Trontinemab

摘要：波士顿新锐药企 Korsana Biosciences 近日完成 1.75 亿美元融资并走出隐匿模式，其首款阿尔茨海默病候选药物 KRSA-028 剑指血脑屏障突破难题，计划 2027 年初启动临床。这款靶向淀粉样蛋白的抗体药物通过改造分子结构规避同类药物的贫血副作用，还拟采用注射给药优化患者体验，为拥挤的阿尔茨海默病研发赛道带来新变数。 融资落地，新锐药企携新药亮相 阿尔茨海默病研发赛道再添新玩家，成立于 2024 年的 Korsana Biosciences 终于揭开神秘面纱。这家总部位于波士顿的生物科技公司，手握 1.75 亿美元融资底气十足，其中 2024 年种子轮融资 2500 万美元，近期完成的 A 轮融资更是斩获 1.5 亿美元，由惠灵顿管理和 TCGX 领投，摩根大通、赛诺菲创投等知名机构纷纷跟投。 掌舵者 Jonathan Violin 博士堪称生物医药领域的创业老手，曾创办多家生物科技公司，还身兼 Fairmount 风投合伙人，这也让 Korsana 从诞生起就自带行业资源优势。目前公司仅有 17 名全职员工，却已与蛋白工程专家 Paragon Therapeutics 联手，挖出了首款核心候选药物 KRSA-028，剑指阿尔茨海默病这一医药研发 “硬骨头”。 借道转铁蛋白，巧破血脑屏障难题 阿尔茨海默病药物研发的一大卡点，就是血脑屏障这道 “天然城墙”，让多数抗体药物难以进入大脑发挥作用。KRSA-028 走了条巧路子 —— 绑定转铁蛋白受体搭 “顺风车”，要知道这种受体本是负责给大脑运输铁元素的，药物借着这个天然通道，就能顺利穿越血脑屏障，精准瞄准脑内形成斑块的异常淀粉样蛋白。 就连公司名字 Korsana 都藏着这个巧思，“Korsa” 在瑞典语里就是 “穿越、横跨” 的意思，算是把研发核心直接刻进了品牌里。不过这条路并非 Korsana 独创，罗氏的 trontinemab 早已进入三期临床，艾伯维也通过收购拿下了同类资产，Denali 的 DNL921 也计划今年上半年启动一期临床，一众药企都盯上了转铁蛋白受体这个 “通关密码”。 改造分子结构，规避同类药物副作用 二代淀粉样蛋白抗体虽解决了一代药物的脑内出血（ARIA）风险，新的问题却接踵而至。罗氏的 trontinemab 就栽在了贫血上，临床中 10%-20% 的患者出现贫血症状，原因就是药物不仅绑定脑内的转铁蛋白受体，还会盯上红细胞前体表面的同类受体，误伤到造血系统。 Korsana 的破局思路很直接：给 KRSA-028 做 “减法”。通过弱化药物的效应功能，既保留其招募免疫细胞清除淀粉样蛋白的核心作用，又能避开对红细胞前体的损伤。Violin 博士透露，临床前数据已经证实，这款药物成功躲开了贫血副作用，这一点和 Denali 的技术思路相似，但他对自家数据信心满满，直言 KRSA-028 的表现更胜一筹。 2027 临床启航，给药方式再升级 按照 Korsana 的规划，KRSA-028 将在 2027 年初正式进入临床阶段，节奏相当紧凑：年中拿出初步安全性数据，年底就计划公布清除淀粉样蛋白斑块的概念验证结果。除了安全性上的打磨，这款药物还想在给药体验上做突破 —— 目前获批的阿尔茨海默病抗体药物都需要静脉输注，费时又麻烦，KRSA-028 则瞄准了普通注射给药，能大大提升患者的用药便捷性。 眼下 Korsana 还在持续拓展研发管线，除了 KRSA-028，也在探索阿尔茨海默病的其他靶点和神经退行性疾病领域，同时也在寻找外部优质资产合作。在拥挤的阿尔茨海默病研发赛道，这家手握重金、技术有针对性的新锐药企，能否凭借 KRSA-028 闯出一片天，2027 年的临床数据将成为关键答案。 参考来源：https://www.fiercebiotech.com/biotech/korsana-crosses-crowded-alzheimers-field-175m-and-anti-amyloid-antibody 识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！ 请注明：姓名+研究方向！ 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

Biologics maker Paragon Therapeutics has spun out its seventh biotech startup, this time in pursuit of Roche in the fight against Alzheimer’s. Like Roche with trontinemab, Korsana Biosciences is attempting to deliver an antibody that shuttles across the blood-brain barrier to thwart the advancement of the memory-robbing disease. Korsana disclosed its lead asset Wednesday along with the news that it raised a $150 million Series A in September to help get to early clinical data. Investors included Fairmount, Venrock Healthcare Capital Partners, Wellington Management, TCGX, JP Morgan Life Sciences Private Capital, Janus Henderson Investors and Foresite Capital. Sanofi’s venture arm, one of the most active biotech investors of late, also took part. The nine-figure Series A marks at least the 15th megaround that private biotech startups have disclosed so far this year. The Waltham, MA-based startup was seeded with $25 million in 2024. The biotech’s battle against Alzheimer’s is much further behind than Roche’s trontinemab program, which is seen as a leading shot in the next wave of Alzheimer’s treatments and entered a set of large Phase 3 trials last year. Trontinemab “is not the end of the road — we do not think it’s the best you can do for these patients,” Korsana CEO Jonathan Violin said in