	-950,000	-379,000	-1,799,000	-686,000	-5,729,000	-1,670,000	-263,000	-524,000	-265,000	-474,000	-28,000	-1,138,000	-1,067,000	-1,430,000	-1,097,000	-1,265,000	-737,000	-1,062,000	-1,885,000	-1,284,000	-2,282,000	-4,253,000	-2,945,000	-4,234,000	-705,000	-1,495,000	-1,354,000	-291,000	-746,000	-2,465,000	-1,484,000	-600,000	-372,000	-368,000	-607,000	-1,179,000
free cash flows	312,967,000	139,437,000	-127,284,000	-103,756,000	39,515,000	116,140,000	-94,488,000	-45,104,000	342,320,000	-74,905,000	-180,366,000	-153,613,000	-131,794,000	-138,874,000	-189,052,000	-172,027,000	-160,098,000	-133,102,000	-252,838,000	-144,812,000	-122,744,000	-151,988,000	-265,778,000	-234,785,000	-218,690,000	267,451,000	-232,559,000	-187,970,000	-199,217,000	-125,395,000	-176,921,000	-123,772,000	-124,041,000	-102,700,000	-136,482,000	-78,337,000	-95,834,000	-91,826,000	-86,382,000	-56,163,000	-60,842,000	-56,720,000	-28,365,000	-40,161,000	-43,901,000	-48,477,000	-42,063,000	-23,247,000	-22,665,000	-23,981,000	-2,770,000	-69,598,000	-517,000	-23,364,000	-30,478,000	-25,683,000	-29,290,000	-27,053,000	-6,333,000	-21,526,000	-25,105,000	-25,744,000	-16,698,000	-18,134,000	-21,325,000	-36,981,000	-654,000	-6,133,000	-18,292,000	90,755,000	-11,603,000	-12,672,000	223,604,000	-9,886,000	-12,315,000	-4,904,000	-3,678,000	-10,847,000	-10,187,000	3,016,000	-6,584,000	-6,618,000	-8,246,000	-4,791,000
cash flows from investing activities:
purchases of property, plant and equipment	-12,142,000	-14,293,000	-8,970,000	-9,094,000	-4,192,000	-8,018,000	-12,973,000	-15,309,000	-17,092,000	-15,919,000	-13,891,000	-21,635,000	-16,510,000	-16,055,000	-17,859,000	-21,886,000	-26,062,000	-11,246,000	-17,178,000	-21,668,000	-12,418,000	-16,658,000	-19,617,000	-38,805,000	-36,058,000	-21,244,000	-44,049,000	-37,513,000	-45,409,000	-22,708,000	-21,257,000	-20,728,000	-25,678,000	-21,651,000	-36,152,000
purchases of marketable securities	-207,971,000	-459,557,000	-401,642,000	-486,708,000	-430,377,000	-297,711,000	-420,115,000	-589,157,000	-421,457,000	-377,141,000	-435,746,000	-723,377,000	-157,309,000	-461,570,000	-634,705,000	-682,968,000	-458,331,000	-168,861,000	-345,954,000												-358,433,000	-391,431,000	-274,842,000	-150,381,000	-86,803,000	-143,647,000	-257,671,000	-193,431,000	-164,561,000	-135,802,000	-80,371,000	-310,053,000	-507,617,000	-125,102,000	-84,163,000	-280,912,000	-487,598,000	-29,108,000	-60,769,000	-87,351,000	-187,077,000	-81,457,000	-38,568,000	-38,894,000	-118,210,000	-75,294,000	-54,062,000	-121,969,000	-41,790,000	-102,980,000	-105,417,000	-100,965,000	-81,111,000	-81,396,000	-131,955,000	-174,301,000	-93,687,000	-88,952,000	-109,756,000	-181,847,000	-101,689,000	-188,130,000	-227,573,000	-30,798,000	-97,893,000	-53,505,000	-56,151,000	-37,408,000	-25,239,000	-51,697,000	-4,799,000	-6,430,000	-7,956,000	-17,186,000
sales and maturities of marketable securities	723,370,000	332,469,000	524,381,000	443,009,000	423,519,000	339,669,000	365,468,000	363,810,000	432,223,000	384,347,000	373,420,000	604,720,000	492,710,000	628,918,000	505,220,000	291,450,000	396,122,000	337,296,000	438,682,000	500,955,000	331,360,000	319,740,000	539,614,000		607,050,000	309,409,000	403,697,000	398,138,000	491,181,000	384,508,000	244,876,000	131,571,000	163,342,000	104,361,000	198,031,000	263,917,000	246,564,000	311,660,000	294,317,000	218,357,000	135,518,000	204,381,000	168,687,000	150,063,000	125,264,000	54,389,000	133,206,000	86,034,000	59,215,000	34,521,000	58,036,000	125,656,000	62,150,000	48,165,000	53,042,000	96,602,000	90,578,000	125,080,000	64,105,000	151,697,000	111,168,000	75,432,000	74,746,000	138,280,000	102,738,000	126,854,000	136,698,000	93,635,000	75,687,000	136,844,000	204,878,000
proceeds from maturity of restricted investments	1,700,000	9,250,000	48,825,000	0	0	17,900,000	39,975,000	0	0	9,250,000	49,225,000	0			9,400,000	16,000,000	15,325,000	0	10,650,000					0
purchases of restricted investments	-1,700,000	-9,250,000	-48,825,000	0	-19,200,000	-17,900,000	-39,975,000	0	0	-9,250,000	-49,225,000	0			-9,400,000	-16,001,000	-15,325,000	-165,000	-10,650,000	-16,000,000	0	0	-9,900,000					0	0
other investing activities								0				381,000	3,500,000	-8,500,000	-75,000	0	0	0	-4,198,000		0
