Powering the Immune System to Transform Lives
Our Therapeutic Focus Areas
Chronic Hepatitis Delta
Chronic hepatitis delta (CHD) is considered by the World Health Organization to be the most severe form of chronic viral hepatitis due to more rapid progression towards liver cancer and liver-related death1. Approximately 70% to 80% of people living with CHD will progress to cirrhosis within five to 10 years of diagnosis if left untreated2.
It is estimated that at least 12 million people are living with chronic hepatitis delta, with the majority of cases remaining undiagnosed3-6.
Vir is working to develop a chronic suppressive therapy that helps address this significant unmet medical need. Our ongoing Phase 2 SOLSTICE trial is evaluating tobevibart (VIR-3434) alone, and in combination with elebsiran (VIR-2218), as a potential treatment regimen for people living with CHD.
Tobevibart is an investigational neutralizing monoclonal antibody that has been engineered for immune engagement. Elebsiran is an investigational siRNA that is designed to enable targeted delivery to the liver and to reduce Hepatitis B surface antigen, a protein which is required for the hepatitis delta virus life cycle.
1 WHO Hepatitis Delta Factsheet - https://www.who.int/news-room/fact-sheets/detail/hepatitis-d
2 CDC https://www.cdc.gov/hepatitis/hdv/hdvfaq.htm
3 Wedemeyer H, Manns MP. Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead. Nat Rev Gastroenterol Hepatol. 2010;7: 31–40. doi: 10.1038/nrgastro.2009.205
4 Miao Z, Zhang S, Ou X, Li S, Ma Z, Wang W, et al. Estimating the global prevalence, disease progression and clinical outcome of hepatitis delta virus infection. J Infect Dis. 2019. doi: 10.1093/infdis/jiz633
5 Stockdale AJ, Kreuels B, Henrion MYR, Giorgi E, Kyomuhangi I, de Martel C, et al. The global prevalence of hepatitis D virus infection: Systematic review and meta-analysis. J Hepatol. 2020;73: 523–532. doi: 10.1016/j.jhep.2020.04.008
6 Chen H-Y, Shen D-T, Ji D-Z, Han P-C, Zhang W-M, Ma J-F, et al. Prevalence and burden of hepatitis D virus infection in the global population: a systematic review and meta-analysis. Gut. 2019;68: 512–521. doi: 10.1136/gutjnl-2018-316601
Chronic Hepatitis B
Around the world, approximately 254 million people live with chronic hepatitis B (CHB)1. Complications from CHB include liver cirrhosis and liver cancer, and the WHO estimates that 1.1 million people died from viral hepatitis B in 20221.
The rate of functional cure (lifelong control of the virus after a finite duration of treatment) with current approved treatments is 3%-7%2-5. Our goal is to deliver the first treatment for CHB with 30% or greater functional cure rate. This further reduces the risk of debilitating disease progression.
Vir’s approach uses a combination regimen of antivirals and immunomodulators, including our investigational antibody tobevibart (VIR-3434), and siRNA elebsiran (VIR-2218).
Our ongoing Phase 2 MARCH Part B trial is evaluating 24 and 48 weeks of tobevibart and elebsiran together, with and without peginterferon alpha, to help us determine if we can achieve a functional cure.
1WHO Global Hepatitis Report 2024
2European Association for the Study of the Liver. J Hepatol. 2017;67:370–398.
3Kim GA, et al. Gut 2014; 63(8):1325-32.
4Konerman MA, Lok AS. Clin Liver Dis 2016;20(4):645-665.
5Liang TJ, et al. Hepatology 2015;62(6):1893-908.
Oncology
One in five people worldwide develop cancer during their lifetime1. Although medicine has made tremendous strides in cancer prevention and treatment, it still remains the second-leading cause of death globally and is the leading or second-leading cause of premature death (before age 70 years) in 112 countries2. As the burden of cancer continues to grow, so does the need for new therapeutic options for patients.
Over the past 30 years, our understanding of cancer has increased dramatically. Today, we know many of the key drivers of this disease, down to the genetic and molecular level3.
HER2, EGFR and PSMA are three examples of molecules well-known to play a key role in cancer. These molecules are over-expressed in a variety of solid tumors, such as breast cancer, colorectal cancer, and prostate cancer, making them attractive targets for cancer therapy. Current cancer therapies targeting these molecules have shown promise, but there remains a high need for more efficacious and better-tolerated treatments options.
We are advancing three investigational assets that leverage our PRO-XTEN masking technology with T-cell engagers targeting HER2, EGFR or PSMA. The PRO-XTEN masking technology is designed to keep the T-cell engagers inactive until they reach the tumor microenvironment, where tumor-specific proteases can cleave off the mask and activate the T-cell engager leading to killing of cancer cells. By driving the activity exclusively to the tumor microenvironment, we aim to limit the toxicity of these agents and potentially increase their efficacy and tolerability.
