MPT0E028 / Anbogen Therap, Formosa Labs - LARVOL DELTA

A Study of ABT-301 Plus Tislelizumab With Bevacizumab in pMMR/Non-MSI-H Locally Advanced or mCRC (clinicaltrials.gov) - P1/2 | N=66 | Recruiting | Sponsor: Anbogen Therapeutics, Inc.

Mismatch repair • MSI-H • New P1/2 trial • pMMR • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor

Anbogen Receives FDA Clearance to Initiate Phase 1/2 Trial of ABT-301 Triplet Therapy for Advanced Colorectal Cancer (PRNewswire) - "Anbogen Therapeutics today announced that the U.S. Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) application for ABT-301, enabling the initiation of a Phase 1/2 clinical trial in combination with tislelizumab and bevacizumab for patients with metastatic colorectal cancer (mCRC). This open-label, multi-center international study plans to enroll 66 patients with proficient mismatch repair (pMMR) or non-microsatellite instability-high (non-MSI-H) mCRC to evaluate the safety and preliminary efficacy of the triplet therapy. Enrollment is planned in Taiwan and Australia. Tislelizumab, a PD-1 monoclonal antibody, used in this trial is provided by BeOne Medicines (formerly known as BeiGene). Further details on this collaboration were disclosed by Anbogen in a press release dated September 27, 2024."

IND • New P1/2 trial • Colorectal Cancer

Synergistic Anti-Tumor Effects of the Novel HDAC Inhibitor, ABT-301, with Immune Checkpoint Inhibitors in Colorectal Cancer Through Regulation of Immune Response and Anti-Angiogenesis (EORTC-NCI-AACR 2024) - "The anti-angiogenic activity was determined by immunohistochemical (IHC) staining for the microvessel marker CD31.. In both subcutaneous CT26 and MC38 models, therapeutic regimen combining ABT-301 with murine anti-PD-1 or anti-PD-L1 antibodies (avelumab) synergistically inhibited tumor growth and yield a statistically significant elevation in the rate of complete remission and overall survival relative to monotherapy. In Conclusion, ABT-301 is an isotype-selective HDAC inhibitor with potent immune modulation and antiangiogenic activity and shows promising synergistic antitumor efficacy when combined with ICIs in CRC. These findings warrant further investigation in clinical trials."

Checkpoint inhibition • IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • CD31 • CD8 • MSI • PECAM1

Anbogen Announces Drug Supply Collaboration with BeiGene to Evaluate Combination Therapy in Colorectal Cancer (PRNewswire) - "Anbogen...today announced a drug supply collaboration to evaluate the combination of Anbogen's HDAC inhibitor, ABT-301, with BeiGene's anti-PD-1 antibody tislelizumab, in patients with mismatch repair–proficient (pMMR) or microsatellite stable (MSS) metastatic colorectal cancer (mCRC) in a global Phase II trial. Under the terms of the agreement, BeiGene will supply tislelizumab to Anbogen for the study....The upcoming Phase II study will investigate the effectiveness of treatment regimens combining ABT-301 and tislelizumab, with and without Bevacizumab, in pMMR/MSS mCRC patients with significant unmet needs....The clinical trial will be conducted in multiple centers and will evaluate the safety, tolerability, and preliminary efficacy of the combination therapy in patients with advanced MSS CRC. The study is expected to begin enrollment in the first quarter of 2025."

Licensing / partnership • New P2 trial • Colorectal Cancer

Anbogen Therapeutics Announces Completion of A+ Round Financing to Advance ABT-301 Phase II Clinical Trial (PRNewswire) - "Anbogen Therapeutics, Inc...has announced the successful closing of a USD 7.3M oversubscribed A+ round financing, which is a direct continuation of the USD 12.5 Million Series A on 1st February, 2024, bringing the total raised to USD 19.8M. The funds from the A+ round will be specifically used to advance the Phase II clinical trial of ABT-301. The financing round was led by KGI Venture Capital and both new and existing investors....The capital raised in the A+ round will primarily be used to support the Phase II clinical trial of ABT-301 in combination with PD-1 inhibitors for treating microsatellite stable (MSS) metastatic colorectal cancer, which accounts for 95% of the metastatic colorectal cancer population that does not benefit from immune checkpoint inhibitors."

