Virus vector

Otsuka, Shape ink potential $1.5B deal to develop eye AAV gene therapies

Published: Sep 08, 2023

By Tristan Manalac


Japan’s Otsuka Pharmaceuticals on Thursday announced a multi-target collaboration with RNA editing biotech Shape Therapeutics to develop intravitreal adeno-associated virus gene therapies for ocular diseases.

While the companies did not provide full details of the financial terms, they revealed that the contract has a potential aggregate value exceeding $1.5 billion, which includes an upfront payment from Otsuka. This sum also takes into account potential development, regulatory and sales milestone payments.

Seattle-based Shape will also remain eligible for tiered royalties on future sales of any product that results from this agreement.

In return, Otsuka will gain access to Shape’s AI-driven AAVid capsid discovery platform and transgene engineering technology. The Japanese pharma will also have the option to expand the agreement to additional targets and tissue types.

By combining high-throughput screening and machine learning, AAVid produces capsids with high target precision and minimal off-target biodistribution, according to the companies. This, in turn, they contend allows for lower gene therapy doses resulting in an overall safer clinical profile.

AAVid’s use of AI technology, in particular, allows the platform to design AAV vectors that overcome typical industry challenges regarding gene therapy delivery, enabling its therapies to “transcend the boundaries of what is possible experimentally,” Shape CEO Francois Vigneault said in a statement.

The partnership will also leverage Shape’s transgene engineering technology in order to optimize expression levels of the therapeutic payloads.

The deal presents a good opportunity to meld Shape’s vector expertise with Otsuka’s experience in ophthalmology and genetic payload design to “target specific disease cell types in the eye and provide a once-in-a-lifetime and curative administration with stable lifetime expression,” Toshiki Sudo, head of the Osaka Research Center for Drug Discovery at Otsuka, said in a statement.

With Thursday’s AAV agreement, Otsuka appears to be starting to build up its ophthalmology portfolio, particularly as its bedrock neurology business suffered back-to-back Phase III failures in July 2023. Data from the DIAMOND 1 and DIAMOND 2 studies showed that the company’s investigational TAAR1 agonist ulotaront, being developed in collaboration with Sumitomo Pharma, could not significantly outperform placebo in schizophrenia.

Otsuka reported another Phase III fail Thursday when a fixed-dose trial of its brexpiprazole—in combination with sertraline—failed to significantly improve symptom severity, as compared with placebo, in patients with post-traumatic stress disorder. Meanwhile, a similar study using flexible dosing met this primary endpoint.

Source: BioSpace