{"id":18611,"date":"2025-02-07T05:04:08","date_gmt":"2025-02-07T10:04:08","guid":{"rendered":"https:\/\/sosv.com\/?p=18611"},"modified":"2025-02-13T17:56:58","modified_gmt":"2025-02-13T22:56:58","slug":"how-ten63-turned-an-academic-project-into-an-ai-platform-for-drugging-undruggable-cancers","status":"publish","type":"post","link":"https:\/\/sosv.com\/how-ten63-turned-an-academic-project-into-an-ai-platform-for-drugging-undruggable-cancers\/","title":{"rendered":"How Ten63 turned an academic project into an AI platform for drugging \u201cundruggable\u201d cancers"},"content":{"rendered":"\n

The website<\/a> of the Donald Lab at Duke University is an early 2000s relic with Comic Sans font, hypertext menu, and photoshopped cartoons. It does not look like the birthplace of a groundbreaking technology in the fight to cure cancer.<\/p>\n\n\n\n

Yet the lab\u2019s  20 years of research into protein design is the foundation of Ten63 Therapeutics<\/a>, a startup out to drug undruggable cancer targets. Ten63\u2019s platform, BEYOND, can analyze 19,290,123 feasible drug compounds per second <\/em>in the search for molecules that might inhibit the proteins that drive cancer. Based on a generative quantum chemistry AI, BEYOND not only discovers hidden (cryptic) pockets within previously undruggable targets but also designs drugs for these previously intractable cancer targets. <\/p>\n\n\n\n

Like the Donald Lab webpage, Ten63\u2019s PhD co-founders Marcel Frenkel, Mark Hallen, and Bruce Donald, don\u2019t take themselves too seriously. It was a mix of chance, curiosity, and grief that brought them together to create  the ambitious suite of algorithms that may one day turn individualized cancer treatment into a routine medical procedure. <\/p>\n\n\n \r\n \r\n

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\r\n Marcel Frenkel, PhD <\/div>\r\n
\r\n Co-founder & CEO, Ten63 <\/div>\r\n <\/div>\r\n <\/div>\r\n <\/div>\r\n
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\r\n Bruce Donald, PhD <\/div>\r\n
\r\n Founder & Chair, Ten63 <\/div>\r\n <\/div>\r\n <\/div>\r\n <\/div>\r\n
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\r\n Mark Hallen, PhD <\/div>\r\n
\r\n Co-founder & CTO, Ten63 <\/div>\r\n <\/div>\r\n <\/div>\r\n <\/div>\r\n \r\n\r\n <\/div>\r\n <\/div>\r\n \r\n <\/div>\r\n\r\n\r\n \n\n\n

In 2014, Marcel Frenkel showed up at a Duke biochemistry retreat. He had a difficult question for every graduate student, postdoc and faculty member who presented, despite being only a second-year grad student himself. Marcel saved his toughest questions for the Donald Lab, which he was already determined to join. Marcel had read papers based on the lab\u2019s research on how OSPREY, a protein design algorithm, could revolutionize the treatment of undruggable diseases including HIV, the subject of his research.<\/p>\n\n\n\n

The lab\u2019s founder and namesake, Bruce Donald, was a professor in five different Duke University departments ranging from math to biochemistry and had long ignored the borders of academia. He had earned a PhD in computer science at MIT after studying Russian Language and Literature as an undergraduate at Yale. At Duke in 2006, he launched the Donald Lab to study protein design, which spans applied math, computer science, biochemistry, and chemistry. <\/p>\n\n\n\n

One major contributor to Osprey was the computational chemist Mark Hallen. Born in Ithaca, New York, the son of PhDs in physics and electrical engineering, hard sciences were pretty much Mark\u2019s destiny.  As a math and chemistry double major at Duke, Mark heard about a lab that had combined math and chemistry in ways that almost sounded like \u201csci-fi.\u201d It was the Donald Lab, and to Mark\u2019s surprise, it was making progress on protein design. He stayed at Duke for his PhD and joined the lab. <\/p>\n\n\n

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Ten63 Therapeutics founders<\/figcaption><\/figure><\/div>\n\n\n

The challenge in protein design is to model trillions of possible protein sequences and find the handful that might work in a specific use case, like inhibiting a drug-resistant tumor. The only efficient way to discover those proteins is through a massive computational effort, hence the Donald Lab\u2019s protein design algorithm, OSPREY. <\/p>\n\n\n\n

Mark\u2019s superpower was to make that algorithm work better. \u201cEvery year Mark would come up with some strikingly new idea,\u201d recalls Bruce Donald. \u201cHe\u2019d read the literature and assimilate it at this very rapid rate and come up with shockingly original takes on it. And then he would implement something that performed better than everything else.\u201d By 2014, OSPREY was being used in clinical trials for biologics and vaccines. <\/p>\n\n\n\n

For ten years, Bruce had pitched his PhD students on starting a company around OSPREY. None had stepped up. Marcel would be different. In his suit at the biochem retreat in Durham, Marcel already believed that only with commercial backing could OSPREY reach its full potential to beat cancer. And beating cancer was a very personal mission for him. When he was accepted, Marcel\u2019s main ambition was to launch Osprey outside academia. <\/p>\n\n\n\n

Born in San Paulo, Brazil, Marcel grew up in a close knit family accustomed to challenging adversaries. His father was a special agent for the Brazilian IRS specialized in investigating organized and financial crimes. His mother, a lawyer, chose to stay home, partially to help Marcel overcome dyslexia. Thanks to her dedication, says Marcel, he attended the University of Notre Dame as a Hesburgh Scholar and varsity athlete for his undergraduate biochemistry degree.<\/p>\n\n\n\n

