Steeling itself for undruggable challenges, Astellas inks $180M deal to bolster mitochondria R&D unit

Steeling itself for undruggable challenges, Astellas inks $180M deal to bolster mitochondria R&D unit

Astellas has ventured off the beaten path for its latest R&D deal, heading to Pittsburgh to partner with low-profile Generian on the discovery of small molecules against undruggable targets. The pact pairs Generian with Mitobridge, an Astellas unit focused on compounds that target mitochondrial function.

Tokyo-based Astellas bought Mitobridge for $225 million upfront in 2017, giving it control of a pipeline that now features a phase 2 acute kidney injury candidate and a phase 1 Duchenne muscular dystrophy prospect. Since inking the Mitobridge deal, Astellas has continued to add to its mitochondria capabilities, acquiring Nanna Therapeutics in 2020 and partnering with Minovia Therapeutics the following year.

Now, Astellas is giving Mitobridge some new toys to play with. The deal sees Astellas make an upfront payment of undisclosed size and commit to milestones that could top out above $180 million to partner with Generian on the identification of novel monovalent small molecules.

Astellas is hunting for small molecules that modulate target proteins through activation, stabilization or degradation, mechanisms that enable researchers to get at otherwise undruggable targets. The general concept has taken off in recent years, with companies such as Pfizer identifying protein degradation as a way to open up previously undruggable targets and betting big to enter the field.

At Generian, which quietly raised $13 million in 2019, researchers are using a high-throughput discovery platform to find small molecules capable of directly binding to targets and modulating protein stability, acting as molecular stabilizers or degraders. The types of targets on Generian’s hit list include E3 ligases, transcription factors and membrane receptors.

Internally, the biotech is advancing candidates against the transcription factor TFEB and protein kinase AMPK. In both cases, Generian is working on candidates to act as molecular stabilizers, although it also has an earlier-stage degrader program against an undisclosed target.

The deal caps off a busy month for the business development team at Astellas, which inked oncology deals with Sutro Biopharma and GO Therapeutics earlier in June. The flurry of activity comes as existing parts of Astellas’ pipeline struggle, with a clinical hold on a Pompe disease trial dealing another blow to its beleaguered gene therapy unit.

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