Paragon Therapeutics, Inc.

10月28日，总部位于英国的Ottimo Pharma走出隐形模式。 前Seagen公司的首席执行官David Epstein，在辉瑞以430亿美元收购Seagen后，现已加入一个新的生物技术公司Ottimo Pharma。 Ottimo Pharma还任命了前罗氏高管、现任BioMarin首席商务官James Sabry为副主席，以及勃林格殷格翰的资深人士Mehdi Shahidi为首席医学官。 Ottimo Pharma在过去三年中一直致力于Jankistomig的临床前开发，Jankistomig是一种双功能抗体，靶向PD1和VEGFR2，这两种受体参与帮助肿瘤生长和逃避免疫系统的分子途径。Ottimo Pharma一直在对该分子进行全面的临床前表征，并预计在2025年底提交IND。 10月29日，GlycoMimetics宣布已与Crescent Biopharma 公司达成收购协议。交易完成后，公司计划以Crescent Biopharma的名义运营，推进旨在治疗实体瘤的肿瘤疗法。Crescent Biopharma的主导项目CR-001是一款PD-1 x VEGF双特异性抗体。 Crescent是第五家利用 Paragon Therapeutics 发现和开发的资产上市的公司。Paragon此前孵化了Apogee Therapeutics、SPYRE THERAPEUTICS、ORUKA THERAPEUTICS和JADE BIOSCIENCES多个自免药物开发上市公司。 Crescent Biopharma 管线 Crescent Biopharma注与实体瘤药物的开发，目前管线中装入了三款药物: PD-1/VEGF双抗CR-001，另外两款为拓扑异构酶的ADC药物 CR-002 和 CR-003。 CR-001是一种四价PD-1 x VEGF双特异性抗体，其形式和药理学与康方生物的ivonescimab相匹配。与目前的市场领导者pembrolizumab相比，ivonescimib具有更优的疗效。该公司预计 CR-001 的 IND 将于 2025 年Q4或 2026 年Q1提交，患者的中期 1 期数据预计将于 2026 年下半年获得。 除了 CR-001，Crescent还在开发 CR-002 和 CR-003，它们是使用拓扑异构酶抑制剂有效载荷针对未公开靶点的抗体-药物偶联物 (ADC)；与具有替代有效载荷的 ADC 相比，具有拓扑异构酶抑制剂有效载荷的 ADC 显示出更高的疗效和安全性。CR-002 是 Crescent 的首个 ADC 项目，旨在成为同类最佳项目，预计将于 2026 年启动第 1 阶段；Crescent计划在项目进入临床阶段时披露 CR-002 的目标。 该交易预计将于 2025 年Q2完成。预计公司交割时的现金余额将为2027年的运营提供资金，包括推进公司的主要项目 CR-001，预计在 2026 年下半年通过对实体瘤患者的初步概念验证临床数据进行推进。 PD-1/VEGF潜力巨大。去年11月，BioNTech超10亿美元引进普米斯PD-L1/VEGF双抗，2024年9月，该双抗产品PM8002注射液的新药研究申请（IND）成功获得CDE的批准。目前，PM8002注射液已在国内针对TNBC、SCLC、非小细胞肺癌（NSCLC）等多个瘤种开展了多项临床试验研究，相关临床研究数据也陆续在重要的国际学术会议上发布，展示了其广阔的应用前景和潜在的巨大临床价值。超10亿美元，BioNTech引进普米斯PD-L1/VEGF双抗 今年5月，康方生物宣布，全球首创PD-1/VEGF双抗依沃西单抗头对头对比Keytruda一线治疗PD-L1阳性NSCLC的三期临床HARMOIN-2（HARMONi-2或AK112-303）达到无进展生存期（PFS）的主要研究终点，显示强阳性结果。里程碑! 国产PD-1/VEGF双抗，头对头击败K药！ PD-1/VEGF双抗的大获成功再次引起了人们的关注。今年8月，宜明昂科将旗下PD-L1xVEGF双特异性抗体IMM2510大中华区以外的开发和商业化权利以5000万美元首付+20亿美元里程碑付款授予Instil Bio。 由此可见，该领域的竞争激烈程度不言而喻。 End 声明：本公众号所有发文章(包括原创及转载文章)系出于传递更多信息之目的，且注明来源和作者。本公众号欢迎分享朋友圈或大群，谢绝媒体或机构未经授权以任何形式转载至其他平台。 转载/商务/投稿 | 联系微信15618157102（sum_Gmi） 商务合作 稿件征集 点击了解详情 往期回顾 1 8月 | 高达22家药企裁员 2 国产首款四价HPV疫苗拟纳入优先审评 3 3. 7亿美元!今年规模最大的生物医药融资诞生

Antibody maker Paragon Therapeutics has formed another company, this time in the bustling cancer space of PD-1xVEGF, and it will go straight onto the public markets. The new biotech, named Crescent Biopharma, will take the place of GlycoMimetics on the Nasdaq, the companies said Tuesday morning. GlycoMimetics has failed multiple mid- and late-stage trials in recent months, including one for acute myeloid leukemia . The PD-1xVEGF space has become quite popular in recent months thanks to Keytruda-beating data from Summit Therapeutics and its Chinese partner Akeso. Former Seagen CEO David Epstein also joined a preclinical biotech, named Ottimo Pharma , on Monday that hopes to get bought out after Phase 1 data. BioNTech is also in the race. Crescent’s program, codenamed CR-001, will have initial proof of concept data in the second half of 2026, the company said. It also has two antibody-drug conjugates, another en-vogue area for oncology R&D. “This transaction and financing enable a potentially rapid development path for CR-001, and for the antibody-drug conjugate programs CR-002 and CR-003,” Crescent interim CEO Jonathan Violin said in a statement. Violin is also a venture partner at Fairmount, which is one of the investors supporting a concurrent $200 million financing for the merger, which will keep the R&D engine humming “through 2027,” the company said. Paragon has formed multiple autoimmune-focused biotechs over the past two years. Apogee went public via a traditional IPO, whereas other startups from its universe have landed on the public markets by way of reverse mergers, including Oruka and Spyre . In August, Paragon debuted another offshoot, named Jade Biosciences , with just a chief scientific officer and $80 million. Crescent’s shareholders will own almost all of the combined company, at 96.9%. The deal is anticipated to close in the second quarter of 2025.

