Roswell Park Comprehensive Cancer Center

US-based biopharma Inovio Pharmaceuticals and China-based Akeso, Inc. announced a clinical collaboration to evaluate a glioblastoma combination therapy pairing Inovio’s DNA medicine candidate INO-5412 with Akeso’s bispecific antibody cadonilimab. The collaboration will assess the combination in a Phase II adaptive platform trial in patients with glioblastoma multiforme (GBM), the most common and lethal primary brain malignancy in adults. Financial terms of the collaboration were not disclosed. The collaboration centers on two distinct immunotherapy assets contributed by each party. Inovio contributes INO-5412, a combination regimen comprising INO-5401, a DNA plasmid encoding three tumor-associated antigens (hTERT, WT1, and PSMA), and INO-9012, a DNA plasmid encoding the pro-inflammatory cytokine interleukin-12 (IL-12). Akeso contributes cadonilimab, also known as AK104, a PD-1/CTLA-4 bispecific antibody (BsAb) designed to achieve dual immune checkpoint blockade with a single molecule. The combination will be studied within the INSIGhT adaptive platform trial framework. Each company retains ownership of its respective drug candidate with no commercial rights involved in the deal. Scientific rationale for the glioblastoma combination regimen The pairing of INO-5412 with cadonilimab reflects a strategy to address GBM’s immunosuppressive tumor microenvironment from multiple angles. INO-5412 is designed to generate antigen-specific cytotoxic T lymphocyte responses against GBM cells expressing hTERT, WT1, and PSMA, while the IL-12 component encoded by INO-9012 is intended to amplify and sustain those responses by promoting a pro-inflammatory milieu at the tumor site. Cadonilimab’s simultaneous blockade of PD-1 and CTLA-4 is intended to release the brakes on T cell activity that the tumor microenvironment imposes through checkpoint-mediated suppression. The rationale for combining these modalities rests on the hypothesis that antigen-directed immune priming (via INO-5412) paired with checkpoint de-repression (via cadonilimab) could produce a more durable anti-tumor response than either approach alone. This is particularly relevant in GBM, where single-agent checkpoint inhibitors have so far failed to demonstrate survival benefits in randomized trials. Development status of participating molecules Inovio has been developing INO-5412 in GBM for several years, previously reporting interim and progression-free survival data from a Phase I/II trial of the combo regimen used in conjunction with cemiplimab (Regeneron’s PD-1 inhibitor) in newly diagnosed GBM patients at the ASCO Annual Meeting in 2022. The collaboration with Akeso marks a shift from a monospecific PD-1 antibody to bispecific targeting. The move to a dual-checkpoint agent reflects the broader oncology field’s interest in whether simultaneous PD-1 and CTLA-4 blockade can overcome resistance patterns observed with PD-1 monotherapy in GBM immunotherapy treatment settings. Cadonilimab has been developed primarily in China across multiple solid tumor indications, including cervical cancer, non-small cell lung cancer, hepatocellular carcinoma, gastric cancer, and esophageal cancer. The molecule’s Fc-null design is intended to reduce Fc-mediated effector functions that can contribute to immune-related adverse events, a persistent limitation of combining separate PD-1 and CTLA-4 antibodies. The GBM indication represents a new therapeutic frontier for cadonilimab. Akeso has not previously disclosed clinical activity for this asset in brain tumors. The blood-brain barrier and the immunologically privileged nature of the central nervous system present distinct pharmacological challenges that will need to be addressed in the trial design. Competitive landscape for GBM immunotherapy GBM remains one of the most treatment-resistant cancers. The standard of care has not changed materially in two decades and consists of maximal safe surgical resection followed by radiotherapy with concomitant and adjuvant temozolomide. Median survival is approximately 15 to 18 months, and nearly all patients experience recurrence. Several other immunotherapy approaches are in clinical testing for GBM. Immunomic Therapeutics is evaluating ITI-1001, a multi-antigen DNA vaccine, in a Phase I trialin newly diagnosed GBM. Roswell Park Cancer Institute has advanced SurVaxM, a survivin-targeting peptide vaccine, into Phase II testing. None of these programs have yet advanced to late-stage registration trials. In the checkpoint inhibitor space, nivolumab failed to demonstrate an overall survival benefit over bevacizumab in the CheckMate 143 trial in recurrent GBM, and pembrolizumab has shown limited single-agent activity in this indication. The combination of a tumor-antigen-directed vaccine with a bispecific checkpoint inhibitor, as proposed in the Inovio-Akeso collaboration, represents a mechanistically distinct approach that has not been tested previously in GBM.

