Etranacogene dezaparvovec

基因治疗CGT的CDMO采购：AAV载体生产的成本结构 ——悬浮vs贴壁/HEK293vsSf9/三质粒转染/空壳率控制 —————————————————————————————— 一、基因治疗——「一次性治愈」背后的供应链挑战 基因治疗（CGT, Cell and Gene Therapy）是制药行业增长最快的赛道之一——全球已有10+款AAV基因治疗产品获批上市（如Zolgensma、Luxturna、Hemgenix）。但CGT的CDMO采购比传统生物药复杂得多——AAV（腺相关病毒）载体的生产涉及「三质粒瞬时转染」或「昆虫细胞/杆状病毒系统」，工艺尚未标准化，不同CDMO的技术平台差异巨大。 AAV载体生产的核心指标是「产量」和「空壳率」。产量决定了单批成本——AAV的产量通常以vg/cell（每个细胞的病毒基因组数）表示，HEK293悬浮转染的典型产量为1-5x10^5 vg/cell。空壳率是指「没有基因组的空病毒壳」占总病毒颗粒的比例——空壳率高意味着有效载体比例低，FDA要求空壳率<30%（有些产品要求<10%）。某药企E在评估CDMO时发现：CDMO-A的产量高（5x10^5 vg/cell）但空壳率高（45%），CDMO-B的产量低（2x10^5 vg/cell）但空壳率低（15%）。最终选择CDMO-B——因为空壳率高不仅降低有效剂量，还可能引起免疫反应（空壳病毒被免疫系统识别引发抗AAV抗体）。 —————————————————————————————— 二、AAV生产的两大技术平台对比 HEK293三质粒转染是目前AAV生产的主流方法——3个质粒分别携带rep/cap基因（衣壳蛋白）、转基因表达框和辅助基因（Ad的E2A/E4/VA RNA）。瞬时转染的效率决定了产量——PEI（聚乙烯亚胺）是最常用的转染试剂，但PEI的批次变异性大，不同厂家PEI的转染效率差异可达2-3倍。某药企F在更换PEI供应商后产量下降了60%——新PEI的分子量分布不同（支链vs直链），导致转染效率降低。 建议在CDMO合同中明确「转染试剂品牌和规格不得变更」，如需变更必须提前通知并做工艺可比性研究。 —————————————————————————————— 三、质粒DNA——AAV生产的「原料」 三质粒转染需要3种质粒DNA——每种质粒都需要GMP级生产。GMP级质粒DNA的市场价格约5-20万/g（取决于质粒大小和产量），一个200L的AAV生产批需要约5-10g质粒DNA——单批质粒原料成本25-200万。质粒DNA的供应商选择要点： (1)GMP资质——需有GMP级质粒生产经验（不是只有科研级）； (2)超螺旋比例——GMP级质粒的超螺旋比例应>90%（低超螺旋比例降低转染效率）； (3)内毒素控制——内毒素<10 EU/mg（内毒素影响AAV产物安全性）； (4)产能和交期——GMP级质粒的生产周期通常8-12周，需提前备货。 某药企G在AAV生产启动前没有提前订购质粒DNA，等CDMO开始生产时才发现质粒供应商产能已满——等了10周才拿到质粒，整个项目延误2.5个月。 —————————————————————————————— 四、AAV灌装——冷链和低吸附的双重挑战 AAV产品的灌装是整个供应链中技术难度最高的环节之一。AAV在室温下不稳定（效价快速下降），需要-60°C以下保存——这意味着灌装必须在低温环境（2-8°C）中快速完成，灌装后的产品立即转入-60°C冻存。某药企H的AAV产品在灌装过程中效价下降了15%——灌装间温度25°C（标准要求2-8°C），AAV在25°C下每分钟效价下降0.3%。后来改用低温灌装线（灌装间2-8°C），效价损失降到2%。低温灌装线的投资比常温线贵50-100%，但对于AAV产品，这是必须的——常温灌装导致的效价损失可能让整批产品不合格。 —————————————————————————————— 五、AAV CDMO采购的3个报价陷阱 AAV CDMO的报价范围很广——一个200L批次的生产费用从500万到2000万不等（取决于产量要求和纯度要求）。低于500万的报价要警惕——可能不含纯化（空壳率高）、不含分析检测、不含质粒DNA。建议在询价时要求CDMO提供「all-in报价」（含生产+纯化+分析+质粒+灌装），避免「低报价高追加」。 —————————————————————————————— 六、基因治疗CDMO采购自检清单 关于AAV的「衣壳血清型」选择，这也是采购人需要了解的重要决策。AAV有13种天然血清型（AAV1-AAV13）和数百种工程变体，不同血清型对组织的趋向性不同——AAV9可以穿越血脑屏障（用于中枢神经系统疾病），AAV8趋向肝脏，AAV2趋向眼睛（视网膜下注射）。但不同血清型的产量差异很大——AAV2的产量通常比AAV9高3-5倍（因为AAV2的包装效率更高）。某药企K在开发一个肝脏靶向基因治疗时，最初选择了AAV8（肝脏趋向性好），但产量只有AAV9的1/3——生产成本高3倍。后来切换到AAV-LK03（工程变体，肝脏趋向性更好且产量与AAV9相当），产量提升了2倍，成本降低了40%。建议在血清型选择时不仅考虑趋向性，还要考虑产量和成本——向CDMO索取不同血清型的历史产量数据作为决策参考。 采购启示：AAV CDMO的「效价测定能力」是选型的关键维度——需要评估CRO是否能做： (1)ddPCR物理滴度（需要有ddPCR设备，不是普通qPCR）； (2)感染滴度（需要有细胞培养和感染检测能力）； (3)空壳率测定（分析型超速离心AUC或电荷检测质谱CDMS）； (4)衣壳蛋白完整性（SDS-PAGE/CE-SDS）。 这些分析方法的开发验证费用约10-20万，但它们是AAV产品质量评估的基础——没有可靠的分析方法，你无法判断CDMO交付的产品是否合格。建议在CDMO采购合同中将「分析方法验证」作为交付物之一，而不是另行收费的项目。 感染滴度的测定方法也会影响结果——目前没有标准化的感染滴度测定方法，不同实验室的结果差异可达5-10倍。某药企J在两家CRO做了同一个样品的感染滴度，结果分别是1x10^11和8x10^11 IU/mL——差了8倍。原因是两家CRO用的细胞系不同（HEK293 vs HeLa）和检测方法不同（qPCR vs 免疫荧光）。建议在CDMO合同中明确感染滴度测定的「标准方法」——指定细胞系、检测方法和接受标准，避免不同实验室的数据不可比。如果需要比较不同CDMO的产品质量，建议用同一份样品在所有候选CDMO做平行检测——数据最接近的CDMO的方法体系与你的最兼容。 AAV产品的效价测定是CDMO采购中最容易产生争议的环节。AAV效价有两个维度：「物理滴度」（vg/mL，通过ddPCR测定病毒基因组数）和「感染滴度」（IU/mL，通过细胞感染实验测定有功能的病毒数）。物理滴度/感染滴度的比值称为「感染比」——好的AAV产品感染比应>10%（即每10个物理颗粒中至少有1个有感染能力）。某药企I的AAV产品物理滴度为1x10^13 vg/mL，但感染滴度只有5x10^11 IU/mL——感染比5%（偏低）。调查发现是纯化工艺中去垢剂（脱氧胆酸钠）的残留导致部分衣壳蛋白变性，降低了感染能力。优化纯化工艺（增加超滤洗涤步骤去除去垢剂）后，感染比提升到15%。 —————————————————————————————— 七、CGT产能瓶颈与「提前锁定」策略 CGT领域的产能瓶颈是采购人最头疼的问题。全球AAV载体产能在2024-2026年持续紧张，III期临床和商业化生产排期平均等待9-14个月。某药企H在III期临床启动前18个月就开始锁定CDMO产能——此时产品还在II期，但如果不提前锁定，等到III期数据出来再找产能，至少延误1年上市。提前锁定的代价是支付「产能预留费」（通常为年产费用的20-30%），但相比延误1年上市的机会成本（可能数亿元收入），这笔费用微不足道。 采购启示： CGT项目的产能锁定应该在临床II期就开始评估，III期启动前12-18个月完成签约。合同中必须包含「产能 escalator」条款——如果临床数据好需要扩大产能，CDMO有义务在6个月内提供额外产能（可约定上限和价格调整机制）。同时要约定「退出条款」——如果临床失败，已支付的产能预留费可部分退还（通常退还50-70%）。 另一个值得关注的趋势是「分散化生产」。CGT产品（特别是自体细胞治疗）的物流窗口极短——从采血到回输通常只有24-72小时。这意味着生产基地必须靠近临床中心，不能集中在一个地方。某药企K的CAR-T产品在美国东海岸和西海岸各建了一个生产基地（通过CDMO合作），运输半径控制在4小时以内。采购人需要评估CDMO的「多地生产」能力——是否能同时在2-3个地点提供GMP产能？这直接影响物流成本和患者可及性。 最后提醒一个关于CGT「原材料供应链」的风险。AAV生产需要大量质粒DNA（三质粒系统），质粒DNA的供应商全球只有不到10家（主要是Cobra Biologics/Aldevron/VGXI等）。如果质粒供应商出现产能问题或质量问题，整个CGT生产链就会断裂。建议在采购CDMO服务时，同时评估其质粒供应链的「双源率」——是否至少有两家质粒供应商？如果只有一家，需要建立战略库存（通常6-12个月用量）作为缓冲。 —————————————————————————————— 您负责专注研发，我帮你搞定采购，关注「做药的老采购」，带你用17年采购经验，从0到1打造采购体系，每周二、周五更新采购实战干货，每周五轮换研发采购/行业洞察/采购人成长。有问题？评论区留言，下期解答。 —————————————————————————————— 「做药的老采购」 17年制药采购实战派 年经手10亿+，单年降本超过20% 每周二、周五更新，关注不亏 下期预告：PROTAC分子采购——靶向蛋白降解的CRO选型

