HBV pol

DOYLESTOWN, Pa., June 8, 2022 /PRNewswire/ -- Antios Therapeutics, Inc. (Antios), a clinical-stage biopharmaceutical company developing innovative therapies to advance treatments that can provide a bridge to a cure for chronic hepatitis B virus (HBV), today announced the acceptance of oral presentations highlighting ATI-2173, Antios' lead therapeutic HBV candidate and the only Active Site Polymerase Inhibitor Nucleotide (ASPIN) for HBV in clinical development, and ATI-1428 and ATI-1645, candidates from Antios' 4th generation capsid assembly modulators (CAM) program. These presentations will be given at the European Association for the Study of the Liver's International Liver Congress 2022 (EASL ILC 2022), taking place June 22 – 26, 2022 at the ExCeL London Exhibition Centre in London, UK. Antios will be presenting the 90-day, Phase 2a study of ATI-2173 in combination with tenofovir disoproxil fumarate (TDF). This double-blind, randomized, placebo-controlled study of 20 adult patients was designed to assess the efficacy and safety of 25 and 50 mg doses of ATI-2173 daily for 90 days in combination with TDF compared with TDF plus placebo (control) in chronic HBV-infected subjects. The primary endpoints included the percentage of patients experiencing adverse reactions and time to HBV viral load relapse. In addition to adverse reactions, as a part of the primary safety endpoint, the safety evaluations recorded off-treatment ALT flares in all treatment groups. Antios will also present preclinical data from ATI-1428 and ATI-1645, which are in investigational new drug enabling development. These candidates are class II CAMs with a novel and unique ultra-potent mechanism of action design that may provide for a more targeted and beneficial antiviral response by the immune system. To date, data in a transgenic mouse model for both compounds provide initial evidence for potent in vitro and in vivo activity, an excellent pharmacokinetic profile, and no accumulation of empty capsids in the hepatocellular cytoplasm. "We see ATI-2173 as a bridge to a cure – an important first step in the ultimate search for a cure for HBV," said Greg Mayes, Chief Executive Officer of Antios. "To date, the data have been encouraging, indicating that combining ATI-2173 with a nucleoside analogue such as TDF in a simple, once-a-day regimen has the potential to completely shut down HBV polymerase activity and viral replication. We look forward to presenting our Phase 2a data, as well as the initial data from our CAM program, at the upcoming International Liver Congress." Antios Therapeutics EASL ILC 2022 Presentation Details: Title: Sustained 12-week off treatment antiviral efficacy of ATI-2173, a novel active site polymerase inhibitor nucleotide, combined with tenofovir disoproxil fumarate in chronic hepatitis B patients, a phase 2a clinical trial (#296) Author/Presenter: Douglas Mayers, M.D. Presentation Type: Oral Presentation Date/Time: June 25, 2022, at 9:15am BST Title: Novel ultra-potent capsid assembly modulators prevent abnormal accumulation of empty capsids and associated T-cell mediated liver injury in a mouse model of hepatitis B virus infection (#291) Author/Presenter: Luca Guidotti, M.D., Ph.D. Presentation Type: Oral Presentation Date/Time: June 25, 2022, at 5:30pm BST About ATI-2173 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. About ATI-1428 and ATI-1645 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 more targeted, productive antiviral response by 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 inducing no 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. About HBV 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. About Antios Therapeutics, Inc. 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 capsid assembly modulators (CAMs) to further expand Antios' portfolio of differentiated molecules in the HBV space. 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 . SOURCE Antios Therapeutics

Antios Therapeutics received a clinical hold on its Hepatitis B virus (HBV) combinatorial therapy from the U.S. Food and Drug Administration on Wednesday. Antios Therapeutics received a clinical hold on its Hepatitis B virus (HBV) combinatorial therapy from the U.S. Food and Drug Administration on Wednesday. The action has resulted in the termination of a collaboration agreement between Antios and Assembly Biosciences . Antios was in two collaborative deals for its therapeutic ATI-2173, an oral drug candidate for chronic HBV. In December 2021, Antios and Arbutus Biopharma announced that the first patient was dosed in a Phase IIa combination trial of ATI-2173 and AB-729, an RNA interference therapeutic. In October 2021, Antios and Assembly Biosciences entered into a clinical collaboration agreement to evaluate ATI-2173 and vebicorvir, an HBV core inhibitor, as a combinatorial treatment for chronic HBV infection. Now, Assembly has chosen to cut ties with Antios over the clinical hold. In a regulatory filing, Assembly stated that Antios notified the company of the clinical hold, which was established based on a safety report involving a patient who received a triple combination therapy and a nucleos(t)ide analog reverse transcriptase inhibitor. Antios CEO Greg Mayes told Fierce Biotech that the company does not believe the adverse event to be related to the therapy, but that the FDA has requested an independent