Severe Acute Respiratory Syndrome

A 98% Sustained Virologic Response at Week 4 (SVR4) Post-Treatment Observed in Initial Data From 52 Patients in Lead-In Cohort in Phase 2 HCV Study Phase 3 SUNRISE-3 Enrollment Surpassed 650 Patients in Monotherapy Arm; First Interim Analysis by the Independent Data Safety Monitoring Board (DSMB) Expected in March 2024 Jan. 08, 2024 -- Atea Pharmaceuticals, Inc. (Nasdaq: AVIR) (“Atea”), a clinical-stage biopharmaceutical company engaged in the discovery and development of oral antiviral therapeutics for serious viral diseases, today announced the achievement of two significant clinical milestones from its Hepatitis C Virus (HCV) and COVID-19 programs. The Company reported positive initial data from the first 52 patients in the lead-in cohort of its Phase 2 combination 8-week study of bemnifosbuvir and ruzasvir (RZR) for the treatment of HCV. Additionally, Atea has enrolled more than 650 patients in the monotherapy arm of its Phase 3 SUNRISE-3 trial for the treatment of COVID-19, and enrollment continues with the current wave. This enrollment milestone allows for the first interim analysis of the study by the DSMB, which is expected this March. “We are excited to share that the initial data from the Phase 2 combination 8-week study showed a 98% SVR4, which exceeds our efficacy criterion of >90% for continuing the study. Based on these data, we plan to imminently reinitiate enrollment to complete the Phase 2 study and topline results are anticipated in the third quarter of 2024,” said Jean-Pierre Sommadossi, PhD, Chief Executive Officer and Founder of Atea. “While direct acting antivirals have transformed HCV treatment, substantial unmet needs still exist, and the rate of new and reinfection currently exceeds cure rates in the US where 2.4 million individuals are estimated to be infected. The key unmet needs identified by healthcare providers in market research recently conducted by Atea include shorter length of treatment with fewer contraindications, particularly drug-drug interactions.” The Phase 2 open label study of bemnifosbuvir and RZR enrolled a lead-in cohort of 60 direct acting antiviral naïve, non-cirrhotic patients across all genotypes. Patients were administered 550 mg of bemnifosbuvir in combination with 180 mg of RZR once-daily for 8 weeks. Preliminary data are being presented as available, with SVR4 data currently available from 52 of the 60 lead-in patients. Including SVR4 as a decision endpoint, is a study design that is intended to substantially shorten the anticipated timeline for the completion of the Phase 2 trial. Clinical trials of other direct acting antiviral therapy combinations have demonstrated that the SVR4 result is highly correlated with SVR12. The initial results for the first 52 patients who reached this timepoint demonstrated a SVR4 rate of 98%, including one patient with poor adherence who did not achieve SVR4. Additionally, very rapid kinetics were observed in all 60 patients across genotypes with viral load near or below the lower limit of quantification (LLOQ) at 4 weeks of treatment, which is supportive of an 8-week treatment regimen for the combination of bemnifosbuvir and RZR. All 60 patients achieved viral load below the LLOQ at the end of the treatment. The combination was generally safe and well tolerated. There were no drug related serious adverse events, no treatment discontinuations and adverse events were mostly mild. The Phase 2 study aims to assess the safety and efficacy of 8 weeks of treatment with the combination of bemnifosbuvir and RZR in treatment-naïve HCV-infected patients, either without cirrhosis and or with compensated cirrhosis. The primary endpoint of the study is SVR12. Approximately 280 treatment-naïve HCV-infected patients, including the lead-in cohort, are expected to be enrolled in the Phase 2 study. The second part of the trial is anticipated to enroll 220 patients across all genotypes. An expanded geographic footprint to include approximately 50 clinical sites in approximately 15 countries is currently being activated. Full enrollment of the study is expected to be completed by mid-2024 with topline results in the third quarter of 2024. “Patient enrollment for SUNRISE-3 is currently correlating with the winter wave, and the high incidence of COVID-19 infection early in this winter season has led to more than 650 patients being enrolled. This is an important milestone, which allows for the first interim analysis by the independent DSMB for safety and futility, and the analysis is expected this March,” continued Dr. Sommadossi. “COVID-19 remains a continuing threat to