AviadoBio Ltd.

Astellas has ended work on a cell therapy that it was exploring for CD20-positive B cell lymphomas, the Japan-based pharma confirmed to Endpoints News on Wednesday. The pharma giant ended a Phase 1 of ASP2802 after a continual evaluation of its resources, a spokesperson said in an emailed statement to Endpoints. “As a result of our prioritization efforts, we have made the difficult decision to terminate ASP2802,” the spokesperson said. “Through this work, we made important progress and have acquired drug development knowledge in key scientific fields, which will serve us well in the future as we evaluate other disease areas.” Astellas was creating an autologous cell therapy, or a treatment derived from a patient’s own cells. Biopharmas are looking to expand the field’s scope with allogeneic approaches that use cells from donors in a bid to make them more scalable and limit manufacturing hurdles. The therapy also contained what Astellas calls a MicAbody, which comprises an antibody-ligand fusion protein. “Arming T cells with MicAbodies enables control of their activity, so in comparison with conventional CAR-T therapy, we believe ASP2802 may offer less long-term toxicity and a more prolonged response,” Astellas has said in previous presentations. The cell therapy was created using technology from its $665 million buyout of CAR-T platform company Xyphos Biosciences in December 2019 . The Astellas spokesperson said the company “remain[s] committed to the Xyphos technology.” “Combining this technology with our capabilities in cell therapy that we have been working on so far, we can create next-generation high-function cells and maximize the value of our technology,” Astellas’ then-CEO Kenji Yasukawa said at the time. Xyphos, which is a subsidiary of Astellas, was active on the dealmaking front last year. It inked an in vivo cell therapy cancer deal with Kelonia Therapeutics and an off-the-shelf cell therapy tie-up for solid tumors with Poseida Therapeutics. Roche is expected to complete its acquisition of Poseida on Wednesday. Astellas didn’t submit an offer as part of Poseida’s M&A process, Endpoints reported last month. Astellas’ cell therapy pipeline also includes ASP7317, which is being explored for the blinding condition geographic atrophy secondary to age-related macular degeneration. The drugmaker has placed an emphasis on the gene therapy side over the years. It has multiple programs in the works and collaborations with Kate Therapeutics , AviadoBio and, as of last month, Sangamo .

The idea is that Sangamo Therapeutics\' capsid could help Astellas better deliver its own genomic medicines for neurological diseases across the blood-brain barrier.\n Astellas is continuing to strengthen its neurological disease gene therapy capabilities, handing Sangamo Therapeutics $20 million upfront to help bypass the blood-brain barrier (BBB).The agreement grants the Japanese pharma the worldwide license to initially use Sangamo\'s proprietary neurotropic adeno-associated virus (AAV) capsid, dubbed STAC-BBB, for one target. The idea is that the capsid—which has shown potential to penetrate the notoriously tricky BBB in preclinical studies—could help Astellas better deliver its own genomic medicines for neurological diseases.Astellas has the option to expand the collaboration to cover another four neurological targets, subject to additional fees. If Astellas fully takes up this option, it could be in line to pay out up to $1.3 billion in milestone payments to Sangamo on top of tiered mid- to high-single-digit royalties on any marketed products.Tokyo-based Astellas formally launched its Astellas Gene Therapies unit in 2021. The past couple of years have seen the company license gene therapies from the likes of Kate Therapeutics and 4D Molecular Therapeutics while also taking $170 million hit on an unsuccessful Duchenne muscular dystrophy candidate from Audentes Therapeutics. The company paid the U.K.’s AviadoBio $50 million in upfront cash and equity investment in October for an AAV-based gene therapy in a phase 1/2 trial for dementia. At the time, Astellas’ chief strategy officer Adam Pearson put the deal in the context of the company’s attempts to expand its gene therapy pipeline “to help a broader range of people living with debilitating, neurodegenerative diseases.”In this morning’s release, Pearson explained that “delivering treatments to the brain and central nervous system remains a highly complex challenge in the field of gene therapy.”“We believe that technologies such as Sangamo\'s STAC-BBB capsid could prove critical in helping us deliver effective transformational treatments to patients suffering from serious genetic neurological conditions,” Pearson added.The deal is another win for Sangamo this year after a tough 2023 that saw the gene-based therapy biotech lose partnerships with both Biogen and Novartis as well as lay off staff. This year has seen the company’s fortunes turn around, as Sangamo has secured a pact with Roche’s Genentech unit and an accelerated approval pathway for its Fabry disease candidate in the last five months.“We strongly believe in the potential of STAC-BBB, our industry-leading, intravenously delivered AAV capsid, to overcome the challenges associated with delivering therapies to the central nervous system,” Sangamo CEO Sandy Macrae, Ph.D., said in this morning’s release. “This agreement underscores the continued industry interest in our STAC-BBB capsid and reinforces our ongoing commitment to partnering with collaborators who understand its unique potential.”

Astellas Pharma and AviadoBio have entered into an exclusive option and licence agreement worth over $2bn for an investigational dementia gene therapy. AviadoBio’s candidate, AVB-101, is currently in phase 1/2 development for patients with frontotemporal dementia (FTD) with progranulin mutations. Astellas will be given the option to receive a worldwide exclusive licence for the development and commercialisation rights to the asset in FTD with progranulin mutations and other potential indications. In exchange, Astellas will make a $20m equity investment in AviadoBio and up to $30m in upfront payments, with AviadoBio also eligible to receive up to $2.18bn in licence fees and milestone payments, plus royalties, if Astellas exercises its option. Accounting for less than one in 30 dementia cases, FTD is a form of early-onset dementia that typically leads to death within three to 13 years from diagnosis. Symptoms typically begin between the ages of 45 and 64 years, and patients commonly experience personality changes, uncharacteristic behaviours, loss of language, apathy and reduced mobility. AVB-101 is delivered as a one-time treatment using a minimally invasive procedure directly to the part of the brain called the thalamus, which has extensive connections throughout the brain, to restore progranulin levels in the frontal and temporal cortex. Astellas’ chief strategy officer, Adam Pearson, said: “We look forward to collaborating with the team at AviadoBio as we expand our gene therapy pipeline to help a broader range of people living with debilitating, neurodegenerative diseases. “AVB-101 represents a truly innovative approach to the treatment of FTD with progranulin mutations and has the potential to be part of the next generation of gene therapy products through the creation of this agreement.” Also commenting on the agreement, AviadoBio’s chief executive officer, Lisa Deschamps, said: “This strategic collaboration will combine our promising gene therapy candidate for FTD with progranulin mutations and delivery expertise with Astellas’ global capabilities in development and commercialisation of gene therapies. “Together, we can further accelerate delivering this investigational medicine to families around the world who so desperately need treatment options for FTD with progranulin mutations and other neurological diseases.”