Accelerating Human Data in Drug Development: Dr. Pascal Descargues

Pascal Descargues, Ph.D., is a scientist, researcher, and founder of the biotechnology company, Genoskin. The company was established in 2011, after Descargues began working on a project to develop more adequate human skin models with the French National Center for Research and the Paul Sabatier University.

Descargues completed his Ph.D. in human pathophysiology at the University of Toulouse, France, in 2006, followed by a two-year postdoctoral fellowship at the University of San Diego. He holds a master’s degree in management from the Toulouse Business School, and he has over 14 years of experience in skin biology research. His research has been published in peer-reviewed journals such as Nature Genetics and The Journal of Investigative Dermatology.

Pharm Exec caught up with Descargues to talk about how Genoskin is responding to the US government’s push to help pharma and biotech leaders speed clinical drug development and testing.

Pharm Exec: Genoskin’s technology enables accelerated generation of actual human data, applicable to all drug development. Give us a big picture of how Genoskin is helping pharma and biotech industry leaders with clinical testing.

Pascal Descargues: Our technology is changing the way clinical testing is conducted globally. Long before COVID-19 highlighted the need for fast, efficient, and equitable clinical trials; we were working in partnership with pharma companies such as GlaxoSmithKline, AstraZeneca, Sanofi, and many others to accelerate drug development.

Keeping in mind that every drug must be tested on skin before it is FDA approved, our technology enables drug developers to speed the efficacy and safety results, compared to traditional models, such as animal testing. We use live human skin which provides safe, accurate, sustainable, and accessible clinical testing for pharmaceutical and biotech companies. Our standardized platform with real human skin is used to characterize the effects of drugs in human skin, and test how the skin can also affect the drugs.

The US Environmental Protection Agency recently issued a memo stating it will drastically reduce animal testing. Additionally, the FDA has invited you to meet with them for guidance on skin testing in pharma and biotech?

Yes, both US government agencies are actively pursuing alternatives to animal testing. The EPA has publicly stated it will reduce animal testing, including reducing mammal study requests and funding 30% by 2025, and completely eliminate the practice by 2035. Also, there is a dramatic attrition rate on translating data generated in animals to relevant data in humans. Without animal models available, pharma companies need to find alternative methods to demonstrate efficacy and safety in preclinical research, before testing any new therapies on humans.

I was recently invited to meet with FDA following discussions at the Society of Toxicology meeting, where Genoskin presented data on two of our skin models. We met with multiple people from the FDA to present our data, and then our teams were invited back to train approximately 150 FDA reviewers on our skin models used to support drug development. Our ex vivo skin model is the only live skin model available for subcutaneous testing in the world.

What is driving consumer and regulatory pressure to move away from animal testing in drug development?

This shift is mostly centered around ethics and scientific relevancy. There is strong consumer pressure to end cosmetics product testing on animals. Yet, the biggest argument in favor of moving away from animal testing comes from the biotech and pharma companies themselves, and it is related to the inherent risks and economics of drug development. The attrition rate between data developed on animals and the correlation in the clinic is extremely low, and the majority of research projects fail before they ever get tested in humans.

Time after time it has been proven that animals are an insufficient predictor of drug safety, or efficacy in humans. Consider the statistics. More than 90% of drugs entering clinical trials fail, despite positive results in preclinical animal tests. In part, this is because animals do not have the same immune systems, nor do they contract many of the same diseases humans do, such as major types of heart disease, some cancers, HIV, Parkinson’s, and Schizophrenia.

Most of these drugs fail because of toxicity or loss of efficacy, which can’t be detected in animals. Even an animal’s laboratory conditions may be a factor in the success of experiments, with test results differing based on the animals age, sex, and diet. Consequently, results may vary from lab to lab. Non-human primates are close, but they are not humans. Even if there is a 1% difference, that is significant when testing for efficacy in humans. The best way to get human data is from humans.

We provide a solution to generate that human data in support of clinical trials. Our technology provides better data faster, that exponentially helps in determining efficacy, thus speeding safer drug development, saving time, and money.

Is Genoskin’s technology limited in use for a specific disease, or condition in testing?

No, we have published data with many of the larger pharmaceutical companies which are developing vaccines, as well as new therapies for cancer, metabolic disease, neuronal disease, as well as other diseases. With the use of our technology, they are learning through real human data how a drug that is administered through human skin, topically, or subcutaneously through an injection, may induce toxicity in the skin. Additionally, they want to understand how a drug administered into the body is affected by the skin functions, including immune cell functions and pathways.

We are looking forward to several pharma companies, who we have been working in partnerships with, to file INDs in 2021, and advance into clinical trials after generating preclinical data using our skin models on a variety of diseases.

How has Genoskin helped vaccine developers during the COVID-19 pandemic?

We are listed on Mass Bio’s website as one of the biotech companies working on Covid-19. Our ex vivo skin model, HypoSkin, is the only human skin model available to test the immunological signature inducted by the vaccines to predict if the vaccine can be safe and effective. Skin-resident immune cells, including antigen presenting cells, are present and active in our models.

This enables our platform to support both efficacy and safety assessment of vaccines, including characterizing the effects of very small changes in formulation and adjuvant choices.

How is Genoskin actually speeding the drug development process, before therapies enter the clinical trials?

Our technology simply provides pharma companies with more data to support the drug development process, and to assist these companies in designing the right clinical trials. For example, Genoskin platforms enable de-risking trials for adverse events during injections, commonly known as injection site reactions. As the world’s first immunocompetent and injectable researchplatform based on living donor skin, we enable primary human data generation. Thanks to the ability to perform multiple parallel characterizations of immunogenicity, efficacy, and safety of multiple formulations in the same donor, our platforms go beyond some of the data that can be achieved in clinical trials.

Pharma is widely known to be challenged by the time and money it takes to bring a drug to market. In many situations, critically ill patients don’t have a lot of time, and pharma doesn’t have the money to waste. Yet our technology is providing an accurate, sustainable, and humane alternative to animal testing, which I predict will be phased out over the next few decades. Our company has tripled in size over the last year, expanding in our US and France labs, and exploring a third lab in Asia. Alternatives to animal testing are not a trend anymore. They are here to stay. Faster, more accurate, and safer drug development is driving this shift in pharma and biotech, and eventually alternatives to animal testing, such as our technology, will be the norm.