NX-1607

These findings suggest that the combination of Cbl-b inhibitors with CDK4/6 inhibitors may have significant synergistic effects in promoting immune cell infiltration and facilitating immune activation. Therefore, this combination represents a promising therapeutic strategy for the treatment of solid tumors.

The study results revealed that KIF13B is a crucial modulator responsible for maintaining proper macrophage efferocytosis to prevent atherosclerotic development through KIF13B/ITCH/CBL/MERTK axis, suggesting that KIF13B will be a potential therapeutic target for the treatment of atherosclerosis in future clinical trials.

Taken together, these findings imply that the inhibition of Cbl-b by NX-1607 may enhance the activation of the MAPK/ERK signaling pathway, thereby sustaining T-cell activation. This provides compelling evidence for the molecular mechanism of NX-1607, underscoring the pivotal role of Cbl-b in controlling signal strength in T-cell activation after T-cell receptor (TCR) engagement.

Notably, compound B2 stands out, showing superior potency in stimulating IL-2 production in T cells and modulating phosphorylation of key proteins in T-cell receptor signaling. Furthermore, B2 demonstrates favorable pharmacokinetics and significantly inhibits tumor growth in vivo, outperforming NX-1607, which is currently in clinical trials.

P1, N=345, Recruiting, Nurix Therapeutics, Inc. | Trial completion date: Feb 2026 --> Feb 2028 | Trial primary completion date: Aug 2024 --> Aug 2026

P1, N=345, Recruiting, Nurix Therapeutics, Inc. | Phase classification: P1b --> P1 | Trial completion date: Feb 2025 --> Feb 2026

P1b, N=363, Recruiting, Nurix Therapeutics, Inc. | N=268 --> 363

Immunomodulatory drugs (IMiDs, e.g., lenalidomide) are approved as monotherapy for follicular lymphoma (FL), MZL, and MCL, in combination with other therapies for diffuse large B-cell lymphoma (DLBCL) and have shown synergy with BTK-targeted therapy...NX-2127 was shown to degrade both wild-type (WT) and C481-mutated (ibrutinib-resistant) BTK protein in vitro...The primary endpoint are dose-limiting toxicities and maximum tolerated dose (Phase 1a), objective response (Phase 1b), and safety (Phase 1a and Phase 1b) of NX-1607...Conclusion Accrual is ongoing. Clinical trial information: NCT04830137.