Oxford-based pharmatech company Exscientia has announced that its third clinical molecule created using artificial intelligence (AI) is set to enter Phase I clinical trials.
DSP-0038 is a dual-targeted 5-HT1A agonist and 5-HT2A antagonist and will be assessed for the treatment of Alzheimer’s disease psychosis.
The candidate is the second molecule to be developed in collaboration between Exscientia and Japanese firm Sumitomo Dainippon Pharma.
Through joint research, the two companies 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.
Exscientia said selective dual targeting presents a significant hurdle for conventional drug discovery, especially in the case of psychiatric indications that require “exceptional selectivity to avoid off-target effects”.
“The successful design of DSP-0038 demonstrates opportunities to design selective molecules with dual activity,” said the firm.
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The Phase I clinical study will take place in the US and will assess DSP-0038 for improved antipsychotic effects against Alzheimer’s disease psychosis, as well as improvements in behavioural and psychological symptoms of dementia including agitation, aggression, anxiety and depression.
“We have been impressed by the outstanding productivity of Exscientia’s AI technologies,” said Sumitomo Dainippon Pharma’s representative director, executive vice president and chief scientific officer Toru Kimura.
“The combination of Exscientia’s AI with our company’s deep experience in monoamine GPCR [G protein-coupled receptor] drug discovery has now led to two molecules reaching our clinical pipeline from this collaboration.”
Exscientia has been able to repeatedly demonstrate the ability of AI to transform how drugs are created. The firm’s next-generation AI-powered drug discovery platform has now discovered three drugs in total.
The two earlier compounds are DSP-1181, announced in 2020 alongside Sumitomo Dainippon Pharma to treat obsessive-compulsive disorder, and Exscientia’s immuno-oncology agent, EXS-21546, announced last month.
EXS-21546 marked the first AI-designed molecule for immuno-oncology to enter human clinical trials and was discovered in just eight months. DSP-1181 completed the exploratory research phase in less than 12 months which Exscientia said is just a fraction of the typical average of 4.5 years using conventional research techniques.
“This is further validation that our AI platform can turn complex biological challenges into high-quality clinical candidates quickly,” said Exscientia CEO Andrew Hopkins.
“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.”