When pediatric oncologist and Peel Therapeutics Chief Executive Officer Joshua Schiffman visits the zoo, he gets as excited as a kid in a theme park. “[I see] a medicine just waiting to be unlocked,” he said, pointing to what he called his favorite slide: images of wild animals and the unique characteristics that make them immune to common human diseases. He marvels at bears avoiding blood clots despite months of hibernation, elephants being immune to cancer, and bats avoiding muscle exhaustion despite flying several miles every night. His passion for translating the knowledge of the natural world into human therapies led him to found Peel Therapeutics, whose approach deviates from the traditional strategy in drug discovery. Instead of asking how to fix what is wrong, they focus on what went right in 100 million years of evolution, turning those insights into beneficial human therapies. 

What inspired you to start Peel Therapeutics?

When I was 15 years old, I was diagnosed with Hodgkin's lymphoma, which led me to become a pediatric cancer doctor. I became fascinated with the genetics of cancer and who got cancer and why. People have known for a while that elephants almost never get cancer, which is surprising given that elephants are 100 times the size of people and have 100 times as many cells. 

My colleagues and I partnered with people who looked at the genomics for that and discovered that elephants have extra copies of the p53 gene, the guardian of the genome. In the laboratory, we investigated how the extra p53 worked and thought about how to make people more like elephants. I met my co-founder, chemical engineer Avi Schroeder, on a trip to Israel. He is very good at delivering drugs anywhere in the body. We teamed up to start a biotech company to deliver the cancer-fighting protein of elephants to people. To come up with a name, I asked him what the Hebrew word for elephant was. He said: The Hebrew word is “pil.” That's how Peel Therapeutics was born.

What insights from animal biology are you applying to develop new therapies?

We started with elephants but quickly realized that other animals can also defeat disease. For example, a bowhead whale lives over 200 years, and they avoid cancer by doing genomic maintenance of their cells. Naked mole rats live 32 years, the equivalent of 700 to 800 human years. Bats run a marathon every single night, flying up to 50 miles looking for food. If humans ran a marathon every night, their muscles would deteriorate, and they would get rhabdomyolysis, or inflamed joints. This doesn’t happen to bats because they have a naturally low inflammatory cascade, which tells me that the next Humira is in the bat’s genome. Giraffes have a thick heart to pump blood to their brain. If humans had a heart that thick, they would die of cardiac output failure because blood would not flow through it. We would save many lives if we figured out how to turn the way a giraffe doesn't get heart scarring into a drug for people at risk for heart disease. All these animals have the same genes and pathways that humans have. What's different is the pattern that the genes in the pathways turn on and off. We are picking out those patterns. 

How does Peel Therapeutics turn nature’s insights into new drug targets?

We use the Darwin Discovery Platform, which has three components. The Darwin Biobank allows us to collect and maintain animal cell lines and tissues from over 1000 species, encompassing 100 million years of living data. The Darwin Lab generates a genomic data set from the cells we have that we can input into Darwin.AI™, which identifies targets within that data set. We can identify the animals that live 200 years versus those that have a shorter lifespan. We can also identify the genes and pathways that predominate in the animals that don't get cancer, and which animals have naturally low inflammation. 

The proprietary effort is ranking those genes and matching those back to human targets. We're not going to our pharma partners and presenting them with 100 possible targets. With Darwin.AI™, we can rank targets to figure out what's been drugged before and what's reported in the literature. Right now, it's too early to disclose the targets, but they are related to cancer and immune disease, and we are currently validating them in the laboratory. 

Your lead drug PEEL-224 is in clinical development for solid cancers. How is it going?

PEEL-224 did not come from the Darwin discovery platform, but it's in Phase 1 clinical trials. It is a toxin called camptothecin from Camptotheca acuminata, a tree from China whose name translates to the “happy tree.” Camptothecin is a topoisomerase I inhibitor that interferes with DNA repair and kills damaged cells. It has had incredible success in patients with advanced solid tumors. We're now in discussions to move it forward through clinical development once the Phase 1 trial is finished. 

We would save many lives if we figured out how to turn the way a giraffe doesn't get heart scarring into a drug for people at risk for heart disease. 
- Joshua Schiffman, Peel Therapeutics

What differentiates PEEL-224 from other cancer drugs is that it has increased bioavailability, thanks to a pegylated carrier. 100 to 1000 times more of the drug reaches the tumor compared to irinotecan, the standard of care for colorectal, pancreatic, and some pediatric cancers. Only one percent of the irinotecan given to the patient reaches the tumor. It works well for a couple of months, but it eventually stops working because the ATP-binding cassette G2 transporter pumps the drug out. We engineered our payload so it checks in and doesn't check out. 

Irinotecan causes severe diarrhea and other side effects, so oncologists typically start patients with half the dose. Our drug avoids this extreme gastrointestinal toxicity. We believe it has the potential to become the new standard of care and replace irinotecan. We've seen disease control rates greater than 75 percent, even in patients who have been treated with multiple lines of therapy. We are also discussing combining PEEL-224 with antibody drug conjugates and immunotherapies. 

What has been the most rewarding part of developing new therapies based on nature?

This is a realization of a journey that began when I was 15 years old and diagnosed with cancer. I wanted to grow up to save lives. Now, I'm able to look at the most powerful drug discovery engine in the world: nature and evolution. It was a very difficult decision to walk away from seeing patients, but I have never had more hope or satisfaction in my entire medical career now that we are finding targets with the Darwin Discovery Platform. I believe we are going to save hundreds of thousands of lives around the world. We are harnessing evolutionary biology in a way that hasn't been done before for drug discovery. We are finding new targets that we can turn into new molecular entities, patents, and develop drugs to improve patient lives.

This interview has been condensed and edited for clarity.