Tobevibart

Highlights from the Data Presentation PHILADELPHIA, PA, USA I November 19, 2024 I Virion Therapeutics, LLC, a clinical-stage biotechnology company, developing novel T cell-based immunotherapies , today announced positive immunologic and continued safety and tolerability data, and anti-HBV immune responses, from the first-ever human study of its novel, first-in-class, checkpoint modifier immunotherapy, VRON-0200, for HBV functional cure, presented by Professor Grace Wong, M.D., from the Chinese University of Hong Kong, as a late breaker poster presentation at The Liver Meeting ® 2024 (The American Association for the Study of the Liver), in San Diego, California, US. These Phase 1b data, on the first 25 chronically infected hepatitis B patients, on nucleos(t)ide antiviral therapy, all of whom received a single, intramuscular (i.m.) injection of VRON-0200, demonstrated that it was safe and well-tolerated, with no significant adverse events reported and no clinically relevant abnormalities in laboratory assessments, including liver function tests. In 22 patients who had at least 28 days of immunologic follow up, a 5.5-fold increase in T cell responses was observed in 7 patients (32%), post-vaccination, with most maintaining responses above their baseline values out to day 91.  Additionally, four patients were observed to have HBV surface antigen (HBsAg) declines ranging from -0.4 to -2.3 log 10 IU/mL, after a single i.m. dose. Professor Wong commented: “Restoring immune function in chronically HBV-infected patients is needed in order to be able to discontinue HBV treatment and eliminate the infection. These results are highly promising for this chronically infected patient population, most of whom were infected at birth, in that a single VRON-0200 injection was able to both stimulate T cell responses, and lower HBsAg, in the blood, but also, that it is safe and well tolerated. The observed declines in HBsAg are of great interest given that VRON-0200 does not directly target HBsAg, and this suggests immune control of the virus in these patients. I look forward to seeing additional data, and longer follow up, from this study.” “These data highlight the potential of VRON-0200 as a simple, easy-to-administer, IFN-sparing immunotherapy, alone or in combination, for HBV functional cure,” said Dr. Sue Currie, COO of Virion, and one of the study authors. “VRON-0200 is the first new immunotherapy, other than monoclonal antibody checkpoint inhibitors and pegylated-interferon, to lower HBsAg without directly targeting it. As a result of these positive data, we are now investigating our first combination therapy with VRON-0200 with a cohort that includes elebsiran (siRNA) plus tobevibart (mAb), with the goal to potentially improve responses and bring a cure to the almost 300 million persons living with chronic HBV.  We look forward to sharing more results in early 2025.” Professor Ed Gane, M.D., from the University of Auckland, and one of the study authors, commented: “The non-immunologic/artificial removal of HBsAg (e.g., siRNA, small molecules), has not been shown to achieve durable off-treatment responses, and may not restore the needed immunity to control HBV infection. What makes these results so exciting is that a single VRON-0200 dose was able to produce HBsAg declines, showing evidence of anti-HBV immune control in these chronically infected patients.  These data, and the upcoming data from the now enrolling combination cohort, will inform future strategies for Functional Cure therapies.” Summary of VRON-0200 Phase 1b clinical trial design More details of the study can be found at ClinicalTrials.gov (Identifier: NCT06070051 ). About Chronic Hepatitis B Despite a preventative vaccine, cases of chronic hepatitis B (HBV) continue to rise, with an estimated 296 million persons infected worldwide and 820,000 deaths per year from HBV-related liver complications. Chronic HBV remains a global health issue with a high unmet medical need since there is no cure available. The current standard of care requires lifelong antiviral therapy to maintain control of the virus. About VRON-0200 VRON-0200 is a therapeutic immunotherapy, administered by intramuscular injection, designed with the goal of providing a functional cure for chronic HBV infection. While the virus itself stimulates HBV-specific CD8+ T cells, for those patients that can’t clear the initial infection, their T cells soon become exhausted, placing limits on their ability to proliferate and control the virus. Preclinical data support the hypothesis that VRON-0200, through checkpoint modification, can amplify, broaden, and enhance T cell responses that may include T cells that are not normally activated during a chronic HBV infection, which results in improved viral control. An ongoing Phase 1b trial has shown VRON-0200 to be safe, well tolerated, and immunogenic, in chronically HBV-infected patients on nucleos(t)ide therapy. About Virion Therapeutics (Virion) Virion Therapeutics, LLC is a clinical-stage company developing novel T cell-based immunotherapies to cure cancer and chronic infectious diseases that utilize proprietary genetically encoded checkpoint modifiers to enhance and broaden CD8+ T cell responses to a tumor or chronic infection. Founded in early 2018 to advance technology licensed from The Wistar Institute, an international leader in biomedical research, Virion has since developed a robust pipeline, including its lead VRON-0200 clinical program, and several additional IND-enabling programs, including its VRON-0300 oncology program for advanced solid tumors, leveraging its proprietary platform technologies. To learn more, visit www.VirionTx.com SOURCE: Virion Therapeutics

