ESMO 2019: Forbius Demonstrates Target Engagement in Phase 1 Immuno-Oncology Clinical Trial with AVID200, First-in-Class TGF-beta 1 & 3 Inhibitor

  • AVID200 is a first-in-class, rationally designed inhibitor of TGF-beta 1 & 3, the main oncogenic TGF-beta isoforms
  • AVID200 demonstrated peripheral target engagement in a Phase 1 clinical trial in solid tumors
  • AVID200 is undergoing additional Phase 1 testing in diffuse cutaneous systemic sclerosis and myelofibrosis

AUSTIN, Texas & MONTREAL--()--Forbius, a clinical-stage protein engineering company that develops biotherapeutics to treat fibrosis and cancer, today reported results from its non-clinical GLP toxicology program with first-in-class selective TGF-beta inhibitor AVID200 and evidence of TGF-beta target engagement in patients treated with this novel immuno-oncology agent at the European Society of Medical Oncology (ESMO) 2019 Annual Congress in Barcelona.

The presentation detailed for the first time that AVID200 administered at doses of ≥1 mg/kg sequestered its target TGF-beta in patient blood over the entire dosing period.

Key highlights of today’s presentation at ESMO (#504P):

  • AVID200 selectively neutralizes TGF-beta 1 & 3 with pM potency in vitro, and increases T-cell-mediated cytotoxicity as well as immune checkpoint inhibitor efficacy in syngeneic mouse tumor models
  • AVID200 was well tolerated in 1- and 6-month GLP toxicology studies in non-human primates
  • AVID200 in patient blood sequestered peripheral TGF-beta over the entire dosing period
  • A Phase 1a AVID200 monotherapy dose-escalation clinical trial is currently enrolling solid tumor patients (AVID200-03; NCT03834662)

About TGF-beta 1 & 3

TGF-beta 1 & 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).

About AVID200 and the AVID200-03 Trial (NCT03834662)

AVID200 is an isoform-selective and highly potent inhibitor of TGF-beta 1 & 3 undergoing Phase 1 clinical testing in solid tumors and fibrotic diseases. TGF-beta 1 & 3 are the principal disease-driving isoforms, while TGF-beta 2 is responsible for normal cardiac function and hematopoiesis.

AVID200's selectivity for TGF-beta 1 & 3 was designed to achieve optimal efficacy while circumventing cardiac and other safety issues that have limited the applicability of older-generation, non-selective TGF-beta inhibitors. Therefore, AVID200 is positioned to be an effective and well-tolerated therapeutic in a variety of clinical settings, including in combination with anti-PD-(L)1 therapy.

AVID200-03 (NCT03834662) is an open label, multicenter, dose-escalation study to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor effects of AVID200 in patients with advanced or metastatic solid tumor malignancies.

About Forbius: Targeting TGF-beta and EGFR Pathways in Fibrosis and Cancer

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 (EGFR) 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 & 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 & 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 (ADC) with a novel tumor-selective mode of action. This program is undergoing Phase 2a clinical trials in EGFR-overexpressing solid tumors.

Contacts

Ilia A. Tikhomirov
info@forbius.com

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Contacts

Ilia A. Tikhomirov
info@forbius.com