many worldwide, with the levels in wastewater higher than this time last year, and COVID-19 continues to be a leading driver of respiratory virus hospitalizations. There is a need for new treatment options to protect those who are most vulnerable to severe outcomes after infection such as the elderly, immunocompromised and those with underlying risk factors.” SUNRISE-3 is a global, multicenter, randomized, double-blind, placebo-controlled, registrational Phase 3 trial evaluating bemnifosbuvir or placebo administered concurrently with locally available standard of care (SOC). The study has a large global footprint targeting approximately 300 clinical trial sites in the U.S., Europe, Japan and rest of the world. Patients are randomized 1:1 to receive either bemnifosbuvir 550 mg twice-daily (BID) or placebo BID for five days. SUNRISE-3 is the only Phase 3 program in high-risk COVID-19 patients with hospitalization as a primary endpoint. This trial is comprised of two study populations based on the type of SOC received: 1) bemnifosbuvir as monotherapy (primary analysis), and 2) the “combination antiviral population,” assessing combination therapy if the SOC includes other compatible antiviral drugs against COVID-19 (secondary analysis). The SUNRISE-3 patient population includes those aged ≥70 years (regardless of other risk factors), individuals aged ≥55 years with one or more risk factors, those aged ≥50 years with two or more risk factors, and individuals aged ≥18 years with specific risk factors, including immunocompromised conditions, all irrespective of COVID-19 vaccination status. The primary endpoint of the trial is all-cause hospitalization or death through Day 29 post-treatment in the monotherapy arm in 2,200 patients. The trial includes two interim analyses by the DSMB to assess safety and futility, to be conducted after approximately 650 and 1,350 evaluable patients, respectively, after completion of Day 29 post treatment in the monotherapy arm. Bemnifosbuvir, a nucleotide polymerase inhibitor, has been shown to be approximately 10-fold more active than sofosbuvir (SOF) in vitro against a panel of laboratory strains and clinical isolates of HCV genotypes 1–5. In vitro studies demonstrated bemnifosbuvir remained fully active against SOF resistance-associated strains (S282T), with up to 58-fold more potency than SOF. The pharmacokinetic (PK) profile of bemnifosbuvir supports once-daily dosing for the treatment of HCV and bemnifosbuvir has been well-tolerated at doses up to 550 mg for durations up to 8-12 weeks in healthy and HCV-infected subjects. RZR, an oral NS5A inhibitor, has demonstrated highly potent and pan-genotypic antiviral activity in preclinical (picomolar range) and prior clinical studies. RZR has been administered to over 1,200 HCV-infected patients at daily doses of up to 180 mg for 12 weeks and has demonstrated a favorable safety profile. RZR’s PK profile supports once-daily dosing. Bemnifosbuvir targets the SARS-CoV-2 RNA polymerase (nsp12), a highly conserved gene which is responsible for both replication and transcription of SARS-CoV-2. Bemnifosbuvir has a unique mechanism of action, with dual targets consisting of chain termination (RdRp) and nucleotityltransferase (NiRAN) inhibition, which has the potential to create a high barrier to resistance. In vitro data confirmed that bemnifosbuvir is active with similar efficacy against all variants of concern and variants of interest that have been tested, including Omicron subvariants BA.4, BA.5, XBB and EG.5.1. Atea is a clinical stage biopharmaceutical company focused on discovering, developing and commercializing oral antiviral therapies to address the unmet medical needs of patients with serious viral infections. Leveraging the Company’s deep understanding of antiviral drug development, nucleos(t)ide chemistry, biology, biochemistry and virology, Atea has built a proprietary nucleos(t)ide prodrug platform to develop novel product candidates to treat single stranded ribonucleic acid, or ssRNA, viruses, which are a prevalent cause of serious viral diseases. Atea plans to continue to build its pipeline of antiviral product candidates by augmenting its nucleos(t)ide platform with other classes of antivirals that may be used in combination with its nucleos(t)ide product candidates. Currently, Atea is focused on the development of orally-available antiviral agents for serious viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, and hepatitis C virus (HCV). For more information, please visit www.ateapharma.com. The content above comes from the network. if any infringement, please contact us to modify.

Patients newly treated with REL-1017 for up to one year experienced rapid, clinically meaningful, and sustained improvements in depressive symptoms and associated functional impairment Long-term dosing with REL-1017 was well-tolerated, with low rates of adverse events and discontinuations due to adverse events, and no new safety signals were detected CORAL GABLES, Fla., Sept. 20, 2023 /PRNewswire/ -- Relmada Therapeutics, Inc. (Nasdaq: RLMD), a late-stage biotechnology company addressing diseases of the central nervous system (CNS), today announced efficacy results for the de novo (or new to treatment) patients (204 patients) and safety results for all subjects (627 patients) from the Phase 3, long-term, open-label, registrational trial (Study 310) of REL-1017 in patients with Major Depressive Disorder (MDD). Detailed efficacy data for rollover population in the study will be presented when available. Patients treated daily with REL-1017 for up to one year experienced rapid, clinically meaningful, and sustained improvements in depressive symptoms and associated functional impairment. REL-1017 was well-tolerated with long-term dosing, showing low rates of adverse events and discontinuations due to adverse events. No new safety signals were detected. "These efficacy and safety results represent real-world potential outcomes for MDD patients when treated with REL-1017," said Cedric O'Gorman, MD, Chief Medical Officer of Relmada. "The rapid and sustained therapeutic effects achieved with REL-1017 suggest the significant therapeutic potential of this promising late-stage product candidate as a mechanistically novel and differentiated treatment for MDD. The early magnitude and trajectory of clinical improvement remain consistent across all trials conducted to date. The long-term sustained clinical improvement, coupled with an extremely well-tolerated profile, adds to our enthusiasm for this agent as a potential therapeutic option for patients and prescribers." Study REL-1017-310 was a long-term, open-label, non-comparative, registrational Phase 3 trial designed to evaluate the efficacy and safety of REL-1017 administered once-daily in patients with MDD for up to one year. In total, 627 patients were enrolled, comprising 423 patients who rolled over (rollover patients/subjects) from placebo-controlled trials with REL-1017 (Studies 301, 302 and 303), and 204 de novo patients who had not previously participated in trials with REL-1017. The trial was concluded when at least 300 patients had been treated for six months and approximately 100 patients had been treated for 12 months. At the time of study conclusion, 418 patients had reached at least six months of treatment, and 118 patients had reached at least 12 months of treatment. Efficacy results are presented below for de novo patients only. Rapid and Sustained Substantial Improvement in MADRS Total Score over Time In de novo patients, the mean MADRS total score was 33.8 at baseline. Treatment with REL-1017 in these patients resulted in mean improvements from baseline in the MADRS total score of 11.3 points at Day 7, 16.8 points at Month 1, 19.9 points at Months 3 and 6, and 22.5 points at Month 12. High Rates of Clinical Response, Both Rapid and Sustained When treated with REL-1017, 26.6% of de novo patients achieved clinical response by Day 7, 51.0% by Month 1, 60.7% by Month 3, 63.4% by Month 6, and 77.2% by Month 12. Clinical response is defined as a ≥50% improvement in MADRS total score. Meaningful Rates of Clinical Remission The virtual absence of depressive symptoms (clinical remission) was achieved by 12.1% of de novo patients at Day 7, 30.1% at Month 1, 44.0% at Month 3, 47.8% at Month 6, and 54.4% at Month 12. Clinical remission is defined as MADRS total score ≤10. CGI-I Scale Also Showed Clinical Improvement As assessed by the Clinical Global Impression of Improvement (CGI-I) Scale, de novo treated patients showed meaningful improvements consistent with MADRS efficacy improvements. Significant Reduction in Functional Impairment associated with MDD Functional impairment across all three separate domains of the Sheehan Disability Scale was improved with REL-1017 treatment by an average of approximately 50% in de novo patients at Month 6, with further improvement out to Month 12. The Sheehan Disability Scale (SDS) is a widely used, patient-rated scale that measures functional impairment associated with MDD across three individual domains: work, social life, and family life. Symptoms of Anxiety in MDD Reduced with REL-1017 Treatment The mean baseline score on the Hamilton Anxiety Rating Scale (HAM-A), which measures symptoms of anxiety, was 20.6 points, reflecting moderate anxiety. De novo patients treated with REL-1017 saw a continual decline in anxiety symptoms over time as measured by the HAM-A. Score improvements were 7.1 points at Day 7, 9.6 points at Month 1, 11.1 points at Month 3, 11.5 points at Month 6, and 13.5 points at Month 12. Long-Term Safety and Tolerability Results REL-1017 was safe and well-tolerated with a pro with that observed in short-term controlled trials, with no new safety signals detected. Safety results presented for Study REL-1017-310 are for all patients (de novo and rollover) in the trial. Discontinuations due to adverse events occurred in approximately 3% of patients during the trial, with no individual adverse event discontinuation occurring in more than 1% of patients. The most commonly reported adverse events deemed to be treatment-related all occurred at rates less than 5% and included headache (4.4%), nausea (4.0%) and dizziness (2.4%). The most commonly reported adverse events (occurring at a rate of ≥5%) were COVID-19 (9.7%), headache (9.7%), upper respiratory tract infection (8.6%), and nausea (5.0%). The occurrence of these adverse events reflected the study being conducted, in part, during the SARS-CoV pandemic. Importantly, there was no significant safety signal for weight gain, sexual dysfunction, cardiovascular issues, dissociative effects, withdrawal phenomena or abuse liability. About REL-1017 REL-1017, a new chemical entity (NCE) and novel NMDA receptor (NMDAR) channel blocker that preferentially targets hyperactive channels while maintaining physiological glutamatergic neurotransmission, is currently in late-stage development for the adjunctive treatment of major depressive disorder (MDD). The ongoing Clinical Research Program is designed to evaluate the potential for REL-1017 as a rapid-acting, oral, once-daily antidepressant treatment. In addition to the long-term, open-label study of REL-1017, the Phase 3 development program for REL-1017 as an adjunctive treatment for MDD also includes the recently initiated Relight (Study 304) Phase 3, randomized, double-blind, placebo-controlled trial and the ongoing Reliance II (Study 302) trial. Relight and Reliance II have the same key study design parameters. About Relmada Therapeutics, Inc. Relmada Therapeutics is a late-stage biotechnology company addressing diseases of the central nervous system (CNS), with a focus on major depressive disorder (MDD). Relmada's experienced and dedicated team is committed to making a difference in the lives of patients and their families. Relmada's lead program, REL-1017, is a new chemical entity (NCE) and novel NMDA receptor (NMDAR) channel blocker that preferentially targets hyperactive channels while maintaining physiological glutamatergic neurotransmission. REL-1017 is in late-stage development as an adjunctive treatment for MDD in adults. Learn more at . Forward-Looking Statements The Private Securities Litigation Reform Act of 1995 provides a safe harbor for forward-looking statements made by us or on our behalf. This press release contains statements which constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Any statement that is not historical in nature is a forward-looking statement and may be identified by the use of words and phrases such as "expects," "anticipates," "believes," "will," "will likely result," "will continue," "plans to," "potential," "promising," and similar expressions. These statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements, including potential failure of clinical trial results to demonstrate statistically and/or clinically significant evidence of efficacy and/or safety, failure of top-line results to accurately reflect the complete results of the trial, failure of the 310 open-label study to accurately reflect the results of the ongoing 302 and 304 blinded, randomized and controlled studies, failure to obtain regulatory approval of REL-1017 for the treatment of major depressive disorder, and the other risk factors described under the heading "Risk Factors" set forth in the Company's reports filed with the SEC from time to time. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Relmada undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Readers are cautioned that it is not possible to predict or identify all the risks, uncertainties and other factors that may affect future results and that the risks described herein should not be a complete list. Investor Contact: Tim McCarthy LifeSci Advisors tim@lifesciadvisors.com Media Inquiries: Corporate Communications media@relmada.com Company Codes: NASDAQ-NMS:RLMD

Atea Pharmaceuticals, Inc. (Nasdaq: AVIR) (“Atea”), a clinical-stage biopharmaceutical company engaged in the discovery and development of oral antiviral therapeutics for serious viral diseases, today announced the dosing of the first patient in the Phase 2 bemnifosbuvir and ruzasvir combination study for the treatment of Hepatitis C Virus (HCV) infection. “The initiation of this Phase 2 combination study marks an important clinical milestone for Atea,” said Jean-Pierre Sommadossi, PhD, Chief Executive Officer and Founder of Atea Pharmaceuticals. “We believe the combination of bemnifosbuvir and ruzasvir has the potential to significantly improve upon the current standard of care by offering a short duration, pan-genotypic, protease inhibitor-free treatment for patients with HCV, with or without cirrhosis.” The open label Phase 2 study is designed to enroll approximately 