1International Agency for Research on Cancer, WHO - Cancer Topics – IARC (who.int), accessed August 2024
2American Cancer Society – Global Cancer Facts, 5th Edition - Global Cancer Facts & Figures-5th Edition
3Understanding Cancer - NIH Curriculum Supplement Series - NCBI Bookshelf
HIV
Over 40 years since the start of the epidemic, HIV remains one of the world’s most serious public health challenges. It is estimated that close to 40 million people worldwide are living with HIV, including 1.4 million children1. In 2023 alone, 1.3 million people worldwide were estimated to have acquired an HIV infection1.
At Vir, we seek to address this elusive virus through the pursuit of an HIV cure, with support from the Bill & Melinda Gates Foundation.
Our approach is based on a cocktail of so-called broadly neutralizing antibodies that have been engineered to enhance the immune system’s T-cells’ response to the virus. Broadly neutralizing antibodies are known to recognize and prevent a range of variants of HIV from infecting cells, which given the diversity of HIV strains worldwide and the virus’ history of generating viral resistance, we believe will be key to finally achieving a much-awaited cure.
RSV
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections among infants, the immunocompromised and elderly populations. It is estimated that, globally, each year, there are 33 million RSV acute lower respiratory infections, resulting in approximately 3.6 million hospitalizations and approximately 100,000 deaths in children under the age of five1.
People with weakened immune systems, lung and heart disease, and infants are at greater risk for RSV infections and complications. We are working on strategies to significantly reduce the risk of acquiring RSV2, potentially offering young children and immunocompromised patients an additional line of defense against this threatening virus.
1You Li et al., Lancet. 2022 May 28; 399(10340): 2047–2064.
2 Per the collaboration agreement announced in February 2021, Vir and GSK are continuing to advance new monoclonal antibody therapeutics for RSV.
Additional programs
We are currently in discussions with potential partners to out license several other Vir programs, including for influenza, COVID-19, and HPV.
Influenza
The World Health Organization considers influenza the next most likely pandemic threat. Each year, nearly a billion people around the world get sick from flu1, resulting in approximately six million hospitalizations and up to 600,000 deaths worldwide2.
Despite the availability of vaccines, there remains a significant unmet patient need as vaccine effectiveness rates are lower among high-risk populations, including those who are immunocompromised3, due to the body’s inability to mount a response to vaccines.
Our investigational neuraminidase-targeting monoclonal antibody candidate VIR-2981 has shown in vitro potent activity against all major strains of influenza A and B viruses, both of which cause seasonal epidemics.
Our goal with VIR-2981 is to achieve a meaningful reduction of medically attended influenza illness, especially for those considered at high risk for severe illness, thus increasing their protection against influenza A and B.
1https://www.who.int/news/item/14-10-2022-influenza-in-the-northern-hemisphere-is-back
2Luliono et al., Lancet. “Estimates of global seasonal influenza-associated respiratory mortality: a modelling study”, 2018 Mar 31;391(10127):1285-1300.
3Restivo et al., Hum Vaccin Immunother., 2018; 14(3): 724-735
COVID-19
Sotrovimab, our investigational monoclonal antibody (mAb) treatment for COVID-19, was identified by our proprietary antibody platform and Fc engineered for immune engagement. We are very proud of the fact that it was delivered in just 15 months during the pandemic and has benefited numerous people around the world.
As new variants continue to emerge and with vaccination rates falling, there remains an unmet need for new therapies for COVID-19. VIR-7229 is our investigational next generation COVID-19 mAb that in development has demonstrated increased potency, breadth, and resistance to viral escape thanks to AI engineering and optimization. In preclinical studies, VIR-7229 has been shown to have high potency against a broad spectrum of variants.
The development of VIR-7229 through the end of Phase 1 is supported by the Biomedical Research and Development Agency (BARDA), part of the U.S. Department of Health and Human Services’ (HHS) Administration for Strategic Preparedness and Response (ASPR)*.
*The development of VIR-7229 has been supported in whole or in part with federal funds from the Department of Health and Human Services (HHS); Administration for Strategic Preparedness and Response (ASPR); Biomedical Advanced Research and Development Authority (BARDA), under Other Transaction Number: 75A50122C00081.
Pre-Cancerous HPV Lesions
Human Papillomavirus (HPV) infection can result in numerous health issues including high-grade squamous intraepithelial lesions (HSIL) which are often a precursor for various types of cancers such as cervical, vaginal, vulvar, anal, penile, and oropharyngeal.
Despite advances in vaccination and screening, HPV-associated cancers and conditions remain significant global health concerns. HPV causes an estimated 630,000 cancers worldwide each year, accounting for about five percent of all cancers1.
At Vir, we are leveraging our T cell-based viral vector platform to develop VIR-1949, an investigational therapeutic vaccine candidate that targets the underlying HPV virus with the goal of eliciting specific types of T cell responses against HPV for a long-lasting immune response. This is key to not only treating the current disease but also clearing underlying infection to prevent disease recurrence locally or in other areas of the body.
VIR-1949 is based on the HCMV vector and is Vir’s first preclinical pipeline candidate to expand our pipeline beyond infectious disease into viral-associated cancer.
1https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-and-cancer