David Dimmock, MBBS, on Accelerating Therapy Discovery and Approval With AI

“The FDA has approved a drug based on 4 patients... So, we believe it is possible, even with very small patient populations to get drugs approved, but to get drugs approved, you need to do all the appropriate studies, which means you need to walk into the studies with a drug with a very high prior probability of success. So having the platform in place enables us to walk in with very high expectations that our drug is going to be safe.”

Creyon Bio has demonstrated proof-of-concept of its AI discovery platform to develop an antisense oligonucleotide (ASO) therapeutic in a case study of a single patient with a de novo heterozygous pathogenic variant causing a missense change in TNPO2. The AI model informed the target and the produced ASO knocked down an allele selective toxic Transportin-2 (TNPO2) protein. The patient was dosed within 1 year of initiating the project with up to 3 doses of up to 40 mg.

Investigators found that multiple doses of the ASO was well-tolerated in the treated child. The child has received 3 doses so far and investigators are anticipating the next dose, as between doses, clinical benefit would wear off and improvements would regress, demonstrating a need to redose with the ASO. After each dose, the child experienced a dramatic clinical benefit, with reductions in seizure frequency subsequent to the second dose and regained developmental milestones. The child also developed new skills following the third dose.

CGTLive® spoke with David Dimmock, MBBS, chief medical officer at Creyon, to learn more about the AI-guided platform and potential future applications of it. He also discussed future plans for the company and its ambitions for its ASO platform.

REFERENCE

Dimmock DP, Bird L, Bouck A, et al. AI Enabled ASO Design Can Lead to Rapid Initiation of Treatment for an Ultra-Rare Disorder Leading to Allele Selective Knockdown of a Toxic Protein and Consequent Clinical Improvement. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #309