Forbius Announces the First Patient Dosed in a Phase 1 Oncology Trial of AVID200, a Novel TGF-beta 1 & 3 Inhibitor

On January 7, 2019 Forbius, a clinical-stage company developing biologics for the treatment of cancer and fibrosis, reported that the first patient was dosed in a Phase 1 clinical trial with AVID200 (Press release, Forbius, JAN 7, 2019, View Source [SID1234532547]). The trial will evaluate safety, pharmacokinetics, pharmacodynamics, and antitumor effects of escalating doses of AVID200 in patients with solid tumors.

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"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.