创新是生物医药领域发展的命脉。如何将一项创新技术、一个创新靶点转换为一类创新疗法是科学界、产业界、投资界共同探讨的命题。医药魔方《创星》栏目，根据InvestGO®独有的评分系统，筛选最值得关注的一批“创新之星”，从科学基础、技术优势、研发潜力等多个维度，洞悉新锐公司获资本青睐的原因，同时，也将总结同领域的全球竞争概况，辅助国内创新药同行的决策判断。 2024年9月26日，治疗精神分裂症的创新药物KarXT成功获FDA批准上市。这款药物的问世标志着精神分裂症领域几十年来的重大突破，它采用了全新的作用机制，不依赖传统的多巴胺或5-羟色胺通路，而是作用于中枢神经系统的毒蕈碱乙酰胆碱受体（mAChR）。KarXT由呫诺美林（xanomeline，M1和M4型mAChR激动剂）和曲司氯铵（trospium，外周mAChR拮抗剂）组成，巧妙的复合设计使KarXT在中枢神经系统激活mAChR的同时，又能控制其引起的外周副作用。KarXT在临床上的亮眼表现引起多家MNC的关注，最终在2023年12月，其原研公司Karuna Therapeutics被BMS以140亿美元的价格并购，成为2023年交易额排名第二的并购案例。而就在该交易达成4个月后，孵化Karuna Therapeutics的PureTech Health宣布成立新公司Seaport Therapeutics，开始一场新的冒险。Seaport Therapeutics和Karuna Therapeutics一样专注于中枢神经系统（CNS）药物研发。来源：Seaport Therapeutics官网 Daphne Zohar担任Seaport Therapeutics的创始人兼首席执行官，她之前担任PureTech Health的创始人兼首席执行官并共同创立了Karuna Therapeutics。Daphne Zohar是一位成功的企业家，从16岁时就开始创业，能够敏锐洞察事物的潜在价值。自创立PureTech Health以来，她为公司带来巨大价值。PureTech Health采用的“Hub and Spoke”经营模式使其能够高效推进研发，目前已开发出了28种疗法，在研产品一部分作为内部管线进行开发，另一部分由PureTech Health成立新的实体公司来推进，如Karuna Therapeutics、Seaport Therapeutics。PureTech Health及其成立的实体公司进行的临床试验80%都取得成功，大约是行业平均水平的6倍。 Daphne Zohar（来源：Seaport Therapeutics官网）另一位联合创始人是Karuna Therapeutics前首席执行官、前首席科学官Steven Paul，在加入Karuna Therapeutics之前，Paul曾担任礼来的研发总裁，负责监督奥氮平（Zyprexa）、度洛西汀（Cymbalta）、xanomeline等CNS药物的开发。在他任职礼来期间，xanomeline已经显示出最初的抗精神病和促认知特性。此外，他还联合创立多家CNS领域的创新药物公司，如Sage Therapeutics等，是CNS药物发现和开发领域的权威专家。 Steven Paul（来源：Seaport Therapeutics官网） Seaport Therapeutics不仅汇聚了Karuna Therapeutics的领导团队，还获得了Karuna Therapeutics投资者的支持。2024年4月9日，其宣布完成1亿美元A轮融资，由ARCH Venture Partners、Sofinnova Investments、Third Rock Ventures和PureTech Health共同领投，其中ARCH、Sofinnova和Third Rock都是Karuna Therapeutics的投资者。10月21日，Seaport Therapeutics又完成2.25亿美元B轮融资，A轮投资者继续跟投。半年狂揽3.25亿美元融资，或许是其与Karuna Therapeutics同样的模式及领导团队，让投资人产生了信任。当然，Seaport Therapeutics的技术平台和管线也同样亮眼。公司的核心技术平台Glyph™，源自澳大利亚莫纳什大学Christopher Porter教授及其研究团队的开创性工作。这一平台的独特之处在于它的药物递送机制：通过直接靶向淋巴系统，绕过传统口服药物必须经历的肝脏首过代谢过程，从而显著提高药物的生物利用度、减少潜在的肝脏毒性并提高患者的整体耐受性。Glyph™平台的设计灵感来源于人体对膳食脂肪的自然处理方式，通过将药物与膳食脂肪分子可逆地结合，形成一种新型前药，这种设计允许药物在口服后随同脂肪分子一起绕过肝脏，直接进入肠道的淋巴管系统。Porter研究团队及其合作者在多个顶尖学术期刊上发表了关于Glyph™平台的研究成果，包括Nature Metabolism、Angewandte Chemie和Journal of Controlled Release。这些研究成果详细阐述了Glyph™平台如何通过淋巴系统实现对药物的有效递送，以及这一技术在不同疗法中的应用潜力，证明了该平台的科学严谨性。 