Akeso Biopharma Co., Ltd.

David Epstein has retired three times. And he quickly went to work when he got back in the saddle earlier this fall as CEO and chair of Ottimo Pharma, a preclinical biotech trying to take a unique twist on one of the oncology field’s buzziest areas. About two weeks before Ottimo emerged from stealth in late October, Epstein and team started corralling investors for a Series A. Now, just two months after that initial sprint for capital, they’ve stapled together a hefty $140 million Series A co-led by OrbiMed, Avoro Capital and Samsara BioCapital. “I even had someone ping me yesterday still trying to get in, but obviously there’s no more room,” Epstein said in an interview with Endpoints News on Dec. 13. The cash infusion will likely take Ottimo through early 2027, the CEO said. Ottimo plans to file an IND for its bifunctional PD-1xVEGFR2 antibody in late 2025. The biotech will study the antibody, codenamed jankistomig, in about 250 to 300 solid tumor patients in a multi-pronged Phase 1/2a study, Epstein said. In addition to monotherapy, Ottimo will explore combinations with chemotherapies and antibody-drug conjugates. Epstein knows a lot about ADCs — another hot area in oncology — thanks to his leadership roles at pioneering company Seagen, which he led to a $43 billion exit to Pfizer last year. The PD-1xVEGF space has garnered outsized attention from clinicians, investors and pharma acquirers ever since Summit Therapeutics and partner Akeso said in May that their experimental medicine topped Merck’s megablockbuster Keytruda. In November, BioNTech bought out its China partner Biotheus, and a day later, Merck licensed a similar drug from Shanghai-based LaNova. “The bispecifics are going to expand the market. Places like triple negative breast cancer — where IO drugs are not really active, often not the standard of care — all of a sudden you have a drug that’s dramatically improving progression-free survival,” Epstein said, referring to data last week on BioNTech and Biotheus’ candidate BNT327. But Ottimo isn’t developing a bispecific. It’s focused on a bifunctional antibody, which Epstein said puts it in a different class than the “at least half a dozen ‘me toos'” in development behind Summit and Akeso’s ivonescimab. “Because of the way we bind,” Epstein said, “regardless of how high the VEGF levels are in the cancer patient, we’re going to continue to work, and that’s not necessarily the case for the other drugs. “We’re a bifunctional antibody, so either arm of our antibody can bind either PD1 or VEGFR2,” Epstein said. He said it could lead to more targeting of the tumor and less systemic toxicity: “We’re going to be first in class.” Ottimo’s molecule was developed by Jonny Finlay, who had the idea in 2019 and took it to European investment firm Medicxi to get the R&D ball rolling, Epstein said. “He designed a really, really good drug,” the CEO said. The biotech said it will explore both IV and under-the-skin formulations. Epstein said he doesn’t see any similar bifunctionals in development. But that could soon change. “They’re actually hard to do, but in today’s world, one of the things that’s changed is people make copies of things pretty darn quick, so I would not be shocked if at some point we see some other bifunctionals,” Epstein said. Joining Epstein on Ottimo’s board are OrbiMed’s Peter Thompson, Avoro’s Mark Chin and Samsara’s Srini Akkaraju. In addition to those three firms, Ottimo’s investor base also includes Medicxi, RTW Investments, Decheng Capital , Janus Henderson, JP Morgan Life Sciences Private Capital and Invus. Before Epstein retires for a fourth time, he might forge another M&A exit to pharma. Ottimo, with a completely virtual workforce in London and the US, will likely take jankistomig through those Phase 1/2a studies and then seek external help. “The right answer to have sufficient muscle to do multiple large Phase 3 trials in parallel around the world and then commercialize, would be with a pharma, either a partner or someone that acquires us,” he said.

