LPL

– Olezarsen met the primary endpoint with statistically significant reduction of fasting triglycerides and showed substantial, clinically meaningful reduction in acute pancreatitis events – – Results demonstrate olezarsen may represent a novel treatment option for this rare, life-threatening disease, for which there are no approved treatments in the U.S. – – Data presented today at ACC 2024 and published in The New England Journal of Medicine – – Ionis to host webcast on Monday, April 8 at 10:00 am ET – CARLSBAD, Calif., April 7, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced full results from the Phase 3 Balance study of Ionis' lead independent investigational medicine, olezarsen, for the treatment of adults with familial chylomicronemia syndrome (FCS). The olezarsen 80 mg monthly dose met the primary endpoint of significantly reducing triglycerides (TGs) in patients with genetically validated FCS at six months. In addition, olezarsen demonstrated robust and sustained reductions in TGs and serum apolipoprotein C-III (apoC-III) levels. Importantly, olezarsen reduced the incidence of acute pancreatitis (AP) events over the 12-month treatment period compared to placebo. Olezarsen also demonstrated a favorable safety and tolerability profile. These results were presented in an oral presentation at the 2024 American College of Cardiology (ACC) Annual Meeting in Atlanta, Georgia and published simultaneously in The New England Journal of Medicine (NEJM). Based on these data, Ionis is pursuing regulatory approval of olezarsen as a potential breakthrough treatment for adults with FCS. "As a physician who has seen first-hand the struggles of people living with FCS and its serious complications, there is significant need for an effective therapy to lower triglycerides and reduce acute pancreatitis events," said Erik Stroes, M.D., professor of medicine, Amsterdam University Medical Centers, and a principal investigator of the Balance study. "Olezarsen represents a potentially life-changing new medicine for these patients who experience debilitating chronic symptoms, including abdominal pain and cognitive symptoms, as well as hospitalizations associated with potentially fatal acute pancreatitis events." Balance Study Results In the study, patients were treated with olezarsen 80 mg (n=22), 50 mg (n=21) or placebo (n=23) once every four weeks. In the 80 mg group, olezarsen met the primary endpoint, with a statistically significant placebo-adjusted reduction in TG levels from baseline to six months (44%, p<0.001). Reductions from six to 12 months were sustained, with olezarsen 80 mg achieving a placebo-adjusted 59% reduction in TGs. ApoC-III placebo-adjusted reductions were robust and sustained at six and 12 months (74% and 81% reductions, respectively). In the 50 mg group, olezarsen reduced TG levels, however this difference was not statistically significant at six months compared to placebo (22%, p=0.078). Reductions from six to 12 months were improved, with