cardiology review of the asset. It does not seem that the deal between Antios and Arbutus is off the table yet, though. The two companies are investigating a different combinatorial treatment than the one which was penned with Assembly. The trial is investigating ATI-2173, AB-729 and tenofovir disoproxil fumarate in patients with chronic HBV infection. However, the clinical trial is bound to face similar setbacks as ATI-2173 undergoes investigation. ATI-2173 is an investigational phosphoramidate prodrug of clevudine monophosphate. The drug works to curb HBV by inhibiting HBV polymerase, and Antios has stated previously that if the drug is approved, it could become the cornerstone of curative treatment for HBV. The mechanism of action behind ATI-2173 is designed to be complementary to other treatments seeking a curative approach to HBV, hence the collaborations. In studies of ATI-2173, a single oral dose demonstrated 82% hepatic extraction. In the Assembly and Antios collaborative trials, ATI-2173 was to be paired with vebicorvir, Assembly’s lead core inhibitor and tenofovir disoproxil fumarate. In Phase II clinical trials, vebicorvir administered with nucleos(t)ide analogue reverse transcriptase inhibitor (NrtI) therapy led to greater viral suppression of both HBV DNA and HBV pgRNA than NrtI therapy alone. Assembly is also in collaborative cahoots with Arbutus Biopharma, testing vebicorvir in combination with AB-729 for patients with chronic HBV infection. The two entered into a collaboration agreement in August 2020, and Assembly recently announced that it anticipates completing enrollment for its clinical trial with Arbutus in the first half of 2022. Assembly is also investigating core inhibitor ABI-H3733 for HBV in a stand-alone monotherapeutic trial. Chronic HBV infection remains an important target for innovative treatment. Although treatment with immune modulator drugs and antiviral drugs can slow down the risk of developing more serious liver disease, there is no complete cure for the condition which can cause cirrhosis, liver failure or liver cancer.

MENDHAM, N.J. and WARMINSTER, Pa., June 29, 2021 (GLOBE NEWSWIRE) -- Antios Therapeutics, Inc. and Arbutus Biopharma Corporation (Nasdaq: ABUS) today announced that the companies have entered into a clinical collaboration agreement to evaluate a triple combination of Arbutus’ proprietary GalNAc delivered RNAi therapeutic, AB-729, Antios’ proprietary active site polymerase inhibitor nucleotide (ASPIN), ATI-2173, and Viread (tenofovir disoproxil fumarate), for the treatment of subjects with chronic hepatitis B virus (HBV) infection. ATI-2173, AB-729 and Viread will be evaluated in combination in a single cohort in the ongoing Antios Phase 2a ANTT201 clinical trial. The multi-center, double-blinded, placebo-controlled, multiple-dose cohort will evaluate the safety, pharmacokinetics, immunogenicity, and antiviral activity of the combination of ATI-2173, AB-729 and Viread. This cohort is expected to initiate in the second half of 2021. Antios will be responsible for the costs of adding this single cohort to its ongoing clinical trial. Arbutus will be responsible for the manufacture and supply of AB-729. “This collaboration with Antios advances our efforts to position AB-729 as a potential cornerstone therapeutic in future HBV combination regimens and reflects our conviction that a combination of agents with complementary mechanisms of action is needed to cure chronic HBV,” stated William Collier, Chief Executive Officer at Arbutus.” Greg Mayes, Chief Executive Officer of Antios said, “ATI-2173 has, to date, demonstrated a well-tolerated safety profile and sustained on- and off-treatment antiviral responses as a monotherapy in patients with chronic HBV. We believe that its unique mechanism of action and early evidence of clinical activity may position ATI-2173 as the backbone of a once-daily curative regimen in combination with other agents for chronic HBV. Our collaboration with Arbutus will test that hypothesis in combination with AB-729, an RNAi drug candidate, and Viread, a nucleotide analogue.” About the Combination Clinical Trial Cohort The combination clinical trial cohort will include 10 subjects with chronic HBV infection assigned 8:2 to active drug (ATI-2173+AB-729) or matching placebos. The active drug (ATI-2173+AB-729) or placebo will be administered in combination with 300 mg of Viread (equivalent to 245 mg of tenofovir disoproxil fumarate). ATI-2173 and Viread will be administered once a day for 90 days. AB-729 will be administered by subcutaneous injection at Day 28 and Day 90. Following this 90 day treatment period, subjects will be followed-up for safety and sustained antiviral responses for 6 additional months. Any subjects whose HBV DNA remains below the limit of quantification (BLQ) at 6 months of follow-up will have HBV DNA and virology samples collected every 3 months off therapy until a detectable HBV DNA level is confirmed, or until 18 months after the 6 months of follow-up, whichever comes first. About AB-729 AB-729 is an RNA interference (RNAi) therapeutic targeted to hepatocytes using Arbutus’ novel covalently conjugated N-acetylgalactosamine (GalNAc) delivery technology that enables subcutaneous delivery. AB-729 inhibits viral replication and reduces all HBV antigens, including hepatitis B surface antigen in preclinical models. Reducing