September 29, 2020 PAP-Q3-20-CL-017
Before first-in-human clinical trials, a new drug must first be tested on human or animal skin as part of the preclinical safety evaluation. Animal models are often used to study percutaneous absorption, wound healing, skin inflammation, and psoriasis. These studies require relevant models in terms of structure and immunology to assess human skin response and to de-risk clinical trials on humans.
There are, however, key differences between human and animal skin. As a consequence, the results obtained using animal models can be difficult to translate to humans, leading to many clinical trial failures. The use of animal models also raises ethical concerns, and there has been increasing movement toward alternative models and computational methods within both industry and regulatory agencies.
Genoskin was founded in 2011 with a focus on finding a skin tissue model closer to human skin. An ideal human skin model would show a structure that is identical to that of real human skin, with all skin cells and appendages, including skin barrier function and cell–cell interactions.
Genoskin provides researchers with the next generation of human skin models and assays for drug testing. We strive to offer the closest alternative possible to in vivo clinical testing by taking into account the complete metabolism and structure of human skin, unlike other models currently on the market.
Genoskin’s innovative models rely on real human skin. These samples are donated after surgery with the informed consent of the individual donors, in full respect of the Declaration of Helsinki. We have secure contracts with every hospital and clinic we work with in order to ensure our biological samples are collected in compliance with a very strict protocol.
Samples are collected after surgery and brought to Genoskin, and human skin models are produced within 24 hours. Safety tests for hepatitis B and C and HIV-1 and -2 are conducted, and only negative samples are used to produce skin models.
Our living human skin models comprise round skin sections (~1 inch diameter) stored in specially designed containers that include a proprietary gel that keeps the tissue alive for at least seven days by maintaining tension on the skin and allowing for the provision of necessary nutrients. Because the skin biopsies hold all the characteristics of their donor, it is possible to study a specific skin type.
The skin models are then incorporated into multi-well testing kits to enable broad efficacy and toxicity studies. The containers can be shipped worldwide and the samples are ready to use. The biopsies are kept in a functional survival state embedded in a gel matrix, which simplifies applying test compounds, both systemically and topically.
Genoskin models help leading pharma and biotech companies evaluate how the skin reacts to a new therapy in regards to absorption, melanin levels, inflammation, or immune response, as well as any changes in a drug caused by the skin. With this information, drug developers can optimize drug formulations and clinical trial designs.
Genoskin has always strived to create innovative skin models with a high predictive value for a wide range of applications.
Genoskin has developed a range of skin models that demonstrate drug effects under a variety of conditions. NativeSkin® Human Skin Models are produced from non-artificial skin — with structure and composition fully equivalent to that of in vivo human skin. These models exhibit normal skin barrier function, a mature stratum corneum, and a functional basal layer; all cell types, glands, and skin appendages of in vivo human skin are preserved.
The NativeSkin models also maintain immunocompetent cells in vitro and are able to mimic the live response of in vivo human skin. NativeSkin® can be cultured for up to 10 days while preserving normal skin integrity, significant cell viability, proliferative cells, and low levels of apoptosis. As a result, Genoskin’s human skin models are a reliable last-line screen prior to in vivo clinical trials.
HypoSkin® is the only live human skin model that allows researchers to study the effects of subcutaneous administration. These models based on donated human skin biopsies from abdominal surgeries contain all three layers of human skin (epidermis, dermis, and hypodermis). HypoSkin® is also useful for studying the skin microbiome and assessing changes in skin microbiota following treatment with dermo-cosmetic products. The Wounded HypoSkin® model, meanwhile, is suitable for the evaluation of topical therapies and dressings in prophylactic administration to prevent wound infection or in the therapeutic treatment of infected wounds.
InflammaSkin® is a fully human T cell–driven ex vivo skin inflammation model based on the NativeSkin® explant technology designed for assessing the efficacy of topic anti-psoriasis and other anti-inflammatory drugs, as well as subcutaneously injected biologics. It is currently the only ex vivo T cell–driven human psoriasis model with a TH17/TH1 phenotype and that contains adipose. With this model, both prophylactic and therapeutic treatments can be evaluated.
FrozenSkin® enables absorption studies. We are currently undergoing extensive research efforts to gain a greater understanding of our existing skin models, such as how different cells (e.g., immune cells) within the skin are activated under various conditions.
We are also in the process of evaluating the activity of specific human skin cytochromes involved in the metabolization of drugs topically applied to NativeSkin®. Our other primary goal is to identify ways to keep our human skin models alive for longer periods while maintaining functionality.
For drug developers that do not have in-house capabilities for performing assays using Genoskin human skin models, we offer a full range of preclinical R&D services. Our skin experts can evaluate the efficacy and toxicity of drug candidates using our ex vivo human skin models — with live human skin responses, all in compliance with ISO 9001 quality standards.
For example, we can identify the optimum human skin model for small molecule and biologic drug candidates taking into account the specifications and potential routes of administration for any given product. Using the recommended model, we develop high-quality data that can be used to facilitate drug development projects to the clinic. For instance, for emerging companies developing COVID-19 vaccines, Genoskin can conduct experiments with our HypoSkin® model to investigate injection site reactions, including the analytical testing required to support such studies. The HypoSkin® platform is, in fact, an excellent model for understanding the primary effects of vaccines on the skin.
While Genoskin is a skin biology company, we are also collaborating on bioinformatics. Our assays generate massive quantities of data regarding lipid, protein, and even DNA behavior and metabolic responses. Genoskin is growing, and our goal is to expand our operations around the world. Today we have two laboratories — one in France and one in the United States — where living skin samples are transformed into innovative assays.
As the movement away from animal testing to alternative testing methods continues, and growing numbers of industry and academic researchers realize that animal skin models have limited predictive value and correlation with actual skin performance, there will be tremendous opportunities for Genoskin to address these key concerns related to drug development. We expect to dramatically increase our skin collection activities in North America and to grow significantly year after year.
After obtaining his Ph.D. in human pathophysiology at the University of Toulouse, Pascal completed a postdoctoral fellowship at the University of San Diego. His interest in skin research was demonstrated by his thesis, i.e. “A rare skin disease called Netherton Syndrome”. In 2009, Pascal started working on his project to develop more adequate human skin models with the French National Center for Research and the Paul Sabatier University, which led to the creation of Genoskin in 2011.