mRNA-4157

Many biopharmas are doubling down on past wins to progress oncology treatments forward. Digital business cards. Gilead’s virtual reality ride. Soccer’s Champions League final. A motorcycle brigade. This year’s American Society of Clinical Oncology (ASCO) conference in Chicago marked a return to its pre-pandemic heyday. “I think that people finally are showing up like in the old days,” Eliav Barr, M.D., Merck & Co.’s senior vice president, head of global clinical development and chief medical officer, told Fierce Biotech on Sunday. “This is maybe a broader commentary on the limitations of virtual meetings. People are, at the end of the day, finding coming to the conference worth the expense of the time spent away from home.” While ASCO has returned to its former opulent glory, investors are still being frugal, companies told Fierce Biotech on the conference floor.  That's because by design, a good number of high-risk—and therefore high-reward—technologies will fail, Mural Oncology’s CEO Caroline Loew, Ph.D., said in an interview. And that’s not something a lot of industry players can afford right now. The current biotech market is different from what occurred during peak COVID-19 because investors will only put money in areas backed by late-stage or proven science, Loew explained. “Whereas several years ago, there was a lot of money in the market, money that went behind many things that were maybe not as robust or well validated as they could have been,” Loew explained. “So, it's not that there aren't investors there ... It's just that they are being much more discriminating and thoughtful.” According to Fierce Biotech’s Layoff Tracker, 90 layoff rounds have been reported by biopharmas this year to date. Many of those include culls at Big Pharmas such as Bayer, Novartis, Johnson & Johnson and Bristol Myers Squibb. Then there’s Takeda, which recently implemented a $900 million restructuring with more than 1,000 job cuts since the start of 2024. While the restructure is designed to make Takeda as lean as possible, oncology remains a main focus, Takeda's president of its Global Oncology Business Unit Teresa Bitetti said in an interview. The restructure zooms in on four key modalities: antibody-drug conjugates, small molecules, bispecifics and cell therapy. It’s a similar story at Pfizer, a Big Pharma that has also announced hundreds of layoffs this year, including reductions and role changes at recently acquired Seagen sites. The company has prioritized three modalities after the $43 billion Seagen buyout: ADCs, small molecules and bispecific antibodies. The strategy is to leverage strengths from ADC-focused Seagen and Pfizer’s medicinal chemistry and bispecifics expertise, Megan O'Meara, M.D., Pfizer’s senior vice president and head of early development for oncology, said.     The combined companies embody “the nimble mindset of a biotech and the resources of a large pharma,” O'Meara said. “We really want to focus on the things that we already have the infrastructure to do really well.” “We've intentionally avoided more niche areas of therapeutic modality for now, such as cellular therapies or radioligands,” O'Meara said.  “Let me put it this way: We’re not actively pursuing radioligands or autologous cell therapy,” Takeda’s Bitetti said in a separate interview. “But I would never say ‘no.’” Astellas CMO Tadaaki Taniguchi, M.D., Ph.D., cited both cost and complications, such as short half-lives and complex chemistry, manufacturing and controls protocols, as reasons not to pursue radioligands. “For us, we’re seeking more the ADC, hybrid approach, or thinking about bispecifics and target-based drug discovery,” Taniguchi said.   The tried and true methods   Part of Pfizer’s research strategy is improving upon past wins, the company’s O’Meara said. “So, taking the learnings from a certain target, and then going back and reverse translating it to make it better for the next generation,” O’Meara explained. At ASCO, Pfizer unveiled phase 3 data on Takeda-partnered Adcetris, an approved ADC from Seagen for Hodgkin lymphoma and other conditions. The new data came from a combination study of the ADC with chemotherapy for patients with newly diagnosed stage 2b/3/4 classical Hodgkin lymphoma and hit both of the trial’s endpoints, demonstrating significantly improved safety and noninferior progression free survival. “We're committed to the medicines that we have, and we keep working to generate more data,” Takeda’s Bitetti said. “And it pays off.” Takeda keeps generating data for marketed products because it helps inform physicians in terms of best practices and can help find improvements in tolerability without undermining efficacy, according to Bitetti. “It’s not one and done for us,” P.K. Morrow, M.D., who joined Takeda as head of the oncology therapeutic area unit in February from CRISPR Therapeutics, told Fierce in a joint interview with Bitetti. “When we look at our therapies that are so beneficial in these disease states, our initial immediate thought is, how can we help more patients outside of just this limited area where we launch?” For Merck, combining new assets with already approved meds is an important strategy used to engineer new paradigms, according to Barr. Though Merck hasn’t recently undergone widespread layoffs like many other pharmas, the company’s patent for blockbuster Keytruda is set to expire in 2028. Before that happens, the company is working to build out a multimodality, diverse pipeline. “There has to be a multifaceted approach to address patients with broad categories of disease,” Barr said.“To try to find a completely new way of attacking the cancer is a more high-risk endeavor and one that's just a little more difficult. But if you can try to create synergies, or … learn why patients did or didn't respond for as long as you'd like to your therapy, then you have an opportunity to target therapies to different tumors.” One of these synergistic approaches is the Merck-Moderna cancer vaccine mRNA-4157 being studied in combination with anti-PD-1 Keytruda. During ASCO, the companies presented three-year data from a phase 2b trial for resected melanoma, finding that mRNA-4157 and Keytruda reduced the risk of recurrence or death by 49% compared to Keytruda by itself. “Cancer is an extraordinarily heterogeneous disease,” Barr said. “We need to be humbled to understand that we can't have a one-size-fits-all approach, or we can but there'll be some patients who don't respond.” For Jazz Pharmaceuticals’ global head of R&D Rob Iannone, M.D., change happens in small doses. The Jazz leader believes that smartly pairing novel drugs with other mechanisms and drugs can contribute to incremental, but important, progress. “A lot of our portfolio is around drugs that are combined,” Iannone said, citing chemotherapy and immunotherapy combinations with the company’s investigational drug zanidatamab, a HER2-targeted bispecific antibody. “I've been to the ASCOs where it's the first presentation of data in a totally new field. I can tell you about the standing ovations for certain new drugs, but I don't know if there'll be one of those at this ASCO,” Iannone said. “But I will say that the incremental progress is really important as well. Despite some of these major advances, patients are still dying from cancer when they could be cured.”