摘要：Generate Biomedicines 登陆纳斯达克，拿下 2024 年来生物科技最大 IPO。这家靠 AI 造药的企业，顶着行业寒冬加急推进上市，募资超 4 亿美元全砸向临床研发，其 AI 设计的长效哮喘药成最大看点，也让市场重新看到 AI 制药的落地可能。 假期连轴转，抢跑上市窗口 今年 2 月，Generate 在纳斯达克敲钟，股票代码 GENB，每股定价 16 美元，2500 万股发完，直接募到 4 亿美元。这个数字，把本月刚上市的 Eikon 和年初的 Aktis 都甩在了后面，成了 2024 年至今最猛的生物科技 IPO。 其实这家公司的团队，去年感恩节就没歇着。节日里连轴加班，就为了赶在 2 月把上市流程走完。CEO 说，谁也说不准这个 IPO 窗口能开多久，赶上了就不能放。 说起来，生物科技的 IPO 市场冷了好几年。2025 年全年都没几家敢冲，直到下半年，XBI 生物科技指数突然涨了 35%，行业并购也多了起来，投资者的兴趣才慢慢回来。Generate 踩准了这个点，成了吃到红利的那一个。4 亿募资，全往药研里砸 拿到的 4 亿美元，Generate 早早就划好了去处。大头 3 亿，全给了一款哮喘药 GB-0895 的三期临床，这款药要在全球招 1600 个患者，规模不小。 剩下的钱也没闲着，1 亿继续做这款药针对慢阻肺的临床，7500 万用来优化 AI 制药平台，还有 1500 万，要把另外两款新药推到临床阶段。一款是帮抗癌药减毒的 GB-4362，一款是针对卵巢癌的 CAR-T 疗法 GB-5267，后者还是和罗斯韦尔公园癌症中心合作的。 坦白讲，这家公司对钱的算计很细。哪怕上市前账上还有 2.215 亿美元现金，CEO 还是说，后续会一直抠着花，钱要全砸在最有希望的药和 AI 平台上。AI 造的药，到底特别在哪？ Generate 最吸引投资者的，还是它的 AI 制药本事。核心产品 GB-0895 就是 AI 设计的，这款抗 TSLP 抗体，被 AI 优化了分子结构，半衰期直接拉到 89 天，半年打一针就行，比传统哮喘药方便太多。 一期临床数据里，这款药在轻中度哮喘患者身上表现还不错，打一针能把炎症指标压半年，安全性也没出大问题。这也是为什么公司敢把 3 亿募资全押在它的三期临床里。 其实 AI 制药不是新鲜事，但 Generate 算走得靠前的。它的平台能靠机器学习设计分子、优化药物，比传统试错法省时间。2022 年安进砸了 19 亿和它合作，2024 年诺华也跟它签了超 10 亿的协议，大厂的眼光，多少能说明点问题。行业回暖，AI 制药能站稳吗？ Generate 的上市，像是给冷了好几年的生物科技行业递了杯热饮。2025 年下半年开始，美股生物科技指数回暖，并购变多，投资者对 AI 制药的信心也在慢慢回来。 但话说回来，AI 制药的路还长。Generate 目前还在亏损，2025 年净亏 2.23 亿美元，能不能靠 AI 造的药实现盈利，还要看后续临床数据。这款半年打一针的哮喘药，能不能在三期临床里站稳，会不会成为 AI 制药的首个爆款，都是未知数。 某种程度上，Generate 的上市，不只是一家公司的事，更像是市场对 AI 制药的一次投票。投的是真金白银，赌的是 AI 能真正改变药物研发的效率。至于结果如何，只能等临床数据慢慢说话了。 参考来源：https://www.fiercebiotech.com/biotech/generate-scores-largest-biotech-ipo-2024-400m-nasdaq-listing 识别微信二维码，添加抗体圈小编，符合条件者即可加入 抗体微信群！ 请注明：姓名+研究方向！ 版 权 声 明 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不本站。

Generate:Biomedicines has earmarked $300 million of its IPO funds to complete a pair of phase 3 asthma trials for its anti-TSLP antibody GB-0895.\n Generate:Biomedicines is the latest biotech to benefit from a renewed appetite from investors for publicly listed drug developers.The Flagship Pioneering-founded company is selling 25 million shares at $16 apiece, in line with the biotech’s predictions earlier this week. It means Generate is on track for the largest biotech IPO since 2024, overshooting Eikon Therapeutics’ $381 million listing earlier this month or Aktis Oncology’s $318 million offering at the start of the year.Generate—which will list its stock on the Nasdaq this morning under the ticker “GENB”—has the opportunity to bank a further $60 million if underwriters take up their option to buy an additional 3.75 million shares at the same price.The company has already earmarked $300 million of the IPO funds to complete a pair of phase 3 asthma trials for its anti-TSLP antibody GB-0895, which are expected to enroll about 1,600 patients. The antibody has been engineered with the help of artificial intelligence to give it an extended half-life, with the aim of developing a long-acting therapy that only needs to be dosed every six months.Generate CEO Mike Nally told Fierce that the company’s AI-powered platform was a draw for investors.“If you think about this generative AI wave that is fueling the broader economy, one of the things that I think people are starting to recognize is that the greatest impact may actually be in drug discovery and development,” Nally said in an interview this morning.