Atea Prescribed drugs, Inc. (Nasdaq: AVIR) (“Atea”), a clinical-stage biopharmaceutical firm engaged within the discovery and improvement of oral antiviral therapeutics for severe viral illnesses, at present introduced new information from the lead-in cohort (n=60) of the Firm’s ongoing Part 2 mixture examine of bemnifosbuvir, an oral nucleotide NS5B polymerase inhibitor, and ruzasvir, an oral NS5A inhibitor, for the remedy of hepatitis C virus (HCV). With an 8-week remedy length, the Part 2 information from the lead-in cohort of non-cirrhotic sufferers confirmed a 97% sustained virologic response price at 12 weeks post-treatment (SVR12), which is the first efficacy endpoint of the examine.
The Firm may also current preclinical information additional demonstrating a excessive barrier to resistance and pharmacokinetics for bemnifosbuvir and a low danger of drug-drug interactions for ruzasvir. These information are being offered on the European Affiliation for the Examine of the Liver (EASL) Congress happening June 5-8, 2024, in Milan, Italy.
“Right this moment, new challenges are hindering progress in the direction of our purpose of HCV elimination within the U.S. and globally. Affected person demographics have modified, and the tempo of latest HCV infections is rapidly outpacing the speed of these being handled. It’s obvious that additional improvements are required to handle the wants of at present’s HCV-infected sufferers,” stated Jean-Pierre Sommadossi, PhD, Chief Government Officer and Founding father of Atea Prescribed drugs. “The information being offered at EASL exhibit a possible best-in-class profile that mixes essentially the most compelling attributes of present HCV drug remedies via the modern mixture of bemnifosbuvir and ruzasvir. We stay up for reporting the total outcomes from our ongoing Part 2 examine throughout the second half of this yr.”
Outcomes from the lead-in cohort of the Part 2 examine additionally confirmed a 100% SVR12 price in members contaminated with genotype 3 (n=13), a traditionally difficult-to-treat genotype of HCV. The mix routine was effectively tolerated, with no drug-related extreme adversarial occasions (SAEs) or remedy discontinuations. Based mostly on these constructive information from the lead-in cohort, the Part 2 examine continues, with the intention of enrolling as much as an extra 220 topics, together with these with compensated cirrhosis.
“Right this moment, a lot of my HCV sufferers current with different situations requiring a number of concurrent therapies and sophisticated lives,” stated Eric Lawitz, MD, The Texas Liver Institute, Scientific Professor of Drugs, College of Texas Well being San Antonio. “I’m excited concerning the preliminary bemnifosbuvir and ruzasvir mixture information. The mix of a brief 8-week remedy length, a low danger of drug-drug interactions, and strong antiviral efficacy throughout all genotypes makes this a pretty routine.”
Greater than 2 million individuals within the U.S. reside with persistent HCV, and roughly 100,000 new persistent instances are identified annually. HCV diagnoses frequently outpace annual remedy charges, as lower than a 3rd of these identified with HCV obtain well timed remedy.
Information Offered at EASL Embrace :
Poster Title: Lead-in Cohort Outcomes From a Part 2 Examine of a Novel 8-Week Mixture Routine of Bemnifosbuvir and Ruzasvir in Sufferers with Continual Hepatitis C Virus An infection (THU-382)
Conclusion: Information from the lead-in cohort of 60 sufferers within the Part 2 medical trial of bemnifosbuvir and ruzasvir in HCV-infected topics confirmed a excessive SVR12 price of 97% within the lead-in cohort with a brief 8-week length of remedy. The first endpoints of the examine are security and SVR12. Viral kinetics have been related in genotype 1 and genotype 3 contaminated topics, together with a 100% SVR12 price in traditionally difficult-to-treat genotype 3 contaminated topics. The mix was usually protected and effectively tolerated. There have been no drug-related severe adversarial occasions or remedy discontinuations, and adversarial occasions have been largely gentle.
