DOYLESTOWN, PA — Antios Therapeutics, Inc. announced new data from the Phase 2a clinical trial of ATI-2173, its lead investigational proprietary drug candidate and the only Active Site Polymerase Inhibitor Nucleotide (ASPIN) in clinical development for HBV.
Antios also announced new data on its 4th generation capsid assembly modulator (CAM) program evaluating ATI-1428 and ATI-1645. In the 90-day Phase 2a trial, adult patients receiving ATI-2173 in combination with tenofovir disoproxil fumarate (TDF) showed slower virologic rebound than patients receiving TDF plus placebo after stopping treatment. Additionally, in a nonclinical study, low oral doses of ATI-1428 and ATI-1645 given once-daily blocked hepatic HBV replication and reduced both serum HBV DNA and RNA to undetectable levels. These data were presented at the European Association for the Study of the Liver’s International Liver Congress 2022 (EASL ILC 2022).
Highlights from the EASL Oral Presentation on ATI-2173
- In the 90-day Phase 2a study, at 24 weeks off-treatment, 75% (n=16) of ATI-2173 plus TDF patients did not meet criteria to restart TDF treatment vs. 0% (n=4) in the TDF alone arm
- In the ATI-2173 plus TDF arms (n=16), alanine aminotransferase (ALT) levels normalized on-treatment and no patients receiving ATI-2173 plus TDF experienced ALT flares during the 24-week off-treatment follow-up period
- All patients completed 90 days of dosing with no serious adverse events or dose-limiting toxicities
“These data reinforce our belief that ATI-2173 can act as a bridge on the path to an HBV cure, with the potential to provide a meaningful clinical benefit to patients,” said Douglas Mayers, M.D., Chief Medical Officer, and Co-Founder of Antios. “The slower virological rebound, ALT normalization on-treatment and no off-treatment ALT flares among those on the ATI-2173 combination regimen highlight the promise of the ASPIN mechanism of action – which we believe can be complementary to all other approaches.”
Highlights from the EASL Oral Presentation on ATI-1428 and ATI-1645
- ATI-1428 and ATI-1645 are 4th generation class II CAMs with a novel and unique ultra-potent mechanism of action designed to provide for a more targeted and beneficial antiviral response with an improved clinical safety profile due to the lack of HBV capsid accumulation in liver cells
- ATI-1428 and ATI-1645 have displayed strong nonclinical antiviral activity in a mouse model against the various HBV genotypes and low EC50 shift against naturally occurring variants associated with resistance to past and current CAMs
- In in vivo mouse experiments, ATI-1428 or ATI-1645 blocked HBV replication in the liver of immunocompetent HBV-replicating mice and prevented unnecessary T-cell mediated liver damage through non-accumulation/degradation of empty capsids in the hepatocyte
- Both compounds show safe and potent in vitro and in vivo activity and excellent pharmacokinetic profiles
“The nonclinical data supports our view that clinical development of 4th generation CAM compounds has the potential to provide a safe and effective approach for treating HBV,” said Luca Guidotti, M.D., Ph.D., Deputy Scientific Director of San Raffaele Hospital and Scientific Advisor to Antios. “By preventing the abnormal capsid accumulation that less potent CAMs induce, these ultra-potent CAMs are designed to not sensitize hepatocytes to unnecessary T cell-mediated killing. This may allow the development of safe and effective combinations with therapeutic strategies aimed at immune reactivation.”
These presentations can be found on the Antios website at https://www.antiostherapeutics.com/scientific-approach/publications-presentations/.
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