Breakthrough Pancreatic Cancer Drug Maker Builds on Illinois Research Roots

While helping to launch the world’s first engineering-based college of medicine, Carle Illinois College of Medicine’s Inaugural Associate Dean for Research, Martin Burke, also co-founded a company that has given new hope to patients with advanced pancreatic cancer.

Revolution Medicines, originally launched in 2014-15 as Midasyn at the University of Illinois Urbana-Champaign by Burke and two colleagues, is the maker of a new experimental drug called daraxonrasib. In a recent Phase 3 clinical trial, the oral medication nearly doubled the median survival of patients with advanced pancreatic cancer. While not a cure, daraxonrasib is being hailed as a miracle drug, offering patients more time and more manageable side effects than standard chemotherapy.

Burke, a renowned organic chemist and Harvard-trained physician, says the results have been both humbling and inspiring. As an originator of the Physician Innovator concept, Burke’s entrepreneurship is tied to both his research at the University of Illinois and his work at CI MED.

Research Foundations

The foundations were laid in Burke’s lab, where he pioneered what is now called blocc chemistry, a modular approach for assembling small molecules via iterative carbon-carbon bond formation. Revolution Medicines was launched with the vision of harnessing this modular chemistry approach to redesign evolution’s small molecules (thus the name Revolution). Drugs derived from such small molecules, often called natural products, can be exceptionally effective in fighting diseases like cancer because they more readily enter cells and can block or disable abnormal proteins via unique mechanisms of action. Daraxonrasib is a small molecule that acts like a molecular glue and switches off mutant KRAS proteins that are the root of most pancreatic cancers.

Photo Credit: Fred Zwicky

These founding concepts of natural product-inspired and modular synthesis-enabled drug discovery are prominent features of the daraxonrasib story. Building on preliminary work by another biotech company, researchers at Revolution Medicines transformed the small molecule natural product sanglifehrin into a refined compound that glues another protein to cancer-causing mutants of KRAS, thereby blocking the growth of pancreatic tumors. And the company’s enabling modular approach for synthesizing daraxonrasib and many of its earlier derivatives leveraged a variant of the foundational iterative carbon-carbon bond forming strategy. 

“Some important initial work by the team at Warp Drive Bio had yielded promising glue-like activity against KRAS. The challenge was that these compounds weren’t very potent or orally bioavailable. The team at Revolution Medicines was able to build on these promising starting points and develop highly potent and orally bioavailable compounds suitable for advancement into clinical trials,” Burke said. 

Daraxonrasib drew worldwide attention following a 60 Minutes interview with former U.S. Senator Ben Sasse, who was diagnosed with Stage IV pancreatic cancer and expected to live only a few months. Sasse was prescribed daraxonrasib after the Food and Drug Administration granted it Breakthrough Therapy designation, which fast-tracked its use in the clinical setting. Sasse called it a miracle drug that, despite some difficult side effects, has helped to extend his time with his family. Seven months into treatment, Sasse reported that his tumors had shrunk by 80%.

Translating Discovery from the Lab to the Clinic

That sense of urgency continues to drive Burke’s work translating scientific discovery into real-world applications, particularly in medical therapeutics. He has co-founded five biotech companies, including Revolution Medicines, which have collectively advanced nine new drug candidates into clinical trials. 

Burke says being a serial entrepreneur allows him to see his scientific discoveries at work. “I think we all want to make an impact. Papers are important, but for many of us that just doesn't feel like enough,” Burke said. “The entrepreneurship thing, it's just this amazingly powerful mechanism to try to translate things out of the lab and into society.” 

Another med-tech venture that Burke co-founded, Sfunga Therapeutics (now called Elion Therapeutics), focuses on natural product-inspired antifungal medications. The company licensed from Burke’s lab a modified version of the drug amphotericin B, a natural product for which his blocc chemistry enabled fundamental understanding of the primary mechanism for cell killing and thus rational targeting of resistant fungal infections without damaging the kidneys. The resulting drug candidate, called turletricin, is now in phase 2 clinical trials. 

Together, the Molecular Maker Lab at Illinois and another Burke co-founded venture, Excelsior Sciences, are expanding a next generation version of Burke’s original blocc chemistry approach to incorporate robotics and AI. 

“Our vision is to democratize molecular innovation. Can we put the power of molecule making into the hands of anyone who wants to wield it for good and thereby not only enable discovery of tomorrow's medicines but things like materials and all kinds of other important molecular tools that impact society?” Burke said. “We think that has a chance to make the world a very exciting and better place.”

Excelsior seeks to speed up the development of new medicines and other compounds by creating ‘smart bloccs’ that can be assembled by robots and understood by artificial intelligence to predict functionality. Using this methodology, Burke foresees cross-disciplinary teams, including physicians, working to identify a medical need and then use AI-guided automated chemical synthesis to develop and rapidly test compounds with the greatest potential to treat the problem.

Modeling the Physician Innovator

As CI MED’s inaugural associate dean of research, Burke was one of the primary architects of the college’s emphasis on medical innovation and entrepreneurship from its inception in 2015, just as Revolution Medicines was taking off.  

“The fact that the company (Midasyn, now Revolution Medicines) was getting launched when all that was happening gave me a sense of, okay, I hope we can set up an environment where more and more of us can do this, and these students [at CI MED] could hopefully have the chance to do it in their own careers,” he said. 

Drawing on his own experiences, Burke helped establish pathways for CI MED students to create solutions that change medicine. He was instrumental in shaping innovation competitions and CI MED’s curriculum, which challenges students to identify and work to solve healthcare challenges.

Burke is now working with CI MED leadership to expand medical students’ access to the tools and connections available through the Molecular Maker Lab for those interested in drug discovery, even if they lack a chemistry background. 

He foresees CI MED students working across disciplines to challenge the traditional practice of medicine. “They chose to come here because they were not satisfied with the field of medicine as it is. They didn't come to learn it and apply it. They came to change it. And then our job, of course, is to give them the resources they need to actually do that,” he said.

Burke credits CI MED’s founders and leaders with setting the stage, but he says ultimately, it’s CI MED’s Physician Innovators in training who will build the future of medicine.

“I think the sooner students can realize they actually own the future and that their ideas are the best ideas that are going to shape that future, the sooner they become very, very powerful,” Burke said. 

Editor's notes:

Dr. Martin D. Burke is the May and Ving Lee Professor for Chemical Innovation at the University of Illinois at Urbana-Champaign and a professor of Biomedical and Translational Sciences at CI MED. He is the founding Director of the Molecular Maker Lab and a co-founder of the Molecule Maker Lab Institute. He is an elected member of the National Academy of Medicine.

This article was written by Beth Hart with video content by Virgil Ward.