18 October 2019 - - US-based protein engineering company Forbius's Phase 1a solid tumor trial exploring the safety and tolerability of AVID200, a first-in-class TGF-beta 1 and 3 selective inhibitor, administered as a monotherapy has fully enrolled, the company said.

Simultaneously, the company completed a Series C financing led by HBM Partners with participation from new and existing investors.

AVID200 is rationally designed to selectively and potently inhibit the main pathogenic TGF-beta isoforms 1 and 3. AVID200 spares TGF-beta 2 for optimal safety. Inhibition of TGF-beta 2 is undesirable as this isoform is important for normal cardiac functioning and hematopoiesis.

These and other toxicities have curtailed the development of earlier generation, non-selective TGF-beta inhibitors.

The AVID200-03 trial (NCT03834662) is an open label, multicenter, dose-escalation study focused on demonstrating safety of AVID200 monotherapy in patients with advanced or metastatic solid tumor malignancies and no other treatment options.

Following a standard 3 + 3 design, a total of 15 patients received AVID200 at 5, 15 and 30 mg/kg once every three weeks. Pharmacokinetics and target engagement were also evaluated.

The recently completed financing funds the company into 2021 which will allow advancement of AVID200 through its clinical proof-of-principle program. HBM Partners led the round, with a number of new and existing investors also participating.

Forbius is a clinical-stage protein engineering company that develops biotherapeutics to treat fibrosis and cancer. We are focused on the transforming growth factor-beta (TGF-beta) and epidermal growth factor receptor pathways.

Forbius' team of TGF-beta biology experts designed a proprietary platform of TGF-beta inhibitors with best-in-class potency and selectivity against the principal disease-driving isoforms 1 and 3.

This novel class of TGF-beta inhibitors has proven highly active in preclinical models of fibrosis and cancer and was well-tolerated in long-term toxicology studies.

Forbius' lead TGF-beta 1 and 3 inhibitor, AVID200, is undergoing Phase 1 clinical trials in two fibrotic indications as well as in solid tumors.

Forbius' lead program targeting EGFR is AVID100. AVID100 is an anti-EGFR antibody-drug conjugate with a novel tumor-selective mode of action. This program is undergoing Phase 2a clinical trials in EGFR-overexpressing solid tumors.

TGF-beta 1 and 3 are the main oncogenic TGF-beta isoforms expressed by many solid tumors. They are believed to play a major role in T-cell suppression, fibrosis, and resistance to anti-PD-(L)1 therapies such as nivolumab (Opdivo) and pembrolizumab (Keytruda) (Chakravarthy et al., Nature Comm., 2018; Tauriello et al., Nature, 2018; Mariathasan et al., Nature, 2018).