net cash from investing activities	501,107,000	-141,381,000	113,769,000	-52,910,000	-30,250,000	33,940,000	-67,620,000	-240,656,000	-10,764,000	-8,713,000	-76,217,000	-139,911,000	313,891,000	142,793,000	-147,419,000	-413,405,000	-88,271,000	157,024,000	71,352,000	-97,888,000	-10,088,000	-441,230,000	113,688,000	-220,850,000	-10,077,000	-289,402,000	102,652,000	248,964,000	96,174,000	62,621,000	-134,814,000	-160,588,000	-137,178,000	-67,671,000	75,076,000	100,391,000	-31,405,000	-44,335,000	117,940,000	78,273,000	48,670,000	-106,936,000	-341,328,000	21,435,000	37,906,000	-228,375,000	-379,780,000	56,048,000	-2,504,000	-53,209,000	-130,840,000	43,513,000	17,853,000	7,601,000	-65,593,000	20,784,000	36,251,000	2,637,000	22,287,000	47,579,000	4,684,000	-26,963,000	-7,462,000	55,619,000	-29,954,000	-45,357,000	34,125,000	3,399,000	-36,451,000	-49,256,000	100,244,000	-87,688,000	-165,889,000	26,004,000	-49,852,000	-4,839,000	2,119,000	-14,616,000	-12,710,000	-47,214,000	4,474,000	3,230,000	-908,000	-14,935,000
cash flows from financing activities:
proceeds from issuance of 0.00% convertible senior notes due 2028
purchases of capped calls related to 0.00% convertible senior notes due 2028
repayment of 1.00% convertible senior notes due 2027
payment of issuance costs for revolving credit agreement
proceeds from exercise of stock options and other types of equity	77,740,000	81,222,000	49,365,000	36,278,000	108,036,000	132,778,000	25,859,000	30,894,000	24,805,000	49,394,000	42,371,000	56,714,000	153,020,000	22,503,000	27,123,000	45,041,000	72,389,000	81,861,000	46,977,000	19,025,000	29,947,000	97,643,000	53,869,000	40,342,000	9,217,000	12,642,000	9,083,000	7,671,000	13,533,000	5,641,000	42,094,000	42,542,000	28,956,000	9,875,000	2,769,000	3,437,000	4,424,000	4,442,000	1,824,000	6,543,000	3,831,000	7,197,000	13,566,000	7,685,000	5,056,000	5,138,000	11,541,000	8,924,000	11,199,000	3,982,000	4,638,000	997,000	4,499,000	628,000	847,000
(repayment of) proceeds from development derivative	-32,076,000	-27,465,000	-5,281,000
net cash from (provided by) financing activities
effect of exchange rate changes on cash, cash equivalents and restricted cash	-927,000	27,506,000	14,058,000	-17,271,000	15,093,000	-3,120,000	-9,941,000	10,897,000	-6,552,000	-130,000	2,176,000	1,619,000	2,024,000	-8,835,000	-2,238,000	-3,050,000	-3,139,000	1,081,000	-3,910,000	2,972,000	2,142,000	435,000	-631,000	366,000	-446,000
net increase in cash, cash equivalents and restricted cash	376,941,000	93,612,000	53,597,000	-133,846,000	131,305,000			-220,326,000				-206,833,000				-274,305,000	348,393,000			-110,000	-84,125,000	112,888,000	-79,235,000	-376,122,000	-213,854,000	411,900,000	305,073,000	103,885,000	-44,645,000
cash, cash equivalents and restricted cash, beginning of period	0	0	968,652,000	0	0	0	814,884,000	0	0	0	868,556,000	0	0	0	822,153,000	0	0	0	499,046,000	0	0	0	549,628,000	0	0	0	422,631,000	0	0	0	646,832,000
cash, cash equivalents and restricted cash, end of period	376,941,000	93,612,000	1,022,249,000	-133,846,000	131,305,000	286,474,000	684,719,000	-220,326,000	375,234,000	-14,435,000	674,411,000	-206,833,000	497,654,000	41,476,000	536,259,000	-274,305,000	348,393,000	366,060,000	382,005,000	-110,000	-84,125,000	112,888,000	470,393,000	-376,122,000	-213,854,000	411,900,000	727,704,000	103,885,000	-44,645,000	-34,485,000	397,876,000
supplemental disclosure of cash flows:
cash paid for interest	23,893,000	14,564,000	66,933,000	12,330,000	16,147,000	8,156,000	30,945,000	5,443,000	9,547,000	3,216,000	13,912,000	1,303,000	14,872,000																																																																	159,000	161,000		181,000	143,000	135,000	108,000
cash paid for taxes	1,277,000	-1,871,000	2,969,000
operating lease right-of-use assets obtained in exchange for new operating lease liabilities	3,842,000	-1,289,000	9,826,000
supplemental disclosure of noncash investing activities:
capital expenditures included in accounts payable and accrued expenses	5,523,000	431,000	3,650,000					-1,349,000	-509,000	1,629,000	4,034,000			-1,800,000	8,318,000	4,185,000	-2,382,000	4,507,000	7,289,000	7,470,000	646,000	-217,000	6,619,000	-4,047,000	-6,970,000	12,860,000	13,033,000