~ U.S. and U.K. regulatory submissions for AMT-130 for Huntington’s disease on track as planned for the third quarter of 2026 ~ ~ Topline four-year data from the Phase I/II study of AMT-130 expected in September 2026 ~ ~ Reported data from the first cohort in the Phase I/IIa trial of AMT-260 for refractory mesial temporal lobe epilepsy showed early biological signals of therapeutic activity and a favorable safety pro ~ Strengthened financial position with $259 million follow-on offering, extending cash runway into 2030 and funding the anticipated commercial launch of AMT-130 and continued pipeline investment ~ ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); ~ uniQure to host earnings call at 8:30 a.m. ET ~ LEXINGTON, Mass. and AMSTERDAM, July 29, 2026 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today reported its financial results for the second quarter of 2026 and highlighted recent progress across its business. “This has been a defining quarter – not just for uniQure, but for the Huntington's disease community,” said Matthew Kapusta, chief executive officer at uniQure . “Following a productive Type B meeting with the FDA, we remain on track to submit our BLA for AMT-130 in the third quarter — a milestone that reflects years of rigorous science, disciplined execution, and an unwavering commitment to the patients and families living with this devastating disease. With four-year data expected in September and the U.K. regulatory activities progressing as planned, we enter the second half of 2026 with real momentum and a clear line of sight to potentially bringing this therapy to the people who need it.” “Beyond AMT-130, we continue to execute across our broader pipeline,” Mr. Kapusta continued. “With a strong balance sheet, we believe we are well-positioned for what will be a transformative period for uniQure and the patients we serve.” Recent Company Developments and Updates Advancing AMT-130 for the treatment of Huntington’s disease In June 2026, the Company held a Type B meeting with the U.S. Food and Drug Administration (FDA). Official meeting minutes received in July 2026 confirmed that the FDA and the Company reached alignment that a Biologics License Application (BLA) submission under the accelerated approval pathway for AMT-130, based on the existing clinical data, is reasonable. In addition, the FDA seeks to align on the confirmatory study design prior to the BLA submission, including consideration of a randomized standard-of-care control design instead of a sham procedure. The FDA also stated that, in accordance with the FDA’s draft public guidance for accelerated approvals, the confirmatory study should be feasible to conduct within a reasonable timeline and be well underway, and potentially fully enrolled, at the time of accelerated approval. Discussions with the FDA to align on the confirmatory study design and analysis are underway and the Company expects to submit a BLA in the third quarter of 2026. The Company plans to initiate the confirmatory study as expeditiously as possible after aligning with the FDA on the trial design. In September 2026, the Company plans to present data from its ongoing Phase I/II studies of AMT-130. The update is expected to include follow-up data on all patients treated with AMT-130 in the first two cohorts, including four years of follow-up on 24 patients (12 patients at the high-dose and 12 patients at the low dose). In March 2026, the Company held a successful pre-submission meeting with the United Kingdom’s (U.K.) Medicines and Healthcare products Regulatory Agency (MHRA) and the regulatory submission is progressing as planned for the third quarter of 2026. Continued clinical progress in pipeline programs AMT-260 for the treatment of refractory mesial temporal lobe epilepsy (MTLE) In June 2026, the Company announced preliminary six-month follow-up data on the first, low dose cohort of six patients in the ongoing Phase I/IIa study. As of the May 29, 2026 data cutoff date, three of six patients in the first, low-dose cohort achieved meaningful reductions in disabling seizures during months four through six of follow-up, ranging from a 79% to 100% decline from baseline. The remaining three patients in the low-dose cohort experienced variable changes in disabling seizures during months four through six of follow-up, ranging from a 33% decrease to a 36% increase compared to baseline. As of the June 19 , 2026 presentation date, there were no Serious Adverse Events (SAEs) related to AMT-260 or the surgical procedure reported. All reported adverse events in the low dose cohort were classified as mild or moderate in severity, with the most common adverse event being headache (N=2). No immunosuppression was required. The Company expects to complete enrollment in the second dose cohort in the Phase I/IIa study in the third quarter of 2026. The Company expects to present updated results from the Phase I/IIa study in the first half of 2027. AMT-191 for the treatment of Fabry disease In June 2026, the Company presented new data from the Phase I/II study of AMT-191 in Fabry disease. The data, with a cutoff date of March 15, 2026, included patient follow-up ranging from three months to more than 18 months and consisted of the following: Dose-dependent elevations were observed across 11 patients in three dose levels with α-Gal A activity ranging from 1- to 16.2-fold above mean normal range (1.38-8.66 nmol; mean normal of 3.57 nmol) at the lowest dose, 14.5- to 229.6-fold at the mid dose, and 58.7- to 143.6-fold at the highest dose. Plasma lyso-Gb3 levels remained stable post-dose across all cohorts, regardless of enzyme replacement therapy (ERT) status. All 11 dosed patients were withdrawn from ERT. AMT-191 continued to show a manageable safety pro all dose levels. No SAEs related to AMT-191 were observed at the low and mid doses. No additional SAEs were observed at the high dose beyond those previously reported in September 2025 in two patients. Per protocol, additional dosing in the mid- and high-dose cohorts remains paused, pending further evaluation of asymptomatic liver enzyme elevations reported in two patients from the mid-dose cohort, which were confirmed as dose-limiting toxicities. These elevations resolved as of the end of May 2026 following a course of immunosuppression as per the study protocol. Focused execution and strong financial position In June 2026, the Company closed an upsized underwritten public offering of 5,686,813 ordinary shares at a public offering price of $45.50 per share, including the full exercise of the underwriters’ option to purchase additional shares. The aggregate gross proceeds to uniQure from the offering, before deducting the underwriting discounts and commissions and offering expenses payable by uniQure, were $259 million. As of June 30, 2026, the Company had cash, cash equivalents and current investment securities of $810.3 million. The Company expects that these resources will be sufficient to fund projected operating expenses into 2030. Financial Highlights Cash Position: As of June 30, 2026, the Company held $810.3 million in cash, cash equivalents