AV-203 / LG Chem - LARVOL DELTA

Neuregulin-induced HER3 activation drives migration in head and neck squamous cell carcinoma via HER2 and FAK signaling pathways. (PubMed, Cell Oncol (Dordr)) - "NRG promotes HNSCC cell migration by activating HER3, forming HER3-HER2 and HER3-FAK complexes, and driving downstream AKT, ERK, and FAK signaling. Targeting the NRG/HER3 axis holds potential as a therapeutic strategy to address perineural invasion and associated clinical challenges in HNC."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ERBB3 • HER-2

Structure-based Virtual Screening and Molecular Dynamics Simulation Studies to Discover New SARS-CoV-2 Main Protease Inhibitors. (PubMed, Sci Afr) - "Computational methods were used to filter two datasets (> 8,000 compounds) based on two criteria: higher binding affinity for M than cocrystallized inhibitor and binding interactions with M catalytic dyad (Cys145 and His41). After virtual screening involving ranking and reranking, eleven compounds were identified to satisfy these criteria and analysis of their structures revealed an unparallel common features among them which could be critical for their interactions with M. However, only the topmost scoring compound (AV-203: K  = 0.31 µM) exhibited relatively stable binding interaction during the period of 50 ns MD simulation and thus is a suitable template for drug development."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

CAN017, a novel anti-HER3 antibody, exerted great potency in mouse avatars of esophageal squamous cell carcinoma with NRG1 as a biomarker. (PubMed, Am J Cancer Res) - "These results were also validated in PDX models of cohort 2 indicated as the powerful anti-tumor activity of CAN017 in PDX models with NRG1 high expression. In our study, HER3-targeting therapy was first demonstrated to have potency in inhibiting ESCC tumor growth, and NRG1 served as a predictive biomarker to screen patients in future clinical trials."

Journal • Preclinical • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • NRG1

Hyperinsulinemia and insulin resistance in the obese may develop as part of a homeostatic response to elevated free fatty acids: A mechanistic case-control and a population-based cohort study. (PubMed, EBioMedicine) - "In obese subjects with normal glycaemia elevated circulating levels of FFA at fasting are the major metabolic derangement candidate driving fasting hyperinsulinemia. Elevated FFA in obese with normal glycaemia were better explained by increased fat mass rather than by adipose tissue insulin resistance. These results support the idea that hyperinsulinemia and insulin resistance may develop as part of a homeostatic adaptive response to increased adiposity and FFA."

Clinical • Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Oncology • Type 2 Diabetes Mellitus

"$AVEO to regain ex-North American rights to AV-203 following the voluntary termination of its collaboration and license agreement by CANbridge Life Sciences ." (@BioStocks)

Licensing / partnership

AVEO Oncology to Regain Ex-North American Rights to AV-203 (Businesswire) - “AVEO Oncology…announced that it will regain its rights to AV-203 outside of North America, its clinical-stage potent humanized IgG1 monoclonal antibody that targets ErbB3 (also known as HER3), following the voluntary termination of its collaboration and license agreement by CANbridge Life Sciences. AVEO will regain rights to AV-203 in all territories outside of North America, and CANbridge has initiated the process to transfer all preclinical data and materials to AVEO. The transfer of rights and termination of the collaboration and license agreement will become effective on September 5, 2021…CANbridge completed their manufacturing obligations under the agreement and AVEO received a $2 million development and regulatory milestone in August 2018...”

Licensing / partnership • Oncology

Aveo Pharmaceuticals: FY 2013 Results (Aveo Oncology) - Anticipated presentation of data from P1 trial for solid tumors at a medical meeting in 2014 

Anticipated P1 data • Oncology

A phase 1 dose escalation study of AV-203, and ERBB3 inhibitory antibody, in subjects with advanced solid tumors (clinicaltrials.gov) - P1, N=90; Recruiting; New P1 trial

New trial • Oncology

Aveo Pharmaceuticals: Jefferies Global Healthcare Conference (Aveo Oncology) - "Phase 1 AV-203 Dose-Escalation, Monotherapy Study Completed"; "22 subjects enrolled: Tumor types: 4 NSCLC (3 sq. 1  adeno); 4 CRC; 2 sq cell skin; one each ovarian, peritoneal, SCLC, endometroid, osteosarcoma, HCC, pancreatic nuroendocrine, bladder, mesothelioma, SCCHN, cervical"; "Most common treatment-related AEs were diarrhea (59%), dry skin and decreased appetite (32% each): 1 DLT observed"; "Encouraging early efficacy and support for NRG-1/HRG biomarker hypothesis: Of 22 patients, 8 SD and 1 PR, 1 of 2 NRG-1/HRG positive patients experienced a PR"   

P1 data • Oncology

AVEO Oncology: Corporate Presentation (Aveo Oncology) - Anticipated patent expiry for composition of matter in 2031; Anticipated patent expiry for NRG-1 biomarker in 2032

Anticipated patent expiry • Oncology

AVEO announces acceptance of Canbridge Investigational New Drug Application for CAN017 (AV-203) trial in esophageal squamous cell cancer (ESCC) in China (Aveo Oncology Press Release) - "AVEO Oncology...announced that the China National Drug Administration (CNDA) has accepted CANbridge Life Sciences’ Investigational New Drug (IND) Application for a Phase Ib/III clinical trial of CAN017 (AV-203)...in esophageal squamous cell cancer (ESCC)...we look forward to the initiation of a Phase Ib/extension clinical trial in ESCC..."

IND • New P1 trial • Non-US regulatory • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

AVEO Oncology announces presentation of AV-203 phase 1 results at 2014 American Society of Clinical Oncology Annual Meeting (Aveo Oncology Press Release) - P1, N=22; Sponsor: AVEO; NCT01603979; "AVEO Oncology...announced the presentation of results from a first-in-human Phase 1 study of AV-203, AVEO’s ErbB3 (HER3) inhibitory antibody candidate. Among the results, the study established a recommended Phase 2 dose of AV-203, demonstrated good tolerability and promising early signs of activity, and reached the maximum planned dose of AV-203 monotherapy. The results were presented in a poster...(Abstract #11113, Poster #395, S Hall A2), at the Tumor Biology General Poster Session of the American Society of Clinical Oncology 2014..."

P1 data • Clinical oncology content • Oncology

Aveo Pharmaceuticals: Q1 2014 Results (Aveo Oncology) - Anticipated presentation of data from P1 dose escalation study for solid tumors at ASCO 2014 (May 30-Jun 3, 2014)

Anticipated P1 data • Oncology

AVEO Oncology: Annual Report 2015 (Aveo Oncology) - Anticipated expiry of patents in US, Europe, Japan, Canada and Australia from 2031 to 2032

Anticipated patent expiry • Oncology