Despite multiple ongoing programs in novel technologies such as cell and gene therapy, Astellas is trying to spend more energy on less risky modalities.
In the last few years, Astellas has invested heavily in novel technologies that are not necessarily the most successful or popular in the industry. With multiple programs now nearing proof-of-concept readouts, yet still “not happy about the pace” of development, Astellas is shifting its focus more to later-stage opportunities, chief strategy officer Adam Pearson said.In 2019, Astellas made big investments in cell and gene therapies with its back-to-back acquisitions of Audentes Therapeutics and Xyphos Biosciences. And last year, the company tacked on collaborations with lentiviral vector delivery specialist Kelonia Therapeutics, allogeneic CAR-T biotech Poseida Therapeutics—which was just bought by Roche—and genomic medicine expert Sangamo Therapeutics.But after a few separate setbacks and an industrywide pullback among large pharmas, Astellas’ cell and gene programs remain in the early stages.“We’re not happy about the pace,” Pearson said on the sidelines of the J.P. Morgan Healthcare Conference in January. “We’d like to go faster, but we have to learn. These are modalities where the learning is part of [the process].”Astellas expects initial clinical readouts for a couple of candidates built on cell and gene technologies in the near future. AT845, an AAV gene replacement therapy designed for Pompe disease, could report data within a year, Pearson said. ASP7317, a regenerative cell therapy for moderate-to-severe geographic atrophy patients, is also “very close” to proof-of-concept results. In cancer cell therapy, Astellas is exploring different technologies, but Pearson said it’s too early to know which ones might work out. For cell therapy, Astellas is focusing on solid tumors and regeneration of the back of the eye. For gene therapy, the Japanese pharma remains hopeful that it can eventually build a presence in neuromuscular disorders because these are the most amenable indications to genetic medicines, he added.“When we enter that market ourselves, it will be difficult to get everything right,” Pearson said. “But one thing we are trying to do is really study what our competitors do and what’s made a success of some of these products and what’s not. What’s helpful for us is that these products are no longer science fiction to doctors.”Despite multiple ongoing programs in cell and gene therapy, Astellas is trying to spend more energy on less risky modalities, the exec said.“We will shift our investment into more somewhat established modalities like bispecifics or immuno-stimulatory ADCs and targeted protein degradation,” Pearson said. “So probably the balance of our investment will be heavier in those areas which are a bit more derisked and where we understand how to make progress.”The company hopes to one day understand how ASP2138, a CLDN18.2xCD3 bispecific, could be different from the company’s newly FDA-approved monoclonal antibody Vyloy. In addition, forthcoming phase 1 data from ASP3082, which targets KRAS G12D mutations, will help Astellas see if its big bet on protein degradation is worthwhile. Astellas will soon have an efficacy readout from a multicohort phase 2 trial for the Pfizer-partnered ADC Padcev to help guide future development of the star drug after its groundbreaking success in bladder cancer.Although antibody-drug conjugates (ADCs) have attracted industry-wide interest and Astellas is one of the few players with a major product in the hot field, Pearson said the modality is not at the moment the focus of the company’s internal pipeline beyond Padcev.Still, if “there was the right, in late-stage, in-licensing opportunity that fitted,” the company might pursue it, Pearson said.That “late-stage” comment reflects a high-level strategy shift at Astellas as it conducts a pipeline review, which led to the recent discontinuation of an early CAR-T prospect aimed at CD20 B-cell lymphomas.“We will continue to go through a prioritization exercise where we will generally shift our resources to focus on slightly later-stage opportunities, whether they be still phase 2 at the moment or life-cycle management, and maybe have room for an in-licensed product to add to that, whilst maintaining kind of a vital level of research in the core areas,” Pearson said.Astellas’ primary focus areas are genetic regulation mostly in neuromuscular diseases, immuno-oncology, blindness and regeneration, and targeted protein degradation. When it comes to acquisitions or licensing, Astellas generally follows those more confined boundaries, even though it doesn’t rule out other opportunities, according to Pearson. The company did branch out recently into women’s health with its hot flash drug Veozah. However, shortly after the drug’s launch, Astellas lowered its peak sales expectations by half to a range of 150 billion Japanese yen to 250 billion Japanese yen ($1 billion to $1.6 billion).“We partly thought about Veozah as a one-off, exciting opportunity to bring a new class to treat an untreated population,” Pearson explained.“We’ve learned a lot from this experience, and we’re really doubling down on the areas where we’ve got this pipeline and a deeper portfolio already,” he added.Veozah, Vyloy and Padcev, together with the geographic atrophy med Izervay and the FLT3 inhibitor Xospata, form the strategic brands in Astellas’ in-market portfolio.The company is undergoing a four-year cost-cutting initiative, which aims to eventually achieve between 120 billion Japanese yen and 150 billion Japanese yen ($800 million to $1 billion) in annual cost savings by the end of its fiscal year 2027 when Pfizer-partnered old prostate cancer drug Xtandi is expected to lose market exclusivity in the U.S.