net cash from financing activities		53,757,000	44,084,000	30,997,000	102,755,000	131,496,000	28,911,000	39,228,000	33,138,000	53,394,000	46,371,000	63,437,000	297,023,000	30,337,000	34,956,000	292,291,000	573,839,000	329,811,000	51,177,000	217,950,000	34,147,000	689,013,000	53,869,000	40,342,000	-20,699,000	412,610,000	390,931,000	5,378,000	12,989,000	5,581,000	41,522,000	706,948,000	28,915,000	386,312,000	2,716,000	3,082,000	4,346,000	154,338,000	16,066,000	6,468,000	3,651,000	7,074,000	598,984,000	7,658,000	4,794,000	5,138,000	718,875,000	7,650,000	11,084,000	3,982,000	178,210,000	966,000	4,499,000	628,000	87,319,000	267,000	0	462,000	9,000	527,000	53,000	2,541,000	542,000	635,000	763,000	1,901,000	210,000	-3,484,000	1,607,000	5,504,000	-472,000	755,000	57,973,000	303,000	-396,000	101,696,000	617,000	1,836,000	62,482,000	52,151,000	-343,000	207,000	602,000
non-cash adjustments to reconcile net income to net cash from operating activities:
stock-based compensation			56,712,000					41,994,000	63,937,000	75,802,000	39,947,000	42,767,000	128,118,000	30,471,000	29,293,000	44,582,000	33,367,000	32,078,000	55,690,000	34,276,000	37,264,000	33,755,000	34,578,000	66,197,000	46,009,000	30,603,000	32,032,000	27,973,000	87,954,000	22,241,000	19,584,000	27,117,000	25,955,000																																																			731,000
unrealized gain on marketable equity securities			956,000																			-45,532,000	-24,111,000						-2,960,000
realized and unrealized losses on marketable equity securities
proceeds from convertible debt												-777,000
purchases of capped calls related to convertible debt												0
(repayment of) proceeds from development derivative liability
repayment of term loan facility
cash paid for income taxes
amortization and interest accretion related to operating leases					13,056,000	9,689,000	11,969,000	10,491,000	10,204,000	10,268,000	12,014,000	10,574,000	10,050,000	10,140,000	10,318,000	10,076,000	11,434,000	10,356,000	10,261,000	10,494,000	10,198,000	9,578,000	9,393,000	9,320,000
operating lease liability					-14,046,000	-10,951,000	-12,840,000	-11,488,000	-11,167,000	-11,020,000	-12,827,000	-11,453,000	-10,284,000	-10,762,000	-10,672,000	-10,766,000	-10,369,000	-10,157,000	-9,060,000	-10,314,000	-13,037,000	-9,199,000	-9,036,000
proceeds from development derivative						-1,282,000	3,052,000	8,334,000	8,333,000	4,000,000	4,000,000	7,500,000	7,833,000	7,834,000	7,833,000	3,500,000	7,700,000	4,200,000	4,200,000	4,200,000
realized and unrealized (gain) loss on marketable equity securities							-78,000
net decrease in cash, cash equivalents and restricted cash							-130,165,000			-14,435,000	-194,145,000			41,476,000	-285,894,000				-117,041,000												-248,956,000
realized and unrealized gain on marketable equity securities												-6,796,000	7,850,000	1,097,000	31,161,000	5,578,000	-18,691,000	4,434,000	-47,016,000	12,584,000
proceeds from the sale of future royalties																0				0	0
(repayment of) proceeds from term loan facility
other financing activities
repayment of term loan												0												0
proceeds from term loan facility																250,000,000	0
proceeds from issuance of common stock to strategic partners, net of closing costs																				0	0
supplemental disclosure of noncash investing and financing activities:
lease liabilities arising from obtaining right-of-use assets																56,000	2,567,000			72,000	19,286,000	12,138,000	2,939,000
receivable and liability related to the sale of future royalties																				0	0
offering proceeds, net of costs																								0	0	0	381,900,000
payment of transaction costs related to sale of future royalties and term loan facility																	-6,250,000				0
change in fair value of liability obligation																								0	0
gain on litigation settlement
proceeds from landlord lease incentive for tenant improvements																				2,860,000	699,000			1,106,000	10,364,000	6,314,000	12,386,000	13,753,000	7,117,000
proceeds from issuance of term loan
payment of transaction costs related to sale of future royalties and term loan
purchases of marketable debt securities																					-329,030,000	-744,012,000	-396,409,000	-630,293,000	-611,069,000	-577,567,000	-256,996,000	-111,661,000	-349,598,000
