Asher Bio Presents New Preclinical Data Further Supporting Development of AB359 for Chronic Hepatitis B Virus at EASL International Liver Conference 2023

Asher Biotherapeutics, a biotechnology company developing precisely-targeted immunotherapies for cancer, autoimmune, and infectious diseases, today announced new preclinical data supporting continued development of AB359, Asher Bio's novel immunotherapy approach for chronic HBV. AB359 is an investigational therapy designed to selectively activate CD8+ effector T cells, thereby offering the potential to enhance the immune response to chronic viral infections, including HBV. The data will be presented in an oral presentation at the International Liver Congresstm, the Annual Meeting of the European Association for the Study of the Liver (EASL) taking place in Vienna, Austria June 22-26, 2023.

"We are excited to share new preclinical data for AB359, which highlight the strength of our cis-targeting platform to generate promising candidates across a broad range of therapeutic areas and, in particular, our ability to develop promising differentiated cytokine therapeutic candidates for the treatment of infectious diseases," said Ivana Djuretic, Ph.D., Founder and Chief Scientific Officer of Asher Bio. "In the case of chronic HBV, we aim to selectively increase the quantity and functionality of CD8+ T cells, which are known to be involved in clearing viral infection, while avoiding the pleiotropy that has historically limited the clinical utility of broadly acting IL-2-based therapies. The new data presented at EASL show that treatment with our molecule significantly invigorated HBV-specific CD8+ T cells, resulting in substantial reductions in key markers of HBV infection. Based on these data, we believe AB359 could offer an improvement over existing antiviral treatments for HBV, which are indicated only for a subset of patients and offer low cure rates. We are seeking partnership opportunities with companies with requisite hepatitis drug development expertise and capabilities to support the advancement of AB359, with the goal of developing a novel immunotherapy for chronic HBV, a major global health burden that impacts over 250 million people worldwide."

New Preclinical Data for AB359, Asher Bio's CD8-Targeted IL-2

In an oral presentation in General Session 1 at the EASL Congress on June 22, 2023, titled, "Selective activation of the IL-2 pathway in CD8+ T cells drives antiviral activity to Hepatitis B Virus (HBV)" lead author and Asher Bio collaborator Matteo Iannacone, M.D., Ph.D., Group Leader San Raffaele Scientific Institute and University, Milan, Italy, described new preclinical in vivo data further supporting the development of AB359 as a promising approach for the treatment of chronic HBV. The data show:

• A murine surrogate of AB359 (muAB359) demonstrated compelling antiviral activity in a mouse model of HBV that recapitulates key features of the CD8+ T cell dysfunction observed in chronically infected HBV patients.
  • A single dose of muAB359 demonstrated significant reduction in two key markers of HBV infection, showing over 100-fold reduction in serum HBV core DNA and a 79% decrease in serum Hepatitis B surface antigen levels.
  • In a challenging delayed therapy setting, treatment with muAB359 demonstrated an ability to re-invigorate highly dysfunctional HBV-reactive CD8+ T cells, whereas no anti-viral activity was detected following treatment with an untargeted representative of the "not-?" IL-2 molecule class.
  • muAB359's antiviral activity was associated with robust increases in the quantity and functionality of HBV-specific CD8+ T cells. In contrast, treatment with an untargeted "not-?" IL-2 molecule showed preferential expansion of IL-2R??^high NK cells, modest CD8+ T cell expansion, and minimal changes to markers of functionality by HBV-reactive CD8+ T cells, resulting in minimal antiviral activity.
• Cynomolgus monkeys dosed with AB359 showed dose dependent, selective expansion of CD8+ T cells, with up to 20-fold CD8+ T cell expansion observed following a single dose.

The presentation will be available in the "Presentations and Posters" section of Asher Bio's website: https://asherbio.com/pipeline/presentations-publications/.

About AB359

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.

About Asher Bio

Asher Bio is a biotechnology company 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. Our lead program AB248, an IL-2 molecule specifically targeted to CD8+ effector T cells, is currently in Phase 1 trials for oncology. 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.