Financing • Colorectal Cancer • Gastrointestinal Cancer • Solid Tumor

MPT0E028, a novel pan-HDAC inhibitor, prevents pulmonary fibrosis through inhibition of TGF-β-induced CTGF expression in human lung fibroblasts: involvement of MKP-1 activation. (PubMed, Eur J Pharmacol) - "Pretreatment with MPT0E028 reduced the fibrosis score and fibronectin, collagen, and α-SMA expression in bleomycin-induced pulmonary fibrosis mice. In conclusion, MPT0E028 induced MKP-1 acetylation and activation, which in turn inhibited TGF-β-stimulated JNK, p38, and ERK phosphorylation; SMAD3 and AP-1 activation; and subsequent CTGF expression in human lung fibroblasts. Thus, MPT0E028 may be a potential drug for treating pulmonary fibrosis."

Journal • Fibrosis • Immunology • Oncology • Pulmonary Disease • Respiratory Diseases • CTGF • EDN1 • FN1 • MAPK8 • SMAD3 • TGFB1

Anbogen Secures 12.5 Million in Series A Funding, Advancing Precision Oncology Drug Development (PRNewswire) - "The raised capital will be directed towards the ongoing development of Anbogen's two main drug candidates, ABT-101 and ABT-301....Phase 2 is scheduled to commence upon the completion of phase 1 trial in 2024....Anbogen has initiated preparations for the Phase 2 clinical trial of ABT-301, combining it with ICIs for the treatment of cancer patients."

Financing • New P2 trial • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Phase I first-in-human trial of ABT-301, an oral pan-HDAC inhibitor, in patients with advanced solid tumors. (ASCO 2023) - P1 | "Preclinical studies showed that ABT-301 had a stronger apoptotic activity and inhibited HDAC activity more potently than vorinostat. ABT-301 was well-tolerated at a daily dose of up to 150 mg and demonstrated objective responses and long-term SD across multiple tumor types at MTD. The safety profile of ABT-301 was superior to known HDAC inhibitors with only predictable HDAC inhibitor-related toxicities observed but no cardiac toxicity, neutropenia, nor lymphopenia elicited. Non-clinical and clinical results suggested the potential clinical development of ABT-301 in combination with myelosuppressive agents and immunotherapies."

Clinical • Metastases • P1 data • Anemia • Anorexia • Colorectal Cancer • Diabetes • Endometrial Cancer • Fatigue • Gastrointestinal Cancer • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Hepatocellular Cancer • Immune Modulation • Lymphoma • Mucositis • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain • Renal Cell Carcinoma • Salivary Gland Cancer • Sarcoma • Solid Tumor • Thrombocytopenia • Thymus Cancer • HDAC11

A Potent Histone Deacetylase Inhibitor MPT0E028 Mitigates Emphysema Severity via Components of the Hippo Signaling Pathway in an Emphysematous Mouse Model. (PubMed, Front Med (Lausanne)) - "Our study showed that the potent HDAC inhibitor MPT0E028 reduced the severity and inflammation of emphysema with improvement in lung function, which could be regulated by Hippo signaling pathway. The MPT0E028 may have therapeutic potential for emphysema."

Epigenetic controller • Journal • Preclinical • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • ELANE • IL6 • SFTPC • SIRT1 • TNFA • TP53

Combination treatment strategy for pancreatic cancer involving the novel HDAC inhibitor MPT0E028 with a MEK inhibitor beyond K-Ras status. (PubMed, Clin Epigenetics) - "The synergistic anti-survival effect of the combination was suggested to occur via compensation of the MEK inhibitor for activated ERK. Our results indicate that this combination strategy could benefit patients with pancreatic cancer beyond K-Ras status."

Journal • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Investigating the potential effects of selective histone deacetylase 6 inhibitor ACY1215 on infarct size in rats with cardiac ischemia-reperfusion injury. (PubMed, BMC Pharmacol Toxicol) - "Our research indicated that HDAC6 inhibition by ACY1215 might reduce infarct size in rats with cardiac IR injury possibly through modulating HIF-1α expression. TGF-β and CRP should be useful biomarkers to monitor the use of ACY1215 in cardiac IR injury."

Journal • Preclinical • CRP • HIF1A

Dose-Seeking Study of MPT0E028 in Subjects With Advanced Solid Malignancies Without Standard Treatment (clinicaltrials.gov) - P1; N=23; Completed; Sponsor: Taipei Medical University; Recruiting ➔ Completed; Trial completion date: Jun 2019 ➔ Jan 2019

Clinical • Trial completion • Trial completion date