Alnylam Pharmaceuticals, Inc.

正文共： 1348字 8图预计阅读时间： 4分钟诺华计划以8亿美元预付款收购位于圣地亚哥的生物科技公司Regulus Therapeutics，该公司专注于microRNA药物的研发。此次收购的核心资产是farabursen，这是一种针对与肾病相关的miR-17的候选药物，刚完成针对多囊肾病患者的1b期临床试验。收购Regulus的协议中，股东将获得每股7美元的现金，这一价格是周二收盘价的两倍多。此外，诺华还承诺，若达到某些未公开的审批标准，将额外支付每股7美元。Regulus成立于2007年，由Alnylam和Ionis联合创立，其技术灵感来源于《自然》杂志上一篇关于合成寡核苷酸抑制microRNA的论文。公司成立初期发展势头良好，曾与赛诺菲和阿斯利康等大型药企合作。然而，近年来研发遭遇连续失败，股价自2021年以来一直未能突破4美元。farabursen于2022年进入临床试验，针对的是研究人员认为与肾病相关的miR-17。目前，多囊肾病患者治疗选择有限，主要依赖托伐普坦等药物来延缓肾功能恶化。诺华在肾病领域的布局并非首次。2023年，诺华以30亿美元收购Chinook Therapeutics，获得了治疗IgA肾病的新药Venrafia。此外，诺华还计划扩展其已获批的IgA肾病药物Fabhalta的适应症，以覆盖更多肾病类型。诺华首席医疗官Shreeram Aradhye在领英上表示，此次收购加强了公司在肾病产品线上的实力，延续了在IgA肾病和补体3肾小球病治疗领域获批后的创新势头。诺华生物医学研究总裁Fiona Marshall此前向BioPharma Dive透露，公司一直在寻找有潜力的早期项目，并将多囊肾病视为肾病产品线的重点攻克目标。她强调，虽然内部研发项目很重要，但如果市场上有更优秀的项目，诺华也会果断收购。参考资料：Novartis to acquire Regulus Therapeutics and farabursen, an investigational microRNA inhibitor to treat ADPKD, the most common genetic cause of renal failureNovartis to acquire Regulus in deal for kidney disease drug其它公开资料图片来源：微信订阅号AI38笔！596亿美元！跨国药企2025年重磅交易达成，中国公司贡献很大2025-05-02【直击现场】「星起点」宣讲会直播：50万资金+专家辅导，寻找下一个代谢病创新药突破者！2025-04-30百济神州索托克拉冲刺上市，引领BCL2抑制剂新纪元！2025-04-30版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn点击这里，查看更多精彩!

When CRISPR pioneer Feng Zhang met with investors to discuss his new drug delivery technology over dinner in the summer of 2021, it didn’t take long to pitch the idea. By the time the appetizers arrived , the investors were sold. But getting the technology to work well enough to test in humans will take longer, and in the meantime, Zhang’s company, Aera Therapeutics , is turning to an older delivery technology for some of its first programs, Endpoints News has learned. The Cambridge, MA-based company initially focused on developing novel protein nanoparticles that promised to deliver CRISPR gene editing therapies into parts of the body that lipid nanoparticles have had a hard time reaching, such as the brain, kidney and muscles. But now Aera is turning to lipid nanoparticles for at least one of its programs. Aera has developed lipid nanoparticles, or LNPs, that target T cells of the immune system. It hopes to create CAR-T cell therapies that quell autoimmune diseases via a simple blood infusion. The so-called in vivo cell therapy approach could reduce the complexity and expense of commercial therapies that require removing a patient’s cells from their body and editing them in the lab, a process known as ex vivo cell therapy. Developing in vivo cell therapies for autoimmune disease, cancer and genetic blood diseases like sickle cell is quickly becoming one of the most competitive parts of the cell and gene therapy field. Only a few companies have begun testing in vivo cell therapies in the clinic, but well over a dozen have declared their intentions to join the race. Aera is undaunted. “We understand it’s very competitive. But at the same time, it’s not solved,” Aera CEO Akin Akinc told Endpoints News . “No one’s really that far ahead,” he added. “In the autoimmune space, there’s probably going to be a lot of winners.” Akinc said that the addition of LNPs doesn’t mean that the company’s work on protein nanoparticles has been harder or slower than expected, though he noted that Aera’s protein nanoparticle therapies are “probably going to be a little bit further off than some of the nearer term applications with LNPs.” “This was going to be a platform build,” Akinc said. “I think the investors, I think all of us, knew that was going to take time.” Aera started working on LNPs about a year and a half ago, according to Akinc. And in some ways, the shift isn’t a total surprise. Akinc helped develop the LNPs used in Onpattro, the first gene-silencing RNAi therapy made by Alnylam Pharmaceuticals, and the first product using fatty bubbles to safely deliver genetic medicines to the human body. LNP scientists are in high demand, but they’re easier to find than experts in protein nanoparticles, a technology that has barely begun to emerge from academic labs. Since both lipid and protein nanoparticles are manufactured synthetically — as opposed to viral vectors, which are grown in cells — Aera has recruited many LNP scientists to its company, and it’s been natural for them to switch between the two platforms, he said. When infused into the bloodstream, LNPs tend to get soaked up by the liver. Figuring out how to redirect them to bone marrow or immune cells, and at doses that can be safely administered and affordably manufactured, is no small feat. Most companies, including Aera, are reluctant to say exactly how they’re doing it. “I can’t give you all the secrets,” Akinc said. “But philosophically, we felt that it didn’t make sense to take standard LNPs for the liver and simply slap on a targeting ligand, right?” Instead, Aera scientists re-engineered the nanoparticle to avoid the liver and then added a targeting molecule — Akinc won’t say what kind — to direct them to T cells. While other companies have begun to share promising results in mice and monkeys, it’s too soon to know if these will hold up when tested in people. The work was disclosed this week in an abstract for the upcoming American Society of Gene & Cell Therapy meeting in New Orleans. Akinc said it’s Aera’s first presentation at a scientific conference. Akinc described the LNP therapy for autoimmune disease as one of several discovery-stage programs at the company. Aera hasn’t named a lead program, disclosed its other programs, or said when it expects to start the first clinical trial. And Akinc emphasized that its work on protein nanoparticles continues. “We’re aiming those at taking big swings at really tough problems that have been difficult to solve with LNPs and viral vectors,” such as delivery of mRNA-based therapies to the brain, he said. And he doesn’t want to use the protein nanoparticles for things that can be done with LNPs. “That’s why we didn’t say let’s do T cell targeting with [protein nanoparticles] because we think we could do that with LNPs,” he said.