proceeds from public offering, net of costs
non-cash imputed interest expense on liability related to the sale of future royalties
fair value adjustments on marketable equity securities																										0	-21,000
accounts payable, accrued expenses and other
sales and maturities of marketable debt securities
proceeds from issuance of common stock to sanofi genzyme																																0	0			0	0	0	14,301,000
proceeds from issuance of common stock to regeneron																								0	0
charge for 401(k) company stock match																									1,178,000	1,001,000	1,089,000	-453,000	1,286,000	1,384,000	942,000	567,000	661,000	523,000	551,000	305,000	421,000	450,000	331,000	209,000	254,000	274,000	247,000	179,000	181,000	175,000	157,000	98,000	104,000	127,000	120,000	54,000	98,000	116,000	96,000	95,000	119,000	136,000	138,000	93,000	131,000	138,000	133,000	96,000	116,000	124,000	125,000	90,000	100,000	102,000	90,000	203,000	65,000	74,000	65,000	38,000	46,000
accounts payable																									-30,088,000	43,502,000	-17,133,000	16,128,000	9,085,000	-693,000	-9,042,000	12,332,000	-8,945,000	2,741,000	-11,067,000	11,560,000	2,128,000	-3,937,000	347,000	2,561,000	310,000	-1,945,000	750,000	9,666,000	-947,000	1,500,000	-1,379,000	3,168,000	-1,806,000	1,429,000	-959,000	-1,029,000	-426,000	1,180,000	-1,461,000	314,000	-2,463,000	2,149,000	-3,512,000	2,751,000	-3,837,000	3,410,000	-5,501,000	4,063,000	1,963,000	-2,266,000	6,141,000	-754,000	-2,898,000	-2,844,000	5,258,000	-3,232,000	1,385,000	2,662,000	-1,079,000	1,619,000	-1,243,000	-235,000	1,947,000	-63,000	373,000	-37,000	752,000	-348,000
accrued expenses and other liabilities
depreciation, amortization and accretion																										9,745,000	12,210,000	-2,228,000	3,246,000
non-cash gain on litigation settlement																												0	0
accrued expenses and other																										16,158,000	-14,731,000	34,115,000	17,981,000	19,028,000	-11,767,000	25,578,000	9,394,000	7,451,000	-10,855,000	3,924,000	5,032,000	6,022,000	-4,305,000	10,818,000	2,434,000	1,523,000	-8,432,000	1,831,000	5,056,000	-1,538,000	3,773,000	-2,324,000	6,914,000	-1,253,000	-1,790,000	-6,269,000	91,000	2,335,000	252,000	716,000	831,000	-870,000	1,780,000	98,000	3,123,000	-1,362,000	-1,208,000	1,420,000	-1,560,000	-872,000	671,000	-858,000	35,000	-593,000	-2,405,000
payments for repurchase of common stock for employee tax withholding																										-32,000	-52,000	-2,293,000	-544,000	-60,000	-572,000	-69,000	-41,000	-94,000	-53,000	-355,000	-78,000	-104,000	-59,000	-75,000	-180,000			-27,000	-262,000	0	-15,703,000	-1,274,000				-31,000	0	0	-328,000
sale of restricted investments
proceeds from issuance of common stock, net of offering costs																																784,475,000	0							0	0	0	496,400,000					0	0	0	173,572,000	0	0	0	86,800,000
proceeds from issuance of long-term debt																																				0	0
repayment of long-term debt
fair value of common stock received in the period for collaboration agreement in other assets
receipt of common stock for exercises of stock options
repurchase of common stock for employee tax withholding in accrued expenses
realized loss on sale of marketable equity securities
billed and unbilled collaboration receivables																														47,807,000	-16,766,000	-19,358,000	761,000	4,052,000	3,877,000	-8,188,000	-5,632,000	-700,000	-516,000	-168,000	1,273,000	704,000	29,830,000	-39,553,000	-295,000	75,000	4,084,000	-3,639,000	-149,000	98,000	-454,000	1,814,000	2,467,000	-2,193,000	-724,000
realized gain on sale of marketable equity securities																																0	0	345,000	1,549,000
proceeds from landlord tenant improvements																																				0												12,000	0	0	192,000	566,000
purchases of restricted investments and increase in restricted cash																																				0