and current investment securities, compared to $622.5 million as of December 31, 2025. The Company expects that these resources will be sufficient to fund our projected operating expenses into 2030. Revenues: Revenue for the three months ended June 30, 2026 was $5.8 million, compared to $5.3 million in the same period in 2025. The increase of $0.5 million is due to an increase in license revenue, compared to the prior period. R&D Expenses: Research and development expenses were $34.0 million for the three months ended June 30, 2026, compared to $35.4 million during the same period in 2025. The $1.4 million decrease was driven by a $3.2 million decrease in other research and development expenses, partially offset by a $1.8 million increase in direct research and development expenses. The decrease in other research and development expenses primarily reflected a $1.5 million decrease in facility expenses, a $1.3 million decrease in employee and contractor-related expenses, including share-based compensation, and a $1.0 million decrease in the fair value of contingent consideration, partially offset by a $0.6 million increase in information technology costs. The increase in direct research and development expenses reflected higher spend on the AMT-260, AMT-162 and AMT-191 programs, partially offset by lower spend on AMT-130, compared to the prior period. SG&A Expenses: Selling, general and administrative expenses were $17.4 million for the three months ended June 30, 2026, compared to $13.5 million during the same period in 2025. The $3.9 million increase was primarily related to a $4.3 million increase in employee and contractor-related expenses, including share-based compensation, mainly as a result of a higher number of employees recruited in the second half of 2025 to support the potential commercial launches of AMT-130, a $0.7 million increase in intellectual property fees, and a $0.7 million increase in information technology costs and other expenses. This was partially offset by a $1.8 million decrease in professional fees, primarily as a result of lower costs incurred in support of the potential commercial launches of AMT-130, compared to the prior period. Other Expense: Other expense increased to $8.0 million for the three months ended June 30, 2026 from $2.2 million during the same period in 2025, primarily due to a $6.0 million increase in costs associated with the supply of HEMGENIX ® to CSL Behring. Other non-Operating Items, net: Other non-operating items, net was an expense of $27.0 million for the three months ended June 30, 2026, compared to a gain of $6.6 million during the same period in 2025. The $33.6 million increase in net non-operating expense was primarily related to a $20.4 million unfavorable change in net foreign currency, from an $18.6 million gain to a $1.7 million loss, and a $16.0 million loss resulting from changes in the fair value of the liability related to pre-funded warrants, compared to nil in the prior period. This was partially offset by a $1.5 million increase in interest income and a $1.2 million decrease in interest expense, compared to the prior period. Net loss: The net loss for the three months ending June 30, 2026, was $81.1 million, or $1.22 basic and diluted loss per ordinary share, compared to a $37.7 million net loss for the comparative period in 2025, or $0.69 basic and diluted loss per ordinary share. Upcoming investor events: 2026 Biotech Summer Summit, August 10 -12 – Newport, RI Investor Conference Call and Webcast Information uniQure management will host an investor conference call and webcast today, Wednesday, July 29th at 8:30 a.m. ET. The event will be webcast under the Events & Presentations section of uniQure’s website at , and following the event a replay will