Can this clinical trial move us closer to an Alzheimer’s treatment?

Exscientia has announced a Phase I clinical study of DSP-0038 in the US for the treatment of Alzheimer’s disease psychosis. DSP-0038 is the third molecule created using Exscientia’s Artificial Intelligence (AI) technologies to enter clinical trials.

The two earlier compounds are DSP-1181, announced in 2020 together with Sumitomo Dainippon Pharma to treat obsessive-compulsive disorder, and Exscientia’s immuno-oncology agent, EXS-21546, announced in early 2021. Joint research between Exscientia and Sumitomo Dainippon Pharma designed DSP-0038 to be a single small molecule that exhibits high potency as an antagonist for the 5-HT2A receptor and agonist for the 5-HT1A receptor, whilst selectively avoiding similar receptors and unwanted targets, such as the dopamine D2 receptor.

Selective dual targeting is a major challenge for conventional drug discovery, and psychiatric indications also require exceptional selectivity to avoid off-target effects. The successful design of DSP-0038 demonstrates opportunities to design selective molecules with dual activity. DSP-0038 will be assessed for improved antipsychotic effects associated with Alzheimer’s disease psychosis, as well as improvements in behavioural and psychological symptoms of dementia which include agitation, aggression, anxiety, and depression.

Toru Kimura, Representative Director, Executive Vice President and Chief Scientific Officer of Sumitomo Dainippon Pharma, said: “We have been impressed by the outstanding productivity of Exscientia’s AI technologies. The combination of Exscientia’s AI with our company’s deep experience in monoamine GPCR drug discovery has now led to two molecules reaching our clinical pipeline from this collaboration.”

Andrew Hopkins, CEO of Exscientia, said: “This is further validation that our AI platform can turn complex biological challenges into high-quality clinical candidates quickly. To have what we believe to be the world’s first three clinical molecules created using AI arising from our own platform – two with Sumitomo Dainippon Pharma – is a wonderful achievement. We hope that through the creation of DSP-0038 improved treatments for Alzheimer’s disease psychosis will be realised.”

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