Approach

Chemistry at the core

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:

KINASE RESISTANCE KINASE SELECTIVITY

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.

Unlike existing therapies, Nuvalent’s small molecule inhibitors are effective in both original and drug-resistant cancers

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.

Non-selective kinase inhibitors lead to side effects but Nuvalent’s drugs only inhibit target kinases, avoiding side effects

Nuvalent’s Unique Goal

At Nuvalent, we apply a patient-focused lens to structure-based drug design. We begin by Collaborating with physician-scientists to understand the complex medical challenges that patients face today. Those insights then form the basis of our precisely targeted “product profiles” that guide each of our programs from discovery through development.”

Henry Pelish, PhD

Senior Vice President, Drug Discovery