– Monthly tobevibart and elebsiran combination achieves rapid 100% virologic suppression at Week 24, sustained through Week 60 – – Undetectable HDV RNA in 41% of participants at Week 24, increasing to 64% by Week 36 and up to 80% by Week 60 across cohorts – – Combination well-tolerated: no treatment-related severe AEs, treatment-related discontinuations or ALT flares – – Following a recent FDA meeting, Phase 3 ECLIPSE registrational program to begin in the first half of 2025 – – New data presented at AASLD The Liver Meeting. Investor conference call November 19, 2024, at 5.15 a.m. PT / 8.15 a.m. ET – SAN FRANCISCO, CA, USA I November 18, 2024 I Vir Biotechnology, Inc. (NASDAQ:VIR) today announced positive results from the SOLSTICE Phase 2 clinical trial evaluating tobevibart alone, or in combination with elebsiran, in people with chronic hepatitis delta (CHD). The most-advanced and potential first-of-its-kind investigational human monoclonal antibody and siRNA combination dosed monthly achieved 100% virologic response and rapid hepatitis delta virus (HDV) RNA suppression. HDV RNA below the lower limit of quantification (< LLOQ), target not detected (TND), the best measure that the virus is cleared from the body, was achieved in 41% (13/32) of participants at Week 24 rising to 64% (14/22) of participants by Week 36. In a cohort that reached Week 60, 80% (4/5) achieved HDV RNA TND. These data were presented in an oral session at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting ® , in San Diego, CA. Based on these results, and following a recent meeting with the FDA, Vir Biotechnology plans to initiate the Phase 3 registrational ECLIPSE program in the first half of 2025 to further evaluate the combination of tobevibart and elebsiran for the treatment of CHD. CHD is a chronic inflammatory liver disease caused by HDV 1 . It is the most severe form of chronic viral hepatitis 2 and on average, people living with CHD will progress to cirrhosis and liver failure within 5 years 3 . There is no approved treatment in the United States. The objective of therapy is to clear the virus, and combination therapy offers the potential to do so by tackling the viral lifecycle through multiple mechanisms. “Achieving HDV RNA suppression with a safe, well-tolerated, and conveniently dosed treatment could be transformative for people living with hepatitis delta. The impressive rates of virologic suppression seen in the SOLSTICE Phase 2 data suggest that tobevibart and elebsiran have the potential to significantly improve patient outcomes,” said Tarik Asselah, M.D., Ph.D., Professor of Hepatology at the Hôpital Beaujon, APHP, Clichy, France, and at the University of Paris-Cité, and Head of the unit Viral Hepatitis UMR1149 at INSERM, France. “New, effective therapeutic options are urgently needed, and I am excited to see this combination advance into a registrational Phase 3 program.” Primary Endpoint Analysis from the Phase 2 SOLSTICE Trial Clinical trial participants were randomized to receive tobevibart 300 mg monotherapy every two weeks (n=33) or a combination of tobevibart 300 mg and elebsiran 200 mg every four weeks (combination de novo arm, n=32). In addition, the participants from previous tobevibart or elebsiran monotherapy cohorts could rollover to receive the combination of tobevibart 300 mg and elebsiran 200 mg every four weeks (combination rollover, n=13). Rates of virologic suppression were evaluated at Week 24, and further assessed at Weeks 36, 48 and 60 in those participants that had reached each timepoint. Further monitoring will continue up to 192 weeks. Rapid and Sustained Virologic Suppression – 100% of participants across combination arms achieved an HDV RNA ≥2 log 10 decrease or below limit of detection (LOD) at Week 24, and this rate was sustained over time in all participants at Weeks 36 (22/22) and those in the rollover cohort that reached Week 60 (5/5). HDV RNA TND was achieved in 41% (13/32) of participants across combination arms at Week 24 and this rose to 64% (14/22) at Week 36. By week 60, this had risen further with 80% (4/5) of participants in the rollover cohort having achieved no detectable viral RNA. Approximately 90% of participants receiving the combination achieved reductions in hepatitis B surface antigen (HBsAg) values below <10 IU/mL at Week 24, with sustained responses at later time points. This indicates suppression of the key biologic mechanisms that HDV requires for viral replication. ALT Normalization – Alanine aminotransferase (ALT) decreased in most participants between Day 1 and Week 24 and normalized in 47% (15/32) of participants in the combination de novo cohort and 56% (5/9) in the rollover cohort by Week 24. These rates were sustained at Week 36. Combined Endpoints – The protocol defined combined endpoint of HDV RNA decrease ≥ 2 log 10 compared to baseline or HDV RNA below LOD and ALT normalization at Week 24 was observed in 47% (15/32) of participants in the combination de novo arm. The more stringent composite endpoint of HDV RNA TND and ALT normalization was achieved in 19% (6/32) of participants in the combination de novo arm at Week 24, which increased to 27% (6/22) by Week 36. This trend was reflected in the combination rollover cohort in which 33% (3/9) of participants achieved this endpoint at Week 24 and 40% (2/5) at Week 60. Rates of HDV RNA suppression and ALT normalization were similar between non-cirrhotic and cirrhotic participants across combination arms. Safety Profile – The safety profile of tobevibart and elebsiran is consistent with previous studies. Treatment-emergent adverse events (TEAEs) were generally mild or moderate and transient across all treatment groups, with influenza-like illness being the most common event. No ALT flares were observed. There were no study-related