net increase in cash and cash equivalents																																443,316,000	-206,626,000	237,592,000	-22,538,000	25,136,000	-102,595,000	39,798,000	50,383,000	31,677,000	-2,044,000	-155,318,000	231,401,000	-7,542,000	1,994,000	-269,862,000	297,420,000	41,329,000			46,399,000		27,564,000	-13,465,000	-8,489,000				15,991,000				-22,521,000	39,381,000	-49,783,000	-79,398,000	35,476,000	-4,945,000	-50,799,000	51,255,000	91,124,000	-95,390,000	116,083,000	17,802,000	-61,293,000	92,439,000	-129,000	-21,159,000	41,047,000					-17,347,000
cash and cash equivalents, beginning of period																																0	0	0	193,617,000	0	0	0	180,895,000	0	0	0	75,179,000	0	0	0	53,169,000	0	0	0	51,405,000	0	0	0	70,228,000	0	0	0	74,599,000	0	0	0	137,468,000	0	0	0	191,792,000	0	0	0	105,157,000	0	0	0	127,955,000	0	0	0	15,757,000	0	0	0	20,272,000	0
cash and cash equivalents, end of period																																443,316,000	-206,626,000	237,592,000	171,079,000	25,136,000	-102,595,000	39,798,000	231,278,000	31,677,000	-2,044,000	-155,318,000	306,580,000	-7,542,000	1,994,000	-269,862,000	350,589,000	41,329,000	-13,135,000	-72,829,000	97,804,000	-24,433,000	27,564,000	-13,465,000	61,739,000	-4,108,000	7,226,000	-23,480,000	90,590,000	27,718,000	-19,301,000	-48,765,000	114,947,000	39,381,000	-49,783,000	-79,398,000	227,268,000	-4,945,000	-50,799,000	51,255,000	196,281,000	-95,390,000	116,083,000	17,802,000	66,662,000	92,439,000	-129,000	-21,159,000	56,804,000	8,579,000	-1,987,000	-3,050,000	12,215,000	-17,347,000
fixed asset expenditures included in accounts payable and accrued expenses																																																			245,000
fair value of common stock received for collaboration agreement in other assets
non-cash stock-based compensation																																			15,717,000	20,651,000	15,581,000	15,816,000	23,480,000	15,520,000	11,848,000	10,179,000	8,236,000	13,438,000	6,352,000	7,680,000	5,591,000	5,406,000	8,845,000	3,377,000	3,075,000	2,722,000	3,386,000	3,096,000	3,156,000	4,082,000	4,258,000	4,214,000	4,122,000	4,212,000	4,511,000	5,068,000	5,327,000	3,940,000	5,634,000	5,417,000	4,736,000	4,123,000	5,017,000	4,882,000	4,004,000	2,604,000	7,922,000	1,786,000	2,160,000	2,609,000	1,714,000	1,606,000	2,375,000	1,002,000	2,196,000	919,000	480,000
deposit for manufacturing facility																																							-9,057,000
realized gain on sale of marketable securities																																				-161,000	-706,000	-954,000	-5,156,000					-1,514,000								-76,000	0	-4,000	-175,000
benefit from intraperiod tax allocation																																											-431,000	-22,091,000	67,000	-315,000	-17,870,000
in-process research and development																																												0	0	-3,890,000	224,656,000
payment for asset acquisition																																												0	0	0	-25,000,000
net cash paid for income taxes
fair value of common stock issued for asset acquisition
difference in fair value of common stock issued to sanofi genzyme less cash proceeds received
purchases of property and equipment																																					-20,298,000	-21,621,000	-2,759,000	-3,099,000	-6,477,000	-1,264,000	-2,110,000	-3,526,000	-3,195,000	-1,852,000	-388,000	-878,000	-950,000	-379,000	-1,799,000	-686,000	-5,729,000	-1,670,000	-263,000	-524,000	-265,000	-474,000	-28,000	-1,138,000	-1,067,000	-1,430,000	-1,097,000	-1,265,000	-737,000	-1,062,000	-1,885,000	-1,284,000	-2,282,000	-4,253,000	-2,945,000	-4,234,000	-705,000	-1,495,000	-1,354,000	-291,000	-746,000	-2,465,000	-1,484,000	-600,000	-372,000	-368,000	-607,000	-1,179,000
purchases of restricted cash and investments
increase in restricted cash																																								-1,183,000	0	0	-288,000									0	0	0	-162,000
net (cash paid for income taxes) cash proceeds from income tax refunds
proceeds from issuance of common stock to genzyme																																									0	0	89,018,000	0	0	0	723,037,000
equity in loss of joint venture																																																				881,000	1,613,000	1,139,000	889,000	954,000	467,000	1,012,000	1,072,000	916,000	1,226,000	3,919,000	1,578,000	1,488,000	740,000	812,000	1,870,000	3,116,000	1,813,000	1,272,000	1,445,000	936,000
gain on issuance of stock by joint venture
net cash proceeds from income tax refunds
difference in fair value of common stock issued to genzyme less cash proceeds received
