Bepranemab

iStock, JHVEPhoto With an upfront payment of $50 million from Roche, the partnership will leverage Dyno Therapeutics’ in vivo gene therapy delivery technology, which synthesizes virus capsids with better functionality and manufacturability. Roche on Thursday inked its second research collaboration deal with Dyno Therapeutics to advance next-generation gene therapies for neurological diseases. Under the terms of the agreement, Roche will make an upfront payment of $50 million and pledge more than $1 billion in preclinical, clinical and commercial milestones, plus royalties on net sales of any product that arises from the partnership. Roche will gain even greater access to Dyno’s in vivo gene therapy delivery platform, which uses AI to optimally and rapidly synthesize adeno-associated virus (AAV) capsids. According to the biotech’s website , this approach can sidestep the common limitations of naturally occurring capsids—which existing gene therapies use—such as problems with existing immunity, payload size and manufacturability. Under the new agreement, Dyno will leverage its delivery technology and take charge of discovering novel AAV capsids with better functionality. Roche will be responsible for capsid validation studies and lead preclinical and clinical development, as well as commercialization activities. The partners have yet to specify what diseases they will prioritize, only revealing that they will go after neurological targets. Boris Zaïtra, Roche’s head of corporate business development, in a statement said that the company is “very pleased to take our partnership with Dyno Therapeutics to the next level.” Roche and Dyno first teamed in October 2020, when the biopharma put $1.8 billion on the line to use Dyno’s platform to develop AAV vectors for gene therapies targeting the liver or the central nervous system. “Our previous collaboration with Dyno Therapeutics gives us great confidence to increase our investment in therapeutic gene delivery, to support our neurological disease portfolio,” Zaïtra said, noting that the new agreement on Thursday will allow Roche to develop novel therapies for “historically difficult-to-treat neurological diseases.” With the new Dyno deal, Roche looks to beef up its neuro pipeline just days after it backed out of an Alzheimer’s disease partnership with UCB, returning rights to the Phase IIa candidate bepranemab. Roche and UCB in July 2020 agreed to work on bepranemab together, with the biopharma paying $120 million upfront and pledging up to $2 billion in milestones. In January 2024, Roche also dumped two Alzheimer’s disease assets , handing them back to Swiss biotech AC Immune. The candidates were the anti-amyloid beta antibody crenezumab and the anti-tau antibody semorinemab. However, Roche’s neuro business has also made forward strides. In March 2024, the company unveiled promising Phase Ib/IIa data for the investigational antibody trontinemab, which it is developing for Alzheimer’s disease. Early data showed that trontinemab could substantially reduce mean amyloid levels in the brain. Last month, Roche also touted strong mid-stage data for its BTK inhibitor fenebrutinib, which the company at the time said resulted in a “near-complete suppression of disease activity” in patients with relapsing multiple sclerosis.

UCB will advance its anti-tau antibody for Alzheimer’s disease solo after Roche and Genentech walked away from the asset known as bepranemab. In 2020, Roche and Genentech spent $120 million upfront and committed up to $2 billion in milestones and royalties for exclusive rights to the candidate, a monoclonal antibody that targets the buildup of tau protein in the brain. On Tuesday, UCB said it regained global rights to bepranemab after the partnership ended. This is not the first time Roche and Genentech have opted out of the anti-tau space. In January, the companies ended a two-decade-long Alzheimer’s partnership with AC Immune after several lackluster readouts, leaving behind an asset targeting amyloid and another one targeting tau. Bepranemab is currently in Phase 2a, with topline data to be presented at the Clinical Trials on Alzheimer’s Disease annual meeting in Madrid later this month. The trial is testing the effects of two doses of bepranemab administered every four weeks versus placebo in people with prodromal or mild Alzheimer’s. Earlier this month, Leerink analysts said positive results for bepranemab could “incrementally de-risk” next-generation anti-tau antibodies. The buildup of tau in the brain creates “tangles” that are thought to trigger cell damage and inflammation in Alzheimer’s. Pharma companies such as Roche and Eli Lilly took an interest in targeting tau several years ago when drugs that zero in on amyloid beta were struggling in the clinic. But the tau approach has yielded mixed results. Lilly’s tau-targeting OGA inhibitor failed a Phase 2 study in August. Biogen’s antisense oligonucleotide asset designed to reduce tau showed hints of efficacy in an early-stage trial late last year. As for Roche, the deal termination comes as part of a broader strategy shift that focuses on cardiometabolic, oncology and neurology drugs. The company has notably made investments in next-generation weight loss approaches . Genentech is still into anti-tau modalities. In August, it spent $50 million in near-term licensing fees and milestones to work with Sangamo on an epigenetic repressor to prevent the production of the protein. Editor’s Note: This article has been updated to correct that Genentech spent $50 million on its deal with Sangamo. A previous version stated it spent $350 million upfront.