It’s hard for preclinical biotech companies to go public these days as investors look for human data that can reduce investment risk. Crescent Biopharma is more than a year away from the clinic, but joining the public markets now enables the biotech to capitalize on a recent groundbreaking cancer drug development still fresh in investors’ minds. Crescent is going public in a reverse merger with GlycoMimetics, the companies announced Tuesday. When the transaction is complete, the merged entity will operate under the Crescent Biopharma name. It will be led by Jonathan Violin, Crescent’s current CEO, who is expected to become interim CEO of the combined company. Crescent will also be capitalized with $200 million from agreements with a select group of investors that have pledged to purchase the combined company’s securities. Those purchases will happen immediately after the merger closes in the second quarter of 2025. Crescent’s lead program is CR-001, a bispecific antibody in development for cancer. Most companies trying to build an investment case talk about how their drugs are differentiated from rivals. Crescent’s executives are doing the opposite, touting similarities to another drug: Summit Therapeutics’ ivonescimab. Last month, that drug posted data showing it topped the blockbuster Merck immunotherapy Keytruda in a head-to-head Phase 3 test. In patients with advanced cases of non-small cell lung cancer, treatment with ivonescimab led to a 49% reduction in the risk of disease progression or death compared to treatment with Keytruda, Summit said. Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech Keytruda is an antibody designed to block a particular checkpoint protein, which in turn enables immune cells to recognize and go after cancer cells. Ivonescimab, discovered by Summit’s China-based partner Akeso, is a bispecific antibody that blocks two targets: PD-1, the same receptor targeted by Keytruda, and the cancer-driving protein VEGF. Crescent’s CR-001 is also a bispecific antibody designed to block both of those targets. Speaking during a Tuesday conference call, Violin said his company’s drug replicates the properties of ivonescimab. Like Summit’s drug, Crescent’s bispecific antibody works by cooperative binding, meaning it is most active in the presence of both VEGF and PD-1. “This enables the molecule to deliver benefits to patients that are more than the sum of its parts, and to do so safely,” Violin said. “This novel format enables VEGF to create ‘daisy chains’ of drug molecule, linking them together and increasing the potency for PD-1 blockade. This unique design also may enable localization of drug to the tumor microenvironment, which may help reduce systemic toxicity.” CR-001 is undergoing the preclinical research that could support an investigational new drug application, which is expected in the fourth quarter of next year or early 2026. Assuming the application is cleared, preliminary clinical data could