ATH-063 significantly increased the number of circulating regulatory T cells (Tregs) across all doses and demonstrated enrichment in six well-described genes related to induced Treg anti-inflammatory activities
No serious adverse effects or dose limiting toxicities were observed at any dose level, and ATH-063 demonstrated favorable pharmacokinetics (PK)
The data provides clinical verification for Athos' Proprietary AI2 (Artificial Intelligence for Autoimmune drug development) computational software platform which generated ATH-063
LOS ANGELES, CA / ACCESSWIRE / October 16, 2024 / Athos Therapeutics, Inc. ("Athos"), a clinical stage biotechnology company pioneering the development of precision small molecule therapeutics for patients with immune-mediated diseases, today announced topline results for the company's Phase 1 clinical trial of ATH-063, an investigational oral small molecule G9A inhibitor and the company's lead asset in development for the treatment of inflammatory bowel disease (IBD).
The clinical trial was a randomized, double-blind, placebo-controlled study in healthy volunteers designed to evaluate safety and PK as well as provide pharmacodynamic (PD) data to provide confirmation of ATH-063's proposed mechanism of action. The trial was conducted as sequential single ascending dose (SAD) (n=32) and multiple ascending dose (MAD) (n=32) arms, and a separate food-effect (FE) (n=12) arm. Four doses (25, 75, 150, and 250 mg) of ATH-063 were administered orally.
PD data showed ATH-063 selective expansion and activation of Tregs, consistent with predictions made by Athos' AI2 platform:
Statistically significant increases (p<0.001) in the number of blood Tregs were observed at all ATH-063 dose levels compared to placebo subjects, and demonstrated correlation between ATH-063 blood levels and number of Tregs
Blood ATH-063 concentration positively correlated with increase in multiple key biomarkers of Treg activity, including strong correlation with FOXP3 (p=0.003)
Induced Tregs demonstrated enrichment of six well-described genes related to Treg anti-inflammatory activities
STAT5A, a key signaling molecule related to induced Tregs, was activated in all cohorts and doses (p=0.0003)
PD data demonstrated correlation with key biomarkers of IBD disease activity, supporting further development of ATH-063 as a treatment for IBD:
Blood ATH-063 concentration correlated (p=0.012)with reduction of OSM, a well-established biomarker related to TNFA resistance
Blood ATH-063 concentration correlated with reduction of calprotectin monomers, which is an established biomarker for IBD
ATH-063 was well tolerated across all dose groups: No serious adverse effect or dose limiting toxicities were observed at any dose level
Robust PK results and dose proportional increases in blood levels: ATH-063 showed favorable PK results with dose-proportional increases in blood ATH-063 concentrations throughout the study
"The results of our first-in-human clinical trial of ATH-063 exceeded our high expectations," said Dimitrios Iliopoulos, PhD, MBA, Founder, President & CEO, Athos. "We used the Athos AI2 drug development platform to identify a previously unrecognized and novel therapeutic target, to create ATH-063, and to preclinically predict the compound's proposed mechanisms of action. We are delighted that these Phase 1 results serve as clinical verification for the predictions made by the Athos AI2 computational engine" added Dr. Iliopoulos.
"Our Phase 1 data showed that once daily, oral dosing of ATH-063 was well tolerated and showed expansion of Tregs," commented Allan Pantuck, MD, MS, FACS, Chairman, Founder & CMO. "We are excited to move to our next stage of clinical development in subjects with moderately to severely active ulcerative colitis. The rapid pace of the ATH-063 program, from initial target identification to a completed Phase 1 trial, was enabled by the use of our innovative approach to leveraging Artificial Intelligence for drug development."
About ATH-063
ATH-063 is a novel, investigational, AI-generated, oral, small molecule, G9A inhibitor in development for the treatment of inflammatory bowel disease and other autoimmune diseases. G9A is a central hub on a gene network that was identified by the Athos AI2 platform through the integration of multi-omic and longitudinal clinical data from Athos' IBD biorepository. ATH-063 is designed to directly target G9A enzymatic activity in human CD4 T cells and GI epithelial cells, acting both by suppressing pro-inflammatory responses through expansion and activation of regulatory T cells and inducing direct mucosal healing through regulation of tight junction proteins.
About Athos Therapeutics
Athos Therapeutics is a clinical stage biotechnology company seeking to develop potential first-in-class therapeutics that significantly impact the lives of patients with autoimmune disorders and chronic inflammatory diseases. The Athos drug development platform begins with over 25,000 high-quality patient samples sourced from premier global hospital systems. Athos' AI2 platform identifies novel drug targets by integrating multi-omic and longitudinal clinical datasets and matches them to its small molecule computational chemistry platform. The AI2 platform includes the Athos data lake, singular well-established omics workflows, and an integrative deep machine learning engine. The company's lead drug compound is ATH-063, an investigational, oral small molecule G9A inhibitor for inflammatory bowel disease. Athos is also developing a pipeline of additional small molecule approaches for various autoimmune diseases. Additional information about Athos Therapeutics can be found at https://athostx.com/