Glyph™平台（来源：Seaport Therapeutics官网） Glyph™平台除了科学研究支持，在临床上也得到了验证。Seaport Therapeutics围绕Glyph™设计了多条管线，且管线具有两个特点，一是聚焦患者需求高度未得到满足的领域，二是优先考虑经过临床疗效验证的药物，利用Glyph™技术实现口服并提高生物利用度、降低副作用等。通过这种方式，Seaport Therapeutics能够快速推进管线进展，填补患者需求。管线情况（来源：Seaport Therapeutics官网） Seaport Therapeutics目前主要推进3条管线，其中进展最为迅速的是SPT-300，这是一种别孕烷醇酮（allopregnanolone）口服前药，处于Ⅱ期临床试验阶段，用于治疗产后抑郁、焦虑症、重度抑郁症等。别孕烷醇酮是γ-氨基丁酸-A（GABAA）受体调节剂，具有经临床验证的快速抗抑郁和抗焦虑活性。2019年，Sage Therapeutics研发的布瑞诺龙（brexanolone，人工合成的别孕烷醇酮）获批上市，是FDA首个批准用于治疗产后抑郁症的药物。但它存在过度镇静和意识丧失的风险，因此必须在获得认证的医疗保健中心，留院观察60小时并在加强监护下静脉给药，这无疑给产后抑郁患者的治疗带来了不便。为了改善这一状况，Sage Therapeutics在2023年推出了另一款针对产后抑郁的口服药物珠兰诺隆（zuranolone），通过对别孕烷醇酮进行结构上的优化解决了口服问题，但它仍然面临着肝脏毒性和首过代谢带来的挑战。此外专注于解决药物口服问题的Lipocine也在尝试利用其技术平台开发可口服的别孕烷醇酮，可能也同样面临这些挑战。值得一提的是，Steven Paul曾是Sage Therapeutics的联合创始人，对于布瑞诺龙和珠兰诺隆的开发以及公司其他管线都做出了重要贡献，因此对于别孕烷醇酮的前药开发或许更有经验和见解。SPT-300的Ⅰ期试验结果显示其耐受性良好，别孕烷醇酮暴露量是其他已发表的口服异孕酮数据的9倍，验证了Glyph™平台提高口服生物利用度的能力。在IIa期试验中，SPT-300大大降低了压力诱导的皮质醇水平，治疗焦虑症效果符合预期，且仅有轻微嗜睡的副作用。 SPT-320是阿戈美拉汀的一种新型前药，正准备开展治疗广泛性焦虑症的Ⅰ期临床研究。阿戈美拉汀于2007年上市，可有效治疗广泛性焦虑症和重度抑郁症，且耐受性高。但是其首过代谢高，生物利用度只有约1%，导致一些患者的肝酶增加，需要频繁的肝功能监测。SPT-320使用Glyph™绕过肝脏首过代谢，很有可能降低用药剂量的同时还能提高阿戈美拉汀的有效全身暴露，并且减少对肝功能的损伤以及监护。 SPT-348是一种创新的非致幻性神经原前药，用于治疗情绪和神经精神障碍。非致幻性神经原是CNS药物中的一个新兴领域，通过增强大脑的可塑性来应对这类疾病，同时避免了传统致幻药物可能带来的不良影响。借助于先进的Glyph™技术平台，SPT-348不仅优化了药物的药代动力学特性，还显著提升了其耐受性，这使得它在维持药效的同时，有效地减少了副作用的发生。Seaport Therapeutics在CNS药物领域内积极拓展，除了以上这3条管线，还在开发多个发现和临床前项目。在CNS药物的开发过程中，常常遇到类药性不足或耐受性问题，导致许多有潜力的新型药物未能成功上市，另外尽管有些药物成功上市，但仍然有很多局限性，如给药方式、生物利用度、毒副作用等。面对这些挑战，Seaport Therapeutics的Glyph™平台，展现出了强大的应对能力。Seaport Therapeutics依靠强大的技术平台和优秀的领导团队，极有可能复制KarXT这样的成功案例，为抑郁症、焦虑症以及其他精神疾病的患者带来新的治疗选择和希望。 -上下滑动查看参考资料 - [1]https://karuna-pharmaceuticals.squarespace.com/about [2]https://puretechhealth.com/ [3]https://seaporttx.com/ [4]DOI: 10.1038/s42255-021-00457-w [5]DOI: 10.3389/fphar.2022.879660 [6]DOI: 10.1016/j.jconrel.2021.02.008 创星公司全球 Septerna | Ceptur | Kelonia Sionna | Aspen | Askgene Terremoto | ReCode | CAMP4 Xilis | Dianthus | Aktis | Orna Pretze | Nested | Matchpoint | Vega CARGO | N1 Life | ITM | Genesis Diagonal | Xaira 中国辐联医药 | 瑞石生物 | 阿泰克可瑞生物 | 星奕昂 | 益杰立科迦进生物 Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

