PF-655 (formerly REDD14NP and RTP801i) is a synthetic siRNA designed to inhibit the expression of Quark’s proprietary target, RTP801. PF-655 is licensed to Pfizer on an exclusive worldwide basis. PF-655 was well tolerated in a Phase I/IIa study completed by Quark on Pfizer’s behalf in patients with wet AMD and is currently being evaluated in
Phase II studies for DME and wet AMD.
Quark discovered the target gene, RTP801, using its BiFAR™ target discovery platform (
PMID: 11884613). Expression of RTP801 is rapidly upregulated in response to ischemia, hypoxia and/or oxidative stress. Intravitreal injection of PF-655 in preclinical animal models of laser-induced choroidal neovascularization (CNV) led to inhibition of RTP801 expression, induction of expression of anti-angiogenic and neurotrophic factors, and subsequent reduction of CNV volume, vessel leakage and infiltration of inflammatory cells into the choroid. The mechanism of action of PF-655 is different from that of different types of VEGF inhibitors. We have determined that PF-655 works in cooperation with VEGF inhibitors in the CNV model, and also decreases retinal blood vessel leakage in diabetic mice. Other beneficial effects such as attenuation of apoptosis in the inner nuclear layer of the retina and reduction of pathological retinal neovascularization were observed in RTP801 knockout mice subjected to the model of oxygen-induced retinopathy (retinopathy of prematurity) (
PMID: 15452091). Reduced pathology was also observed when RTP801 knockout mice were evaluated in a variety of non-ocular disease models, including cigarette smoke-induced lung injury and emphysema (
PMID: 20473305), suggesting a more global function for RTP801 in pathological processes underlying acute and chronic stress-induced diseases.
Quark owns intellectual property covering the RTP801 gene, its RNA and protein products and sequences, specific antibodies, methods of gene inhibition and siRNA drug candidates for use in treating various indications. For PF-655 the Company has siRNA structure-related technology licenses from Silence Therapeutics and from Alnylam Pharmaceuticals.