PM-8002

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.