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Cancer is well represented in the Astellas Pharma portfolio and pipeline, but the drugmaker has made diversification a key part of its growth strategy. Newer products in its drug lineup include a vision-loss disorder drug and a first-in-class therapy for menopause symptoms. Cell and gene therapies are also a key part of Astellas’s growth strategy, building off of its 2020 acquisition of gene therapy developer Audentes Therapeutics. Within gene therapy, the Tokyo-based company is focused neuromuscular disorders, Chief Medical Officer Tadaaki Taniguci said in an interview last week during the annual J.P Morgan Healthcare Conference in San Francisco. “Our strategy in the past is more developing our capability,” Taniguci said. “We actually acquired Audentes, developing our capabilities toward gene therapy. But now we see that the more important thing for us is to really bring in clinical-phase assets to our pipeline.” Exclusive Improving the Healthcare Financial Experience to Help Care Flow Zelis CEO Amanda Eisel shares her perspective on how the company is solving the problems of a fragmented health financial system to benefit all. By Stephanie Baum The Astellas pipeline is split nearly 50/50 between internally developed drug candidates and assets from acquisitions or external collaborations. Audentes brought AT132, a gene therapy for the rare neuromuscular disease X-linked myotubular myopathy. This program has been beset by setbacks due to patient deaths in the trial. But Audentes also brought programs for two rare other rare disorders, Pompe disease, an inherited disorder that leads to muscle weakness, as well as Friedreich’s ataxia, which causes cardiomyopathy. Both programs are in early clinical development. Astellas is still expanding its gene therapy prospects through deals. Last October, the company paid AviadoBio $50 million for the option to license the biotech’s lead gene therapy, which is in early clinical development for frontotemporal dementia, a neurodegenerative disorder with no FDA-approved treatments. The deal structure is similar to a 2022 agreement that gave Astellas the option to license a Taysha Gene Therapies program for Rett syndrome, a disorder that leads to developmental problems. Phase 1/2 safety and efficacy data for this Rett therapy, TSHA-102, are expected in the first half of this year. Astellas remains willing to strike deals that give it new tools that expand its capabilities in gene therapy, Taniguci said. The company is already developing gene therapies delivered to their bodily destinations carried aboard adeno-associated viruses (AAV). These engineered viruses preferentially go to the liver. In 2021, Astellas began a research collaboration with Dyno Therapeutics focused on discovering novel capsids — the protein shells that envelop a genetic payload — for delivery to skeletal and cardiac muscle. Last month, Astellas began a partnership with Sangamo Therapeutics, securing the right to use one of that biotech’s proprietary capsids to penetrate the brain and reach neuronal targets, which Taniguci said fits with his company’s neuromuscular disease strategy. Penetrating the blood-brain barrier “is the one biggest challenge to overcome to target the [central nervous system],” he said. “So they help us to create much better access to the target organ. We see more platform development together with them to actually create the next generation of gene therapy.” Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech In oncology, the company’s top products are Xtandi, a small molecule drug for prostate cancer, and Padcev, an antibody drug conjugate for bladder cancer. A Phase 3 study is evaluating Padcev in combination with the Merck immunotherapy Keytruda as a treatment for muscle-invasive bladder cancer. Data are expected in Astellas’s next fiscal year, which starts on April 1. Additional clinical studies are testing Padcev in non-muscle-invasive bladder cancer and other solid tumors. Astellas is pursuing other approaches to cancer. Its in-house R&D has yielded ASP3082, the company’s lead targeted protein degrader drug for cancer. This drug candidate targets the cancer-driving protein KRAS G12D. At the European Society of Medical Oncology (ESMO) meeting last September, Astellas reported preliminary Phase 1 data showing anti-tumor activity in patients with pancreatic, colorectal, and non-small cell lung cancers. Taniguci noted the results indicate a dose-dependent degradation of the target protein. Astellas will need to show differentiation from other companies developing KRAS G12D-targeting drugs, such as Revolution Medicines and Bristol Myers Squibb, via the pharma giant’s acquisition of Mirati Therapeutics. But Astellas envisions potentially bringing its targeted protein degradation approach to multiple KRAS mutations. “This is a new technology that we started using for KRAS G12D, but we also have a pan-KRAS product coming to the clinic pretty soon,” Taniguci said. “We also started expanding more to other targets. We cannot disclose yet, but [there’s] a lot of excitement.” Astellas’s newest cancer drug is Vyloy, which in October became the first FDA-approved drug targeting claudin 18.2, a protein highly expressed in gastrointestinal cancers. This internally developed drug is a monoclonal antibody. The Astellas pipeline includes another program targeting claudin 18.2, but with a bispecific antibody. This program, ASP2138, is in Phase 1 testing. Women’s health is a newer piece of Astellas’s portfolio coming with the 2023 FDA approval of Veozah, a non-hormonal drug for treating vasomotor symptoms caused by menopause. The first-in-class therapy is a small molecule designed to block neurokinin 3, a receptor that plays a role in regulating body temperature. Last month, the FDA added a black box warning on the product’s label, flagging the risk of severe liver injury. Taniguci said liver toxicity is a known risk that was first observed in clinical trials. None of those cases were severe. In the market, the product has been used by about 100,000 patients. “Liver tox is relatively rare, but sometimes we see the severe cases,” Taniguci said. “That’s why I think it’s important to provide cautions for the patient and physician to use this important medicine. But of course we believe that the benefit/risk balance is really positive. So that’s why we still hear a lot of patients willing to use Veozah in treatment of [vasomotor symptoms].”