discontinuations in the combination arms, and no treatment-related severe adverse events (SAEs) were reported. “People living with hepatitis delta in the US have no approved treatment options, and therapies are limited globally. At Vir Biotechnology we are committed to changing that,” said Marianne De Backer, M.Sc., Ph.D., MBA, Chief Executive Officer, Vir Biotechnology. “We are confident that our regimen has the potential to deliver transformative benefits for patients, and we will build on our strong SOLSTICE data to start our Phase 3 registrational ECLIPSE program as soon as possible in 2025.” Phase 3 Registrational ECLIPSE Program Following a meeting with the FDA, Vir Biotechnology finalized the design of the Phase 3 registrational clinical program, ECLIPSE, which evaluates the tobevibart and elebsiran combination in people living with CHD. This program, which will commence in the first half of 2025, will include three randomized, controlled trials designed to evaluate the combination therapy in comparison to deferred treatment or bulevirtide. All studies will enroll both cirrhotic and non-cirrhotic participants. ECLIPSE 1 and 2 are Phase 3 trials designed to provide the registrational efficacy and safety data needed for submission to global regulatory agencies. ECLIPSE 3 is a Phase 2b trial designed to provide important supportive data, particularly in Europe, to help establish appropriate pricing and reimbursement in key markets. In June 2024, the U.S. Food and Drug Administration (FDA) granted fast track designation for the combination of tobevibart and elebsiran for the treatment of CHD. This designation is intended to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Vir Biotechnology announced today that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) issued a positive opinion on the application for orphan drug designation of tobevibart and elebsiran for the treatment of CHD. This designation supports the development of treatments for life-threatening or chronically debilitating conditions with significant unmet medical need. Investor Conference Call Vir Biotechnology will host an investor conference call on November 19, 2024 at 5.15 a.m. PT / 8.15 a.m. ET. A live webcast will be available on https://investors.vir.bio/ and will be archived on www.vir.bio for 30 days. About the Phase 2 SOLSTICE Trial SOLSTICE is a Phase 2 study to evaluate the safety, tolerability, and efficacy of tobevibart, alone or in combination with elebsiran, in people with chronic hepatitis delta. This Phase 2 study is a multi-center, open-label, randomized study. Primary endpoints include proportion of participants with undetectable hepatitis delta virus (HDV) RNA (defined as HDV RNA equal or greater than 2 log 10 decrease from baseline or below limit of detection) up to week 24, alanine aminotransferase (ALT) normalization (defined as ALT below upper limit of normal) up to week 24, and treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) up to 118 weeks. Secondary endpoints include proportion of participants with undetectable HDV RNA and different timepoints and up to 192 weeks. More information about this trial can be found at clinicaltrials.gov (NCT05461170). About Tobevibart and Elebsiran Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen. It is designed to inhibit the entry of hepatitis B and hepatitis delta viruses into hepatocytes, and to reduce the level of circulating viral and subviral particles in the blood. Tobevibart, which incorporates Xencor’s Xtend™ and other Fc technologies, has been engineered to have an extended half-life and was identified using Vir Biotechnology’s proprietary monoclonal antibody discovery platform. Tobevibart is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis B and patients with chronic hepatitis delta. Elebsiran is an investigational hepatitis B virus-targeting small interfering ribonucleic acid (siRNA) designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen. Current data indicates that it has the potential to have direct antiviral activity against hepatitis B virus and hepatitis delta virus. Elebsiran is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis B and patients with chronic hepatitis delta. It is the first asset in Vir Biotechnology’s collaboration with Alnylam Pharmaceuticals, Inc. to enter clinical studies. Tobevibart and elebsiran are also being evaluated as a potential functional cure for chronic hepatitis B. Vir Biotechnology recently presented positive safety and efficacy end-of-treatment results from the MARCH Phase 2 clinical study evaluating combinations of tobevibart and elebsiran, alone or in combination with pegylated interferon alfa (PEG-IFNα), in participants with chronic hepatitis B in a late-breaker oral presentation at AASLD The Liver Meeting ® . About Vir Biotechnology, Inc. Vir Biotechnology, Inc. is a clinical-stage biopharmaceutical company focused on powering the immune system to transform lives by discovering and developing medicines for serious infectious diseases and cancer. It’s clinical-stage portfolio includes infectious disease programs for chronic hepatitis delta and chronic hepatitis B infections and programs across several clinically validated targets in solid tumor indications. Vir Biotechnology also has a preclinical portfolio of programs across a range of other infectious diseases and oncologic malignancies. Vir Biotechnology routinely posts information that may be important to investors on its website. References: 1 NIH National Institute of Diabetes and Digestive and Kidney Diseases Hepatitis D – NIDDK (nih.gov) , accessed September 2024 2 WHO Hepatitis Delta Factsheet – Hepatitis D (who.int) , accessed September 2024 3 CDC What is Hepatitis D – FAQ | CDC SOURCE: Vir Biotechnology