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Merck & Co – known as MSD outside the US and Canada – has acquired Yale University oncology spinout Modifi Biosciences in a deal worth $1.3bn. The agreement gives Merck access to preclinical compounds designed to exploit DNA repair defects in difficult-to-treat cancers, including glioblastomas. Modifi, formed in 2021, has developed a new class of small molecules that target cancer cells lacking expression of a key DNA repair protein called MGMT. Approximately half of all glioblastomas and up to 80% of gliomas lack MGMT, which Modifi says makes these cancers a “natural first target” for its approach. Emerging research has also indicated that this MGMT deficiency is seen in many other tumour types. Merck has acquired all outstanding shares of Modifi for $30m upfront, with Modifi shareholders eligible to receive potential milestone payments totalling up to $1.3bn. David Weinstock, vice president, discovery oncology, Merck Research Laboratories, said: “DNA repair defects are a frequent hallmark of tumour cells and a major cause of resistance to cancer therapy. The… Modifi Biosciences team has developed an innovative approach that we believe has potential for treating some of the most refractory cancer types.” Also commenting on the deal, Modifi’s co-founder, Ranjit Bindra, said: “In founding Modifi Biosciences, we sought to radically change the oncology treatment paradigm for cancer patients with glioblastoma and other tumours. “We are honoured to have Merck recognise the potential of our science, and as an oncology company, [it is] perfectly positioned to advance our innovations through clinical trials and commercialisation.” Merck has made a number of acquisitions this year. In July, it completed its previously announced acquisition of EyeBio in a deal worth $3bn, giving it access to a late-stage candidate for diabetic macular oedema and neovascular age-related macular degeneration, as well as a preclinical pipeline targeting retinal diseases. The company also announced in April that it had acquired University at Buffalo laboratory spinout Abceutics in a deal worth $208m to improve antibody-drug conjugates safety, and acquired immuno-oncology company Harpoon Therapeutics and its pipeline of T-cell engagers for approximately $680m in March.

Biotech investment firm Samsara BioCapital has added three new venture partners in recent months to expand its network, support first-time CEOs in its portfolio and guide more companies by way of board seats. One of the venture partners also has government policy experience, giving the California firm an in-house expert to advise on some of the biggest legislative forces in drug development today, including the Inflation Reduction Act and the ongoing Biosecure bill. The eight-year-old firm has added former Chinook Therapeutics CEO Eric Dobmeier, ex-Atreca CEO John Orwin and previous Alnylam public policy and government relations leader Alan Eisenberg. Samsara now has 14 venture partners, founder and managing partner Srini Akkaraju told Endpoints News in an interview. The team’s expansion comes as Samsara’s portfolio companies have hit some key milestones in recent months, including multiple megarounds, EyeBio’s up to $3 billion exit to Merck , OnKure’s reverse merger with Reneo Pharmaceuticals, IPO planning at Upstream Bio and a Nasdaq listing for Alumis . Akkaraju is quite familiar with Dobmeier and Orwin by way of Seagen. Akkaraju served on the antibody-drug conjugate pioneer’s board for 17 years until 2020, during which Orwin was also a board member. Dobmeier had risen to the role of chief operating officer at the Seattle biotech before departing to become an executive at Silverback Therapeutics and then Chinook, which he oversaw until its $3.2 billion exit to Novartis last year. The Samsara founder said biotech is innovating at a faster clip than ever before, and the deal flow far exceeds the levels he saw in the early days of his investing career two decades ago. That calls for experienced veterans to help guide nascent companies. “The reality is the science and the innovation and the ideas, there’s more of them than experienced CEOs to run these [biotechs],” Akkaraju said. “But everybody has to be a first-time something, and first-time CEOs are always going to be there, and they’re an important part of our ecosystem. I personally think people like Eric and John are phenomenal to help these first-time CEOs do their job as well as they possibly can and grow a little bit faster into it.” Orwin was already chair of Samsara portfolio company Cargo Therapeutics. He’s also on the boards of Travere Therapeutics, AnaptysBio and Nested Therapeutics. Meanwhile, Eisenberg had spent about a decade at the Biotechnology Innovation Organization before working on government relations for Celgene and then Alnylam. “We’ve all been talking about Biosecure, we’ve been talking about the IRA for the last couple of years and the impact that will have and changes to Medicare Part D, etc. We read about it, we see it, and we talk to people about it. We get a little bit of, I’d say, a rudimentary understanding,” Akkaraju said. “Then, Alan’s come in and provided us a much greater level of understanding of this.” Investors could rely on outside experts and call them up when they need counsel on matters related to government policy, IRA implications and the like. But Akkaraju said he’d “rather have that person at the table all the time.” Akkaraju noted the trio of new team members — who are part-time — is not a sign that Samsara will ramp up the number of investments it makes. “It certainly has an impact on deal flow because all of these guys have great networks out there that will bring in opportunities,” Akkaraju said, but “it’s all about doing as good of a job as we possibly can in making a decision to do a deal and managing the investment and working with the portfolio company.”