come in the second half of 2026, Violin said. Because CR-001 replicates the properties of Summit’s drug, Crescent believes data from a few dozen patients can “connect the dots” back to data from hundreds of ivonescimab-treated patients. “We know the ivonescimab data has catalyzed massive interest in advancing next-generation checkpoint inhibitor therapy — the PD1/PDL1 class is currently a $50 billion market and growing, so when something beats the leader of such a large and important drug class, we expect competition,” Violin said. “We anticipate this will be similar to what we have seen recently in the obesity field — and we believe we have the advantage of strategic design. CR-001 was crafted specifically to thread the same immunotherapy needle as ivonescimab, putting us in a strong competitive position.” presented by Health IT Accelerating Claim Processing: Strategies to Shorten the Life of a Claim These strategies and practices can significantly shorten the life cycle of claims, leading to quicker resolutions and improved financial outcomes. By Greenway Health Competition includes BioNTech and Instil Bio, both of which struck alliances in the past year with China-based companies for rights to bispecific antibodies that target both PD-1 and VEGF. Both programs are in clinical development in China. Crescent is the fifth company to emerge from Paragon Therapeutics, a firm that conducts biotechnology research and forms new companies around that science. The first Paragon spinout was Apogee Therapeutics, which emerged in late 2022 with a lead drug candidate in development for atopic dermatitis. Last year, Apogee raised more than $300 million in a traditional IPO that came ahead of the start of Phase 1 testing. Crescent’s pipeline of drugs from Paragon includes two preclinical antibody drug conjugates, CR-002 and CR-003. The company isn’t disclosing much detail about either program, but Violin said CR-002 “targets a highly compelling pathway” and the drug offers “the chance to be first in class.” GlycoMimetics was focused on developing treatments for cancer and inflammatory diseases with small molecules that inhibit carbohydrate interactions on the surface of cells. In July, FDA told the company its lead drug candidate, uproleselan, a potential treatment for advanced cases of acute myeloid leukemia, needed an additional clinical trial. Subsequently, the company laid off staff announced it would explore strategic alternatives. Crescent said it intends to determine potential paths forward for uproleselan. The private investment in the newly merged Crescent will be led by Fairmount, Venrock Healthcare Capital Partners, BVF Partners, and an unnamed “large investment management firm.” Other participants include Paradigm BioCapital, RTW Investments, Blackstone Multi-Asset Investing, Frazier Life Sciences, Commodore Capital, Perceptive Advisers, Deep Track Capital, Boxer Capital Management, Soleus, Logos Capital, Driehaus Capital Management, Braidwell LP, and Wellington Management. When the business combination closes, Crescent’s stockholders will own about 96.9% of the company; GlycoMimetics stockholders will own about 3.1%. Crescent believes its capital will be sufficient to last into 2027. By then, Crescent and its peers should have more data demonstrating how their respective bispecific antibody cancer drugs are working in patients. Photo by Flickr user Lengyal Mark via a Creative Commons license