On May 26, 2022, biopharmaceutical company Nurix Therapeutics, Inc. (“Nurix”) shared via news release that positive data was available from an ongoing Phase 1a dose escalation study. Within the study, Nurix is evaluating NX-2127 for individuals with B-cell malignancies. Following the positive data, Nurix has began enrolling individuals within a Phase 1b expansion cohort to continue understanding how the therapy may help those with chronic lymphocytic leukemia (CLL).

What is NX-2127?

In a presentation from Dr. Daniel Robbins, PhD, he explains that NX-2127 is a BTK degrader. Historically, BTK inhibitors have shown promise in patients with B-cell malignancies. However, some patients are unable to tolerate BTK inhibition, while it is ineffective in others. Through its immunomodulatory properties, NX-2127 has the potential to overcome these obstacles and offer more effective treatment. As Dr. Robbins explains further:

NX-2127 is a novel, hetero-bifunctional, orally administered, Chimeric Targeting Molecule (CTM) that induces the degradation of Bruton’s Tyrosine Kinase (BTK) in cells through recruitment of cereblon (CRBN), a component of the CRL4-CRBN ubiquitin ligase complex.

So far, the Phase 1a study has evaluated the safety, efficacy, clinical activity, pharmacokinetic profile, and pharmacodynamic profile of NX-2127 in adults with relapsed or refractory (R/R) B-cell malignancies, such as CLL, mantle cell lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma. So far, the study has found that NX-2127 contributes to sustained BTK degredation; 100mg is safe and effective; and patients with mutations associated to treatment resistance have found NX-2127 to be effective.

Altogether, 40 individuals with CLL will enroll in the expansion study. All participants will have been on at least two prior treatments that were ineffective. During this study, patients will receive 100mg NX-2127 each day to evaluate its impact. More data will be available in the future.

Chronic Lymphocytic Leukemia (CLL): An Overview

In those with chronic lymphocytic leukemia (CLL), a type of blood and bone marrow cancer, some sort of genetic alteration occurs in the DNA of blood-producing cells. This causes the production of ineffective lymphocytes. While lymphocytes normally help your body fight infections, these ineffective lymphocytes crowd out healthy cells and cause a variety of health issues. Although CLL is considered to be a rare cancer, it is also the 2nd most common leukemia in adults. In many cases, symptoms do not appear until later stages. When symptoms do appear, these can include:

• Fatigue
• Fever and night sweats
• Unintended weight loss
• Enlarged – but painless – lymph nodes
• Upper left abdominal pain
• Enlarged spleen
• Frequent infections
• Easy bruising