tax benefit from stock-based compensation
other than temporary impairment on equity securities																																																								0
benefit from intraperiod tax allocation on marketable securities																																																3,021,000	-2,270,000	-2,884,000	-562,000
income taxes receivable																																																								0	0	0	10,669,000
cash (paid for income taxes) proceeds from income tax refunds
net decrease in cash and cash equivalents																																																								-4,108,000	7,226,000				-19,301,000																						-8,057,000
income taxes payable																																																												30,000	1,000	-1,000	-5,546,000	4,327,000	-512,000	796,000	-5,078,000	2,248,000	-855,000	1,268,000	-47,000	201,000
proceeds from issuance of shares to novartis																																																												0	0							0	0
effect of exchange rate on cash																																																												0	0			-4,000	-4,000	-23,000	-90,000	-11,000	55,000	-1,000	10,000	-19,000	-310,000	-114,000	-84,000	195,000	67,000	3,000	-22,000	26,000	94,000	-237,000	-112,000
(cash paid for income taxes) proceeds from income tax refunds
decrease in restricted cash																																																																	0	3,152,000	2,999,000
investment in joint venture																																																																0	0	0	-10,000,000	0
proceeds from issuance of common stock																																																								267,000	0	462,000	9,000	527,000	53,000	1,548,000	542,000	635,000	763,000	747,000	210,000		2,567,000													10,000	37,000
net proceeds from income tax refunds
collaboration receivables																																																									-719,000	-158,000	2,300,000	1,431,000	1,477,000	-1,853,000	1,539,000	-1,022,000	835,000	-26,000	-1,643,000	19,952,000	-19,014,000	4,554,000	-4,649,000	98,000	493,000	-1,221,000	-564,000	1,018,000	-1,256,000	-475,000	-2,507,000
non-cash income tax benefit
impairment on equity investment																																																																				0
repayments of notes payable																																																																				-3,946,000	-960,000	-937,000	-915,000	-892,000	-872,000	-794,000	-775,000	-734,000	-602,000	-477,000	-446,000
supplemental disclosure of cash flows
non-cash license expense																																																																								0	0	0	7,909,000	0	0			0	0
disposals of property and equipment																																																																								-1,000
decrease (increase) in restricted cash
proceeds from notes payable																																																																								0	0			387,000	1,031,000	2,205,000	377,000
supplemental disclosure of non-cash financing activities
common stock issued in connection with license agreements
proceeds from landlord for tenant improvements																																																																					0				0				0
proceeds from issuance of common stock to novartis
deferred income tax benefit
proceeds from issuance of common stock, net of issuance costs																																																																							443,000	1,647,000	58,845,000	140,000	379,000	102,043,000	188,000	108,000	62,551,000	52,303,000
deferred income tax provision																																																																					-16,000	48,000	-16,000	0
investment in regulus therapeutics llc
accrued expenses																																																																									1,645,000	2,679,000	2,815,000	-641,000	525,000	934,000	-207,000	946,000			-2,190,000	-1,085,000
deferred rent																																																																									-151,000	176,000	-107,000
sales of marketable securities																																																																									70,046,000	58,297,000	49,395,000	48,957,000	59,016,000	25,257,000	14,013,000	5,083,000	9,645,000	10,028,000	7,655,000	1,000,000
loss on disposal of equipment
realized foreign currency losses																																																																												115,000	49,000	72,000	19,000
