Building Immunity to Cancer: Nurix’s Immuno-Oncology Program
Targeted Protein Elevation: CBL-B Inhibition
Casitas B-lineage lymphoma proto-oncogene-b (CBL-B) is an E3 ligase that is expressed in immune cells and in the context of cancer, acts as a brake on the immune system. CBL-B functions as an intracellular checkpoint that negatively regulates T cell activation, NK cell activity, and immune response through degradation of specific proteins.
Conversely, inhibition of CBL-B with a small molecule drug activates T cells, a goal in the treatment of cancer, where T cells and the entire immune system can be mobilized to destroy a tumor. Nurix has developed two CBL-B inhibitors, NX-1607 for oral administration and NX-0255 for ex vivo use in combination with adoptive cell therapies such as tumor infiltrating lymphocytes (TIL) or chimeric antigen receptor T cells (CAR T).
| Drug Program | Target/Delivery | Therapeutic Area | Discovery | IND enabling | Phase 1a | Phase 1b | ||
|---|---|---|---|---|---|---|---|---|
| Targeted Protein Degradation | ||||||||
| NX-2127 Degrader | BTK + IKZF (Oral) | B-cell malignancies |
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| NX-5948 Degrader | BTK (Oral) | B-cell malignancies |
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| NX-0479 / GS-6791 Degrader | IRAK4 (Oral) | Rheumatoid arthritis and other inflammatory diseases |
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| Drug Program | Target/Delivery | Therapeutic Area | Discovery | IND enabling | Phase 1a | Phase 1b | ||
| Targeted Protein Elevation | ||||||||
| NX-1607 Inhibitor | CBL-B (Oral) | Immuno-oncology |
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| Drug Program | Target/Delivery | Therapeutic Area | Discovery | IND enabling | Phase 1a | Phase 1b | ||
| Discovery Pipeline | ||||||||
| Wholly Owned | 5 targets | Undisclosed |
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| Gilead Sciences | 4 Targets | Undisclosed |
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| Sanofi | 5 Targets | Undisclosed |
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| Targeted Protein Degradation | NX-2127 DegraderBTK + IKZF (Oral) - B-cell malignancies |
Preclinical IND-Enabling Phase 1a Phase 1b |
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| NX-5948 DegraderBTK (Oral) - B-cell malignancies |
Preclinical IND-Enabling Phase 1a Phase 1b |
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| NX-0479 / GS-6791 DegraderIRAK4 (Oral) - Rheumatoid arthritis and other inflammatory diseases |
Preclinical IND-Enabling Phase 1a Phase 1b |
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| Targeted Protein Elevation | NX-1607 InhibitorCBL-B (Oral) - Immuno-oncology |
Preclinical IND-Enabling Phase 1a Phase 1b |
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| Discovery Pipeline | Wholly Owned 5 targets - Undisclosed |
Preclinical IND-Enabling Phase 1a Phase 1b |
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| Gilead Sciences4 Targets - Undisclosed |
Preclinical IND-Enabling Phase 1a Phase 1b |
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| Sanofi5 Targets - Undisclosed |
Preclinical IND-Enabling Phase 1a Phase 1b |
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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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