olezarsen 50 mg achieving a placebo-adjusted 44% reduction in TGs. Olezarsen-treated patients had markedly fewer AP events during the 12-month period, compared to placebo. Eleven episodes of AP occurred in the placebo group versus one episode in the 80 mg olezarsen group and one episode in the 50 mg group. Furthermore, there was a substantially greater time to the first event with olezarsen compared to placebo (one year (80 mg) and 102 days (50 mg), vs. nine days for placebo). Olezarsen-treated patients experienced a placebo-adjusted 84% reduction in all-cause hospitalizations between baseline and 12 months. A favorable safety and tolerability profile was observed, with a higher number of treatment-emergent adverse events (TEAEs) in the placebo group. There were no serious TEAEs related to olezarsen. The most common AEs were COVID-19, abdominal pain and diarrhea, none of which were more frequent in patients treated with either dose of olezarsen versus placebo. Serious AEs occurred in 14% of patients treated with olezarsen 80 mg, 19% treated with olezarsen 50 mg, and 39% treated with placebo. "Balance is the first clinical study to validate the association of reduced triglyceride levels with reduced incidence of acute pancreatitis events in patients with severely elevated triglycerides. This important finding supports the potential for olezarsen to be the standard of care for patients with FCS, if approved. These data further strengthen our confidence for a successful outcome in the ongoing Phase 3 CORE studies evaluating olezarsen in the much more prevalent severe hypertriglyceridemia patient population," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "Our team looks forward to working closely with the FDA to advance the first potential treatment for FCS in the U.S., and to successfully delivering Ionis' first independent commercial launch later this year, assuming priority review. We offer our sincerest gratitude to the patients and investigators who participated in this pivotal study." The ACC Balance presentation can be found on Ionis' website after today's presentation at 10:08 am ET. In addition to the Balance data, a late-breaking abstract entitled, "Efficacy and Safety of Olezarsen in Patients with Hypertriglyceridemia and High Cardiovascular Risk: Primary Results of the Bridge-TIMI 73a Trial" was also presented at ACC and published in NEJM. Webcast Ionis will host a webcast to discuss the detailed results from the Balance study on Monday, April 8 at 10:00 am ET. Interested parties may access the webcast here. A webcast replay will be available for a limited time. About the Balance Study The global, multicenter, randomized, double-blind, placebo-controlled Phase 3 Balance study (NCT04568434) enrolled 66 patients aged 18 and older with confirmed FCS. Patients in the study received background therapies including statins, fibrates and omega-3 fatty acids. Patients were randomized in a 1:1:1 ratio to receive olezarsen 80 mg or 50 mg or placebo