Poster Title: Bemnifosbuvir is a Potent HCV NS5B Inhibitor with a Favorable Antiviral Profile and Excessive Resistance Barrier (SAT-402)
Conclusion: Viral resistance is a vital consideration for direct-acting antiviral (DAA) use as it could influence the efficacy of remedies for HCV an infection. Outcomes demonstrated that bemnifosbuvir is at the least ten-fold stronger than sofosbuvir, a medicine to deal with HCV infections, throughout all genotypes examined and isn’t immune to resistance-associated substitutions (RASs) which were discovered to change the exercise of sofosbuvir. Whereas the C223H mutation was discovered to be the first bemnifosbuvir RAS in genotype 1b, a number of further substitutions at different NS5B areas have been required to confer significant resistance, suggesting that bemnifosbuvir offers a excessive barrier to resistance. Based mostly upon the info demonstrated thus far, it’s anticipated that the bemnifosbuvir and ruzasvir mixture ought to have a extra compelling antiviral profile in opposition to main HCV NS5A RAVs than the present commonplace of care.
Poster Title: Absorption, Distribution, Metabolism, and Excretion of [14C]-Bemnifosbuvir in Rats (SAT-411)
Conclusion: This preclinical examine in rats was carried out to raised perceive the tissue distribution, metabolites, and excretion routes following bemnifosbuvir remedy. Following a single oral dose in rats, bemnifosbuvir has favorable general absorption, distribution, metabolism, and excretion (ADME) properties, together with good bioavailability (>60%) and broad distribution to tissues with low penetration into the mind. Bemnifosbuvir was extremely and quickly metabolized to the metabolite AT-273, according to the proposed metabolic and activation pathway.
Poster Title: Low Danger of Drug-Drug Interactions for Ruzasvir Based mostly Upon In Vitro Metabolism and Transporter Interplay Research (SAT-412)
Conclusion: Many sufferers contaminated with HCV are additionally taking a number of co-medications, which can influence remedy selections. This preclinical examine aimed to additional perceive the danger of drug-drug interactions (DDIs) for ruzasvir by analyzing its metabolism in human liver microsomes and cells. Based mostly on these in vitro information and static DDI danger evaluation fashions, ruzasvir has a low potential to be a perpetrator of DDIs through inhibition or induction of CYP450. Equally, it has a low potential to inhibit OATP1B1 and OATP1B3 transporters. The relevance of bile salt export pump (BSEP) inhibition to DDIs is proscribed.
About Hepatitis C Virus
Hepatitis C virus (HCV) is a blood-borne, positive-sense, single-stranded (ss)RNA virus that primarily infects liver cells. HCV is a number one explanation for persistent liver illness and liver transplants, spreading through blood transfusion, hemodialysis, and needle sticks. An estimated 50 million individuals globally reside with persistent HCV an infection, with roughly 1 million new infections and 242,000 deaths occurring annually. Most HCV-related deaths are on account of liver scarring (cirrhosis) and liver most cancers (hepatocellular carcinoma). Injection drug use accounts for round 30% of latest HCV instances globally and roughly 60% within the U.S. Yearly, HCV diagnoses within the U.S. outpace remedy charges, as lower than a 3rd of these identified with HCV obtain well timed remedy.
About Bemnifosbuvir and Ruzasvir for Hepatitis C Virus (HCV)
Bemnifosbuvir is an oral, purine nucleotide prodrug designed to inhibit viral replication by impairing viral RNA polymerase, a key part within the replication equipment of enveloped constructive single-stranded RNA viruses, resembling human coronaviruses and HCV. Atea is creating bemnifosbuvir together with ruzasvir, an oral NS5A inhibitor for the remedy of HCV. As single brokers, each bemnifosbuvir and ruzasvir have demonstrated potent pan-genotypic antiviral exercise in opposition to HCV. The mix of bemnifosbuvir and ruzasvir has exhibited synergistic in vitro exercise in opposition to HCV with no pharmacokinetic (PK) drug-drug interactions in wholesome volunteers.
In vitro research have proven bemnifosbuvir to be roughly 10-fold extra lively than sofosbuvir (SOF) in opposition to a panel of laboratory strains and medical isolates of HCV GT 1–5. In vitro research have additionally demonstrated that bemnifosbuvir remained absolutely lively in opposition to SOF resistance-associated strains (S282T), with as much as 58-fold extra efficiency than SOF. The PK profile of bemnifosbuvir helps once-daily dosing for the remedy of HCV. Throughout each HCV and COVID-19 applications, bemnifosbuvir has been administered to over 2,100 topics and has been well-tolerated at doses as much as 550 mg for durations up 12 weeks in wholesome topics and sufferers.