抗体药物偶联物并购上市批准

2024-10-22

·Outsourcing Pharma

Seaport Therapeutics closes $225 million Series B to develop neuropsychiatric drugs

Seaport has developed a platform called Glyph designed to enhance efficacy and reduce the side effects of potential drug candidates. The original research behind the platform came from Monash University in Australia. Potential medications developed using Glyph are absorbed like fats in the diet through the lymphatic system. The Series B adds to Seaport’s $100 million Series A round that was announced in April, alongside the launch of the company, meaning they now have $325 million in total funding. The round was led by General Atlantic and had several new investors including T. Rowe Price Associates, Inc., Foresite Capital, Invus, Goldman Sachs Alternatives, and CPP Investments. The original investors in Seaport also contributed to the Series B including ARCH Venture Partners, Sofinnova Investments, Third Rock Ventures, and co-founder PureTech Health. American entrepreneur Daphne Zohar is both a co-founder and CEO of Seaport. Zohar was previously co-founder and CEO of PureTech Health, which was launched almost 20 years ago. Since then, PureTech has developed 29 therapeutic candidates across a range of different indications, three of which have FDA approval. PureTech has also launched several successful spin-out companies including Karuna Therapeutics, which was acquired by BMS earlier this year and was behind the successful development and recent approval of the schizophrenia drug Cobenfy (KarXT). Zohar was also a co-founder of Karuna. “Seaport is advancing novel therapeutics that have proven clinical efficacy but had previously been held back by an issue we can now address with our Glyph platform,” said Zohar in a press statement. googletag.cmd.push(function () { googletag.display('text-ad1'); }); “This financing enables the important clinical work that brings us another step closer to delivering new medicines to make a difference in the lives of patients and their families.” The quest for better psychiatry medicines Seaport is hoping to use its oversubscribed fundraising rounds to create better psychiatric drugs that are more effective, last longer and have fewer side effects than those currently on the market. The Glyph platform allows previously discovered potential neuropsychiatric therapies, that may have been abandoned due to adverse events, or poor absorption, or similar, to have a new lease of life, as well as new potential drug candidates. “The development of important new neuropsychiatric medicines is often halted due to poor drug-like properties or unacceptable tolerability, challenges that our Glyph platform can now uniquely address,” said Steve Paul, co-founder and Board Chair at Seaport. “For instance, xanomeline was an effective drug that faced tolerability challenges, but once resolved, led to the FDA approval of Cobenfy for schizophrenia. With Glyph, we believe each of Seaport’s programs could create similar life-changing value for patients.” Seaport currently has three candidate medicines in its pipeline. The most advanced, SPT-300 is a prodrug of allopregnanolone being developed to treat major depressive disorder with or without anxious distress. Allopregnanolone has been shown to quickly reverse the symptoms of depression and anxiety, but previously was only effective in an intravenous format. Seaport has developed an oral version of this candidate, which is now at phase 2b. The other two candidates are at an earlier stage and include SPT-320, a novel prodrug of agomelatine soon to enter phase 1 studies for the treatment of generalized anxiety disorder and SPT-348, a prodrug of a non-hallucinogenic neuroplastogen in development for the treatment of mood and other neuropsychiatric disorders.

