Atavistik Bio Announces Publication Describing Foundational Technology for its AMPS Platform

Atavistik Bio recently announced a new publication in the journal Science by Atavistik Bio co-founder Jared Rutter, PhD, describing the foundational technology upon which the company’s proprietary Atavistik Metabolite-Protein Screening (AMPS) platform is built.

Over millions of years, metabolites have evolved to be important regulators of protein function. They can activate, stabilize, or inhibit target proteins, often in an allosteric fashion, and can also dictate interactions across complex networks to influence diverse cellular processes. These highly conserved protein-metabolite interactions hold vast disease-relevant and therapeutically actionable information; however, they are frequently low affinity and have historically proven challenging to systematically discover.

The Science paper, titled Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase (Hicks et al), describes the development and ability of MIDAS to identify these interactions. Together with postdoctoral fellow, Kevin Hicks, PhD, Dr. Rutter, Distinguished Professor of Biochemistry and HHMI Investigator at the University of Utah, developed the MIDAS technology.

“We have long known that protein-metabolite interactions drive critical cellular processes and, therefore, could hold significant therapeutic potential. However, the tools to effectively and systematically identify or interrogate these interactions have been limited,” said Dr. Rutter. “We’re pleased to describe for the first time in this Science manuscript the ability of the MIDAS technology to systematically identify and characterize the complex network of protein-metabolite interactions and their regulatory significance. Unlocking how these interactions enable cellular homeostasis may help inform data-driven therapeutic approaches to address cellular dysregulation that drives a broad range of diseases.”

Marion Dorsch, PhD, President and Chief Scientific Officer at Atavistik Bio, added “It’s very exciting to share details of our foundational technology with the broader scientific community, as we believe it has the potential to revolutionize small molecule drug discovery. The powerful insights described in the Science paper present just an initial understanding of this technology’s ultimate potential. With our AMPS and structure-based drug design platforms, we have layered in powerful data analytics and AI to significantly augment the systematic, scalable application of this protein-metabolite screening technology to identify new allosteric binding sites and engineer highly specific novel small molecule modulators. We believe our approach will enable us to advance transformative therapeutics for patients across a broad range of diseases, starting with precision medicines for cancer and inborn errors of metabolism.”

In the Science publication, Drs. Rutter, Hicks and their colleagues’ analysis of 33 enzymes from human carbohydrate metabolism via MIDAS identified more than 800 protein-metabolite interactions, including known as well as many previously unknown interactions from diverse metabolic pathways. The researchers then functionally validated a subset of interactions, including the isoform-specific inhibition of lactate dehydrogenase (LDH) by long-chain (LC) acyl-coenzyme A (CoA), revealing a novel interpathway regulation between fatty acid and carbohydrate metabolism and pointing to new ways to identify isoform-selective inhibitors for LDH. These findings are one example of the numerous highly conserved protein-metabolite interactions that regularly enforce homeostasis throughout the body, which could, in turn, lead to therapeutic approaches to correct for disease-related dysregulation.

Atavistik Bio, located in Cambridge, MA, is pioneering a systematic, scalable approach to identify and harness highly conserved protein-metabolite interactions to revolutionize small molecule drug discovery. Combined, our AMPS and structure-based drug design platforms leverage advanced data analytics and AI to unlock functional allosteric binding sites and engineer novel, highly specific small molecule drugs to activate, inhibit or stabilize targets. Our breakthrough approach has the potential to deliver transformative medicines for patients across a broad range of diseases, with an initial internal development focus on precision medicines for cancer and inborn errors of metabolism. For more information, visit atavistikbio.com.