(February 17, 2018)
The presentation (CO.22) demonstrated the potent anti-fibrotic effects of AVID200, a selective TGF-β1 and TGF-β3 inhibitor, in animal models of established fibrosis, as well as in Scleroderma patient-derived fibroblasts in culture. The presentation also featured findings on clinical biomarkers demonstrating that the expression of TGF-β1 and TGF-β3, but not TGF- β2, correlates positively with the severity of fibrosis in scleroderma patients as measured by the modified Rodnan Skin Score.
AVID200 is an isoform-selective TGF-β inhibitor that blocks TGF-β1 and -β3 ligands with pM potency. TGF-β’s are a family of secreted ligands that play key roles in fibrosis and resistance to immune checkpoint inhibitors. Of the three TGF-β isoforms found in humans, TGF-β1 and -β3 are strongly implicated in several disorders with blockade of these ligands resulting in reversal of these diseases. In contrast, inhibition of TGF-β2 is undesirable, since neutralization of TGF-β2 is associated with promotion of cancer metastasis, negative effects on hematopoiesis and cardiac toxicity.
Applying its TGF-β structure-activity expertise and through using a novel protein-engineering approach, Forbius has developed AVID200, which is significantly more active against TGF-β1 and -β3 compared to TGF-β2. AVID200 blocks TGF-β1 and -β3 with low pM potency, which enables efficient trapping and removal of these ligands in vivo. AVID200 is undergoing IND-enabling development for use in fibrotic diseases and cancer immunotherapy with clinical studies planned for 2018.
Forbius is a clinical stage company that designs and develops biotherapeutics for treatment of cancer and fibrotic diseases. Forbius’ medicines are designed to radically transform patients’ lives. Our strength is to use our knowledge of biology and diverse protein engineering technologies to design superior inhibitors of validated biological pathways.
We have particularly deep expertise in targeting Transforming Growth Factor-Beta (TGF-β) and Epidermal Growth Factor (EGF) pathways. For both of these pathways, there is a significant body of evidence validating their role as drivers of multiple life-threatening conditions. However, in the case of the EGF pathway, the majority of patients do not benefit from currently marketed EGFR inhibitors. In the case of the TGF-β pathway, no agent targeting this pathway has yet been approved. By using multiple complimentary platform technologies, Forbius’ team overcame barriers that prevented the development of effective therapeutics targeting these pathways.