Our Approach

Nuvalent combines deep expertise in structure-based design with clinical insights from physician-scientists to precisely inhibit clinically proven kinase targets and solve for the dual challenges of kinase resistance and selectivity.

Kinase inhibitors have fueled the targeted therapy revolution in oncology, and remain at the leading edge of precision medicine. However, the clinical utility of currently approved kinase inhibitors is limited by two key challenges:

The Kinase Resistance Problem

Cancer cells are constantly mutating. Treatment with currently available kinase inhibitors often results in the emergence of cancer cells harboring new mutations. These mutations can provide resistance to existing therapies.
Nuvalent designs innovative molecular structures that precisely engage the target kinase in the original cancer and the mutated target kinase in the drug-resistant cancer. This enables our therapies to treat both the original tumor and tumors with emergent resistance mutations.

The Kinase Selectivity Problem

The drug binding sites of different kinases are often very similar in structure, making it challenging to design molecules that uniquely inhibit a single target.

In some cases, the similarities between kinases can enable one molecule to be repurposed to treat multiple different tumor types. However, this compromise means allowing inhibition of off-target kinases, which can lead to significant adverse events and insufficient target inhibition, decreasing the duration of clinical responses.
Nuvalent is committed to the development of novel drug candidates that prioritize kinase selectivity in order to minimize adverse events and drive durable responses. We apply our deep expertise in structure-based design to address the selectivity challenge, resulting in precisely targeted therapies designed uniquely for specific patient populations.
Nuvalent’s Unique Goal
Matthew Shair, Ph. D.
Matthew Shair, PhD
Founder, Scientific Advisor
Matthew shares how Nuvalent uses modern structure-based design and innovative chemical solutions to enable the precision targeting of driver kinases.
Henry Pelish, Ph. D.
Henry Pelish, PhD
Senior Vice President, Drug Discovery
Henry discusses how both patient needs and insights from treating physicians inform Nuvalent’s approach to drug design.

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