hepatitis B surface antigen is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus. Based upon clinical data generated thus far in an ongoing single- and multi-dose Phase 1a/1b clinical trial, AB-729 has demonstrated positive safety and tolerability data and meaningful reductions in hepatitis B surface antigen. About ATI-2173 ATI-2173 is a novel, orally-administered, liver-targeted Active Site Polymerase Inhibitor Nucleotide (ASPIN) molecule designed to deliver the 5’-monophosphate of clevudine to the liver. This L-nucleoside’s active 5’-triphosphate has unique antiviral properties as a non-competitive, non-chain terminating HBV polymerase inhibitor that distorts the active site of HBV polymerase resulting in potent HBV antiviral activity and extended off-treatment suppression of HBV DNA. ATI-2173 targets the liver, delivering high levels of the unique 5’- triphosphate while limiting systemic exposure to the parent L-nucleoside. ATI-2173 has the potential to become an integral part of a curative combination regimen for chronic hepatitis B. About HBV 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 (CHB) represents a significant unmet medical need. The World Health Organization estimates that over 250 million people worldwide suffer from chronic HBV infection, while other estimates indicate that approximately 2 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. About Arbutus Arbutus Biopharma Corporation is a publicly traded (Nasdaq: ABUS) biopharmaceutical company primarily focused on discovering, developing and commercializing a cure for people with chronic hepatitis B virus (HBV) infection. The Company is advancing multiple product candidates with distinct mechanisms of action that it believes have the potential to provide a new curative regimen for chronic HBV infection. Arbutus has also initiated a drug discovery and development effort for treating coronaviruses (including COVID-19). For more information, visit . About Antios Antios Therapeutics is a clinical-stage biopharmaceutical company focused on the development of innovative therapies to treat and cure viral diseases. Antios is currently developing ATI-2173, aiming to provide chronic hepatitis B-infected patients with a curative combination regimen. Arbutus Forward-Looking Statements and Information This press release contains forward-looking statements within the meaning of the Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, and forward-looking information within the meaning of Canadian securities laws (collectively, “forward-looking statements”). Forward-looking statements in this press release include statements about our expectations for the collaboration; the timing and expected trial design of the Phase 2a clinical trial to be initiated by the parties pursuant to the agreement; and Arbutus’ belief that AB-729 has the potential to become a cornerstone therapeutic in multiple future HBV combination regimens. With respect to the forward-looking statements contained in this press release, Arbutus has made numerous assumptions regarding, among other things: the effectiveness and timeliness of preclinical studies and clinical trials, and the usefulness of the data; the timeliness of regulatory approvals; the continued demand for Arbutus’ assets; and the stability of economic and market conditions. While Arbutus considers these assumptions to be reasonable, these assumptions are inherently subject to significant business, economic, competitive, market and social uncertainties and contingencies, including uncertainties and contingencies related to the ongoing COVID-19 pandemic. Additionally, there are known and unknown risk factors which could cause Arbutus’ actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements contained herein. Known risk factors include, among others: the parties may never realize the expected benefits of the collaboration; anticipated clinical trials may be more costly or take longer to complete than anticipated, and may never be initiated or completed, or may not generate results that warrant future development of the candidate; Arbutus may elect to change its strategy regarding its product candidates and clinical development activities; economic and market conditions may worsen; market shifts may require a change in strategic focus; and the ongoing COVID-19 pandemic could significantly disrupt clinical development programs. A more complete discussion of the risks and uncertainties facing Arbutus appears in Arbutus’ Annual Report on Form 10-K, Arbutus’ Quarterly Reports on Form 10-Q and Arbutus’ continuous and periodic disclosure filings, which are available at and at . All forward-looking statements herein are qualified in their entirety by this cautionary statement, and Arbutus disclaims any obligation to revise or update any such forward-looking statements or to publicly announce the result of any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, except as required by law. Arbutus Contact Information Investors and Media William H. Collier President and CEO Phone: 267-469-0914 Email: ir@arbutusbio.com Pam Murphy Investor Relations Consultant Phone: 267-469-0914 Email: ir@arbutusbio.com Antios Contact Information Investors: Lee Roth Burns McClellan lroth@burnsmc.com +1 (212) 300-8331 Media: Ryo Imai / Robert Flamm, PhD Burns McClellan rimai@burnsmc.com / rflamm@burnsmc.com +1 (212) 300-8315 / +1 (212) 300-8364