临床2期并购

2024-10-21

·EndPoints

Former Karuna crew quickly assembles $225M for next neuro bet at Seaport

The team at Seaport Therapeutics, a Boston neuropsychiatry biotech, is having a good fall season. Seaport said Monday it has pieced together $225 million from hefty crossover names and some of the biggest specialists in the industry, just six months after launching with $100 million . The company had been targeting $150 million for the Series B, CEO Daphne Zohar told Endpoints News . Just last month, the Seaport team’s previous neuroscience biotech, Bristol Myers Squibb-owned Karuna Therapeutics, notched an FDA approval for a new type of schizophrenia treatment . Seaport is chaired by former Karuna leader Steve Paul. General Atlantic led the Series B. Others taking part in the raise include T. Rowe Price, Foresite Capital, Invus, Goldman Sachs Alternatives, Canada Pension Plan Investment Board, ARCH, Sofinnova Investments, Third Rock and Seaport incubator PureTech Health. Seaport spun out of publicly traded PureTech, which Zohar had run as CEO until launching the new company in April. Seaport immediately got an influx of interest from investors after that launch round, she said. The Series B marks the 80th nine-figure private financing of the year for the biotech industry, according to an Endpoints tally. The biotech is developing prodrugs of molecules that have already been tested or approved. Seaport aims to improve them so they avoid the liver. Its so-called Glyph platform “cloaks” a small molecule “as if it were a dietary fat,” co-founder and chief scientific officer Michael Chen previously told Endpoints. That helps the gut’s lymphatic system take up the drug and bypass the liver, where it could’ve gotten eaten up and seen its effectiveness in treating brain health conditions dwindle. The platform could apply to other therapeutic areas, and Seaport has been getting inbound interest from potential partners, Zohar said. “We call it Glyphing — I guess it’s a verb now — Glyphing molecules that belong to other pharma companies, actually helping these drugs make it to patients,” Zohar said. “That’s one of the things that we hope to be able to do now that we have the resources to continue to grow the team.” Seaport believes it has a registration-enabling trial in its sights, with a Phase 2b on its way for SPT-300, a prodrug version of allopregnanolone. The neurosteroid is key to the postpartum depression medicines Zulresso and Zurzuvae at Sage Therapeutics, where Paul recently retired from the board. Seaport’s trial will include patients with major depressive disorder with or without anxious distress. About half of MDD patients have diagnosable anxious distress, Seaport chief medical officer Antony Loebel said. He recently joined from Sunovion Pharmaceuticals. Chen said these patients “tend to respond less well to SSRIs or SNRIs, [are] slower to respond, have worse quality and worse outcomes.” SPT-300 is part of a wave of depression drug R&D. Key clinical readouts loom in MDD for drugs from companies like Johnson & Johnson , Neumora and Alto Neuroscience . Seaport’s pipeline also includes preclinical prodrugs of agomelatine (SPT-320) for generalized anxiety disorder and a prodrug of a non-hallucinogenic neuroplastogen (SPT-348) for mood and other neuropsychiatric disorders. With the biotech firing on all cylinders and plenty of capital at hand to get to critical clinical data, Zohar is feeling good. “I’m enjoying my brief hiatus as a private CEO right now,” Zohar said. Ultimately, though, Seaport will have to be a public company if it wants to succeed at being a “major player in depression, anxiety and other neuropsychiatric disorders.”