Durham's Ten63 Uses Fast Computing for Drug Discovery

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Marcel Frenkel, Ph.D., co-founder and CEO of Durham -based drug company Ten63 Therapeutics, never thought he’d be focusing the majority of his time and energy on the fight against cancer.

As a fencing champion in his native Brazil who competed in several World Cups, and a biochemist by trade, Frenkel knows a thing or two about fighting and outsmarting difficult opponents. Frenkel initially worked on developing an HIV vaccine that could teach the immune system to outsmart the HIV virus and maintain efficacy despite the virus’s ability to mutate.

It wasn’t until his mother began feeling consistent and unsettling back pain that his future trajectory began to unfold.

“One day my mother came to visit, and she mentioned she was feeling a little bit of back pain. At the time, we didn't think much of it,” said Frenkel.

Marcel Frenkel, Ph.D.
Marcel Frenkel, Ph.D. -- Ten63 photo

When the back pain didn't resolve, Frenkel and family came to the realization that the problem was bigger than originally imagined. Lab results returned a diagnosis of pancreatic cancer. With a dismal prognosis, Frenkel’s mother began the fight of her life.

“My mom was this amazing woman – kind and infinitely brave. She really wanted to live and was willing to fight. We went to doctor after doctor, and we heard the same thing every time: ‘There’s nothing we can do.’ In the end, what happened was that my mom, unfortunately, passed away. This idea that there was nothing we could do, I just couldn't accept that. It became my mission to try and make it so that no other patient had to hear those words.”

It was because of this deeply emotional experience, and a fortunate discovery of the work being conducted by Bruce Donald, Ph.D., at Duke University, that Ten63 Therapeutics began to take shape. Donald is the James B. Duke professor of computer science, and professor of chemistry and biochemistry.

“(He) was developing this idea of taking these algorithms that had been extremely successful in robotics and applying them in a novel way to drug discovery and protein design,” said Frenkel. “I looked at the technology and was convinced of the impact it could have; this ability of searching chemical and conformational space so efficiently that you could stay a step ahead of disease, as well as investigate the conformational and chemical probabilities around the target, could potentially checkmate cancer.”

Frenkel teamed up with Donald and another scientist in the Donald lab, Mark Hallen. Hallen had a unique way of translating complex biophysical and chemical ideas into extremely efficient mathematical algorithms.

“Hallen was able to find the missing piece to the technology which would allow us to design new molecules with unprecedented speed and accuracy,” said Frenkel. The three worked together for the next five years. In 2019, they co-founded Ten63 Therapeutics.

With a mission of changing the paradigm of cancer outcomes, and a current pipeline of six oncology-focused targets, Ten63 is using computational drug discovery with the goal of designing what it says are advanced therapeutics at varying stages of preclinical development that show potential for enhanced durability against previously undruggable targets.

Using its proprietary BEYOND platform, a disease-agnostic drug-discovery engine that the company says efficiently combines physics and AI in search algorithms, Ten63 aims to pursue validated targets that exceed the reach of conventional therapeutic research.

According to the company, BEYOND’s unique search algorithms can search through nearly 19.5 million compounds per second, or roughly the same number of compounds explored experimentally in the history of humanity. As a result, BEYOND can find the best molecules for a given drug discovery project out of more than 100 trillion options. 

"The platform searches this vast chemical space completely, as if each molecule were examined one at a time," explained Frenkel. "The next-best method at this level of accuracy would require over 1,000 years to search this same space. This allows Ten63 to find solutions that no other method can find."

“The way we validated our approach was by going after a protein that was discovered in 1979 called c-Myc,” he said. “It’s always been known as this holy grail in cancer that drives up to 70% of all cancers, and it has this ability to regulate thousands of genes within the body. Some refer to it as the master regulator of cancer. There has been a huge desire to pursue c-Myc among the scientific community, but the ability to do so has been extremely challenging and nobody has been able to crack it.”

Frenkel and team began comparing a variety of molecules from these previous efforts to the output from its BEYOND-fueled findings. What they found was that BEYOND could out compete, by orders of magnitude, the top molecules that had been discovered over the last 40 years of attempts from both industry and academia. “This really showed us that we were headed in the right direction. What we had was something that could deliver great value and could potentially help us crack these targets for the first time.”

Ten63 has the backing of several strong institutional investors, including SOSV, Morpheus Ventures and Draper Associates and Draper Dragon.

Frenkel says the company name Ten63 "refers to 10^63, the total number of possible drug-like molecules that follow Lipinski's rules.” The founders decided the name would provide insight into the company's differentiation and ability to explore a vast chemical space.

Looking ahead, Frenkel and company are excited to get deeply involved in the local RTP life-sciences ecosystem by working with other great companies in the area. Meanwhile, the team continues to work hard and focus on its mission of improving patient lives.

“It has been an exciting and challenging journey,” said Frenkel. “We know the objective is very difficult, but the mission to improve outcomes for thousands of patients like my mother is worth it.”

John Wallace, NCBiotech Writer
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