Alnylam CEO Yvonne Greenstreet, M.D., characterizes Amvuttra's entrance in the suddenly competitive ATTR-CM market as a "category growth story." With attention focused on their recently approved drugs for transthyretin amyloid cardiomyopathy (ATTR-CM), there was a serendipitous timeliness to Alnylam and BridgeBio presenting their quarterly updates on consecutive days.While BridgeBio blew away analyst projections on Wednesday, reporting sales of $37 million for Attruby in its first full quarter on the market, Alnylam countered with positive news as well for Amvuttra on Thursday.Since Amvuttra earned its FDA label expansion to treat patients with ATTR-CM so late in the first quarter on March 20, there were no significant sales to report for the indication. But the company is pointing to encouraging signs in its uptake.“Our first priority out of the gate was the access setup and we’re pleased to say it’s progressing exactly to plan, enabling the second half growth story that we have portrayed,” Tolga Tanguler, Alnylam’s chief commercial officer, said during a conference call.Tanguler explained that 80% of TTR volume in the U.S. flows through 170 health systems, and that the company had gained formulary placements of Amvutta within four weeks of the label expansion at more than half of the systems. He added that a “majority” have initiated Amvuttra treatment for ATTR-CM patients.Tanguler also reported early feedback from patients and doctors indicates “excitement for a new mechanism of action in ATTR-CM.”“What we’re hearing from prescribers is that the Amvuttra’s disruptive value proposition resonates and is enabling this early encouraging launch momentum,” Tangular said.Alnylam and BridgeBio are challenging powerhouse Pfizer, which has dominated the market with its booming Vyndaqel franchise. In 2024, the Pfizer treatments achieved sales of $5.4 billion, which was up from $3.3 billion in 2023.Alnylam CEO Yvonne Greenstreet, M.D., said there is plenty of room for new options for ATTR-CM patients.“We really are in a category growth story,” Greenstreet said. “What we’re seeing is continued evidence of a large, growing, and frankly, unsatisfied market and I think we’re very excited to be able to participate.” Alnylam points to its experience with treating patients with polyneuropathy caused by hereditary transthyretin amyloidosis (hATTR-PN). The company earned approvals for Onpattro (2018) and Amvuttra (2022) to treat the condition.“We are finding that in categories where the majority of patients remain untreated, more treatment options mean more voices helping to raise disease awareness ultimately accelerating category growth and increasing the number of patients on therapy,” Tanguler said. “We believe about 80% of the addressable patient population remains untreated. This bodes well for the opportunity ahead in ATTR-CM.” In the first quarter, sales for Amvuttra and Onpattro came in at $310 million and $49 million, which were up a combined 37% year over year and 4% sequentially. The combined $359 million TTR franchise sales were in line with the analysts' forecast of $355 million.In 2024, sales of the two treatments were at $1.22 billion. With the new indication for Amvuttra, the company is sticking to its previously announced guidance for the pair to generate between $1.6 billion and $1.725 billion in 2025.For the company overall, revenue was up in the quarter 20% to $594 million. Alnylam is guiding to overall sales of between $2.05 billion and $2.25 billion, which would be a 31% increase year over year at midpoint.