Pieris' lead compound is PRS-050, an anti-VEGF (Vascular Endothelial Growth Factor) 40 kD PEGylated Anticalin discovered and developed internally at the company. During the first half of 2010, the compound began clinical testing in a Phase I dose-escalation trial to evaluate safety and tolerability in cancer patients, with a target oncology indication of treating solid tumors. The results of the Phase I, presented at the AACR-NCI-EORTC international Conference on Molecular Targets and Cancer Therapeutics in November 2011, demonstrated PRS-050 to be safe and well-tolerated, with no maximum tolerated dose (MTD) reached. Based on this and the lack of immunogenicity, the data support PRS-050 advancing into a Phase II clinical study.
VEGF's role in cancer angiogenesis, the mechanism by which cancer tumors increase blood vessel development to deliver key nutrients and oxygen, enabling further growth, is well established both scientifically and clinically. PRS-050's mechanism of action is in principle similar to marketed monoclonal antibody approaches in that it binds the VEGF ligand and all splice variants of VEGF-A to inhibit tumor growth. Preclinical evaluation of PRS-050 indicates several features that may increase efficacy and safety and, therefore, illustrate clinical superiority.
PRS-050 holds promise in differentiating from standard of care in both efficacy and safety. Due to its smaller size, PRS-050 is expected to demonstrate higher levels of tissue penetration in animal models, indicating that it may be able to infiltrate tumors more efficiently, and bind VEGF within the tumor structure. This and a shorter half-life support use in treatment when rapid and effective VEGF removal is paramount. Contributing to its safely profile, PRS-050 has not been shown to aggregate, thereby lowering an innate immune system response against the compound. A further safety-related benefit is that PRS-050 does not suffer from any Fc-mediated effector function side effects, such as platelet-activated thrombosis.
As a product of the Anticalin platform, Pieris has established freedom to operate for PRS-050 as being outside of the antibody space. This proprietary position and already established GMP production indicate reduced costs for compound production and royalty considerations, while maximizing speed to market ahead of other antibody or antibody-like programs.