Pipeline

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

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

NX-2127 is an oral small molecule that combines the activity of a targeted BTK degrader with cereblon immunomodulatory activity of an IKZF degrader. 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.

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 leading FDA approved agents. NX-5948 lacks cereblon immunomodulatory activity, differentiating it from NX-2127, and has demonstrated the ability to cross the blood brain barrier in animal models. NX-5948 has also demonstrated activity in animal models of autoimmune disease.

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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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. In multiple preclinical animal models of both colorectal cancer and triple negative breast cancer, NX-1607 demonstrates anti-tumor activity and prolongs survival. The combination of NX-1607 with an anti-PD-1 antibody provides 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 anti-PD-1 antibodies. 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 in multiple oncology indications is ongoing.

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Drug-enhanced Cell Therapy Programs

DeTIL-0255 (drug-enhanced tumor-infiltrating lymphocytes for solid tumors)

DeTIL-0255 is a cellular therapy that incorporates our proprietary small molecule CBL-B inhibitor NX-0255 in the cell expansion process of tumor infiltrating lymphocytes (TIL). We call this drug-enhanced TIL, or DeTIL. While DeTIL-0255 incorporates a CBL-B inhibitor, we are also exploring combining other targeted agents, such as its proprietary protein degraders, to enhance T cell expansion and phenotypes.

We are planning to first develop DeTIL-0255 in multiple solid tumors as a monotherapy and later to combine it with our proprietary oral CBL-B inhibitor, NX-1607. A Phase 1 clinical trial of DeTIL-0255 in gynecological malignancies is ongoing.

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