via subcutaneous injection once every four weeks for 53 weeks. The primary endpoint was the percent change from baseline in fasting triglyceride levels at six months compared to placebo. Secondary endpoints included percent changes in triglyceride levels at 12 months, percent changes in other lipid parameters, and adjudicated acute pancreatitis event rates over the treatment period. About Olezarsen Olezarsen is an RNA-targeted investigational LIgand Conjugated Antisense (LICA) medicine being evaluated for people at risk of disease due to elevated triglyceride levels, including those with familial chylomicronemia syndrome (FCS). Olezarsen is designed to inhibit the body's production of apoC-III, a protein produced in the liver that regulates triglyceride metabolism in the blood.1,2 The U.S. FDA granted olezarsen Fast Track designation for the treatment of FCS in January 2023, as well as Orphan Drug designation and Breakthrough Therapy designation in February 2024. In addition to FCS, Ionis is evaluating olezarsen for the treatment of severe hypertriglyceridemia (sHTG) in Phase 3 clinical trials. Olezarsen is an investigational medicine that has not been reviewed or approved for the treatment of any disease by any regulatory authority. About FCS FCS is a rare, genetic disease characterized by extremely elevated triglyceride levels. It is caused by impaired function of the enzyme lipoprotein lipase (LPL).3 Because of limited LPL production or function, people with FCS cannot effectively break down chylomicrons, lipoprotein particles that are 90% triglycerides.3,4 FCS is estimated to impact one to 13 people per million in the U.S.5,6,7 People living with FCS are at high risk of acute pancreatitis (AP) in addition to other chronic health issues such as fatigue and severe, recurrent abdominal pain.3,8,9 People living with FCS are sometimes unable to work, adding to the burden of disease.9 Currently, there are no U.S. FDA-approved therapies for the treatment of FCS and standard triglyceride lowering therapies are generally ineffective in patients with FCS.10,11 People living with this condition currently rely solely on nutrition management through extremely restrictive and difficult to manage diets to navigate the health risks associated with FCS.11,12 About Ionis Pharmaceuticals, Inc. For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionispharma.com and follow us on X (Twitter) and LinkedIn. Forward-looking Statements This press release includes forward-looking statements regarding olezarsen, Ionis' business, and the therapeutic and commercial potential of Ionis' commercial medicines, additional medicines in development and technologies. Any statement describing Ionis' goals, expectations, financial or other projections, intentions, or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended Dec. 31, 2023, and most recent Form 10-Q, which are on file with the SEC. Copies of these and other documents are available at . Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc. Ionis Pharmaceuticals Investor Contact: D. Wade Walke, Ph.D. - [email protected] - 760-603-2331; Ionis Pharmaceuticals Media Contact: Hayley Soffer - [email protected] - 760-603-4679 1Alexander VJ, et al. Eur Heart J 2019;40(33):2785-2796. 2Tardif JC, et al. Eur Heart J 2022;43(14):1401-1412. 3Gaudet D, et al. N Engl J Med. 2014;371:2200-2206. 4Ginsberg HN, et al. Eur Heart J. 2021;42:4791-4806. 5Pallazola VA, et al. Eur J Prev Cardiol 2020;27(19):2276-8. 6Warden BA, et al. J Clin Lipidol 2020;14(2):201-6. 7Tripathi M, et al. Endocr Pract 2021;27(1):71-6. 8Bashir B, et al. Metabolites. 2023;(5):621. 9Davidson M, et al. J Clin Lipidol. 2018;12(4):898-907.e2. 10Gouni-Berthold I. J Endocr Soc. 2019;4(2):bvz035. 11Paquette M, et al. Atherosclerosis. 2019;283:137-142. 12Williams L, et al. J Clin Lipidol. 2018;4:908-919. SOURCE Ionis Pharmaceuticals, Inc.

▲5月30-31日 第八届广州生物医药创新者峰会 扫码立即报名 注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。2023年12月，艾伯维宣布以87亿美元收购神经科学领域的生物技术公司Cerevel Therapeutics，囊获多款治疗精神神经类疾病的候选产品组合；紧接着，百时美施贵宝宣布以140亿美元现金收购Karuna Therapeutics，拓展了在神经科学疾病领域的布局。（关联阅读：140亿美金的小分子！Karuna制药背后有何来头？）随着近段时间神经科学领域交易频现，多家跨国药企大举并购入局，曾被称为新药研发“黑洞”的CNS领域似乎又重新激起了行业内的热情。一些拥有后期资产的神经科学公司或有可能成为大型制药公司潜在的并购标的。专注于CNS的加拿大制药公司药融云数据www.pharnexcloud.com显示，Xenon Pharmaceuticals是加拿大一家专注于神经科学疾病领域的生物制药公司，主要以小分子、离子通道药物开发为专长，致力于提供创新疗法，以改善神经系统疾病患者的生活。目前该公司正在推进以神经病学为重点的新型产品管线，以解决高度未满足的医疗需求，重点是癫痫，并与学术和行业合作者开展新药研发项目，专注于神经系统药物开发30年的Neurocrine Biosciences是该公司的合作伙伴。截图自药融云数据库Xenon创立于1996年，2014年登陆纳斯达克（NASDAQ:XENE），截至2024年3月22日，该公司市值超过33.19亿美元，是加拿大少有的市值较高的创新药企。Xenon的过去：“世界首个”基因疗法与疼痛研究Xenon创立之时正值基因组技术取得长足发展的时期，最初公司名为Xenon Bioresearch，2004年更名为Xenon Pharmaceuticals。Xenon当时的定位是一家以临床遗传学为基础的生物制药公司，依托其Extreme Genetics发现平台，研究具有极端特征的罕见人类疾病（包括由离子通道突变引起的疾病），通过识别和表征导致这些特征的单基因缺陷，深入了解人类疾病生物学，以更好地选择治疗靶点。（from families to genes, from genes to drugs.）荷兰生物技术公司uniQure的Glybera（alipogene tiparvovec）被认为是“西方世界首个基因治疗药物”，2012年获欧盟批准治疗脂蛋白脂肪酶缺乏症（LPLD），后因价格原因撤市。Glybera最初的活性成分来自于Xenon的平台。Xenon曾与不列颠哥伦比亚大学（UBC）的合作者一起证明了，人类脂蛋白脂肪酶（LPL）的单基因突变，称为LPLS447X突变，可引起LPL酶活性增加，从而降低甘油三酯水平。2000年8月，Xenon与UBC签订了一项许可协议，根据该协议，Xenon获得了根据UBC控制的若干知识产权利益的全球独家许可，以开发和商业化基因治疗技术和化合物，包括与LPL突变有关的产品，即LPLS447X。几乎同一时间，Xenon与荷兰AMT公司（Amsterdam Molecular Therapeutics，成立于1998年）签订了分许可和研究协议，将根据Xenon控制的若干知识产权授予AMT全球独家分许可，以开发和商业化与LPL突变相关的技术和化合物，即LPLS447X。随后Xenon与UBC和AMT合作开展临床前研究，此后AMT便开发了携带LPLS447X基因的LPL基因治疗产品Glybera。不过该药的上市申请曾因受试者只有27例，以及疗效持续性等质疑三次被拒绝。最终AMT面临资金严重短缺的问题，经营困难，在2012年4月被刚成立的uniQure公司收购。同一年，Glybera终获欧盟批准，uniQure在次年与意大利凯西制药（Chiesi）建立合作，共同将Glybera商业化。不过该药定价高达100万美元，成为当时全球最昂贵药物，获批之后仅卖出一剂，而且是在该患者的主治医生想尽办法为其争取到了医疗保险，才得以支付。如此天价让Glybera再也没有被卖出，直到2017年uniQure与凯西制药宣布放弃Glybera，库存中余下的3份分别以1欧元“卖”给了三名欧洲患者。疼痛研究曾是Xenon的另一个重点。2001年，Xenon得知加拿大纽芬兰的一个家庭有四个成员对疼痛无感，其中一个孩子甚至被钉子穿过了脚都感觉不到疼痛，该公司认为这与遗传学有关。根据新闻报道和口耳相传，Xenon追踪并研究了来自世界各地12个对疼痛不敏感的家庭，Xenon通过研究这些家族的基因组，借助其Extreme Genetics平台发现了对疼痛不敏感的人群的共同特征：单个基因SCN9A的突变，这一突变会导致钠离子通道Nav1.7的功能丧失，进而使人对疼痛不敏感，也就是先天性无痛症（CIP）。这也提示了Nav1.7可能作为镇痛药物开发的关键靶点。基于此，Xenon开发了Nav1.7的小分子抑制剂，拟用于各种伤害性疼痛和神经性疼痛，如红斑性肢痛症（EM）、带状疱疹后神经痛（PHN）、膝骨关节炎疼痛、牙痛等。