AVA-ADR / Avammune - LARVOL DELTA

First-in-class Zα-domain-targeted ADAR1 p150 inhibitor demonstrates potent antitumor efficacy in high IFN syngeneic melanoma (AACR 2026) - "Additionally, we evaluated the potential of this ADAR1 p150 inhibitor as a novel payload delivered via PD-L1-targeted ADCs. A series of ADAR1 p150 inhibitors (AVA-ADR) were identified using a high-throughput binding assay, Zα domain binding confirmed by FRET assay... To our knowledge no selective small molecule inhibitors of ADAR1 p150 targeting the Za domain have been reported so far. Our SAR approach yielded several next generation Zα binders with nM potency demonstrating effective and competitive displacement of the tightly bound Z-DNA. Next generation compounds demonstrate low nM interferon dependent toxicity in OE21 cell lines."

Clinical • IO biomarker • Melanoma • Oncology • Solid Tumor • ADAR • IFNB1 • IGF2BP1 • ZBP1

Discovery of a first-in-class ADAR1 p150 inhibitor targeting the Zα-domain with potent anti-tumor efficacy in syngeneic mouse models (SITC 2025) - "The anti-tumor efficacy of AVA-ADR-001 was assessed in a B16F10 syngeneic melanoma mouse model, both as a monotherapy and in combination with anti-PD-1 therapy.Results We identified novel series of small-molecule inhibitor of ADAR1 p150 that elicits a robust interferon response in an MDA5-dependent manner...Second-generation AVA-ADR compounds are stable, orally bioavailable, first-in-class ADAR1 inhibitors that induce robust interferon responses both in vitro and in vivo. These inhibitors achieve substantial tumor growth inhibition as a monotherapy and demonstrate synergistic efficacy when combined with anti-PD-1 therapy."

IO biomarker • Preclinical • Melanoma • Oncology • Solid Tumor • ADAR • IFIH1 • IGF2BP1 • ZBP1

Discovery of a potential first-in-class inhibitor targeting ADAR1 p150 isoform with strong anti-tumor efficacy in syngeneic melanoma mouse model (SITC 2024) - "The anti-tumor efficacy of AVA-ADR-001 was evaluated in B16F10 syngeneic melanoma mice model as monotherapy and in combination with anti-PD-1...2nd generation AVA-ADR compounds are stable/orally bioavailable first-in-class ADAR1 inhibitor that demonstrated significant IFN induction in-vitro and in-vivo, demonstrating significant tumor growth inhibition as monotherapy and synergistically in combination with Anti -PD1. Ethics Approval Ethics approval for all studies were obtained from institutional review boards."

IO biomarker • Preclinical • Melanoma • Oncology • Solid Tumor • ADAR • IFIH1 • IGF2BP1 • ZBP1

Discovery of a potential first-in-class Za targeted small molecule inhibitor of ADAR1 p150 which demonstrates strong anti-tumor efficacy (AACR 2024) - "To our knowledge, AVA-ADR-001 and AVA-ADR-703 are the first selective Zα-targeted small molecule inhibitor and degrader of ADAR1 p150 respectively to be disclosed. As a powerful and targeted first-in-class ADAR1 inhibitor, AVA-ADR-001 has demonstrated a strong induction of interferon (IFN) in a number of cancer cell lines and in vivo. AVA-ADR-001 has also demonstrated strong in vivo anti-tumor efficacy as monotherapy and in combination with anti-PD1."

Clinical • Hematological Malignancies • Melanoma • Multiple Myeloma • Oncology • Skin Cancer • Solid Tumor • ADAR • CXCL10 • IFIH1 • IFNB1

Discovery of a potential first-in-class small molecule inhibitor of ADAR1 p150 which demonstrates strong anti-tumor efficacy in B16F10 syngeneic melanoma model (SITC 2023) - "Conclusions To our knowledge, AVA-ADR-001 is the first disclosure of a selective small molecule inhibitor of ADAR1 p150. AVA-ADR-001 is a potent and selective first-in-class ADAR1 inhibitor which has shown significant IFN induction in vitro and in vivo in the tumor microenvironment resulting in substantial tumor growth inhibition as monotherapy and synergistically in combination with Anti-PD1."

Clinical • IO biomarker • Melanoma • Oncology • Solid Tumor • ADAR • IFIH1

Development of a novel ADAR1 inhibitor as a potent immunomodulator for the treatment of solid tumors (AACR 2023) - "To our knowledge no selective small molecule inhibitors of ADAR1 have been reported so far and AVA-ADR-001 is the first disclosure of such an inhibitor. AVA-ADR-001 is a potent and selective first-in-class ADAR1 inhibitor which has shown significant IFN induction in various cancer cell lines and in vivo in the tumor microenvironment resulting in substantial tumor growth inhibition as monotherapy and synergistically in combination with Anti-PD1. Considering the immune-suppressive and pro-metastatic role of ADAR1, AVA-ADR-001 serves as a promising starting point for novel ADAR1 inhibitors as therapeutic modalities in cancer immunotherapy."

Immunomodulating • Esophageal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Melanoma • Multiple Myeloma • Oncology • Solid Tumor • ADAR • CXCL10 • IFIH1 • IFNB1

AVA-ADR-001 Supresses Tumor Growth and Induces Anti-tumor Immunity by Selectively Inhibiting ADAR1 p150 (SITC 2022) - "AVA-ADR-001 is a potent and selective first-in-class ADAR1 inhibitor which has shown significant IFN induction in various cancer cell lines and in vivo in the tumor microenvironment resulting in substantial tumor growth inhibition as monotherapy and synergistically in combination with Anti-PD1. Considering the immune-suppressive and pro-metastatic role of ADAR1, AVA-ADR-001 serves as a promising starting point for novel ADAR1 inhibitors as therapeutic modalities in cancer immunotherapy."

Esophageal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Melanoma • Multiple Myeloma • Oncology • Solid Tumor • ADAR • CXCL10 • IFIH1 • IFNB1