Bioinsider guest post: Dr. Joshua Schiffman, CEO of PEEL Therapeutics
Neutrophil-Targeting Peptides as a Treatment for COVID-19
“My longstanding interest in animals made PEEL Therapeutics an amazing means to draw on my appreciation of nature and biology, specifically evolution, and combine it with my experience practicing medicine.”
PEEL Therapeutics is introducing a natural peptide that evolved in newborns to block inflammation as a new therapeutic approach to help with the current COVID-19 pandemic
Dr. Emily Le, producer of Therapeutic Pipeline for COVID-19 Virtual Meeting, got together with PEEL co-founder and CEO Dr. Joshua Schiffman to learn more about his research and how it can be applied to addressing the complications associated with COVID-19. Among other things, babies and elephants are discussed.
EL: I understand that PEEL Therapeutics is inspired by nature for its approach to pharmaceutical discoveries. You are a co-founder of PEEL Therapeutics. Were you interested in nature as a young boy? Tell us how your interactions with nature helped in the ultimate creation of PEEL Therapeutics.
JS: Since I can remember, I have always been interested in nature. Part of my childhood was spent in rural areas of Connecticut and the wooded New England forests became like a playground to me. We moved to Providence, Rhode Island when I was 8 years old and I spent plenty of time at the zoo marveling at the animals. When I eventually reached college, I became fascinated by Darwin and his theories after taking several animal-behavior courses.
Along with medicine, the role of evolution in functional biology has always been an important focus of mine. Several years ago, we helped with the discovery of extra elephant p53 (EP53) that contributes to cancer resistance in these large and long-lived animals. Together with my co-founder, we knew that we needed to find a way to blend advanced technology with millions of years of elephant evolution to introduce new drugs to impact patient lives. My longstanding interest in animals made PEEL Therapeutics an amazing means to draw on my appreciation of nature and biology, specifically evolution, and combine it with my experience practicing medicine.
EL: There are a lot of scary accounts about how COVID-19 causes fatal blood clots in infected patients. Tell us about your “eureka moment” when you realized that neutrophil extracellular traps (NETs) could be linked to COVID-19-induced blood clots?
JS: Excellent question! Prior to COVID-19, we had been very focused on the role of NETs in sepsis. We had very strong preclinical evidence, published and unpublished, with our academic collaborators that PEEL NTPs lead to remarkable improvement in mice with sepsis. We knew that NTPs naturally inhibit NETs and prevent the multiorgan damage in sepsis due to clotting of the vessels leading to vital organs.
The “eureka moment” came when reports began to be published that: 1) nearly hundred percent of COVID-19 fatalities are due to sepsis with respiratory failure, and 2) that COVID-19 was a disease of microthrombi with coagulopathy throughout the patient’s body. This mirrored exactly the pathophysiology observed in our mice with sepsis, and so we knew at that point that we needed to demonstrate the role of NETs in COVID-19.
After we began our study with colleagues at the University of Utah, we saw that NET levels in COVID-19 patients correlate with disease severity (more NET associate with more severe illness) and we knew that our hunch was correct: NTPs may have an important therapeutic role in the COVID-19 pandemic.
EL: How do you think your inflammatory neutrophil-targeting peptides (NTPs) will stack up against traditional drugs in development like antibodies or small molecules, which typically work by neutralizing COVID-19 from binding to human cells?
JS: We are asked this question often. There will, undoubtedly, be many approaches to fighting COVID-19. At PEEL Therapeutics, our focus continues to be on the innate immune system and what nature has provided in her armamentarium to inhibit inflammation. PEEL NTPs originate from peptides found in the first few days of newborn life and, therefore, we expect the side effects to be minimal compared to other therapeutic approaches now in development. Furthermore, it will be difficult to block every viral particle from entering all cells and therefore inflammation due to an overactive NETosis response is still a patient risk.
PEEL NTPs can work in conjunction with other therapies to limit the endothelial damage, microthrombi, and cytokine storm caused by inappropriate NET release. Targeting the root cause of immunothrombosis through NET prevention, we feel, will be the best approach to stopping the downstream inflammation leading to trouble in COVID-19 patients. Although there will be a role for targeting and modulating cytokine release, we prefer PEEL Therapeutics’ strategy of preventing the NETs that lead to the inflammation in the first place.
EL: Do you take excursions to far away ecosystems to get inspired for your next discovery?
JS: I wish there was time these days to take excursions. Most of my travels involve literature searches and trying to stay on top of the latest evolution and animal-focused articles. Reading about the “super powers” and biological adaptations of animals makes me feel like a kid in a candy store. I let my mind wander and think how these nature-based discoveries can be used as the next drug to develop to help people – how have the animals already solved human disease. I love it!
EL: Do you partner with ecological organizations and NGOs to promote your philosophical ideals?
JS: We have not formally partnered with ecological organization or NGOs, although we have given several talks to politicians and government officials to promote the work we’re doing and the importance of studying nature. We also have ties through our academic partners with the Kenya Wildlife Service where our work on making new medicines from what we learned about elephants is very helpful for their conservation efforts. Finally, we have developed a very strong relationship with Closer to Cure Foundation after receiving award funding. We’re working closely with CTCF on awareness and fundraising efforts for their non-profit organization that promotes research that translates evolutionary biology into medicines for patients.
EL: What do you want the Bioinsider attendees to gain from your talk?
JS: We would like for Bioinsider attendees to appreciate how studying evolutionary biology can inform drug development and design. All of the assets in PEEL Therapeutics originate from an observation made in nature. Evolution provides hundreds of millions of years of research and development on biological solutions to the most challenging problems in health and disease. Specifically, we want Bioinsider attendees to understand the role of NETs in COVID-19 and how our company is introducing a natural peptide that evolved in newborns to block inflammation as a new therapeutic approach to help with the current COVID-19 pandemic.