an interview with Endpoints News. Korsana anticipates entering Phase 1/2 with its candidate KRSA-028 around the end of this year or early next year. It expects Phase 1 healthy volunteer results in mid-2027 and then initial data on KRSA-028’s amyloid plaque-clearing capabilities around the end of that year. The nimble 17-employee startup is betting one of its advantages will be a delivery route that eliminates the need to go to infusion centers, Violin said. Korsana is cooking up a subcutaneously delivered medicine, whereas Roche is testing an IV-formulated antibody. Korsana also hopes to tamp down on concerning side effects that have affected the inaugural class of approved amyloid-targeted medicines, namely Eli Lilly’s Kisunla and Biogen and Eisai’s Leqembi. While those treatments ended a bleak “graveyard” period for Alzheimer’s drug development, they can carry the risk of concerning side effects known as amyloid-related imaging abnormalities, which can signal brain swelling and bleeding. ARIAs are a “challenge for anyone to contemplate,” Violin said. That’s one way that trontinemab has changed the game so far in clinical testing. “The data that Roche has released is compelling, not only to take less drug, but plaques are cleared much more quickly, much more robustly and the rate of ARIA is substantially diminished,” Violin said. Other companies want to join Roche in the brain-shuttle arena. AbbVie acquired Aliada for $1.4 billion in 2024. Novartis has launched a broad approach through pacts with SciNeuro , Sironax and BioArctic . The latter is also teaming with Bristol Myers Squibb and Eisai . Roche itself is doubling down on the blood-brain-barrier approach with Manifold Bio , among others. With the competitive pressure dialed up, Korsana is staying relatively quiet on development plans, including which stage of Alzheimer’s progression it intends to attack and what type of treatment course it’s eyeing. Leqembi is meant to be taken chronically, while Lilly’s Kisunla is supposed to be stopped after amyloid plaques sink to a certain level. The best data so far are in mild cognitive impairment, but some analyses suggest that “earlier intervention is better,” Violin said. “We’ll see some data readouts from companies like Lilly before we need to make decisions.” Kisunla is in a Phase 3 trial of patients with preclinical Alzheimer’s. Korsana’s existing funds will get the startup past its early clinical data readouts, Violin said. The company’s runway goes into 2028. With the padded reserves, Korsana can remain “opportunistic” on its next financing steps, Violin said. Other Paragon spinouts made quick leaps onto public markets. Spyre Therapeutics , Oruka Therapeutics and Crescent Biopharma all announced reverse mergers at the time of their unveilings. (Violin was CEO of Crescent when it decided to jump onto the Nasdaq.) Another Paragon offshoot, Jade Biosciences , went the reverse merger route just a few months after disclosing its launch. Apogee Therapeutics took a traditional IPO path. All of those companies have done private placements or additional financings since going public.