Dr. Manfred Schuster, CEO of RMB Research GmbH recently spoke about his upcoming presentation “Development of the Pharmacologically Highly Active Endogenous Protein Stathmin-1 to Treat Chronic Wounds” to be presented at 13th Annual Recombinant Protein Therapeutics conference taking place January 9-10 in San Diego, CA.
Q. How does Stathmin-1 function in healing chronic wounds?
The intra-cellular activity of the endogenous protein Stathmin is well known, while its extra-cellular function has been discovered recently. Importantly it only becomes pharmacologically active in an inflammatory environment, as present in chronic infected wounds. There, it interrupts the vicious inflammation circle in which the healing process gets stuck, and activates the most prominent cell types involved in the wound healing process. It is uptaken by endothelial, epithelial and immune cells via endocytosis and activates the NF-Kb pathway via TLR-stimulating. Depending on the target cell, this leads to a concerted secretion of cytokines and growth factors.
Q. How did you identify and rectify the mistakes identified from previous development activities?
First my colleagues and myself identified a couple of inconsistencies in the GMP batch documentation. The specification for bacterial endotoxins was missing and a potency assay was used which was rather a content assay. In fact, the previous formulation contained elevated levels of bacterial endotoxins, which, when applied to open wounds, caused a safety issue and led to the discontinuation of the clinical investigation. The reason for missing potency assay became obvious when we failed to reproduce it for more than 6 months, and eventually realized that the API requires an inflammatory background to show pharmacological activities. This important result was key to understand the mechanism of action and to develop a pharmacologically potent formulation. Having establish such an assay we found out that our API gets inactivated by proteases which are present in wound fluids. As consequence we developed a novel ultra slow-release formulation for our API, which also protects it from proteolytic degradation and of course does not contain bacterial endotoxins. This new drug product is the basis for our ongoing development activities.
Q. When do you expect Stathmin-1 topical treatment to move into the clinic?
We will complete missing preclinical development activities by 2017 and plan to investigate safety and tolerability of our novel drug product in healthy volunteers in 2018.
Q. What are you most looking forward to at the upcoming PepTalk?
I would like to meet with friends and get an insight into recent protein science!
Development of the Pharmacologically Highly Active Endogenous Protein Stathmin-1 to Treat Chronic Wounds
Stathmin-1 is a small, highly conserved protein, which was identified as an intra-cellular modulator of the eukaryotic cytoskeleton. We overtook development of this pharmacologically potent biologic and have started to investigate its therapeutic potential in a topical formulation to eventually treat chronic, not healing wounds. This presentation highlights our troubleshooting program, which identified and overcame several mistakes from previous development activities, and describes how we will address further clinical issues.
About the Speaker:
Manfred Schuster, Ph.D., CEO, RMB-Research
Dr. Schuster has some 20 years of experience in pharmaceutical and biotech industry. He studied biochemistry, biotechnology and pharmaceutical quality management and is also certified as QP. He recently co-founded Remute Bio and RMB-Research as well as Apeiron Biologics AG in 2005 where he worked as COO until 2015. In this function he built up the company and developed an enzyme substitution therapy from the idea until an exclusive license deal of € 250 M with GlaxoSmithKline in Phase II and an orphan antibody-based immuno-therapy against neuroblastoma until submission for market approval in Europe. He previously worked for six years at Igeneon AG and for three years at Novartis.