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Pipeline

Innovative Drugs Designed to Improve Patients’ Lives

Nurix is advancing three internally discovered and wholly owned clinical-stage drug-candidates designed to treat patients with hematologic malignancies, solid tumors and inflammatory diseases. Nurix’s pipeline comprises both Targeted Protein Degraders to eliminate disease causing proteins and E3 ligase inhibitors that target key control elements in immune regulation (Targeted Protein Elevation). Drug discovery alliances with Gilead Sciences, Sanofi, and Pfizer further enhance our pipeline, each focusing on the discovery and development of Targeted Protein Degraders and Degrader-Antibody Conjugates against a set of unique targets.

Drug ProgramMOATarget/DeliveryTherapeutic AreaDiscovery - Lead OpIND enablingPhase 1aPhase 1b
Hematology/Oncology
NX-5948 TPD BTK B-cell malignancies

 

NX-2127 TPD BTK + IKZF B-cell malignancies

 

NX-1607 TPE CBL-B Immuno-oncology

 

Multiple TPD Undisclosed Undisclosed

 

Multiple TPD Undisclosed Undisclosed

 

Multiple TPD Undisclosed Undisclosed

 

Multiple DAC Undisclosed Oncology

 

Drug ProgramMOATarget/DeliveryTherapeutic AreaDiscovery - Lead OpIND enablingPhase 1aPhase 1b
Inflammation & Immunology
NX-5948 TPD BTK Inflammation/autoimmune

 

NX‑0479/GS‑6791 TPD IRAK4 Rheumatoid arthritis and other inflammatory diseases

 

Multiple TPD Undisclosed Inflammation/autoimmune

 

Hematology/Oncology
NX-5948 - TPDBTK - B-cell malignancies

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

NX-2127 - TPDBTK + IKZF - B-cell malignancies

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

NX-1607 - TPECBL-B - Immuno-oncology

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Undisclosed

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Undisclosed

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Undisclosed

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - DACUndisclosed - Oncology

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Inflammation & Immunology
NX-5948 - TPDBTK - Inflammation/autoimmune

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

NX‑0479/GS‑6791 - TPDIRAK4 - Rheumatoid arthritis and other inflammatory diseases

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Inflammation/autoimmune

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

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

BTK Degraders

The U.S. Food and Drug Administration and global regulatory agencies have approved several inhibitors of Bruton’s tyrosine kinase (BTK), which are now the standard of care across multiple tumor types. We believe that removal of the BTK protein through Targeted Protein Degradation could generate superior outcomes for patients who no longer respond to or do not tolerate current therapies, including patients whose tumors have acquired resistance to current therapies through mutations in the BTK protein.

BTK is a validated clinical target for the treatment of hematologic malignancies and autoimmune diseases. BTK is a master regulator of B-cell activity, and inhibition of BTK results in improved clinical outcomes for patients with a variety of B-cell mediated cancers such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL).

We have developed two unique and functionally distinct BTK degraders that harness cereblon (CRBN), an E3 ligase active in hematopoietic cells. Cereblon itself is the target for a class of drugs with immunomodulatory activity, including lenalidomide and pomalidomide that induce cereblon to degrade so-called neosubstrates Ikaros (IKZF1) and Aiolos (IKZF3). We have designed two BTK degraders with and without the ability to induce neosubstrate degradation, creating two functionally distinct drug candidates to address the unmet medical needs across indications and lines of therapy.

BTK
Drug ProgramMOATarget/DeliveryTherapeutic AreaDiscovery - Lead OpIND enablingPhase 1aPhase 1b
Hematology/Oncology
NX-5948 TPD BTK B-cell malignancies

 

NX-2127 TPD BTK + IKZF B-cell malignancies

 

NX-1607 TPE CBL-B Immuno-oncology

 

Multiple TPD Undisclosed Undisclosed

 

Multiple TPD Undisclosed Undisclosed

 

Multiple TPD Undisclosed Undisclosed

 

Multiple DAC Undisclosed Oncology

 

Drug ProgramMOATarget/DeliveryTherapeutic AreaDiscovery - Lead OpIND enablingPhase 1aPhase 1b
Inflammation & Immunology
NX-5948 TPD BTK Inflammation/autoimmune

 

NX‑0479/GS‑6791 TPD IRAK4 Rheumatoid arthritis and other inflammatory diseases

 

Multiple TPD Undisclosed Inflammation/autoimmune

 

Hematology/Oncology
NX-5948 - TPDBTK - B-cell malignancies

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

NX-2127 - TPDBTK + IKZF - B-cell malignancies

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

NX-1607 - TPECBL-B - Immuno-oncology

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Undisclosed

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Undisclosed

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Undisclosed

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - DACUndisclosed - Oncology

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Inflammation & Immunology
NX-5948 - TPDBTK - Inflammation/autoimmune

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

NX‑0479/GS‑6791 - TPDIRAK4 - Rheumatoid arthritis and other inflammatory diseases

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Inflammation/autoimmune

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

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.

