Alpine Immune Sciences, Inc.

▎Armstrong 近两年来MNC纷纷扫货自免产品，包括单抗、双抗、TCE、CAR-T等，这股热潮也蔓延至资本市场，一些历经波折的biotech有了逆风翻盘的机会。 Alpine Alpine Immune成立于2015年，早期核心管线为CD28/ICOS拮抗剂，但临床开发并不顺利，肿瘤管线同样推进不顺利。 最近几年，Alpine的核心管线才转为TACI-Fc融合蛋白Povetacicept，今年即将推进到三期临床。 Alpine Immune的市值长期徘徊在10亿美元左右，伴随着自免风口的到来，今年4月，Vertex以49亿美元收购Alpine。 TCE：Cullinan、同润生物、恩沐生物 TCE领域的B细胞靶向CD3双抗，原本主要用于血液瘤，在资本市场上关注度并不高。随着CD19 CAR-T在自免领域的开拓性探索，行业开始高度关注TCE在自免领域的潜力。Cullinan Oncology的核心管线CD3/CD19双抗，率先在今年4月宣布转战自免赛道，并很快完成2.8亿美元增发募资。同时，Cullinan Oncology将名字也直接改成了Cullinan Therapeutics。 同润生物的首发管线同样为CD3/CD19双抗CN201，同润生物在2018年完成1.5亿美元A轮融资，此后未再融过资。今年8月，默沙东以7亿美元引进同润生物的CN201。根据CN201今年ASCO会议上汇报了血液瘤的一期临床数据，其中5mg以上剂量对于FL/MCL/MZL/SLL的ORR达到100%。安全性方面，CRS发生率为7%，且均为1级或2级，同时没有神经毒性。 恩沐生物成立于2016年，首发管线CMG1A46为一款CD3/CD19/CD20三抗，如今推进到血液瘤一期临床阶段。 恩沐生物的融资并不算顺利，2021年A+轮融资后，与博锐生物做过一次授权合作，此后近三年无新的融资。 前不久，恩沐生物完成主流美元基金Foresite Capital的新一轮融资，并一起推动了昨日与葛兰素史克的授权合作，后者以3亿美元预付款+5.5亿美元的价格引进了CMG1A46的全球权益。 总结 虽然自免风口带来了新的机会，但也要看到真正实现逆风翻盘的，还是那些分子设计上具有显著差异化优势，并且经过初步临床验证的biotech。Alpine的Povetacicept亲和力远高于Vera的Atacicept和荣昌生物的泰它西普，并经过二期临床验证。同润生物的CN201安全性优势显著，且B细胞淋巴瘤疗效显著。恩沐生物的CMG1A46同时覆盖CD19、CD20两个经过验证的B细胞靶点，且为活性更强的2+1价态设计。 Armstrong技术全梳理系列 GPRC5D靶点全梳理； CD40靶点全梳理； CD47靶点全梳理； 补体靶向药物技术全梳理； 补体药物：眼科治疗的重要方向； Claudin 6靶点全梳理； Claudin 18.2靶点全梳理； 靶点冷暖，行业自知； 中国大分子新药研发格局； 被炮轰的“me too”； 佐剂百年史； 胰岛素百年传奇； CUSBEA：风雨四十载； 中国新药研发的焦虑； 中国生物医药企业的研发竞争； 中国双抗竞争格局； 中国ADC竞争格局； 中国双抗技术全梳理； 中国ADC技术全梳理； Ambrx技术全梳理； Vir Biotech技术全梳理； Immune-Onc技术全梳理； 亘喜生物技术全梳理； 康哲药业技术全梳理； 科济药业技术全梳理； 恺佧生物技术全梳理； 同宜医药技术全梳理； 百奥赛图技术全梳理； 腾盛博药技术全梳理； 创胜集团技术全梳理； 永泰生物技术全梳理； 中国抗体技术全梳理； 德琪医药技术全梳理； 德琪医药技术全梳理2.0； 和铂医药技术全梳理； 荣昌生物技术全梳理； 再鼎医药技术全梳理； 药明生物技术全梳理； 恒瑞医药技术全梳理； 豪森药业技术全梳理； 正大天晴技术全梳理； 吉凯基因技术全梳理； 基石药业技术全梳理； 百济神州技术全梳理； 百济神州技术全梳理第2版； 信达生物技术全梳理； 信达生物技术全梳理第2版； 中山康方技术全梳理； 复宏汉霖技术全梳理； 先声药业技术全梳理； 君实生物技术全梳理； 嘉和生物技术全梳理； 志道生物技术全梳理； 道尔生物技术全梳理； 尚健生物技术全梳理； 康宁杰瑞技术全梳理； 科望医药技术全梳理； 科望医药技术全梳理2.0； 岸迈生物技术全梳理； 礼进生物技术全梳理； 康桥资本技术全梳理； 余国良的抗体药布局； 荃信生物技术全梳理； 安源医药技术全梳理； 三生国健技术全梳理； 仁会生物技术全梳理； 乐普生物技术全梳理； 同润生物技术全梳理； 宜明昂科技术全梳理； 派格生物技术全梳理； 迈威生物技术全梳理； Momenta技术全梳理； NGM技术全梳理； 普米斯生物技术全梳理； 普米斯生物技术全梳理2.0； 三叶草生物技术全梳理； 贝达药业抗体药全梳理； 泽璟制药抗体药全梳理； 恒瑞医药抗体药全梳理； 齐鲁制药抗体药全梳理； 石药集团抗体药全梳理； 豪森药业抗体药全梳理； 华海药业抗体药全梳理； 科伦药业抗体药全梳理； 百奥泰技术全梳理； 凡恩世技术全梳理。