在全球疼痛治疗药物市场日渐庞大，阿片类药物带来成瘾性危机的背景下，业界对新型镇痛药物需求迫切，Xenon的研究成功吸引了制药大厂的目光，2011和2012年间，该公司就Nav1.7小分子抑制剂TV-45070（前称XEN402）和GDC-0276（后称RG-7893）、GDC-0310（RG6029）分别与Teva和罗氏旗下基因泰克达成了合作。不过，针对Nav1.7靶点的药物开发十分困难，全球尚未有该靶点药物成功获批。2017年6月，Xenon与Teva宣布TV-45070局部疗法治疗带状疱疹后神经痛（PHN）的2期临床研究既未达到主要终点，也未达到次要终点。2018年3月，两家公司宣布终止TV-45070的开发合作。另根据药融云数据库www.pharnexcloud.com提供信息，Xenon与基因泰克合作的两款Nav1.7抑制剂也已停止开发。截图自药融云数据库此外，Xenon还在2009年与默沙东（通过其瑞士子公司Essex Chemie AG）合作，开发治疗心血管疾病的新型小分子候选药物，该合作已在2012年结束。新药研发九死一生，曾经的轰轰烈烈到最后也可能落得一地鸡毛。研发管线进展经历了管线和战略的逐步调整，Xenon现在的目标是建立一家完全整合且盈利的生物制药公司，通过发现、开发和商业化创新疗法，专注于改善癫痫和其他神经系统疾病患者的健康。其战略关键包括：● 利用自身的发现能力，基于该公司对离子通道疾病遗传学的理解，结合专有的生物学和药物化学资产和专业知识，确定开发新的候选产品、药物靶点和/或现有候选产品的新适应症；● 通过临床开发推进选定的专有候选产品；● 有选择地建立合作关系，使公司潜在地扩展内部能力和/或获得更广泛的商业机会；● 通过适应症扩展、收购或引进外部候选产品，识别进一步扩大产品线的机会；● 选择单独或与其他公司合作将候选产品商业化。Pipeline更新至2023年12月与2014年IPO时相比，现在Xenon的临床管线已是大换血，其领先候选产品XEN1101是一款新型小分子Kv7.2/Kv7.3钾通道开放剂，主要开发适应症是癫痫和抑郁症。药融云数据www.pharnexcloud.com显示，该药原研单位是博士伦公司。2017年4月，Xenon与1st Order Pharmaceuticals签订资产购买协议，获得了XEN1101（前称为1OP2198）相关的所有权利。而在此之前，1st Order从加拿大制药公司Bausch Health Companies的间接子公司Valeant Pharmaceuticals Luxembourg S.a.r.l.以及Valeant Pharmaceuticals Ireland Limited、Bausch Health收购了1OP2198，并承担了某些义务，包括潜在的里程碑和特许权使用费。2018年，Xenon从Bausch Health买断了与XEN1101相关的所有未来应支付给Bausch Health的里程碑付款和特许权使用费。对于癫痫适应症，尽管目前市场上有多种抗癫痫药物（ASM），但由于多达50%的患者难以控制癫痫发作或患有严重的难治性癫痫，因此存在大量未满足医疗需求。局灶性癫痫发作（FOS）占美国癫痫人群中最大的部分，全面性癫痫是第二大常见的癫痫形式，约80%的成年全面性癫痫患者会经历原发性全面强直阵挛癫痫（PGTCS）。XEN1101治疗局灶性癫痫发作（FOS）：Xenon公司正在开展XEN1101治疗局灶性癫痫发作的3期临床研究，其中包括两项相同的3期临床试验，分别是X-TOLE2和X-TOLE3，这些试验是在2b期X-TOLE临床试验之后设计的（X-TOLE试验显示，在难治性FOS群体中，XEN1101对于癫痫发作的减少具有统计学意义）。这两项多中心、随机、双盲、安慰剂对照试验正在评估15 mg或25 mg剂量的XEN1101与食物一起作为辅助治疗的临床疗效、安全性和耐受性，每项研究大约有360名局灶性癫痫发作（FOS）患者。主要疗效终点是XEN1101与安慰剂相比，从基线到双盲期间（DBP）的月度癫痫发作频率的中位百分比变化（MPC）。公司预计X-TOLE2研究的患者入组将于2024年下半年完成。XEN1101治疗原发性全面强直阵挛癫痫（PGTCS）：该公司正在开展一项名为X-ACKT的3期临床试验，以支持XEN1101治疗另一项癫痫适应症，即PGTCS的潜在监管递交。这项多中心、随机、双盲、安慰剂对照研究正在评估25 mg剂量XEN1101作为辅助治疗在大约160名PGTCS患者中的临床疗效、安全性和耐受性。主要疗效终点是XEN1101与安慰剂相比，从基线到双盲期间（DBP）的月度PGTCS发作频率的中位百分比变化（MPC）。XEN1101治疗癫痫的开放标签扩展研究：在X-TOLE2、X-TOLE3或X-ACKT试验中度过双盲期后，符合条件的患者可以进入长达三年的开放标签扩展（OLE）研究。此外，正在进行的X-TOLE第2b期OLE研究将继续为XEN1101提供重要的长期数据。XEN1101治疗重度抑郁症（MDD）：2023年11月27日，Xenon报告了XEN1101在MDD患者中的2期概念验证X-NOVA临床试验的顶线结果。该试验是一项随机、双盲、安慰剂对照的多中心临床研究，评估了在168名中度至重度抑郁症（MDD）患者中使用10mg和20mg剂量XEN1101的临床疗效、安全性和耐受性。该试验的主要终点是给药第6周时根据Montgomery-Åsberg抑郁量表（MADRS）评分变化，将XEN1101与安慰剂进行比较。根据顶线结果，XEN1101 10mg组平均减少数值为15.61，20mg组为16.94，而安慰剂组为13.90，未达到统计学上的差异，但XEN1101 20mg组与安慰剂组之间存在明确的剂量反应和临床意义，并且该研究达到了次要疗效终点。另外XEN1101在安全性方面也非常出色，且结果显示XEN1101与显著的体重增加无关（体重增加是许多抗抑郁药物的常见副作用）。因此，该试验虽未达到主要终点，但Xenon当日股价却上涨了17.8%。次月，Xenon宣布完成了3.45亿美元的大规模公开募股。截图自雪球Xenon正在积极评估各种临床和监管途径，以支持XEN1101治疗MDD的后期临床开发，预计将于2024年启动3期临床研究。Xenon还在评估XEN1101未来开发的其他潜在适应症。此外，Xenon正与美国西奈山伊坎医学院合作，支持一项由研究者发起的2期概念验证、随机、平行、安慰剂对照的多中心研究，该研究涉及XEN1101治疗约60名MDD患者。研究的主要目的是评估XEN1101对大脑奖励回路的影响，通过功能性磁共振成像（fMRI）评估的双侧腹侧纹状体活动的变化来衡量。次要目标是分别使用MADRS和Snaith-Hamilton快感量表（SHAPS）测试XEN1101与安慰剂相比，对抑郁症和快感缺乏临床测量的影响。与Neurocrine合作的NBI-921352：NBI-921352是一种选择性Nav1.6钠离子通道抑制剂，正在由Xenon与Neurocrine Biosciences合作开发治疗癫痫，Neurocrine拥有NBI-921352（前称为XEN901）的独家许可。