280 HCV-infected, direct-acting antiviral naive patients across all genotypes, including a 60 patient lead-in cohort. Patients will be administered 550 mg bemnifosbuvir in combination with 180 mg ruzasvir once-daily for eight weeks. The primary endpoints of the study are safety and sustained virologic response (SVR) at Week 12 post-treatment. Other virologic endpoints include virologic failure, SVR at Week 24 post-treatment and resistance. Preliminary data from the 60 patient lead-in cohort are anticipated in the fourth quarter of 2023. “Despite significant treatment advances, there remains a large, underserved HCV patient population that continues to grow dramatically due to the opioid crisis, injection drug use and HCV reinfection. According to the World Health Organization, an estimated 58 million people globally have chronic HCV infection, about 1.5 million new infections occur per year and nearly 300,000 people die every year from HCV-related liver diseases,” added Dr. Sommadossi. About Hepatitis C Virus (HCV) HCV is a blood-borne, positive sense, single stranded RNA virus, primarily infecting cells of the liver. HCV is a leading cause of chronic liver disease and liver transplants and spreads via blood transfusion, hemodialysis and needle sticks. In the United States, injection drug use accounts for approximately 60% of all new cases of HCV. Diagnosis of HCV is made through blood tests, including molecular tests that allow for the detection, quantification and analysis of viral genomes and the classification of an infection into specific viral genotypes. Infection becomes chronic in 75% to 85% of cases, with an incubation period lasting from two to 26 weeks. HCV is classified into seven genotypes and 67 subtypes, with genotype 1 being responsible for more than 70% of HCV cases in the United States. Patients with HCV are also classified by liver function status: compensated cirrhosis (liver scarring) denotes those patients that do not yet have impaired liver function, while decompensated cirrhosis describes patients with moderate to severe liver function impairment. The HCV patient population continues to grow dramatically in the United States. A large portion of the current increase in incidence is attributable to the opioid crisis, injection drug use and HCV reinfection. The prevalence of HCV in the US is expected to continue to remain steady over the coming years as rising HCV incidence offsets the number of new patients treated. The HCV market is estimated at approximately $3.5 billion in global net sales in 2022, with approximately 50% attributable to the US. About Bemnifosbuvir and Ruzasvir for Hepatitis C Virus Bemnifosbuvir has been shown to be approximately 10-fold more active than sofosbuvir (SOF) in vitro against a panel of laboratory strains and clinical isolates of HCV genotypes 1–5. In vitro studies demonstrated bemnifosbuvir remained fully active against SOF resistant S282T and GT1a/3a NS5A resistance associated variants (RAVs) tested and was shown to be at least 10 times more potent than SOF. In clinical studies to date, the pharmacokinetic (PK) profile of bemnifosbuvir supports once-daily dosing for the treatment of HCV and bemnifosbuvir has been well tolerated at doses up to 550 mg for durations up to 8-12 weeks in healthy and HCV infected subjects. Rapid and highly potent pan-genotypic antiviral activity was observed with bemnifosbuvir in HCV infected subjects, regardless of cirrhosis status. Ruzasvir (RZR), an oral NS5A inhibitor, has demonstrated highly potent and pan-genotypic antiviral activity in preclinical (picomolar range) and clinical studies. In vitro, ruzasvir retained high potency against GT1a/3a NS5A RAVs and was shown to be 5 to10-fold more potent than velpatasvir. Ruzasvir has been administered to over 1,200 HCV-infected patients at daily doses of up to 180 mg for up to 24 weeks and has demonstrated a favorable safety profile. Ruzasvir’s PK profile supports once-daily dosing. The combination of bemnifosbuvir and ruzasvir for the treatment of HCV is in Phase 2 development. About Atea Pharmaceuticals Atea is a clinical stage biopharmaceutical company focused on discovering, developing and commercializing oral therapies to address the unmet medical needs of patients with serious viral infections. Leveraging the Company’s deep understanding of antiviral drug development, nucleos(t)ide chemistry, biology, biochemistry and virology, Atea is developing novel product candidates to treat single stranded ribonucleic acid, or ssRNA, viruses, which are a prevalent cause of serious viral diseases. Atea plans to continue to build its pipeline of antiviral product candidates through using its internal discovery capabilities augmented by in-licensing. Currently, Atea is focused on the development of orally-available antiviral agents for serious viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, and hepatitis C virus (HCV). For more information, please visit www.ateapharma.com The content above comes from the network. if any infringement, please contact us to modify.