David Epstein was ready to retire when an opportunity came along he couldnt pass up.Epstein had just sold Seagen, a large cancer drugmaker, to Pfizer for $43 billion and thought it a fitting capstone to a career that included stops at Novartis and Flagship Pioneering. Like others winding down work in the life sciences, Epstein intended to step back and advise up-and-coming drugmakers by joining their boards of directors.But then Epstein got a call from Francesco de Rubertis, a partner at the venture capital firm Medicxi. De Rubertis was building a company around a medicine with the potential, he believed, to unseat immune-boosting drugs like Merck & Co.s Keytruda that have revolutionized cancer care over the last decade. A similar medicine, from biotechs Summit Therapeutics and Akeso, beat Keytruda in a head-to-head Phase 3 trial earlier this year. De Rubertis convinced Epstein his startup had something even better.When you see a drug that has a possibility of transforming tens of thousands of lives, its a big deal, Epstein said. I said hey, I can do this. Lets have some fun.Epstein pushed off retirement and took the job. In late October, he became chair and CEO of De Rubertis startup, a small drugmaker based in London and Boston, and called Ottimo Pharma. He assembled an executive team and a group of high-powered investors to fund the drug that had caught de Rubertis eye. Led by OrbiMed, Avoro Capital and Samsara BioCapital, those investors put $140 million into a Series A round the company announced Thursday.Ottimo hopes to stand out in whats become an ultra-competitive area of oncology research. The company is developing a cancer drug that blocks two cellular pathways PD-1 and VEGF that are linked to tumors ability to grow and evade the immune system. It trails Summit and Akeso, as well as a handful of other biotechs with drug programs in or nearing human testing. Ottimo intends to ask regulators late next year to start its first trial.Summit and Akeso havent yet proven their medicine, ivonescimab, can help people live longer than Keytruda. The Phase 3 trial supporting its benefit also has important limitations. And its unclear whether PD-1 and VEGF-blocking medicines will clearly outperform drugs like Keytruda which target PD-1 alone against a similarly wide range of tumors. Several promising cancer immunotherapies have disappointed in advanced testing over the past decade.Epstein is convinced, though. In his view, PD-1 and VEGF medicines will supplant PD-1-only therapies, unlocking a market currently worth tens of billions of dollars. The new drugs, he argues, could expand that market even more if theyre able to treat tumors that other immunotherapies cant, or help people stay on therapy for longer.These drugs are going to work, he said. The question only is how big is the order of magnitude going to be, and across how many different tumor types?Epstein also claims Ottimos drug could stand out from its rivals. The company has designed a bifunctional antibody, meaning both of the antibody's “arms“ are able to interact with both of its targets. Summit and Akeso's antibody, by comparison, has separate arms aimed at each target.One of Ottimos targets, VEGF receptor 2, is also found preferentially around tumors. The result could be a drug that targets tumors more precisely and be administered at higher doses, Epstein said.Ottimo has a long ways to go to back up Epsteins confidence. The company intends to start treating patients in a clinical trial in late 2025 or early 2026, by which time Summit and Akeso could have data that allow them to seek a U.S. approval.Yet given the number of cancer types and potential drug combinations, Epstein argues there are many opportunities even for latecomers.This molecule is designed to be better, he said. Its our job to prove that.Gwendolyn Wu contributed reporting. '

Last month, BioNTech went all-in on VEGF bispecific antibodies. On Tuesday, to validate its bet, the company shared early survival data from a mid-stage trial in an aggressive form of breast cancer. The median overall survival was still immature at the October cut-off in the China-based Phase 1b/2 study . The trial tested BioNTech’s PD-L1xVEGF bispecific, dubbed BNT327, plus nab-paclitaxel chemotherapy in patients with first-line locally advanced or metastatic triple-negative breast cancer (TNBC). Just over 80% of subjects given the regimen were still alive at 12 months, according to results presented Tuesday at the San Antonio Breast Cancer Symposium. Although, the OS rate then dropped to 78.1% at 15 months and 69.7% at 18 months. The study enrolled 42 participants, 15 of whom died before matured survival rates were collected. VEGF bispecifics caught investors’ attention in September when Summit Therapeutics and Akeso’s candidate beat Merck’s Keytruda on the risk of progression or death in a China-based Phase 3 study in certain lung cancer patients. Despite Merck also inking a VEGF bispecific deal, its chief medical officer Eliav Barr cautioned the modality has yet to convincingly pan out on OS — an important endpoint for payers. BioNTech’s data on Tuesday showed the BNT327 regimen hit 13.5 months of median progression-free survival, marking a slight increase from the 13.3-month median PFS reported back in September. At the time, the drug also showed a 73.8% confirmed objective response rate in the Phase 1b/2 primary endpoint. One of the main questions is whether the positive early signal from China can be replicated in broader populations. The German drugmaker is enrolling for a separate Phase 2 study of BNT327 and chemotherapy in first- and second-line TNBC that includes sites in the US, UK and Australia. Back in China, BNT327 is also being evaluated for non-small cell lung cancer, where it produced a 57.8% confirmed ORR in a Phase 2 test in certain EGFR-mutant patients. BioNTech snapped up partner Biotheus and BNT327 for $800 million in cash and up to $150 million in milestones in November. Later that same week, Merck secured a global licensing deal with LaNova Medicines for its Phase 1 PD-1xVEGF candidate, dubbed LM-299. That agreement featured $588 million upfront .