be archived for 90 days. Analysts wishing to participate in the question and answer session should access the live call by dialing (646) 307-1963 or toll-free (800) 715-9871 and entering conference ID 5075555. If you are joining the conference call, please join 15 minutes before the start time. About uniQure uniQure is delivering on the promise of gene therapy – single treatments with potentially curative results. The approvals of uniQure’s gene therapy for hemophilia B – an historic achievement based on more than a decade of research and clinical development – represent a major milestone in the field of genomic medicine and ushers in a new treatment approach for patients living with hemophilia. uniQure is now advancing a pipeline of proprietary gene therapies for the treatment of patients with Huntington's disease, refractory temporal lobe epilepsy, Fabry disease, and other severe diseases. uniQure Forward-Looking Statements This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "could," “establish,” "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," “seek,” "should," "will," "would" and similar expressions. Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this press release. Examples of these forward-looking statements include, but are not limited to, statements concerning: the Company’s cash runway and its ability to fund its operations into 2030; the Company’s ability and plans to strategically advance its programs, including the potential commercialization of AMT-130; the Company’s plans and timing with respect to future interactions with regulatory authorities and regulatory updates related to AMT-130; the Company’s plans to conduct a confirmatory study for AMT-130, including the design, timing, endpoints and control arm of such study, and to align with the FDA on such study prior to BLA submission as well as the potential use of a concurrent standard-of-care control arm rather than a sham procedure; expectations regarding the timing of a BLA submission and receiving accelerated approval of AMT-130; the Company’s plans to complete enrollment in the second dose cohort in the Phase I/IIa study for MTLE in the third quarter of 2026; the Company’s plans to provide further clinical updates, including plans to announce topline four-year data from the Company’s AMT-130 program in September 2026 and updated results from the Phase I/IIa study in MTLE in the first half of 2027; and the Company’s plans to attend upcoming investor events. The Company’s actual results could differ materially from those anticipated in these forward-looking statements for many reasons. These risks and uncertainties include, among others: risks associated with the clinical results and the development and timing of the Company’s programs, including the risk that clinical results will be unable to demonstrate data sufficient to support further clinical development or regulatory approval in any country where approval is pursued; the risk that the FDA ultimately concludes that the Phase I/II trial data for AMT-130 are not sufficient to support a BLA or accelerated approval; the risk that more patient data become available that results in a different interpretation than the one derived from preliminary, interim or topline data; the Company’s interactions with regulatory authorities, including the FDA and MHRA, which may affect the initiation, timing and progress of clinical trials and pathways and timing for regulatory approval; whether the measurements that the Company is evaluating are viewed as robust and sensitive measurements of disease progression suitable for regulatory approval; the Company’s ability to conduct and fund any required confirmatory study for AMT-130; the Company’s ability to successfully complete any required confirmatory