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Consolidated Statements of Cash Flows - USD ($) | 12 Months Ended
--- | ---
Dec. 31, 2017 | Dec. 31, 2016 | Dec. 31, 2015
Operating activities |  |  |
Net loss | $ (95,154,000) | $ (112,444,000) | $ (106,794,000)
Adjustments to reconcile net loss to net cash used in operating activities: |  |  |
Depreciation and amortization | 3,244,000 | 2,257,000 | 1,365,000
Write-off of assets in progress |  | 862,000 |
(Gain) loss on disposal of property and equipment | (10,000) | 91,000 | 46,000
Accretion of discounts and amortization of premiums on marketable securities | (193,000) | 178,000 | 660,000
Reversal of deferred rent upon lease amendment | (209,000) |  |
Accretion of debt discount related to debt financing |  |  | (115,000)
Cash-settled portion of stock compensation expense | 0 | 602,000 | 387,000
Stock compensation expense | 14,917,000 | 14,126,000 | 9,316,000
Amortization of intangible assets | 1,194,000 |  |
Loss on extinguishment of debt |  |  | 1,671,000
Changes in operating assets and liabilities: |  |  |
Accounts and other receivables | 488,000 | 52,000 | (667,000)
Inventories | (312,000) |  |
Prepaid expenses and other current assets | (1,830,000) | 560,000 | 1,631,000
Restricted cash and other assets | (936,000) | (103,000) | (211,000)
Accounts payable | (1,915,000) | 1,181,000 | 1,246,000
Accrued liabilities and other long term liabilities | 3,198,000 | (11,759,000) | 9,017,000
Deferred revenues |  | (2,654,000) | (10,111,000)
Net cash used in operating activities | (77,518,000) | (107,051,000) | (92,559,000)
Investing activities |  |  |
Purchases of marketable securities | (227,672,000) | (126,754,000) | (208,936,000)
Proceeds from maturities of marketable securities | 119,638,000 | 220,760,000 | 130,110,000
Purchases of property and equipment, net | (669,000) | (7,757,000) | (6,970,000)
Net cash (used in) provided by investing activities | (108,703,000) | 86,249,000 | (85,796,000)
Financing activities |  |  |
Proceeds from issuances of common stock, net | 185,936,000 |  | 183,897,000
Payment of debt |  |  | (10,988,000)
Proceeds (withholding) from exercise of stock options and restricted stock awards, net | 1,613,000 | (84,000) | 531,000
Proceeds from Employee Stock Purchase Plan | 293,000 | 615,000 | 291,000
Proceeds from exercise of warrants |  |  | 228,000
Net cash provided by financing activities | 187,842,000 | 531,000 | 173,959,000
Effect of exchange rate changes on cash and cash equivalents | 674,000 | (252,000) | (303,000)
Net increase (decrease) in cash and cash equivalents | 2,295,000 | (20,523,000) | (4,699,000)
Cash and cash equivalents at beginning of year | 24,289,000 | 44,812,000 | 49,511,000
Cash and cash equivalents at end of year | 26,584,000 | 24,289,000 | 44,812,000
Supplemental disclosure of cash flow information |  |  |
Cash paid during the year for interest |  |  | 720,000
Accrual for litigation settlement and insurance recovery (Note 9) |  | 4,975,000 |
Release of accrual for litigation settlement and insurance recovery (Note 9) | 4,975,000 |  |
Non-cash investing and financing activities: |  |  |
Disposal of fully depreciated property and equipment | 86,000 | 2,354,000 | 1,436,000
Net change in unrealized (loss) gain on marketable securities | $ (83,000) | (8,000) | $ 11,000
Astra Zeneca |  |  |
Supplemental disclosure of cash flow information |  |  |
Return of unused development funding to AstraZeneca AB (Note 10) |  | 7,200,000 |
Milestone payment from AstraZeneca AB (Note 10) |  | $ 7,200,000 |

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- Definition Cash outflow for purchase of trading, available-for-sale securities and held-to-maturity securities. + References Reference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher FASB -Name Accounting Standards Codification -Topic 320 -SubTopic 10 -Section 45 -Paragraph 11 -URI http://asc.fasb.org/extlink&oid=82896770&loc=d3e26853-111562 Reference 2: http://www.xbrl.org/2003/role/presentationRef -Publisher FASB -Name Accounting Standards Codification -Topic 230 -SubTopic 10 -Section 45 -Paragraph 13 -Subparagraph (a),(b) -URI http://asc.fasb.org/extlink&oid=98514028&loc=d3e3213-108585 + Details
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- Definition The cash outflow associated with the acquisition of long-lived, physical assets that are used in the normal conduct of business to produce goods and services and not intended for resale; includes cash outflows to pay for construction of self-constructed assets. + References Reference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher FASB -Name Accounting Standards Codification -Topic 230 -SubTopic 10 -Section 45 -Paragraph 13 -Subparagraph (c) -URI http://asc.fasb.org/extlink&oid=98514028&loc=d3e3213-108585 + Details
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- Definition The cash inflow from the additional capital contribution to the entity. + References Reference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher FASB -Name Accounting Standards Codification -Topic 230 -SubTopic 10 -Section 45 -Paragraph 14 -Subparagraph (a) -URI http://asc.fasb.org/extlink&oid=98514028&loc=d3e3255-108585 + Details
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- Definition The cash inflow from issuance of rights to purchase common shares at predetermined price (usually issued together with corporate debt). + References Reference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher FASB -Name Accounting Standards Codification -Topic 230 -SubTopic 10 -Section 45 -Paragraph 14 -Subparagraph (a) -URI http://asc.fasb.org/extlink&oid=98514028&loc=d3e3255-108585 + Details
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- Definition The cash inflow associated with the sale or maturity (principal being due) of securities not classified as either held-to-maturity securities or trading securities which are classified as available-for-sale securities. + References Reference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher FASB -Name Accounting Standards Codification -Topic 230 -SubTopic 10 -Section 45 -Paragraph 12 -Subparagraph (a),(b) -URI http://asc.fasb.org/extlink&oid=98514028&loc=d3e3179-108585 Reference 2: http://www.xbrl.org/2003/role/presentationRef -Publisher FASB -Name Accounting Standards Codification -Topic 320 -SubTopic 10 -Section 45 -Paragraph 11 -URI http://asc.fasb.org/extlink&oid=82896770&loc=d3e26853-111562 + Details
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- Definition The cash inflow associated with the amount received from the stock plan during the period. + References Reference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher FASB -Name Accounting Standards Codification -Topic 230 -SubTopic 10 -Section 45 -Paragraph 14 -Subparagraph (a) -URI http://asc.fasb.org/extlink&oid=98514028&loc=d3e3255-108585 + Details
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- Definition The cash outflow during the period from the repayment of aggregate short-term and long-term debt. Excludes payment of capital lease obligations. + References No definition available. + Details
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- Definition The aggregate amount of noncash, equity-based employee remuneration. This may include the value of stock or unit options, amortization of restricted stock or units, and adjustment for officers' compensation. As noncash, this element is an add back when calculating net cash generated by operating activities using the indirect method. + References Reference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher FASB -Name Accounting Standards Codification -Topic 230 -SubTopic 10 -Section 45 -Paragraph 28 -Subparagraph (a) -URI http://asc.fasb.org/extlink&oid=98514028&loc=d3e3602-108585 + Details
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