ArriVent Biopharma, a company that secures rights to drugs from emerging markets to develop them for Western markets, is adding to its pipeline with a Phase 1-ready drug candidate from China that has potential applications in gastrointestinal cancers. The company on Wednesday announced it paid $47 million up front to license MRG007, a drug developed by Lepu Biopharma, a Shanghai-based developer of cancer therapies. MRG007 is an antibody drug conjugate (ADC), a type of therapy made by linking a toxic drug payload to a targeting antibody. Lepu has not disclosed the target of the drug, nor has ArriVent. But ArriVent said that based on preclinical studies, it believes the Lepu ADC has best-in-class potential. presented by Sponsored Post 3D Medical Animation Services: A Revolution in Healthcare Education and Marketing 3D medical animation services have emerged as a groundbreaking tool in the healthcare industry, revolutionizing the way medical concepts are taught, understood, and marketed. By Start Grid It’s possible the drug class ArriVent is referring to is drugs that target claudin 18.2, a protein highly expressed in gastrointestinal cancers. Claudin 18.2, or CLDN18.2, is a top target for GI cancer drug research. This past October, Astellas Pharma’s Vyloy became the first FDA-approved CLDN18.2-targeting drug. Vyloy, a monoclonal antibody, is approved for use with chemotherapy to treat advanced cases of gastroesophageal junction adenocarcinoma, a rare type of GI cancer. The Japanese pharma company’s clinical development program for the drug also includes testing the drug in GEJ cancers with a checkpoint inhibitor and chemotherapy. A separate study is evaluating the drug in pancreatic adenocarcinoma. Other companies are pursuing CLDN18.2, but with ADCs. AstraZeneca’s AZD0901 is in Phase 3 testing in advanced gastric and GEJ cancers. Elevation Oncology’s ADC, EO-3021, is in early clinical development for advanced solid tumors, including GI cancers. Data are expected in the first half of this year. According to ArriVent, MRG007 has shown robust antitumor activity in preclinical models of GI cancers. The research also shows a favorable therapeutic index based on studies that could support an investigational new drug application. The company said it plans a submission for the first half of this year. The initial focus will be in colorectal and pancreatic cancers as well as other GI cancers. ArriVent’s most advanced program is firmonertinib (also known as furmonertinib), a brain-penetrating oral small molecule licensed from Shanghai-based Allist Pharma. This drug is already approved in China. ArriVent has advanced the drug to Phase 3 testing in non-small cell lung cancer driven by EGFR exon 20 insertion mutations. The ArriVent pipeline also includes two discovery-stage ADCs, one from Aarvik Therapeutics and the other from Jiangsu Alphamab Biopharmaceuticals. Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech The deal for the Lepu ADC comes nearly a year after ArriVent debuted on the Nasdaq with a $175 million IPO. ArriVent, which is based in Newtown Square, Pennsylvania, has rights to develop MRG007 for all indications outside of greater China, where Lepu retains rights. Lepu could receive up to $1.16 billion in milestone payments, plus royalties from sales of a commercialized product. “Expanding our pipeline with MRG007 furthers our mission to develop novel medicines for cancers with high unmet needs worldwide and accelerates our ADC portfolio by adding a program which plans to enter the clinic in the near-term,” Arrivent Chairman and CEO Bing Yao said in a prepared statement. “We look forward to collaborating with Lepu Biopharma in advancing this program globally.” Image: Getty Images