“As a company that’s been kind of at the forefront of that, we’re equally excited by that future,\" the CEO added. “And I think our investors were as well.”After a lull of biotech IPOs in 2025, Generate has joined a growing list of drug developers taking the leap to the public markets. CEOs of companies that had already made the move this year told Fierce they had detected a positive change in sentiment toward biotech IPOs in recent months.Nally agreed that it had been a “pretty dark winter for biotech over the last few years in terms of the IPO market.”He attributed a “really nice rise” in the XBI biotech index in the later months of 2025, combined with a “wave of mergers and acquisitions,” as fueling a renewed interest from investors in the sector.But without a “great degree of certainty on how long the [IPO] window will be open,” Generate didn’t want to waste the opportunity. Nally’s team had “worked feverishly over the Thanksgiving holiday” and throughout the festive period to ready an IPO for February, the CEO explained.Beyond the $300 million needed for its phase 3 studies, Generate has plenty of other ways to spend the IPO proceeds. They include $100 million to complete an ongoing phase 1b study of GB-0895 for chronic obstructive pulmonary disease and then to initiate the next phase of clinical development. Generate has also estimated that $75 million will be required to fund platform innovation and carry several programs through development candidate nomination and into investigational-new-drug-enabling activities.Generate’s two other publicly named drugs include GB-4362, a monoclonal antibody designed to neutralize free monomethyl auristatin E (MMAE) as an add-on therapy to antibody-drug conjugates with an MMAE payload. There’s also GB-5267, an armored, MUC16-directed CAR-T developed in partnership with the Roswell Park Comprehensive Cancer Center and initially being aimed at platinum-resistant ovarian cancer.The biotech has previously said that $15 million of the proceeds will be needed to take GB-4362 and GB-5267 into the clinic. Founded by Flagship in 2018 as a machine-learning-enabled drug discovery player under the leadership of Merck & Co. veteran Mike Nally, Generate has had no problem attracting either investor interest or Big Pharma backing. In 2022, Amgen inked an agreement worth up to $1.9 billion biobucks to develop five initial programs, leaving room for the potential to nominate up to five more programs later. Amgen has already taken up its option in part, with the pair currently working on six undisclosed programs together.Then, in 2024, Novartis inked a deal potentially worth more than $1 billion to develop protein therapeutics across multiple indications.The biotech brought in $370 million via a series B back in 2021 followed by $273 million in a series C in 2023. At the end of 2025, Generate still had $221.5 million in cash and marketable securities available and a deficit of $676.3 million, according to Monday\'s Securities and Exchange Commission filing. Despite an impressive IPO haul and plenty of cash in the bank, Nally told Fierce that the biotech would continue to be “very efficient with our capital.” That not only means prioritizing its most promising candidates but also maintaining “technology leadership in this generative AI wave of therapeutics.” Editor\'s note: This article was updated at 11 a.m. ET on Feb. 27 to include CEO commentary.