BARCELONA — In the span of 30 minutes, 29-year Merck veteran Eliav Barr can analogize drug development dealmaking to Reese’s candy, call himself an “old fart” when asked about career plans, get real about the flood of ADCs and explain why subcutaneous forms of big medicines, like Keytruda, are “quite sexy” for patients. He also answers questions about the Summit Therapeutics data that everybody is talking about and lays out a vision for a bold claim: revolutionizing the treatment of small cell lung cancer. Endpoints News caught up with the Merck Research Laboratories chief medical officer on the sidelines of the annual European Society for Medical Oncology congress in Spain. Below are highlights from the interview. Subcutaneous Keytruda is on the horizon: In the days leading up to ESMO, Roche nabbed the first FDA approval for a subcutaneous PD-(L)1 inhibitor. It marked a key moment for patients, giving them an easier-to-use option for the immunotherapy class. Merck will play catch up and release KEYNOTE-D77 data on its under-the-skin version of Keytruda later this year or in early 2025, Barr said. The drugmaker expects “two flavors” of the subcutaneous version: dosing every three or six weeks. Going from an infusion to an under-the-skin delivery is “quite sexy” for patients because it’s a quicker treatment and can be done outside a cancer center, meaning patients don’t have to expose themselves to “all the bugs in the hospital” and the dreary associations that come with visiting a cancer facility, Barr said. Summit has ‘some unknowns yet’: It feels like everyone has been talking about the Keytruda-topping data from Summit Therapeutics and Akeso’s ivonescimab, a bispecific antibody targeting PD-1 and VEGF. But the data, from a study in China, will have to bear out in additional studies before the medicine can head to the FDA for approval. Barr said it will be a “race between efficacy and toxicity” given the history of side effects seen with VEGF inhibitors. “Can you create a molecule that provides the VEGF effect but doesn’t end up with toxicity that causes more harm than good,” he said. VEGF inhibitors can lead to hypertension among a long list of other toxicities . “If you look at the data that they’ve shown so far, they’ve shown some really exciting data, but where there’s somewhat less efficacy, you start to see that catch up with the toxicity, or at least what seems like it,” Barr said. More work needs to be done on ivonescimab. “But if it works, it’s going to be really important,” he added. Big plans in small cell lung: Merck is relatively new to the area of small cell lung cancer, which comprises about 10% to 15% of all lung cancers. But the company now has two big shots on goal for the disease in which patients have a much lower five-year survival rate than those with non-small cell lung cancer. As Merck partnered on Daiichi’s ADC candidate I-DXd, which is now in Phase 3 , another mechanism of action for small cell lung cancer caught the eyes of Barr. Data on Harpoon Therapeutics’ T cell engager in the same disease led him to think: “‘Chocolate? Peanut butter? Mmm, Reese’s.'” “So I told our business development [team], ‘Go fetch me that drug,’ and so we did,” Barr said. Merck paid $680 million earlier this year to acquire Harpoon. A few months later, Merck said Daiichi would help it develop the T cell engager. “Daiichi looked at the data and said, ‘Wow, that’s really cool,'” Barr said. “We said, ‘Well if you want to help us with that, that would be really good because then we’d both have the same stake in the two drugs so everyone is working toward the same goal.'” With the two drugs, Barr said he hopes “we can revolutionize small cell [lung cancer] therapy, hopefully, get it to where we have it in non-small cell lung cancer, where we started off with single-digit five-year survival and now it’s triple of that.” Further bets on T cell engagers: After Harpoon, Merck doubled down on T cell engagers with a $700 million upfront acquisition of a CD3 x CD19 bispecific antibody from Curon Biopharmaceuticals. It will investigate the medicine’s potential in lupus and other autoimmune diseases as well as cancer, Barr said. Research on CAR-T cell therapies in autoimmune diseases has propelled the field in recent quarters, but Barr said T cell engagers are “sure as hell more scalable.” A publication in the New England Journal of Medicine earlier this month also showed the potential of a BCMA-targeted T cell engager having “CAR-T like responses” in autoimmune patients, Barr said. “What is a real serendipity — I can’t say that I knew this, but I’ll take luck when I get it — Harpoon has a BCMA T cell engager,” Barr said. “Now we can do a bake-off between the two and see which one is going to be the best one for which kinds of patients.” ‘Keep going shopping’: Merck has made a few acquisitions this year and is “always looking,” Barr said. The company is looking across multiple therapeutic fields. It made a big return to ophthalmology with its up to $3 billion EyeBio purchase in May. The companies quickly moved into late-stage testing this month. “We keep looking. It has to be something that’s really different, transformational,” Barr said. “That’s why we went to T cell engagers. There’s a limit on how many ADCs you’re going to get at this point.” No plans to leave: Multiple medical and science executives have departed or announced plans to leave large pharmaceutical companies this year, including Pfizer, Sanofi, AbbVie, Gilead and others. But Barr doesn’t plan to leave behind Merck. “I’m happy. I’m an old man. I like where I sit,” Barr said, confirming he’s not going anywhere else. “I’d love to be able to say I’m young and moving on, but I’ve got a few more years to go.”