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

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 inhibitory signaling proteins.

Inhibition of CBL-B with a small molecule drug activates T and NK cells, a goal in the treatment of cancer, where T cells and the entire immune system can be mobilized to destroy a tumor.

Drug ProgramMOATarget/DeliveryTherapeutic AreaDiscovery - Lead OpIND enablingPhase 1aPhase 1b
Hematology/Oncology
NX-5948 TPD BTK B-cell malignancies

 

NX-2127 TPD BTK + IKZF B-cell malignancies

 

NX-1607 TPE CBL-B Immuno-oncology

 

Multiple TPD Undisclosed Undisclosed

 

Multiple TPD Undisclosed Undisclosed

 

Multiple TPD Undisclosed Undisclosed

 

Multiple DAC Undisclosed Oncology

 

Drug ProgramMOATarget/DeliveryTherapeutic AreaDiscovery - Lead OpIND enablingPhase 1aPhase 1b
Inflammation & Immunology
NX-5948 TPD BTK Inflammation/autoimmune

 

NX‑0479/GS‑6791 TPD IRAK4 Rheumatoid arthritis and other inflammatory diseases

 

Multiple TPD Undisclosed Inflammation/autoimmune

 

Hematology/Oncology
NX-5948 - TPDBTK - B-cell malignancies

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

NX-2127 - TPDBTK + IKZF - B-cell malignancies

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

NX-1607 - TPECBL-B - Immuno-oncology

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Undisclosed

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Undisclosed

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Undisclosed

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - DACUndisclosed - Oncology

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Inflammation & Immunology
NX-5948 - TPDBTK - Inflammation/autoimmune

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

NX‑0479/GS‑6791 - TPDIRAK4 - Rheumatoid arthritis and other inflammatory diseases

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Inflammation/autoimmune

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

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.

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.

Drug ProgramMOATarget/DeliveryTherapeutic AreaDiscovery - Lead OpIND enablingPhase 1aPhase 1b
Hematology/Oncology
NX-5948 TPD BTK B-cell malignancies

 

NX-2127 TPD BTK + IKZF B-cell malignancies

 

NX-1607 TPE CBL-B Immuno-oncology

 

Multiple TPD Undisclosed Undisclosed

 

Multiple TPD Undisclosed Undisclosed

 

Multiple TPD Undisclosed Undisclosed

 

Multiple DAC Undisclosed Oncology

 

Drug ProgramMOATarget/DeliveryTherapeutic AreaDiscovery - Lead OpIND enablingPhase 1aPhase 1b
Inflammation & Immunology
NX-5948 TPD BTK Inflammation/autoimmune

 

NX‑0479/GS‑6791 TPD IRAK4 Rheumatoid arthritis and other inflammatory diseases

 

Multiple TPD Undisclosed Inflammation/autoimmune

 

Hematology/Oncology
NX-5948 - TPDBTK - B-cell malignancies

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

NX-2127 - TPDBTK + IKZF - B-cell malignancies

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

NX-1607 - TPECBL-B - Immuno-oncology

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Undisclosed

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Undisclosed

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Undisclosed

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - DACUndisclosed - Oncology

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Inflammation & Immunology
NX-5948 - TPDBTK - Inflammation/autoimmune

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

NX‑0479/GS‑6791 - TPDIRAK4 - Rheumatoid arthritis and other inflammatory diseases

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

Multiple - TPDUndisclosed - Inflammation/autoimmune

Preclinical

IND-Enabling

Phase 1a

Phase 1b

 

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)

IRAK4 is a serine/threonine kinase that acts as a central mediator of TLR and IL-1R signaling and has emerged as a therapeutic target in multiple chronic inflammatory diseases, including RA. In addition to its kinase activity, IRAK4 has a kinase-independent scaffolding function, which is essential for formation of the Myddosome oligomeric complex and subsequent production of proinflammatory cytokines. The function of IRAK4 is only partially impacted by inhibition of kinase activity. Full suppression of IRAK4 function can only be achieved by elimination of both enzymatic and scaffolding activity.

In March 2023, Gilead Sciences exercised its option to exclusively license NX-0479, designated GS-6791, which is the first development candidate resulting from the previously announced Nurix-Gilead collaboration to discover, develop, and commercialize a pipeline of innovative targeted protein degradation therapies. NX-0479/GS-6791 is a potent, selective, oral IRAK4 degrader that targets both the scaffold and kinase functions of the IRAK4 protein kinase to block inflammatory responses downstream of toll-like receptors (TLR) and the pro-inflammatory IL-1 cytokine family of receptors (IL-1Rs). Degradation of IRAK4 by NX-0479/GS-6791 is hypothesized to have more sustained and deeper inhibition of TLR/IL-1Rs signaling as compared to kinase inhibition due to its impact on additional signaling nodes.

Inflammation