Pumis Biotechnology (Zhuhai) 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.

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 .

Duality Biologics and BioNTech say interim data on one of their partnered ADCs look encouraging, with a preliminary cut from the trial showing that nearly a third of treated patients had unconfirmed responses. In the 238 evaluable patients with at least one post-baseline tumor assessment, 32.4% had an unconfirmed overall response, and the disease control rate was 82.4%. Among the 73 patients with small-cell lung cancer, the unconfirmed ORR was 56.2% and the DCR was 89%. Notably, in patients with castration-resistant prostate cancer (CRPC), radiographic progression-free survival data are not yet mature, but data presented on Friday at ESMO Asia in Singapore show that a median rPFS reached 7.2 months, and the six-month rPFS rate was 94.7%. The Phase 1/2a basket trial is testing various doses of BNT324, also called DB-1311, in 277 heavily pretreated patients. Early positive data were also reported on patients with cervical cancer, hepatocellular carcinoma, head and neck squamous carcinoma, and melanoma. Roughly 61% of enrolled patients had undergone two or more lines of prior therapy. But more data need to be collected. The study’s primary endpoints are safety and objective response rate, so the responses will have to be confirmed. Secondary measures include duration of response, disease control rate and progression-free and overall survival. BNT324 is a topoisomerase I inhibitor-based conjugate targeting the transmembrane glycoprotein B7-H3. Several companies are investigating B7-H3 as a target, including Merck with ifinatamab deruxtecan. A trial of MacroGenics’ B7-H3-directed antibody in head and neck cancer was shuttered after several patient deaths. According to DualityBio, its candidate showed a “manageable” safety profile across all evaluated patients and tumor types in its early trial. The most common treatment-related side effects were nausea, decreased neutrophil count, anemia, decreased white blood cell count, decreased appetite and decreased platelet count. BNT324 has US fast track status for advanced/unresectable or metastatic CRPC and orphan drug designation for advanced or metastatic esophageal squamous cell carcinoma. It is one of three clinical-stage ADCs being developed by BioNTech and DualityBio under a partnership they set up in April 2023. They plan to test some of these ADCs in combination with a bispecific antibody targeting PD-L1 and VEGF-A, dubbed BNT327 or PM8002, in solid tumors. The bispecific is under joint development by BioNTech and Biotheus.