Antios Therapeutics' ATI-2173 Demonstrates Suppression of Hepatitis B Virus in Phase 2a Study; ATI-1428 and ATI-1645 Exhibit Potent Antiviral Activity in a Nonclinical Study

• New data presented in two separate oral presentations at the European Association for the Study of the Liver's International Liver Congress 2022 (EASL ILC 2022)
• Following 90 days of dosing, ATI-2173, in combination with tenofovir disoproxil fumarate (TDF), was generally well-tolerated with alanine aminotransferase (ALT) normalization and no ALT flares off-treatment
• Antios' capsid assembly modulators (CAMs) ATI-1428 and ATI-1645 show safe and potent in vitro and in vivo activity and excellent pharmacokinetic profiles

DOYLESTOWN, Pa., June 25, 2022 /PRNewswire/ -- Antios Therapeutics, Inc. (Antios), a clinical-stage biopharmaceutical company developing transformative treatments for hepatitis B virus (HBV), today 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).

• 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."

• 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/.  

ATI-2173, Antios Therapeutics' lead once-daily, oral drug candidate for treating HBV, is an investigational phosphoramidate prodrug of clevudine monophosphate. ATI-2173 has the potential, if approved, to be a bridge to a potential cure for HBV. It is the only Active Site Polymerase Inhibitor Nucleotide (ASPIN) for HBV in clinical development, and its mechanism of action is designed to be complementary to other approaches that also seek to achieve a functional cure.

ATI-1428 and ATI-1645 are 4th generation, class II capsid assembly modulators (CAMs) both with a novel and unique ultra-potent mechanism of action design that may provide for a safer and more productive interaction with the immune system. Derived from a novel chemical scaffold, these CAMs have shown strong in vitro and in vivo activity in a transgenic mouse model of HBV infection. As CAMs with an ultrapotent design preclinically inducing no abnormal accumulation of empty capsids based on an initial preclinical mouse study, ATI-1428 and ATI-1645 represent promising candidates for clinical development and have entered investigational new drug enabling development. ATI-1428 and ATI-1645 were acquired by Antios in November of 2021 from San Raffaele Hospital (OSR), Istituto Nazionale Genetica Molecolare (INGM), and IRBM/Promidis, a collaboration of Italian research institutes and a global contract research organization.

Hepatitis B is a potentially life-threatening liver infection caused by HBV. HBV can cause chronic infection, which leads to a higher risk of death from cirrhosis and liver cancer. Chronic HBV infection represents a significant unmet medical need. The World Health Organization estimates that up to 300 million people worldwide suffer from chronic HBV infection, while other estimates indicate that approximately two million people in the United States suffer from chronic HBV infection. Approximately 900,000 people die every year from complications related to chronic HBV infection despite the availability of effective vaccines and current treatment options.

Antios Therapeutics is a clinical-stage biopharmaceutical company focused on the development of innovative therapies to treat and cure viral diseases. Its lead drug candidate ATI-2173 – the only Active Site Polymerase Inhibitor Nucleotide (ASPIN) for HBV in clinical development – has the potential, if approved, to become a potential bridge to a cure for chronic HBV. Antios is also developing a novel series of 4th generation Class II capsid assembly modulators (CAMs) to further expand Antios' portfolio of differentiated molecules that could lead to a cure for HBV. HBV is a major unmet global health problem affecting up to 300 million people worldwide, more than hepatitis C and HIV combined. For more information, please visit www.antiostherapeutics.com.

SOURCE Antios Therapeutics