Menten AI at APS 2023

July 1, 2023

APS 2023: Design of cyclic peptides with drug-like potency and in vivo efficacy using generative AI

Our Associate Director Protein Design, Dr. Stephan Kudlacek, represented Menten AI at the 28th American Peptide Symposium (APS 2023) this year and discussed how Menten AI developed the world’s most advanced generative AI platform for the design and optimization of macrocyclic peptide therapeutics. In his poster presentation, Dr. Kudlacek addressed Menten AI's platform and how it overcomes historical challenges in peptide therapeutics. The poster walked potential partners through Menten AI's platform applications including our target assessment, hit discovery, and computational optimization capabilities. Menten AI's novel approach to design membrane permeable cyclic peptide binders was also discussed in the context of hard-to-drug therapeutic targets.

Abstract

Cyclic peptides are a validated therapeutic modality in use for a variety of treatments. 46% of approved peptide drugs are cyclic, and more cyclic peptides are currently in clinical trials. Cyclic peptides can be engineered to overcome the historical challenges peptides have faced in drug development. These engineered cyclic peptides contain the favorable selectivity and high affinity of proteins, and the beneficial features of small molecules, including cell permeability and oral bioavailability. Menten AI is a drug design company which has developed a proprietary generative AI platform to design drug-like cyclic peptides for internal and external drug discovery programs against disease-relevant targets. Using our platform, we designed cyclic peptides with nanomolar in vitro potencies that demonstrate in vivo efficacy, without the need for experimental optimization. One peptide demonstrated functional in vitro inhibition but no initial in vivo efficacy. Following one round of in silico optimization, a derivative of this peptide was identified that displayed improved systemic exposure and in vivo efficacy. We also present the latest development of the platform to perform de novo cell-permeable cyclic peptide design.