09 January 2019 | News
AVID200 is a rationally designed and highly potent TGF-beta 1 & 3 inhibitor
Forbius, a clinical-stage company developing biologics for the treatment of cancer and fibrosis, announced that the first patient was dosed in a Phase 1 clinical trial with AVID200. The trial will evaluate safety, pharmacokinetics, pharmacodynamics, and antitumor effects of escalating doses of AVID200 in patients with solid tumors.
“Our goal is to significantly expand the number of cancer patients who benefit from checkpoint blockade and other immunotherapies. AVID200 was designed to have the potency and isoform selectivity to effectively counteract the highly immunosuppressive effects of TGF-beta in the tumor microenvironment and reverse resistance to immunotherapy,” commented Dr. Maureen O’Connor-McCourt, CSO of Forbius.
AVID200 selectively neutralizes TGF-beta 1 & 3 with best-in-class pM potency, thus neutralizing the principal immunosuppressive TGF-beta isoforms. AVID200’s optimal selectivity was also designed to circumvent cardiac and other safety issues that have limited the applicability of older-generation, non-selective TGF-beta inhibitors.
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 immunotherapeutics such as nivolumab (Opdivo) and pembrolizumab (Keytruda) (Chakravarthy et al., Nature Comm., 2018; Tauriello et al., Nature, 2018; Mariathasan et al., Nature, 2018).
AVID200’s immuno-oncology mode of action focuses on the reversal of both immunosuppression and fibrosis in the tumor stroma. In syngeneic mouse tumor models, AVID200 treatment led to T-cell activation, increased immune cell infiltration, and increased efficacy of immune checkpoint agents.
Forbius is a clinical-stage protein engineering company that designs, develops, and commercializes biotherapeutics for the treatment of fibrosis and cancer. Our current focus is the development of agents targeting the transforming growth factor-beta (TGF-beta) and epidermal growth factor receptor (EGFR) pathways.
Our lead program targeting the TGF-beta pathway is AVID200. AVID200 is a rationally designed and highly potent TGF-beta 1 & 3 inhibitor. This TGF-beta isoform selectivity was chosen in order to achieve an optimal therapeutic index. The AVID200 program has been cleared by the FDA for two Phase 1b clinical trials in fibrotic indications, as well as a Phase 1 clinical trial in solid tumors. Additional clinical trials in fibrotic indications are planned for 2019.
Forbius' lead program targeting the EGFR pathway is AVID100. AVID100 is an anti-EGFR antibody-drug conjugate. This program has completed a Phase 1 clinical trial and has commenced Phase 2a clinical trials in EGFR overexpressing solid tumors.