Therapy Areas: Cardiovascular
Forbius Demonstrates Target Engagement in Phase 1 Immuno-Oncology Clinical Trial with AVID200, First-in-Class TGF-beta 1 and 3 Inhibitor
1 October 2019 - - US-based Forbius, a clinical-stage protein engineering company that develops biotherapeutics to treat fibrosis and cancer, has 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 2019 Annual Congress in Barcelona, the company said.

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 the ESMO presentation include that AVID200 selectively neutralises TGF-beta 1 and 3 with pM potency in vitro, and increases T-cell-mediated cytotoxicity as well as immune checkpoint inhibitor efficacy in syngeneic mouse tumor models

According to the company, 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; and a Phase 1a AVID200 monotherapy dose-escalation clinical trial is currently enrolling solid tumor patients (AVID200-03; NCT03834662).

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).

AVID200 is an isoform-selective and highly potent inhibitor of TGF-beta 1 and 3 undergoing Phase 1 clinical testing in solid tumors and fibrotic diseases.

TGF-beta 1 and 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 and 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.
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