Asher Bio 在 AASLD 2022 上展示了 AB359 的新數據

StephenW

Asher Bio 在 AASLD 2022 上展示了 AB359 的新數據，AB359 是一種高度選擇性的 CD8 靶向 IL-2 療法，用於治療慢性乙型肝炎 (HBV)
東部夏令時間 2022 年 11 月 4 日上午 08:00

加利福尼亞州南舊金山--(BUSINESS WIRE)--(美國商業資訊)--Asher Biotherapeutics, Inc. (Asher Bio) 今天宣布，該公司是一家專注於開發精確利用特定免疫細胞對抗癌症、慢性病毒感染和自身免疫性疾病的療法的生物技術公司新的臨床前數據證明 AB359 作為慢性 HBV 的新型免疫治療方法的概念驗證。 AB359 是 Asher Bio 的 CD8 靶向白細胞介素 2 (IL-2) 免疫療法，用於治療慢性病毒感染。這些數據將在 2022 年 11 月 4 日至 8 日在華盛頓特區舉行的美國肝病研究協會 (AASLD) 2022 年年會上以海報形式呈現。

    “CD8+ T 細胞中 IL-2 通路的選擇性激活驅動乙型肝炎病毒 (HBV) 模型中的抗病毒活性”
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“我們很高興分享 AB359 的這些基礎臨床前數據，證明了我們的順式靶向方法的廣泛適用性，有可能克服細胞因子療法和免疫療法在包括腫瘤學和現在的慢性病毒感染在內的一系列治療領域的關鍵缺陷，”說Andy Yeung 博士，Asher Bio 首席技術官兼聯合創始人。 “慢性 HBV 是一個主要的全球健康負擔，影響全球超過 2.5 億人。然而，現有的抗病毒標準護理藥物僅適用於一部分患者，並且治愈率較低。使用我們的模塊化順式靶向平台，我們開發了 AB359 來選擇性激活 CD8+ T 細胞，這對於清除病毒很重要，但在慢性 HBV 患者中會出現功能障礙。我們期待通過臨床前開發繼續推進 AB359。”

CD8+ T 細胞已被證明參與清除一些病毒感染，包括 HBV。雖然在清除病毒感染的 HBV 患者中可檢測到功能性 HBV 反應性 CD8+ T 細胞，但在慢性 HBV 患者中檢測到它們具有挑戰性，這表明 CD8+ T 細胞對 HBV 抗原的反應可能在慢性感染患者中存在缺陷。此外，在概括 HBV 誘導的 CD8+ T 細胞功能障礙的臨床前 HBV 模型中，觀察到基於 IL-2 的治療可減少這種 CD8+ T 細胞缺陷，這表明 IL-2 治療可能為重振對 HBV 的免疫力提供了一種有希望的方法。 Asher Bio 開發 AB359 作為慢性 HBV 的新型免疫療法，它選擇性地作用於 CD8+ T 細胞以避免多效性，這種多效性在歷史上限制了廣泛作用的基於 IL-2 的療法的臨床應用。

在題為“CD8+ T 細胞中 IL-2 通路的選擇性激活驅動乙型肝炎病毒 (HBV) 模型中的抗病毒活性”的海報展示中，主要作者 Kelly Moynihan 博士，高級總監和項目團隊負責人Asher Bio 描述了 AB359 的分子設計，並提供了支持 AB359 作為一種新型免疫治療方法開發的臨床前體外和體內數據，這可能有助於為慢性 HBV 開發治愈性治療方案的持續努力。數據顯示：

    與“非α”IL-2 和 IL-15 分子類別的非靶向代表相比，AB359 (muAB359) 的鼠替代物在體外和體內對 CD8+ T 細胞具有出色的活性，後者僅表現出適度的 CD8+ T細胞活化，反而對 NK 細胞表現出最強的活性。
    在 HBV 轉基因小鼠模型中，該模型概括了在慢性感染 HBV 患者中觀察到的 CD8+ T 細胞功能障礙的關鍵特徵，muAB359 表現出比代表性的“非α”IL-2 更好的 HBV 控制。
        用 muAB359 治療導致表達 HBV 的肝細胞的細胞溶解水平更高，血清 HBV DNA 減少約 7 至 13 倍，肝臟中 HBV 核心抗原水平下降更強烈。
        使用 muAB359 觀察到對 HBV 反應性 CD8+ T 細胞的優越藥理學，導致 HBV 反應性 CD8+ T 細胞的數量和功能增加 20 倍。
        雖然“非α”IL-2 對 NK 細胞具有更強的作用，但這種 NK 細胞活化與血清 HBV DNA 或肝臟中 HBV 核心抗原水平的顯著降低無關。
    在對野生型小鼠進行 muAB359 治療後，未觀察到肝毒性的證據。

海報演示將在 Asher Bio 網站的“演示文稿和海報”部分提供：https://asherbio.com/pipeline/presentations-publications/。

關於阿舍生物

Asher Bio 是一家生物技術公司，專注於開發療法，以精確地利用特定的免疫細胞來對抗癌症、慢性病毒感染和自身免疫性疾病。我們利用我們專有的順式靶向平台來開發旨在克服

StephenW

Asher Bio Presents New Data Demonstrating Preclinical Proof-of-Concept for AB359, a Highly Selective CD8-Targeted IL-2 Therapy, for Chronic Hepatitis B (HBV) at AASLD 2022
November 04, 2022 08:00 AM Eastern Daylight Time

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.

    “Selective activation of the IL-2 pathway in CD8+ T cells drives antiviral activity in a hepatitis B virus (HBV) model”
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“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.
    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