Targeted therapies have changed the game for cancer patients with tumor-driving mutations such as ALK or ROS. But cancer cells can go around these drugs, developing resistance so that they can continue to grow. Nuvalent is working on a new kinase inhibitor aimed at overcoming this facet with fewer side effects than the conventional alternatives, and it starts with lung cancer.
The company is launching $ 50 million from Deerfield Management to bring two non-small cell lung cancer programs to the clinic. They plan to begin a phase 1/2 study for the first, NUV-520, ROS1 inhibitor, in the second half of this year and for the second, NUV-655, an ALK inhibitor in the first half of 2022. both designed for patients with advanced cancer against conventional alternatives.
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Kinase protectors work by binding to a specific site on a specific enzyme kinase produced by tumor-driving mutations. Over time, cancer cells develop resistance by altering that binding site so that the drug no longer responds there, said Nuvalent founder Matt Shair, Ph.D., professor of chemistry and bio- chemical studies at Harvard University.
“You have to design a molecule that goes back to that binding site, and it becomes harder and harder to do that as you go through subsequent treatment cycles,” he said.
Nuvalent uses structure-based and chemically based drug design to design small molecules that fit into these modified binding sites and – crucially – do not bind to other target-like enzymes these drugs but found in healthy cigarettes.
“If you take ROS1, there is a ROS1-like over-target kinase called TRK,” Shair said. ROS1 inhibitors that also bind to TRK can cause side effects that cause patients to decide to discontinue treatment or to stop doctors prescribing the highest, most effective dose of the drug.
While Nuvalent’s initial focus on cell lung cancer is not insignificant, it can expand in any direction.
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“ROS1 and ALK are known to be present in other tumor types… We could see strategies where we study the activity of these specific fertilizers in patients with other tumor types,” said Nuvalent CEO Jim Porter , Ph.D. said.
In addition to coping with stress, Nuvalent could eventually develop drugs for the original, noninvasive enzymes targeted by previous generations of kinase inhibitors. If it can deliver new drugs according to well – known targets, but with fewer side effects, more patients could benefit from targeted treatment.
The founders of Nuvalent came together in 2017 to find out how they could meet the needs of cancer patients through a new biotech company. Shair and Porter’s chemistry background is a big part of the Nuvalent approach, but oncologists also play a key role in oncologists.
“We have the potential to make an impact here and the best source of figuring goes out directly to the doctors,” Porter said. “We introduced this understanding from their perspective early in the company: What are the medical needs of the patients you treat? What are the limitations of conventional therapies for these patients? And as chemists, could we try to come up with solutions to those specific needs? ”
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As it moves toward the clinic, Nuvalent looks forward to developing new employees, partners and investors, and implementing what it has. learning from his major programs to the pipeline at an earlier stage.
“We already have three more projects at the detection stage and we are replenishing that with even more projects,” said Shair. “We see our potential ideas being implemented with many, many targets in the targeted kinase therapy space. ”