On February 2, 2023 Exscientia plc (Nasdaq: EXAI) reported that EXS4318 (‘4318) a compound precision designed by Exscientia and in-licensed by Bristol Myers Squibb in August 2021, has entered Phase 1 clinical trials in the United States (Press release, Exscientia, FEB 2, 2023, View Source [SID1234626804]). The compound is in development for immunology & inflammation (I&I) indications. Bristol Myers Squibb will oversee the clinical and commercial development and Exscientia is eligible for milestone payments and, if approved, tiered royalties on net product sales.
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"We are excited for Bristol Myers Squibb to begin clinical evaluation of ‘4318, the first Exscientia I&I candidate to enter the clinic. PKC theta is an attractive immune modulating drug target; however, it has been challenging for the field to design a small molecule with the required potency as well as selectivity against other closely related kinases," said David Hallett, Ph.D., Chief Scientific Officer at Exscientia. "Our expert-led AI design platform was able to deliver a balanced candidate which has demonstrated high on-target activity while maintaining high selectivity and favourable therapeutic index in IND-enabling studies. This is a significant milestone for Exscientia that illustrates the strength and flexibility of our precision design platform in efficiently developing high quality therapeutics."
Expert drug hunters using the Company’s AI generative design platform identified EXS4318 within 11 months after initiating design and was the 150th novel compound synthesised in this programme. The target product profile was particularly challenging due to the need for sustained, high levels of target inhibition to drive efficacy as well as the requirement for low daily dose in humans. PKC theta is structurally similar to several related kinases making it difficult to achieve the high levels of selectivity required to avoid off-target effects.
PKC theta, previously referred to as Kinase X by Exscientia, was one of the first small molecule programmes that formed part of the original Bristol Myers Squibb collaboration signed with Celgene in 2019. In May 2021, Bristol Myers Squibb and Exscientia expanded the collaboration in I&I and oncology, with increased economics for Exscientia. EXS4318 is the fourth drug candidate invented by Exscientia to enter the clinic.
About PKC theta
PKC theta plays a critical role in controlling T cell function and is a key driver of several highly prevalent autoimmune diseases. PKC theta inhibitors have potential in inflammatory and immunologic diseases.