PDX PHARMACEUTICALS, INC. — Department of Health and Human Services SBIR Phase I: 100

Description

This revised Phase I SBIR proposal aims at developing a topical formulation of siRNA nanoparticle that delivers siRNA to treat skin fibrosis Our platform has inherent antioxidant and anti inflammatory properties further benefitting the treatment of skin fibrosis for which there is no effective treatment Upon completion the platform will have broad applicability since siRNA can be designed to knock down any gene responsible for other diseases such as psoriasis skin disorders and skin cancers Our patent pending delivery platform is a hybrid of mesoporous silica nanoparticles and co polymer coating which is more effective and safer than the siRNA polyplex counterpart Preliminary data following intradermal injection of the siRNA NP shows promising efficacy for treating skin fibrosis in mice A topical formulation to be developed in this Phase I proposal will significantly reduce patient burden and thus is an integral step towards clinical translation of this technology Aim We will screen appropriate vehicles for a topical siRNA NP formulation to maximize penetration to epidermis and dermis and siRNA knockdown efficacy in a D human skin model Aim We will apply the optimized topical formulation to deliver siRNA against HSP to treat fibrosis in a D human skin model and benchmark against a current treatment corticosteroid Aim Ultrasound and targeting agent anti EGFR antibody will be applied on the nanoparticle to enhance penetration and cellular uptake potentially leading to greater treatment efficacy which will be validated in in vivo mouse study Aim Preliminary toxicity studies in cell lines D human skin and mice will be performed The Go No go criteria include effective topical formulation that can penetrate both epidermis and dermis layers andgt knock down of target HSP genes reduction of anti fibrotic markers NOX SMA COL I and dermal thickness to the baseline level andlt non specific cell death and more favorable safety and efficacy profile than the topical corticosteroid counterpart This project is led by PDX Pharmaceuticals LLC a spin off company from Biomedical Engineering Department at OHSU The team consists of Ngamcherdtrakul PhD the lead developer of the siRNA nanoparticle platform as the contact PI and Yantasee PhD MBA Associate Professor at the BME of OHSU and Oregon Nanomedicine Signature Researcher as OHSUandapos s PI Hardee PhD a former vice president of ISIS Pharmaceuticals will serve as our formulation consultant We utilize leased space and state of the art equipment at OHSU and enjoy clinical expertise at OHSU School of Medicine Prof Leachman MD PhD the chair of the OHSUandapos s Dermatology Department and the pioneer of the first in human siRNA targeting an inherited skin disorder will serve as our clinical consultant Project Narrative Small interfering RNA siRNA is capable of knocking down gene expression in a precise manner providing great potential to treat skin diseases and disorders associated with aberrant gene expression To date there is no topical formulation of siRNA available and work in this field has been very limited Therefore we propose to develop a safe and effective topical siRNA formulation based on a well designed antioxidant nanoparticle and apply it to treat skin fibrosis for which there is no effective treatment