AVS100 / Avstera - LARVOL DELTA

AVS100, a Novel Selective HDAC6 Inhibitor Reprograms Metabolism to Drive Weight Loss in DIO Mice (OBESITY WEEK 2026) - No abstract available

Preclinical

Macrophage-Centric Phenotypic Screening Identifies Tetrazolone-Based HDAC6 Inhibitors That Reprogram the Tumor Immune Microenvironment and Improve Immune Checkpoint Blockade. (PubMed, J Med Chem) - "Building on the HDAC6 inhibitor SS-208, we synthesized a novel class of tetrazolone-based compounds with potent selectivity and minimal cytotoxicity...Combination with anti-PD-1 therapy further enhanced immune infiltration, increased effector memory and central memory T-cells, and improved antitumor efficacy. This study establishes a functional screening framework for identifying immunomodulatory compounds and supports the clinical potential of macrophage-targeted HDAC6 inhibitors as adjuncts to immune checkpoint blockade."

Checkpoint inhibition • Journal • Melanoma • Oncology • Solid Tumor

Development of selective HDAC6 inhibitors to improve cancer immunotherapy (AACR 2024) - "We initially designed in silico 980 compound derivatives from previously reported HDAC6i, such as SS208, Nexturastat A, and Suprastat. Two of these compounds, SM-06-09 and SM-05-947, will be further tested in syngeneic murine melanoma models for their ability in tumor regression and antitumor immunity. This study has yielded important insights into developing new and improved HDAC6is with minimal cytotoxicity, and we believe our work will help advance cancer research and ultimately lead to better patient outcomes."

IO biomarker • Melanoma • Oncology • Solid Tumor • TNFA

The HDAC6-specific inhibitor AVS100 (SS208) blocks M2 polarization of tumor associated macrophages and potentiates immunotherapy in preclinical tumor models (AACR 2024) - "Altogether, we have performed the preclinical characterization of a novel small molecule inhibitor targeting HDAC6 for solid cancers. AVS100 had an antitumoral effect as single agent and improved the efficacy of immune checkpoint inhibition by blocking the immunoregulatory tumor microenvironment and increasing T-cell immunity."

IO biomarker • Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • CD8 • MRC1

Functional classification of tumor-associated macrophages and changes in TAM subpopulations in response to various immunotherapies (AACR 2025) - "Samples from mice with SM1 melanoma tumors that have been treated with ɑ-PD-1 immune checkpoint blockade, the novel HDAC6 inhibitor SS208, combination SS208 + ɑ-PD-1, and adoptive cell therapy (ACT) using HDAC6 inhibition show changes in the proportions of putative subpopulations, most notably a significant decrease in "Pro-Angiogenic/Arginine Metabolism" macrophages within tumors after all treatments, an increase in "Antigen Presenting/Phagocytosis" macrophages in mice treated with ɑ-PD-1 therapy, and an increase in proliferating macrophages in mice treated with ACT...The proposed functions of these subpopulations have been further confirmed by in vitro and ex vivo functional assays from isolated TAMs. Additionally, we outline an efficient method for applying the proposed subpopulation gene signature to bulk RNA seq data of macrophages, which allows for more accurate analysis of changes in TAM subpopulation in response to therapy."

Clinical • IO biomarker • Melanoma • Oncology • Solid Tumor • CSF1

The HDAC6 inhibitor AVS100 (SS208) induces a pro-inflammatory tumor microenvironment and potentiates immunotherapy. (PubMed, Sci Adv) - "Last, AVS100 showed no mutagenicity, toxicity, or adverse effects in preclinical good laboratory practice studies, part of the package that has led to US Food and Drug Administration clearance of an investigational new drug application for initiating clinical trials. This would be a first-in-human combination therapy of pembrolizumab with HDAC6 inhibition for locally advanced or metastatic solid tumors."

Biomarker • IO biomarker • Journal • Tumor microenvironment • Colon Cancer • Colorectal Cancer • Melanoma • Oncology • Solid Tumor • CD8

Avstera Therapeutics Announces FDA Clearance of IND Application for AVS100, a Novel Highly Selective HDAC6 Inhibitor Targeting Solid Tumors (PRNewswire) - "Avstera Therapeutics Corp...today announced the U.S. FDA clearance of its Investigational New Drug application (IND) for AVS100, a novel highly selective oral HDAC6 inhibitor intended to treat locally advanced or metastatic solid tumors in a Phase I clinical study...The Phase Ia/b clinical trial for AVS100 is targeting locally advanced or metastatic solid tumors. This trial is an open label, dose-escalation and confirmation study to characterize the safety, tolerability, pharmacokinetics, and MTD of AVS100 when administered as a monotherapy and in combination with pembrolizumab...Avstera intends to initiate the Phase Ia/b clinical trial in the first half of 2024. The principal investigator of the study is Apostolia M Tsimberidou, MD, PhD, FASCO, FAAAS, Professor of Medicine at MD Anderson Cancer Center, Houston, TX."

IND • New P1 trial • Oncology • Solid Tumor

Avstera Therapeutics Receives FDA Orphan Drug Designation on AVS100 for Treatment of Advanced Stage Melanoma (PRNewswire) - "Avstera Therapeutics Corp...has announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to Avstera's AVS100 compound, which is a highly specific HDAC6 inhibitor, for the treatment of stage IIB through IV melanoma."

Orphan drug • Melanoma • Oncology • Skin Cancer • Solid Tumor

Avstera Therapeutics Closes Seed Round to Advance its Lead Programs Targeting Solid Tumors (PRNewswire) - "Avstera Therapeutics...has announced the completion of its seed round to advance its lead cancer programs geared towards targeting solid tumors. The company intends to use proceeds to enable its lead highly specific HDAC6i for IND filing targeting locally advanced and metastatic solid tumors by the end of next year."

Financing • IND • Oncology • Solid Tumor