Forbius: First Patient Dosed in a Phase 1b Myelofibrosis Trial of AVID200, a Novel TGF-beta 1 & 3 Inhibitor

  • Investigator-initiated trial to evaluate AVID200’s safety, anti-fibrotic activity, and ability to restore hematopoiesis in patients with myelofibrosis
  • AVID200 is a rationally designed, highly potent inhibitor of TGF-beta 1 & 3, the principal drivers of fibrosis in myelofibrosis and other fibrotic diseases
  • AVID200 spares TGF-beta 2, the isoform that promotes hematopoiesis and normal cardiac function

Austin, TX and Montreal, QC (Apr. 24, 2019) – Forbius, a clinical-stage company that develops novel biologics for the treatment of fibrosis and cancer, announced today that the first patient has been dosed in a Phase 1b trial assessing AVID200, a novel TGF-beta 1 & 3 inhibitor, in patients with myelofibrosis (MF). This multicenter trial is sponsored by the Icahn School of Medicine at Mount Sinai and the Myeloproliferative Neoplasm Research Consortium (MPN-RC), with the support of a peer-reviewed NIH grant.

AVID200’s novel dual mode of action in MF centers around its anti-fibrotic effects and ability to restore hematopoiesis, as demonstrated in MF patient cells and in vivo models of the disease (Varricchio et al., 2018). Notably, treatment of cells from MF patients with AVID200 promoted proliferation of normal hematopoietic progenitors while decreasing the proportion of MF malignant progenitor cells.

“This clinical trial will evaluate the ability of AVID200 to achieve the disease-modifying outcomes of reversing bone marrow fibrosis and restoring normal hematopoiesis. Preclinical data demonstrate that selective neutralization of TGF-beta 1 & 3 by AVID200 results in both of these critical outcomes. We believe that AVID200 has the potential to become the first disease-modifying treatment for MF,” commented Dr. Ronald Hoffman, founder of the MPN-RC and Director of the Myeloproliferative Disorders Research Program at the Icahn School of Medicine at Mount Sinai.

The single-arm, dose-escalation Phase 1b trial (AVID200-02; NCT03895112) plans to enroll up to 24 patients with primary MF, post-essential thrombocythemia MF, or post-polycythemia vera MF with > grade 2 bone marrow fibrosis. Outcome measures include safety, response, clinical and hematological improvement, as well as assessment of the degree of bone marrow fibrosis.

About AVID200 and the AVID200-02 Trial

AVID200 is an isoform-selective and highly potent inhibitor of TGF-beta 1 & 3, the two principal pro-fibrotic TGF-beta isoforms. These TGF-beta isoforms are central regulators in the pathogenesis and progression of fibrotic diseases, including MF (Chagraoui et al., 2002). AVID200 was rationally designed to be minimally active against TGF-beta 2, which is a promoter of hematopoiesis and normal cardiac function. This optimal selectivity positions AVID200 to be an effective and well-tolerated therapeutic for MF and other fibrotic diseases.

AVID200-02 (NCT03895112) is an investigator-initiated, open-label, multicenter, Phase 1b trial to evaluate the safety and anti-fibrotic activity of AVID200, as well as its ability to restore normal hematopoiesis in patients with MF.

About the Myeloproliferative Neoplasm Research Consortium (MPN-RC)

The MPN-RC was founded in 2006 and is the only independent, multicenter, international consortium of scientists and clinicians dedicated to developing novel therapeutic strategies for MF and other myeloproliferative neoplasms (MPN). The MPN-RC is funded by the NIH to conduct clinical trials based on the most promising preclinical MPN research. The goal of the consortium is to adapt quickly in response to scientific advances and a changing clinical landscape, in order to develop effective therapeutics for MPN patients.

About Myelofibrosis (MF)

MF is a rare, life-threatening blood cancer characterized by progressive bone marrow fibrosis, which causes ineffective hematopoiesis. Approximately 30,000 people in the US alone are affected by this disease. Currently, there are no approved therapies targeting the underlying bone marrow fibrosis available to MF patients.

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

Forbius is a clinical-stage protein engineering company that designs and develops novel biologics 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.





Claudia Resch