Ruzasvir has demonstrated extremely potent and pan-genotypic antiviral exercise in preclinical (picomolar vary) and medical research. Ruzasvir has been administered to over 1,200 HCV-infected sufferers at day by day doses of as much as 180 mg for 12 weeks and has demonstrated a good security profile. Ruzasvir’s PK profile helps once-daily dosing.
In regards to the Part 2 Examine
Atea is at the moment conducting a world Part 2 medical trial in treatment-naïve, persistent HCV-infected sufferers both with out cirrhosis or with compensated cirrhosis. This examine is designed to guage the security and efficacy of eight weeks of remedy with the mixture consisting of once-daily bemnifosbuvir 550 mg and ruzasvir 180 mg. As much as roughly 280 treatment-naïve sufferers throughout all HCV genotypes, together with the lead-in cohort of 60 sufferers with out cirrhosis, are anticipated to be enrolled on this Part 2 medical trial.
The first endpoints of the examine are security and sustained virologic response (SVR) at 12 weeks post-treatment (SVR12). Different virologic endpoints embody virologic failure, SVR at 24 weeks post-treatment (SVR24) and resistance. Topline outcomes from all sufferers enrolled within the Part 2 examine are anticipated within the second half of 2024.
About Atea Prescribed drugs
Atea is a clinical-stage biopharmaceutical firm targeted on discovering, creating and commercializing oral antiviral therapies to handle the unmet medical wants of sufferers with severe viral infections. Leveraging the Firm’s deep understanding of antiviral drug improvement, nucleos(t)ide chemistry, biology, biochemistry and virology, Atea has constructed a proprietary nucleos(t)ide prodrug platform to develop novel product candidates to deal with single stranded ribonucleic acid, or ssRNA, viruses, that are a prevalent trigger of significant viral illnesses. Atea plans to proceed to construct its pipeline of antiviral product candidates by augmenting its nucleos(t)ide platform with different courses of antivirals which may be utilized in mixture with its nucleos(t)ide product candidates. At the moment, Atea is concentrated on the event of orally-available antiviral brokers for extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, and hepatitis C virus (HCV). For extra info, please go to www.ateapharma.com .
Ahead-Trying Statements
This press launch consists of “forward-looking statements” inside the that means of the Non-public Securities Litigation Reform Act of 1995. Ahead-looking statements on this press launch embody however aren’t restricted to the Firm’s plans referring to the date and time of the shows on the convention, the time of anticipated launch of further medical information and the potential of bemnifosbuvir together with ruzasvir to deal with HCV. When used herein, phrases together with “expects,” “could,” “will,” “anticipates,” “plans,” and related expressions are meant to establish forward-looking statements. As well as, any statements or info that confer with expectations, beliefs, plans, projections, aims, efficiency or different characterizations of future occasions or circumstances, together with any underlying assumptions, are forward-looking. All forward-looking statements are based mostly upon the Firm’s present expectations and varied assumptions. The Firm believes there’s a cheap foundation for its expectations and beliefs, however they’re inherently unsure. The Firm could not understand its expectations, and its beliefs could not show appropriate. Precise outcomes may differ materially from these described or implied by such forward-looking statements because of varied essential components, together with, with out limitation, the essential components mentioned and up to date infrequently beneath the caption “Danger Components” within the reviews the Firm recordsdata with the SEC, together with annual reviews on Form10-Okay, quarterly reviews on Form10-Q, present reviews on Type 8-Okay and different filings every of that are accessible on the SEC’s web site at www.sec.gov. These and different essential components may trigger precise outcomes to vary materially from these indicated by the forward-looking statements made on this press launch. Any such forward-looking statements symbolize administration’s estimates as of the date of this press launch. Whereas the Firm could elect to replace such forward-looking statements sooner or later sooner or later, besides as required by legislation, it disclaims any obligation to take action, even when subsequent occasions trigger our views to vary. These forward-looking statements shouldn’t be relied upon as representing the Firm’s views as of any date subsequent to the date of this press launch.
Contacts
Jonae Barnes
SVP, Investor Relations and Company Communications
617-818-2985
Barnes.jonae@ateapharma.com
Will O’Connor
Precision AQ
212-362-1200
will.oconnor@precisionaq.com