Otsuka Pharmaceutical’s 2018 purchase of Visterra seems to be paying off after its anti-APRIL antibody passed a registrational test in a rare kidney disease. The IgA nephropathy (IgAN) antibody, named sibeprenlimab, hit the trial’s primary endpoint by achieving a “statistically significant and clinically meaningful” reduction in 24-hour urine protein-to-creatine ratio versus placebo at nine months, according to a Tuesday release . The study enrolled 530 people with IgAN who were taking standard of care. Otsuka said it plans to review the interim data with the FDA with an eye to accelerated approval. Bank of America Securities analysts said sibeprenlimab could become a first-in-class biologic for IgAN with approval possible as soon as the second half of next year. The Phase 3 trial is ongoing and expected to end in 2026. The company is tracking the study’s secondary endpoints like change in kidney function over 24 months. The Japanese company added sibeprenlimab to its pipeline as part of its $430 million buyout of Visterra in 2018. The monoclonal antibody works by blocking APRIL, a cytokine that plays a key role in B cell dysregulation and the overproduction of galactose-deficient IgA1. The APRIL target has been at the heart of several major deals, including Vertex’s $4.9 billion acquisition of Alpine Immune Sciences and its dual BAFF/APRIL antagonist povetacicept, which is set to enter Phase 3 development this year. Last year, Novartis spent $3.2 billion on Chinook Therapeutics and its pipeline of kidney drugs, including anti-APRIL antibody zigakibart. Otsuka has projected its drug could reach more than 100 billion Japanese Yen ($663 million) in peak sales. The BofA analysts’ expectations were even higher at around 505 billion Japanese Yen ($3.3 billion) in 2035. Jefferies analysts said cross-trial comparisons suggest sibeprenlimab has best-in-class potential, as well as more convenient dosing. IgAN affects around 390,000 people in the US, EU and Japan, the analysts added. It is the leading cause of kidney disease in young people.

An experimental medicine Otsuka Pharmaceutical acquired in a buyout six years ago has succeeded in a Phase 3 trial in a rare kidney disease, the company said Tuesday.The drug, called sibeprenlimab, met its main goal in a study in IgA nephropathy, or IgAN, a chronic condition that can lead to kidney failure. Upon a pre-specified, interim analysis after nine months of treatment, the company said sibeprenlimab therapy was associated with a statistically significant and clinically meaningful reduction, versus placebo, in the amount of protein in participants urine a marker of kidney health.Otsuka didnt provide specifics, making the magnitude of the drugs effects unclear. It also said, without details, that the drugs safety profile was consistent with previously reported data. But the company intends to discuss with the Food and Drug Administration the possibility of an accelerated approval filing while the study continues. The trial is expected to wrap up in early 2026.For Otsuka, the results are a measure of validation for its bet on Visterra, a Waltham, Massachusetts-based biotechnology startup and sibeprenlimabs developer. Visterra was founded in 2008 around a type of antibody drug discovery technology that originated at MIT. The company initially used that technology to develop drugs for infectious diseases before broadening its therapeutic scope, and tried, unsuccessfully, to go public in 2017.Otsuka stepped in a year later and acquired the company for $430 million in upfront cash. Visterra has since operated as a wholly owned subsidiary of Otsuka and has still been run by its longtime CEO, Brian Pereira. The company now has a pipeline of drugs mostly for immune diseases and led by sibeprenlimab, which, following Tuesdays study results, could become the first treatment of its kind for IgAN.Some estimates hold that upwards of 130,000 people in the U.S. have IgAN, a progressive autoimmune condition that damages the kidneys. While several therapies are available, there remains room for improvement, as patients with the disease still see their kidney function decline.The need for better therapies, along with a growing understanding of the diseases underlying biology, has made IgAN a focus of an increasing number of drug companies. Since 2023, Novartis, Biogenand Vertex Pharmaceuticals have all acquired biotechs with IgAN drugs in testing. Travere Therapeutics and Calliditas Therapeutics have recently launched IgAN medicines. Others, including Q32 Bio and Vera Therapeutics, are advancing would-be therapies as well.These emerging medicines are more commonly aimed at immune-mediated drivers of the disease, analysts at the investment bank Piper Sandler wrote in a recent report. Sibeprenlimab targets a protein dubbed APRIL thats implicated in the progression of IgAN. The drug Vertex acquired in a buyout of Alpine Immune Sciences aims at APRIL and a second protein called BAFF. Felzartamab, which Biogen acquired in its acquisition of HI-Bio, blocks the protein CD38.Otsukas trial results suggest that by targeting APRIL, we could provide a new therapeutic strategy for people living with this progressive kidney disease,“ said John Kraus, the executive vice president and chief medical officer of Otsukas pharmaceutical development and commercialization division, in a statement. '