Unveiling Promising New Treatments for Hepatitis: Arbutus Presents Clinical and Preclinical Data at Global Summit

Arbutus Biopharma Corporation (Nasdaq: ABUS) unveiled groundbreaking clinical and preclinical data for two of its most promising antiviral therapies: AB-729, an RNAi therapeutic, and AB-161, an innovative oral HBV specific RNA destabilizer, at the Global Hepatitis Summit 2023 in Paris.

This exciting news from Arbutus, a clinical-stage biopharmaceutical company with a special focus on developing innovative treatments for viral diseases, proves that the company is continuing to make strides in the fight against hepatitis.

Dr. Man-Fung Yuen, Chief of the Division of Gastroenterology and Hepatology at The University of Hong Kong, presented data on nine patients with chronic hepatitis B virus infection (cHBV) who completed 48 weeks of treatment with AB-729 and stopped taking nucleos(t)ide analogue (NA) therapy 24 weeks later.

It has been over 1.5 years since the last AB-729 dose for 7 of these 9 patients, and they remain off NA therapy with low HBV DNA and HBsAg levels below baseline. Furthermore, no adverse effects or ALT flares have been observed during follow-up. These results demonstrate the potential of AB-729 as an effective and safe treatment for cHBV.

The results of the AB-729 study are incredibly encouraging, with low levels of HBsAg and HBV DNA persisting in the majority of patients for at least 18 months after their last dose. What’s even more remarkable is that these patients have not experienced any ALT flares, indicating that the body is controlling the virus.

This is a huge step forward compared to the current treatments available for cHBV, which can involve 48 weeks of interferon treatment or life-long NA therapy to keep the virus suppressed. We are excited to continue monitoring these patients for a potential functional cure.

Seven HBV DNA negative, HBeAg positive patients enrolled in a trial had post-treatment follow-up data presented by Professor Yuen. Results showed that the mean log10 change from baseline in HBsAg was -2.57 IU/mL at week 48 and -1.86 IU/mL at follow-up week 48.

Furthermore, mean log decline in HBeAg was greater than 1.0 log10 at the last follow up visit, despite some patients having low HBeAg levels at baseline. Remarkably, one patient achieved both HBsAg and HBeAg below the lower limit of quantitation (LLOQ), with detectable anti-HBs antibodies. Additionally, two other patients had either HBsAg or HBeAg <LLOQ during the trial.

Professor Yuen continued to be amazed by the post-treatment follow-up data from AB-729-001 clinical trial, which has proven that AB-729 treatment is highly effective in reducing HBsAg levels, no matter the dose, dosing interval, or the patient’s baseline characteristics.

William Collier, Arbutus’ President and Chief Executive Officer, expressed his confidence in AB-729’s potential as a key component of a curative combination treatment for chronic HBV. He noted that AB-729 is the only RNAi therapeutic in development for HBV which has demonstrated its ability to reduce HBV DNA and HBsAg and stimulate the immune system in a clinical setting. Collier is dedicated to advancing AB-729 to provide a viable treatment option.

This year, two Phase 2a clinical trials are underway to evaluate the potential of AB-729 in treating HBV. One trial is exploring the combination of AB-729 with Vaccitech’s VTP-300, an HBV antigen-specific immunotherapeutic, while the other is assessing its use with pegylated interferon alfa-2a (IFN). We eagerly await the preliminary results from these trials, which could bring us one step closer to a much-needed HBV treatment.

At the same congress, Dr. Angela M. Lam, Vice President of Biology at Arbutus Biopharma, presented groundbreaking preclinical antiviral data on AB-161, a potent small-molecule HBV RNA destabilizer being developed as an orally administered antiviral agent for cHBV infection. The data demonstrate that AB-161 suppresses HBV RNA and HBsAg production both in vitro and in vivo, reducing circulating HBsAg levels in a dose-dependent manner in mice.

Furthermore, mechanism of action studies show that AB-161 promotes viral transcript degradation and reduces viral proteins and viral replication. Preclinical pharmacokinetic data and repeat dose toxicology studies reveal enhanced liver concentrations and lack of peripheral neuropathy.

Dr. Michael J. Sofia, Chief Scientific Officer of Arbutus Biopharma, is thrilled to share the new data on AB-161 and its potential to offer a functional cure for cHBV. These data show it has the ability to selectively degrade HBV RNAs, reducing HBsAg levels and inhibiting viral replication.

Compared to other classes of HBV inhibitors, AB-161 has a highly differentiated mode of action. This makes it an exciting prospect for a combination regimen. A Phase 1 clinical trial in healthy subjects has been initiated and the initial data is expected to be shared in the second half of this year.

About AB-729

Arbutus’ AB-729, an innovative RNA interference (RNAi) therapeutic, is designed to reduce all HBV viral proteins and antigens, including hepatitis B surface antigen. Through advanced covalently conjugated N-Acetylgalactosamine (GalNAc) delivery technology, AB-729 is able to be administered via subcutaneous injection.

Clinical trials have shown AB-729 to be safe and well-tolerated, while providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA. Phase 2a clinical trials are currently underway, with promising results.

About AB-161

AB-161 is a breakthrough oral small molecule RNA destabilizer that is designed to target the liver and specifically combat hepatitis B virus (HBV). By targeting the host proteins PAPD5/7, which regulate the stability of HBV RNA transcripts, AB-161 selectively degrades HBV RNAs, thus reducing HBsAg levels and inhibiting viral replication. As such, this all-oral treatment regimen offers a unique and effective approach to treating chronic HBV and is a crucial part of developing a comprehensive treatment plan.

About HBV

Hepatitis B is an insidious virus that can cause serious and potentially life-threatening damage to the liver. According to the World Health Organization, an estimated 290 million people around the world are living with chronic HBV infection. In the United States alone, around 2.4 million people are affected.

Unfortunately, despite the availability of vaccines and treatments, 820,000 people die annually from complications associated with the virus. This is an alarming statistic and demonstrates the need for more effective measures to combat this condition.

About Arbutus

Arbutus Biopharma Corporation (Nasdaq: ABUS) is a clinical-stage biopharmaceutical company developing pioneering therapeutics to treat viral diseases. Our research is targeted at Hepatitis B virus (HBV) and SARS-CoV-2, as well as other coronaviruses.

To combat HBV, we are developing a unique combination of an RNAi therapeutic, an oral PD-L1 inhibitor and an oral RNA destabilizer with the aim of providing a functional cure for chronic HBV patients by suppressing viral replication, reducing surface antigen and reawakening the immune system.

Our lead compound AB-729 is the only RNAi therapy with evidence of immune re-awakening, and is currently being tested in multiple phase 2 clinical trials. We are also exploring the potential of our PD-L1 portfolio to treat oncology applications, as well as actively researching and developing novel, orally active agents for treating coronaviruses, including SARS-CoV-2.

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