changes in operating assets and liabilities, net of effects of acquisition:
proceeds from sale of equipment
proceeds from issuance of preferred stock, net of issuance costs
deferred financing costs incurred in connection with the equipment line of credit																																																																																				0
common stock issued to max planck innovation
fair value of warrant issued in connection with equipment line of credit included as deferred financing costs
conversion of redeemable convertible preferred stock into common stock																																																																																				0
accretion of redeemable convertible preferred stock																																																																																				0
deferred tax asset																																																																													38,000	37,000	38,000
changes in operating assets and liabilities
supplementary information:
series b preferred stock issued for garching license
charge for purchased in-process research and development
realized foreign currency
acquisition of ribopharma ag, net of cash acquired
proceeds from bank debt																																																																																			565,000
repayments of bank debt
repayment of debt assumed in acquisition
realized foreign currency exchange gains																																																																																	1,000
purchases from landlord reimbursement of tenant improvements
collaboration receivable																																																																																			-1,008,000	2,084,000
prepaid expenses and other current assets																																																																																	-65,000	-247,000	-18,000	60,000
proceeds from issuance of series d convertible preferred stock
proceeds from note payable																																																																																	0
repayments of note payable
deferred financing costs incurred in connection with note payable
gain on disposal of equipment
collaboration and license receivables
accrued liabilities
deferred financing costs incurred in connection with initial public offering
beneficial conversion feature on issuance of series d convertible preferred stock
cash flows from operating activities
adjustments to reconcile net income to net cash flows used in operating activities:
loss on disposal of property and equipment
charge for purchased in-process r&d
changes in operating assets and liabilities; net of acquisition
cash flows from investing activities
proceeds from landlord reimbursement of tenant improvements
proceeds from the sale of equipment																																																																																				10,000
acquisition of ribopharma ag, net of acquired cash
cash flows from financing activities
proceeds from the issuance of common stock, net of issuance costs																																																																																				-88,000
proceeds from issuance of series a redeemable convertible preferred stock, net of issuance costs
proceeds from issuance of series b redeemable convertible preferred stock, net of issuance costs
proceeds from issuance of series c redeemable convertible preferred stock, net of issuance costs
repayment of bank debt																																																																																				0
repayment of debt assumed in ribopharma acquisition
effect of exchange rate changes on cash																																																																																				23,000
supplemental disclosure of noncash financing activities
fair value of warrants issued in connection with equipment line of credit included as deferred financing costs																																																																																				0
gain on disposal of property and equipment
proceeds from issuance of series d convertible preferred stock, net of issuance costs
proceeds of bank debt
deferred financing costs incurred in connection with the acquisition of ribopharma
net cash from (used by) financing activities

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