At Duke, Marcel\u2019s initial research focused on HIV, but in 2014 his mother was diagnosed with pancreatic cancer. The doctors said that nothing could be done. Marcel began to research what technology could treat previously untreatable cancers and, after meeting Bruce at the Duke retreat, applied to the Donald Lab. <\/p>\n\n\n\n

\u201cHe read probably 20 to 50 papers on his own every day and absorbed them all somehow,\u201d says Bruce. When a friend of Bruce\u2019s was diagnosed with a rare breast cancer, Marcel knew which inhibitors to try and which clinical trial to join. Thanks to Marcel\u2019s advice, Bruce\u2019s friend was soon tumor-free to the shock of her doctors. <\/p>\n\n\n\n

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“What IndieBio gave us was not only a community of founders, with whom we’ve remained very strongly connected, but also a community of investors. We went from being scientists to entrepreneurs. I don’t think we could have achieved that anywhere else.\u201d <\/p>\nMarcel Frenkel, Co-founder & CEO, Ten63<\/cite><\/blockquote>\n\n\n\n

Bruce credits Marcel with bringing \u201cthe lab to the next level.\u201d When the lab needed more computers, Marcel wrote grants to get them. When the lab needed more grad students, Marcel recruited them. When the lab needed to develop new ways to target previously undruggable proteins, he dedicated himself to finding solutions. When Marcel\u2019s mother died in 2015, he and Mark became more determined than ever to shift Osprey from an academic to a clinical setting.<\/p>\n\n\n\n

\u201cThey did everything you would expect a scientist to do but I think that they were also preparing the technology and the vision for escape,\u201d recalls Bruce. Rather than focus on postdocs or job opportunities in industry, the two talked about how to turn OSPREY into a business. <\/p>\n\n\n\n

Marcel officially asked Bruce and Mark to join him in launching this new venture, originally called Gavil\u00e1n Biodesign, which launched in December 2018. From the beginning, says Marcel, \u201cIt was very impact driven. It was about how we can change the lives of patients like my Mom.\u201d<\/p>\n\n\n\n

\"Mark
Left to right: Mark Hallen, PhD, Co-founder & CTO, Bruce Donald, PhD, Founder & Chair, SAB, Marcel Frenkel, PhD, Co-founder & CEO<\/figcaption><\/figure>\n\n\n\n

One big technical challenge remained. OSPREY\u2019s algorithms could only be applied to proteins, a very specific albeit vital area. To design next-generation cancer therapeutics, OSPREY\u2019s algorithms had to extend to other chemical spaces and become more accurate. Mark, who was working at the Toyota Technological Institute at Chicago (TTIC), supplied that next foundational piece. \u201cMark had been working for years on a way to drastically enhance OSPREY\u2019s accuracy and generalize OSPREY\u2019s algorithms to all the chemical space\u201d says Marcel. \u201cConceptually, this is like jumping from special to general relativity.\u201d  Ten63\u2019s BEYOND platform has added nearly 1 million lines of code to OSPREY and extended its applicability into all drug-like chemical space. Today the platform searches proteins and over 100 trillion drug-like molecules with unprecedented accuracy.  <\/p>\n\n\n\n

Early in 2019, they began applying to startup programs that could teach them to operate like entrepreneurs. They joined SOSV\u2019s IndieBio startup development program in San Francisco, where they booked an over-priced Airbnb in the Haight Ashbury neighborhood of San Francisco, and each day  took two buses to get to the IndieBio lab. \u201cIt was one of the best moments of our lives,\u201d says Marcel.<\/p>\n\n\n\n

At IndieBio, they changed the name to Ten63, which stands for 10 to the 63rd power, the estimated number of compounds with therapeutic properties. <\/p>\n\n\n\n

\"Ten63
Ten63 Therapeutics team<\/figcaption><\/figure>\n\n\n\n

\u201cIndieBio was a 6-month MBA on how to start and build a founder-led company,\u201d recalls Marcel. \u201cWhat IndieBio gave us was not only a community of founders, with whom we’ve remained very strongly connected, but also a community of investors. We went from being scientists to entrepreneurs. I don’t think we could have achieved that anywhere else.\u201d <\/p>\n\n\n\n

When investor meetings and the IndieBio Demo Day in San Francisco arrived in June 2019, Bruce flew in from Duke. He brought a tweed jacket and tie, only to be advised that he should wear jeans and a hoodie. Soon after IndieBio, the company got to work targeting Myc, a protein that is thought to drive 70% of all cancers, including pancreatic cancer.<\/p>\n\n\n\n

At present, Ten63 is developing their own internal pipeline and working with pharmaceutical companies, including Boehringer Ingelheim, to discover therapeutics for currently untreatable diseases. The company has raised $21.4 million in venture funding from SOSV, Hatteras Venture Partners, Yosemite, Morpheus Ventures, Draper Associates, and others. <\/p>\n\n\n\n

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Marcel Frenkel, PhD, Co-founder & CEO, Mark Hallen, PhD, Co-founder & CTO, Bruce Donald, PhD, Founder & Chair, SAB<\/figcaption><\/figure>\n\n\n\n

By and large, cancer patients remain confined to traditional chemotherapy, which is highly toxic to the patient. Ten63 believes BEYOND can create such specifically targeted therapeutics that patients will carry on with normal, healthy lives while undergoing cancer treatment. <\/p>\n\n\n\n

\u201cOur mission at Ten63,\u201d says Marcel, \u201cis to use next-generation algorithms to discover new therapeutics so that patients  have options when facing currently incurable diseases.\u201d<\/p>\n\n\n\n

<\/div>\n\n\n\n

By Richard Ellis
Photos by Amy Stern Photography<\/p>\n","protected":false},"excerpt":{"rendered":"

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