2023年11月，Neurocrine宣布评估NBI-921352在成年局灶性癫痫发作（FOS）患者中疗效的2期临床试验未能证明癫痫发作频率显着降低，Neurocrine不再计划NBI-921352在FOS患者中的进一步开发。不过根据当时的新闻稿透露，另外一项2期临床试验正在进行中，旨在评估NBI-921352在2至21岁的SCN8A基因突变相关发育性癫痫性脑病（SCN8A-DEE）患者中的疗效；作为双方合作的一部分，Neurocrine还在继续推进临床前双选择性Nav1.2/1.6抑制剂。临床前项目：Xenon继续利用其广泛的离子通道专业知识和药物发现能力来识别经过验证的药物靶点并开发新的候选产品。近期的重点是针对Kv7、Nav1.1和Nav1.7的开发候选药物，Xenon预计多个候选药物将在2024年和2025年进入IND-enabling研究。财务状况Xenon Pharmaceuticals目前主要通过出售权益性证券、从被许可方和合作者处获得资金以及债务融资来为公司运营提供资金。截至2023年9月30日，Xenon累计赤字为6.204亿美元。迄今为止，Xenon的收入主要来自合作和许可协议。以下是2022、2021以及2020年度Xenon公司的收入概况：根据Neurocrine的协作条款，2021年9月，基于NBI-921352在欧洲的临床试验申请的监管批准，Xenon收到了总额为1000万美元的里程碑付款（包括450万美元的现金和550万美元的普通股股权投资）。2022年1月，基于美国FDA批准扩大NBI-921352用于SCN8A-DEE人群的研究，包括2至11岁的受试者，Xenon收到了总额为1500万美元的里程碑付款（包括675万美元的现金和825万美元的普通股股权投资）。2021年，Xenon确认了与非阿片类药物疼痛管理公司Pacira BioSciences之间针对PCRX301的全球开发和商业化权利协议相关的300万美元收入，其中包括FDA批准IND申请的100万美元里程碑付款和1b期临床试验启动的200万美元里程碑付款。此后Xenon未从该合作中获得收入。2022年11月，Pacira BioSciences做出终止PCRX-301临床开发的战略决策。Pacira BioSciences通过在2021年11月收购Flexion Therapeutics，获得PCRX301（前身为FX301）的全球权利，再之前称为XEN402（也称funapide），该药是一种Nav1.7抑制剂，配制为热敏水凝胶缓释制剂。以下为Xenon在2020至2022年的运营开支情况：该公司2022年R&D费用为1.058亿美元，G&A费用为3281万美元，增长主要是因为临床试验的推进以及人员相关成本。2022年度净亏损为1.254亿美元。以下为2023年前三季度收入情况：本年度尚未获得许可和合作相关收入。以下为2023年前三季度运营开支情况：截至2023年9月30日，Xenon公司持有现金和现金等价物及有价证券共6.391亿美元，预计将足够覆盖公司2026年之前的运营支出。此文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐参考：NMPA/CDE；药融云数据www.pharnexcloud.com；FDA/EMA/PMDA；相关公司公开披露（正文图片均来自企业官方，除非另有说明）；https://www.xenon-pharma.com/；https://newsinteractives.cbc.ca/longform/glybera；https://www.wired.com/2017/04/the-cure-for-pain/；https://investor.xenon-pharma.com/news-releases/news-release-details/xenon-pharmaceuticals-confirms-closing-transaction-teva-and；https://investor.xenon-pharma.com/news-releases/news-release-details/xenon-expands-ion-channel-neurology-pipeline-acquisition-new；https://investor.xenon-pharma.com/news-releases/news-release-details/xenon-pharmaceuticals-provides-update-partnered-program；等等 本文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐 活动推荐  8月 • NDC2024生物医药创新博览会  关键词：  抗体、多肽、核酸、核药，XDC、小分子、注册、临床、CMC（点击下方图片查看详情）▼【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

- Expanded Access Program initiated to make investigational plozasiran available to patients with familial chylomicronemia syndrome - New SHASTA-2 Phase 2 clinical data in patients with severe hypertriglyceridemia to be presented at ACC.24 PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced that it has initiated an Expanded Access Program (EAP) to make investigational plozasiran available outside of a clinical trial for patients with familial chylomicronemia syndrome (FCS) who meet certain program eligibility criteria. Arrowhead will also present new final Phase 2 clinical data from the double-blind portion of the SHASTA-2 study of plozasiran in a late-breaking oral presentation at the upcoming American College of Cardiology 73rd Annual Scientific Session & Expo (ACC.24), being held in