ABT-101 / National Health Research Institutes, Anbogen Therap - LARVOL DELTA

Discovery of novel AXL and MER inhibitors as potential anticancer and immunomodulatory drugs (AACR 2024) - "Drawing on our experience in the discovery of an anti-EGFR and anti-HER2 clinical candidate, we introduced several AXL-active and MER-active pharmacophores into DBPR112. BPR5K230 effectively addressed sorafenib resistance in the Hepa 1-6 model and exhibited significant synergistic antitumor effects when combined with an anti-PD-L1 antibody in the EMT-6 model. As a result, BPR5K230 represents a promising dual AXL/MER kinase inhibitor, and further preclinical evaluation is underway for its development as a potential anticancer and immune-modulating drug."

Immunomodulating • IO biomarker • Oncology • AXL

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 1b/2 Study to Evaluate ABT-101 in Solid Tumor and NSCLC Patients (clinicaltrials.gov) - P1/2 | N=61 | Recruiting | Sponsor: Anbogen Therapeutics, Inc. | Phase classification: P1b/2 ➔ P1/2 | N=121 ➔ 61

Enrollment change • HER2 exon 20 • Metastases • Phase classification • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Discovery of novel AXL and MER inhibitors as potential anticancer and immune modulator drugs (ESMO 2023) - "Methods Based on our experience in the discovery of an anti-EGFR and anti-HER2 clinical candidate, we introduced several AXL-active and MER-active pharmacophores into DBPR112...Our compound also overcome erlotinib-acquired resistance via the combination with erlotinib in the PC9 xenograft model...Moreover, 5K230 displayed anti-tumor efficacy in several mouse xenograft models. Further preclinical evaluation of 5K230 is underway to develop it as a promising anticancer and immune modulator drug."

Oncology • AXL

Phase 1b/2 Study to Evaluate ABT-101 in Solid Tumor and NSCLC Patients (clinicaltrials.gov) - P1b/2 | N=121 | Recruiting | Sponsor: Anbogen Therapeutics, Inc. | Trial completion date: Nov 2023 ➔ May 2027 | Trial primary completion date: Apr 2023 ➔ Nov 2026

HER2 exon 20 • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

AnBogen Therapeutics Receives Approval from U.S. FDA for Phase Ib/II Protocol Amendment for ABT-101 (PRNewswire) - "AnBogen Therapeutics...announces today that U.S. Food and Drug Administration (FDA) has approved an investigational new drug (IND) protocol amendment for its phase Ib/II trial of ABT-101, an orally administered, irreversible, mutant selective tyrosine kinase inhibitor targeting oncogenic mutations of HER2 Exon20 insertion expressed in non-small cell lung cancer (NSCLC)."

Clinical protocol • FDA event • HER2 exon 20 • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • HER-2

Discovery of clinical candidate DBPR112, a furanopyrimidine-based epidermal growth factor receptor inhibitor for the treatment of non-small cell lung cancer (ESMO 2019) - P1; "The results of the multi-objective optimization obtained the clinical candidate, compound 78 (DBPR112), which not only displayed a potent inhibitory activity against EGFR L858R/T790M double mutations, but also exhibited 10-fold potency better than 3rd generation inhibitor, osimertinib, against three EGFR and one HER2 exon 20 insertion mutations, since there are currently no EGFR-directed therapies approved specifically for the treatment of this mutation. X-ray co-crystal study of EGFR WT Kinase and compound 78 revealed the potential of future design for mutant-selective inhibitors. Finally, furanopyrimidine 78 was selected as a clinical candidate to conduct all preclinical experiments and is currently undergoing phase 1 clinical trial in Taiwan. Clinical trial identification: NCT03246854."

Clinical

Discovery of a Furanopyrimidine-Based Epidermal Growth Factor Receptor Inhibitor (DBPR112) as a Clinical Candidate for the Treatment of Non-Small Cell Lung Cancer. (PubMed, J Med Chem) - "In this work, we optimized compound 2 by scaffold hopping and exploiting the potent inhibitory activity of various warhead groups to obtain a clinical candidate, 78 (DBPR112), which not only displayed a potent inhibitory activity against EGFR double mutations but also exhibited tenfold potency better than the third-generation inhibitor, osimertinib, against EGFR and HER2 exon 20 insertion mutations. Overall, pharmacokinetic improvement through lead-to-candidate optimization yielded 4-fold oral AUC better that afatinib along with F = 41.5%, an encouraging safety profile, and significant antitumor efficacy in in vivo xenograft models. DBPR112 is currently undergoing phase 1 clinical trial in Taiwan."

Clinical • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

A Study of DBPR112 in Patients With Head and Neck Cancer and EGFR Mutated Lung Cancer (clinicaltrials.gov) - P1; N=6; Terminated; Sponsor: National Health Research Institutes, Taiwan; N=24 ➔ 6; Trial completion date: May 2019 ➔ Sep 2019; Recruiting ➔ Terminated; Trial primary completion date: May 2019 ➔ Sep 2019; No more funding

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination

Newly added product (clinicaltrials.gov) - P1, Head and Neck Cancer; Non-Small Cell Lung Cancer; Lung Cancer

Pipeline update