The Advanced Research Projects Agency for Health (ARPA-H), part of the U.S. Department of Health and Human Services (HHS), has announced a significant new initiative through its CATALYST (Computational ADME-Tox and Physiology Analysis for Safer Therapeutics) program. This groundbreaking effort will fund the development of human physiology-based computer models designed to more accurately predict the safety and efficacy profiles of Investigational New Drug (IND) candidates.

The current process of drug development is lengthy, costly, and fraught with inefficiencies. More than 90% of drug candidates fail to make it to the market, with nearly half of those failures stemming from inadequate efficacy—often due to incorrect dosing or poor distribution to target areas in the body. In addition, approximately a quarter of these failures are attributed to unanticipated safety issues that arise during clinical trials but go undetected during preclinical phases. Enhanced preclinical predictions could lead to reduced drug development costs and increased focus on orphan drugs.

“Imagine a future where we could accurately forecast drug safety and efficacy even before clinical trials start,” said ARPA-H Director Dr. Renee Wegrzyn. “CATALYST is an initial step toward that reality, as it strives to revolutionize drug safety testing, improve outcomes for rare diseases, and better represent under-served populations in clinical trials.”

The CATALYST program seeks to minimize reliance on traditional preclinical animal testing, which has often proven inadequate in predicting human outcomes. Instead, it envisions faster, more precise, and cost-effective in silico models—simulations grounded in human physiology. By engaging drug developers to bring these concepts into the real world, CATALYST could move from discovery to practical application within a few years.

"The current bottleneck in drug development lies in our inability to accurately predict clinical effects, with animal models proving inadequate for such predictions,” explained CATALYST Program Manager Dr. Andy Kilianski. “CATALYST will break through these bottlenecks by developing superior in silico models, which will not only expedite the creation of orphan drugs but also improve patient safety and reduce development costs."

To achieve its ambitious goals, CATALYST will invite proposals across three areas: deep learning and data discovery for drug safety models, tools for building living systems models and advanced in-silico models of human physiology. If successful, these innovations will significantly enhance preclinical and clinical drug safety assessments, creating a regulatory toolset for more reliable predictions.

In collaboration with the U.S. Food and Drug Administration’s Modernization Act, ARPA-H aims to align CATALYST's tools with regulatory standards, ensuring that computational models developed are ready for clinical trials. Ultimately, the program will facilitate the adoption of these advanced predictive models in regulatory filings, transforming the landscape of pharmaceutical drug development.

Multiple awards are expected under this new initiative, with resources contingent on the quality of proposals and available funding. More details, including proposal guidelines and information on Proposers’ Day, can be found on the CATALYST program page.