Atlanta on April 6-8, 2024. “Arrowhead is committed to supporting patients living with various lipid disorders and the physicians who treat them. To that end, we are pleased that Dr. Daniel Gaudet, Professor of Medicine at Université de Montréal and President and Scientific Director of ECOGENE-21, will present final data in a late-breaking oral presentation at ACC.24 from the SHASTA-2 study of plozasiran in patients with severe hypertriglyceridemia,” said Bruce Given, M.D., interim chief medical scientist at Arrowhead. “Our Phase 3 PALISADE study of plozasiran in patients with FCS is nearing completion and we are further supporting the patient community by initiating an expanded access program for patients and physicians interested in receiving treatment with plozasiran outside of a clinical trial. In addition, Arrowhead medical affairs representatives will be hosting a company booth at ACC.24 with resources for physicians to learn more about the mechanism of cardiometabolic diseases we are studying and our pipeline of RNAi therapeutics that leverage Arrowhead’s proprietary TRiM™ platform.” Arrowhead is committed to bringing new investigational medicines to patients with serious diseases as quickly and efficiently as possible. The company’s EAP is a potential pathway for patients with serious or immediately life-threatening diseases or conditions to gain access to an investigational medical product for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available. The plozasiran EAP is for individuals living with FCS. As with any investigational medicine that has not been approved by regulatory authorities, investigational plozasiran may or may not be effective in treating your diagnosis or condition, and there may be risks associated with its use. If you are a patient or caregiver wishing to know more about this plozasiran EAP for FCS, please discuss this EAP and all treatment options with your treating physician. If you are a treating physician and are seeking information about the plozasiran EAP or would like to request access for a patient, please contact EAP@arrowheadpharma.com. Details about the ACC.24 presentation are listed below. American College of Cardiology 73rd Annual Scientific Session & Expo – April 6-8, 2024 Title: Plozasiran (ARO-APOC3), An Investigational RNAi Therapeutic, Demonstrates Profound and Durable Reductions in APOC-3 and Triglycerides (TG) in Patients With Severe Hypertriglyceridemia (SHTG), SHASTA-2 Final Results Date/Time: April 7, 2024, 9:00 a.m. EDT Presenter: Daniel Gaudet MD, PhD Session: Late-Breaking Clinical Trials II Presentation materials may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website after the oral presentation concludes. About Plozasiran Plozasiran, previously called ARO-APOC3, is a first-in-class investigational RNA interference (RNAi) therapeutic designed to reduce production of Apolipoprotein C-III (APOC3) which is a component of triglyceride rich lipoproteins (TRLs) and a key regulator of triglyceride