With only burns to show in gene therapy, Astellas inks deal with AAV specialist Dyno in push for a better capsid

On the hunt for a better AAV capsid for gene therapy, Eric Kelsic’s Dyno Therapeutics has set itself apart with its focus on machine learning to help speed discovery. Now, Japanese drugmaker Astellas — fresh off a slate of gene therapy burns — is taking a bet on Dyno as it looks to the future.

Astellas and Dyno will work together as part of an R&D pact to develop next-gen AAV vectors for gene therapy using Dyno’s CapsidMap platform directed at skeletal and cardiac muscle, the companies said Wednesday. Under the terms of the deal, Dyno will design AAV capsids for gene therapy, while Astellas will be responsible for conducting preclinical, clinical and commercialization activities for gene therapy product candidates using the capsids.

Dyno will get $18 million upfront, and is eligible for potential downstream payments worth $235 million per product and $1.6 billion in total.

‘This was always a part of our long term strategy and we do realize that it’s essential to our long term goal — as we look across the landscape, Dyno stood out to us,’ SVP of gene therapy research and technical operations Mathew Pletcher said in a call with Endpoints News.

CapsidMap uses in vivo experimental data and machine learning to create new AAV capsids, which are the cell-targeting protein shells of viral vectors that are designed to optimize tissue targeting and immune-evading properties. CapsidMap can simultaneously deliver across multiple organs, Dyno says.

The company spun out of George Church’s lab three years ago, and this year raised $100 million in its Series A fundraising round. Its focus on machine learning, Dyno CEO Eric Kelsic says, sets it apart from others in the gene therapy space. With the product, comes a huge amount of data surrounding in vivo data, which is relevant for improving the performance of CapsidMap.

‘In the past, (companies have) taken a lottery ticket approach: buy a lot of tickets, and see what works, but chance of success is pretty low,’ Kelsic told Endpoints. ‘But now, we can learn a lot about the protein fitness landscape … and how do you use that to make a better capsid?’

The Dyno deal comes as Astellas looks to turn the page on its acquisition of gene therapy specialist Audentes in 2019, as its lead program has run into a series of serious safety issues in the clinic.

Less than a year after Astellas bought out Audentes for $3 billion, that program was roiled by a patient death in May 2020. Two additional patients in the study had died by August, leading to a modified trial for the drug, dubbed AT132. At the time, no patients taking the lower dose had developed any serious side effects. In September, Astellas announced a fourth boy had died in that trial.

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Stéphane Bancel, Moderna CEO

Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?