SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Asher Biotherapeutics, Inc. (Asher Bio), a biotechnology company focused on developing therapies to precisely engage specific immune cells to fight cancer, chronic viral infection and autoimmune disease, today announced new preclinical data demonstrating proof-of-concept for AB359 as a novel immunotherapy approach for chronic HBV. AB359 is Asher Bio’s CD8-targeted interleukin-2 (IL-2) immunotherapy for the treatment of chronic viral infection. The data will be presented in a poster presentation at the American Association for the Study of Liver Disease (AASLD) 2022 Annual Meeting, being held in Washington, DC, on November 4-8, 2022.
“We are pleased to share these foundational preclinical data for AB359, demonstrating the broad applicability of our cis-targeting approach to potentially overcome key shortcomings of cytokine therapeutics and immunotherapies across a range of therapeutic areas, including oncology and now chronic viral infection,” said Andy Yeung, Ph.D., Chief Technology Officer and Co-founder of Asher Bio. “Chronic HBV is a major global health burden, which affects over 250 million people worldwide. Existing antiviral standard of care medicines, however, are indicated for only a subset of patients and offer low cure rates. Using our modular cis-targeting platform, we developed AB359 to selectively activate CD8+ T cells, which are important for clearing viruses, but become dysfunctional in patients with chronic HBV. We look forward to continuing to advance AB359 through preclinical development.”
CD8+ T cells have been shown to be involved in clearing some viral infections, including HBV. While functional HBV-reactive CD8+ T cells are detectable in HBV patients that clear viral infection, they are challenging to detect in patients with chronic HBV, suggesting the responses of CD8+ T cells against HBV antigens may be deficient in chronically infected patients. In addition, in preclinical HBV models that recapitulate HBV-induced CD8+ T cell dysfunction, IL-2-based treatment was observed to reduce this CD8+ T cell defect, suggesting that IL-2 therapy may offer a promising approach to reinvigorate immunity against HBV. Asher Bio developed AB359 as a novel immunotherapy for chronic HBV, which selectively acts on CD8+ T cells to avoid the pleiotropy that has historically limited the clinical utility of broadly acting IL-2 based therapies.
In a poster presentation titled, “Selective activation of the IL-2 pathway in CD8+ T cells drives antiviral activity in a hepatitis B virus (HBV) model,” lead author Kelly Moynihan, Ph.D., Senior Director and Project Team Leader at Asher Bio, described the molecular design of AB359 and presented preclinical in vitro and in vivo data that support the development of AB359 as a novel immunotherapy approach, which could contribute to ongoing efforts to develop curative therapeutic regimens for chronic HBV. The data show:
- A murine surrogate of AB359 (muAB359) enabled superior activity on CD8+ T cells in vitro and in vivo, as compared to an untargeted representative of the “not-α” IL-2 and IL-15 molecule class, which demonstrated only modest CD8+ T cell activation, and instead showed strongest activity on NK cells.
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In a transgenic mouse model of HBV that recapitulates key features of the CD8+ T cell dysfunction observed in chronically infected HBV patients, muAB359 demonstrated greater HBV control than a representative “not-α” IL-2.
- Treatment with muAB359 resulted in higher levels of cytolysis of HBV-expressing hepatocytes, approximately 7 to 13-fold greater reduction in serum HBV DNA and a stronger decrease in HBV core antigen levels in the liver.
- Superior pharmacology on HBV-reactive CD8+ T cells was observed with muAB359, resulting in 20-fold higher numbers and greater functionality of HBV-reactive CD8+ T cells.
- While the “not-α” IL-2 had a stronger effect on NK cells, this NK cell activation was not associated with substantial decreases in serum HBV DNA or HBV core antigen levels in the liver.
- No evidence of liver toxicity was observed following muAB359 treatment in wild-type mice.
The poster presentation will be available in the “Presentations and Posters” section of Asher Bio’s website: https://asherbio.com/pipeline/presentations-publications/.
About Asher Bio
Asher Bio is a biotechnology company focused on developing therapies to precisely engage specific immune cells to fight cancer, chronic viral infection and autoimmune disease. We utilize our proprietary cis-targeting platform to develop therapies engineered to overcome limitations of other immune-based treatments by selectively activating specific immune cell types with validated disease fighting functionality. Our candidates feature an antibody connected to a modified immunomodulatory protein, such as a cytokine. Our candidate design is intended to enable our candidates to selectively activate the desired immune cells and not other cells that contribute to toxicity or immune suppression. Asher Bio was founded by Ivana Djuretic and Andy Yeung with support from Third Rock Ventures and is located in South San Francisco. For more information, please visit www.asherbio.com and follow us on Twitter @AsherBio and on LinkedIn.