metabolism. APOC3 increases triglyceride levels in the blood by inhibiting breakdown of TRLs by lipoprotein lipase and uptake of TRL remnants by hepatic receptors in the liver. The goal of treatment with plozasiran is to reduce the level of APOC3, thereby reducing triglycerides and restoring lipids to more normal levels. In multiple clinical studies, investigational plozasiran demonstrated reductions in triglycerides and multiple atherogenic lipoproteins in patients with familial chylomicronemia syndrome (FCS), severe hypertriglyceridemia (SHTG), and mixed dyslipidemia (MD). Plozasiran has demonstrated a favorable safety pro date with treatment emergent adverse events reported that reflect the comorbidities and underlying conditions of the study populations. Plozasiran is currently being investigated in the Phase 3 PALISADE clinical study in patients with FCS, which is on schedule to be completed in the middle of 2024. Phase 2 studies in patients with SHTG and MD, SHASTA-2 and MUIR respectively, are complete and additional Phase 3 studies are planned to begin shortly. About Arrowhead Pharmaceuticals Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit , or follow us on X (formerly Twitter) at @ArrowheadPharma or on LinkedIn. To be added to the Company's email list and receive news directly, please visit . Safe Harbor Statement under the Private Securities Litigation Reform Act: This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as “may,” “will,” “expect,” “believe,” “anticipate,” “hope,” “intend,” “plan,” “project,” “could,” “estimate,” “continue,” “target,” “forecast” or “continue” or the negative of these words or other variations thereof or comparable terminology are intended to identify such forward-looking statements. 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These forward-looking statements include, but are not limited to, statements about the initiation, timing, progress and results of our preclinical studies and clinical trials, and our research and development programs; our expectations regarding the potential benefits of the partnership, licensing and/or collaboration arrangements and other strategic arrangements and transactions we have entered into or may enter into in the future; our beliefs and expectations regarding milestone, royalty or other payments that could be due to or from third parties under existing agreements; and our estimates regarding future revenues, research and development expenses, capital requirements and payments to third parties. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties, including the impact of the ongoing COVID-19 pandemic on our business, the safety and efficacy of our product candidates, decisions of regulatory authorities and the timing thereof, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other documents filed with the Securities and Exchange Commission from time to time. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances. Source: Arrowhead Pharmaceuticals, Inc.