Decorin gel to reduce scarring (2019)

This project could enable patients with DEB to use a gel on their skin containing a protein, decorin, to heal wounds and reduce symptoms such as the excessive scarring that contributes to contracture, webbing and fusion of fingers and toes.

Dollop of gel product

Dr Marc de Souza set up FIBRX Derm Inc (Biotech) in California, USA with Prof Jean Tang and support from DEBRA UK and other funders. Previous research discovered that a human protein called decorin may help to reduce scarring in families suffering with dystrophic epidermolysis bullosa (DEB). This work is to find a reliable way to make decorin protein that can be incorporated into a gel for future testing. If this can be done, tests on safety and effectiveness could lead to a gel DEB patients could apply to their skin to reduce symptoms.

About our funding:

Research leader	Dr Mark de Souza and Prof Jean Tang
Institution	FIBRX Derm Inc
Type of EB	DEB
Patient involvement	Phase 1/2 trial on less than 10 people
Funding amount	$250,000 (Total $7.2M - $250K towards the project from DEBRA UK in conjunction with funding of $4.2M from EB Research Partnership, EB Medical Research Foundation, debra of America, DEBRA and CureEB. With an additional $3M award from the Peer Reviewed Medical Research Program (PRMRP) of the U.S. Department of Defense.)
Project length	Investment in pharmaceutical company (2019)
Start date	December 2019
DEBRA internal ID	Fibrx

Latest progress summary:

Due 2023.

About our researchers:

FIBRX Inc Founding Team:
Mark de Souza, PhD

Founding President and CEO, Chromaderm, Inc. Phase 2 topical PKC-beta inhibitor for the treatment of melasma.
Former Executive Chairman, PellePharm. Phase 3 topical hedgehog inhibitor for the treatment of basal cell nevus syndrome, which has received breakthrough designation from FDA.
Co-founder, former President and CEO, Lotus Tissue Repair, acquired by Shire for $320 million for its recombinant collagen VII protein replacement therapy for rare genetic skin disease, dystrophic epidermolysis bullosa.
15+ years of early stage commercial experience. VP Business Development, Dyax. Led the business development team at Dyax since 2003. Generated more than $200 million in non-dilutive financing for Dyax from 50+ technology and product licensing transactions.

James W. Fordyce

Founding EVP and CFO, Chromaderm, Inc. Phase 2 topical PKC-beta inhibitor for the treatment of melasma.
Co-founder, former EVP and CFO, Lotus Tissue Repair, acquired by Shire for $320 million for its recombinant collagen VII protein replacement therapy for rare genetic skin disease, dystrophic epidermolysis bullosa.
Founder, Prince Ventures LP >25 years of venture capital investment experience. Responsible for numerous early stage investments in life science: Genentech, Inc., Applied Biosystems Inc., Centocor, Inc., Regeneron Pharmaceuticals, Inc., Dyax Corp.

Erkki Ruoslahti, MD, PhD

Distinguished Professor and former President, Sanford Burnham Medical Research Institute.
Member of the National Academy of Sciences, Institute of Medicine, AAAS, and EMBO.
Founder of Telios, pioneering work in matrix biology, integrins, RGD peptides, decorin in fibrotic diseases.

Advisory Team
Jean Tang, MD, PhD

Professor of Dermatology, Stanford University.
Co-Founder, PellePharm.
Led multiple clinical trials at EB Research Clinic, Stanford University.

Hal Landy, MD (Medical Advisor)

Former Medical Advisor, Lotus Tissue Repair.
Former CMO, Enobia Pharma, led multiple trials at Genzyme (including in scleroderma), Serono.

Deborah Ramsdell (Regulatory Advisor)

Regulatory Advisor, PellePharm, Chromaderm.
30+ years of regulatory consulting, including 10 years at FDA-CBER.

Sheila Magil, PhD (CMC Advisor)

Former CMC Advisor, Lotus Tissue Repair.
Senior Consultant, BioProcess Technology Consultants.

Fred Reno, PhD (Pre-clinical Pharmacology and Toxicology Advisor)

Pharmacology and Toxicology Advisor, PellePharm, Chromaderm.
30+ years of experience.

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Why this research is important:

An anti-scarring therapy like decorin, which has a well-elucidated mechanism of action, may have the potential to improve the quality of life for patients affected by DEB by decreasing the scarring associated with the chronic cycles of skin blistering and wound healing.

Researcher’s abstract:

Project Title: Development of Topical Human Recombinant Decorin as an Anti-Scarring Therapy for dystrophic epidermolysis bullosa.

Patients with dystrophic epidermolysis bullosa (DEB), especially those with the recessive form of the disease (RDEB), have extremely fragile skin and oral mucosa which results in severe skin and oral blisters that heal with extensive scarring. Many RDEB patients also suffer from oesophageal strictures, and contracture and fusion of the digits, which results in pseudosyndactyly, (e.g., ‘mitten deformity’ of the hands and feet, in which fingers and toes become fused).

This research is investigating the potential of an engineered form of the naturally occurring human protein, decorin, as an anti-scarring agent. Decorin helps to provide maintenance and development of the extracellular matrix in the skin which provides support and various functions including the communication between cells.

Previously, DEBRA UK funded research by Professor Zambruno (2013), who identified that TGF-β (transforming growth factor), a molecule which contributes to the function of cells, seemed to be associated with more severe symptoms, leading to scarring. In this research it was also discovered that decorin inhibited the levels of TGF-β. A case study of identical twin men with RDEB, showed decorin was expressed almost twice as much in the twin, who had a moderate scarring phenotype (the observable traits seen in the body “the clinical picture”), as compared with his identical twin brother who had a severe scarring phenotype. Both had similarly depressed C7 (collagen 7) levels. It was hypothesized that decorin may help to control TGF-β activity which leads to scarring.

These data recently led the FIBRX team to hypothesize that a topical (gel) formulation of human recombinant decorin (hrDecorin), an engineered form of the native protein, would be an ideal anti-scarring therapeutic for DEB (both dominant and recessive DEB). This research will begin the process of investigating whether a topical hrDecorin gel will reduce scarring in DEB skin.

Main aims of this stage of the research:

To manufacture, develop and test a simple, stable, topical gel formulation of hrDecorin suitable for human clinical trials.
Conduct critical toxicology and preliminary safety studies to support the submission of an Investigational New Drug (IND) application to US Food and Drug Administration (FDA). An IND is required for advancing to human clinical trials.

Funding of this preliminary work will allow FIBRX to proceed with all the activities necessary to file an IND with the FDA, Dermatology & Dental Division, leading to the conduct of a first in man clinical trial with a topical gel formulation of hrDecorin. FIBRX plans to raise funds for this clinical study in the future. At the current time, the required pre-clinical IND-enabling work is being supported by a number of funders including the PRMRP Program of the US Department of Defense. The proposal meets core PRMPR strategic requirements, “topical therapeutics to enhance wound healing in EB” and “development of novel therapeutics to reduce EB symptoms and improve quality of life”. The core strategies of the PRMPR are a guide to help industry partners work towards finding drugs and treatments for EB.

Researcher’s progress update: