Pipeline

Eliminating a Bad Actor in Cancer: Nurix’s Targeted Cancer Therapy Programs

NX-5948 (BTK degrader for B-cell malignancies)

NX-5948 is an oral small molecule degrader of BTK. Preclinical data support the activity of NX-5948 in tumor models harboring either wild-type BTK or BTK with mutations conferring clinical resistance to FDA approved agents. NX-5948 has demonstrated the ability to cross the blood brain barrier in animal models creating potential therapeutic utility in central nervous system (CNS) lymphoma and other diseases in the brain. NX-5948 has also demonstrated activity in animal models of autoimmune disease including models of rheumatoid arthritis and multiple sclerosis.

NX-5948 is being tested in an ongoing Phase 1 trial for patients with B-cell malignancies who have failed prior treatments.

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NX-2127 (BTK + IKZF degrader for B-cell malignancies)

NX-2127 is an oral small molecule degrader of BTK and cereblon neosubstrates IKZF1 (Ikaros) and IKZF3 (Aiolos). Cereblon immunomodulatory drugs that induce degradation IKZF1 and IKZF3 such as lenalidomide and pomalidomide are FDA approved for a variety of hematologic malignancies including multiple myeloma, follicular lymphoma, and mantle cell lymphoma. We hypothesize that the combination of BTK degradation and cereblon immunomodulatory activity will have enhanced therapeutic benefit in patients suffering from a variety of B-cell malignancies.

Initial clinical data support the activity of NX-2127 in patients whose tumors harbor either wild-type BTK or BTK with mutations conferring clinical resistance to FDA approved agents. Initial clinical data also confirm potent BTK degradation with once daily oral dosing. NX-2127 is being tested in an ongoing Phase 1 trial for patients with B-cell malignancies who have failed prior treatments.

Building Immunity to Cancer: Nurix’s Immuno-Oncology Program

NX-1607 (oral CBL-B inhibitor for solid tumors)

NX-1607 is an oral, small molecule CBL-B inhibitor with the potential to enhance innate and adaptive immune responses. In multiple preclinical animal tumor models NX-1607 demonstrated anti-tumor activity and prolonged survival. The combination of NX-1607 with an anti-PD-1 antibody provided additional benefit in animal models. The anti-tumor activity of NX-1607 is dependent on both CD8+ T cells and NK cells.

We are planning to develop NX-1607 in multiple solid tumors and lymphoma as monotherapy or in combination with other complementary therapies such as chemotherapy and potentially check point inhibitors. NX-1607 may also have utility in combination with cell therapies such as TIL or CAR T. A Phase 1 clinical trial of NX-1607 as a single agent therapy and in combination with paclitaxel chemotherapy in multiple oncology indications is ongoing.

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Harnessing the Ubiquitin Proteasome System to Block Inflammation

Despite major advances in the past 20 years, chronic inflammatory and autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis represent areas of high clinical unmet need. Drivers of B-cell and T-cell activation and proliferation are often critical nodes for potential therapeutic intervention in these diseases. Traditional enzyme inhibitors are capable of blocking a portion of the disease-causing signal from critical proteins. However, these proteins more often work within a complex, and degradation of these proteins shuts down both the enzymatic function and the so-called scaffold function, resulting in more complete blockade of the disease-causing signal pathway.

NX-5948 (BTK degrader)

BTK plays a central role in B cells and myeloid cells by controlling downstream signaling of multiple receptors, including B cell receptor (BCR), Toll-like receptors (TLR), and Fc receptors. Specifically, as a critical component of BCR signaling, BTK governs B cell development, proliferation and antibody production. In macrophages, microglia, and mast cells, BTK controls activation processes, including the production of histamine through degranulation in mast cells and the secretion of inflammatory cytokines in macrophages. In brain-resident microglia, BTK controls microglia phagocytic ability, migration and cytokine production.

BTK targeting agents have emerged as treatment for a growing number of autoimmune disorders.

BTK participates in signaling pathways through both its kinase and scaffolding functions.

NX-5948, a brain-penetrant, potent, and selective BTK degrader, is predicted to exert a more complete elimination of signaling pathways compared to classical BTK inhibitors by targeting both the kinase and scaffolding functions of this important protein.

NX-0479/GS-6791 (IRAK4 degrader)