study for AMT-130; the risk that accelerated approval, if granted, may be subject to post-approval requirements that are difficult or costly to satisfy; the Company’s ability to continue to build and maintain the infrastructure and personnel needed to achieve its goals; the Company’s effectiveness in managing current and future clinical trials and regulatory processes; the continued development and acceptance of gene therapies; the Company’s ability to demonstrate the therapeutic benefits of its gene therapy candidates in clinical trials; the Company’s ability to obtain, maintain and protect intellectual property; and the Company’s ability to fund its operations. These risks and uncertainties are more fully described under the heading "Risk Factors" in the Company’s periodic filings with the U.S. Securities & Exchange Commission (“SEC”), including the Company’s Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q, and in other filings that the Company makes with the SEC from time to time. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and, except as required by law, the Company assumes no obligation to update these forward-looking statements, even if new information becomes available in the future. uniQure Contacts: FOR INVESTORS: FOR MEDIA: Chiara Russo Direct: 781-491-4371 Mobile: 617-306-9137 c.russo@uniQure.com Tom Malone Direct: 339-970-7558 Mobile:339-223-8541 t.malone@uniQure.com uniQure N.V. UNAUDITED CONSOLIDATED BALANCE SHEETS June 30, December 31, 2026 2025 (in thousands, U.S. dollars) Current assets Cash and cash equivalents $ 413,027 $ 80,240 Current investment securities 397,308 542,301 Accounts receivable 5,778 5,863 Prepaid expenses 10,245 20,506 Other current assets and receivables 7,911 7,076 Total current assets 834,269 655,986 Non-current assets Property, plant and equipment, net $ 11,376 $ 13,800 Other investments 30,267 30,237 Operating lease right-of-use assets 11,606 12,525 Intangible assets, net 62,101 72,790 Goodwill 24,587 25,355 Deferred tax assets, net 6,362 8,654 Other non-current assets 4,535 5,561 Total non-current assets 150,834 168,922 Total assets $ 985,103 $ 824,908 Current liabilities Accounts payable $ 4,979 $ 5,170 Accrued expenses and other current liabilities 51,133 41,292 Liability related to pre-funded warrants 24,242 12,595 Current portion of operating lease liabilities 2,991 3,862 Total current liabilities 83,345 62,919 Non-current liabilities Long-term debt 50,147 49,699 Liability from royalty financing agreement 489,333 473,199 Operating lease liabilities, net of current portion 9,696 9,832 Contingent consideration 18,113 18,736 Deferred tax liability, net 7,726 7,967 Other non-current liabilities, net of current portion 2,693 3,655 Total non-current liabilities 577,708 563,088 Total liabilities 661,053 626,007 Shareholders' equity Total shareholders' equity 324,050 198,901 Total liabilities and shareholders' equity $ 985,103 $ 824,908 uniQure N.V. UNAUDITED CONSOLIDATED STATEMENTS OF OPERATIONS Three months ended June 30, 2026 2025 (in thousands, U.S dollars, except share and per share amounts) Total revenues $ 5,841 $ 5,262 Operating expenses: Cost of license revenues (350 ) (656 ) Research and development expenses (33,964 ) (35,383 ) Selling, general and administrative expenses (17,367 ) (13,500 ) Total operating expenses (51,681 ) (49,539 ) Other income 1,598 2,597 Other expense (7,961 ) (2,185 ) Loss from operations (52,203 ) (43,865 ) Non-operating items, net (27,015 ) 6,571 Loss before income tax expense $ (79,218 ) $ (37,294 ) Income tax expense (1,841 ) (425 ) Net loss $ (81,059 ) $ (37,719 ) Basic and diluted net loss per ordinary share $ (1.22 ) $ (0.69 ) Weighted average shares used in computing basic and diluted net loss per ordinary share 66,243,879 54,807,967