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Pipeline

Innovative Drugs Designed to Improve Patients’ Lives

Our pipeline includes internally discovered and wholly owned drug-candidates designed to treat patients with hematologic malignancies, solid tumors, autoimmune diseases, and viral diseases. It comprises both Chimeric Targeting Molecules (CTMs) for targeted protein degradation to eliminate disease causing proteins and Ligase Inhibitors that target key control elements in immune regulation. Drug discovery alliances with Gilead Sciences and Sanofi further enhance our pipeline, each focusing on the discovery and development of CTMs against a set of unique targets.

Drug CandidateTarget (Delivery)Therapeutic AreaDiscoveryLead OptimizationPreclinicalPhase 1Phase 2Phase 3
Protein Degradation Chimeric Targeting Molecule (CTM) Portfolio
NX-2127 BTK + IMiD Activity (Oral) B-cell malignancies

 

NX-5948 BTK (Oral) B-cell malignancies and autoimmune disease

 

KINASE-CTM3 Undisclosed T-cell malignancies and autoimmune disease

 

COVID-CTMs 3 targets Anti-viral

 

Drug CandidateTarget (Delivery)Therapeutic AreaDiscoveryLead OptimizationPreclinicalPhase 1Phase 2Phase 3
Ligase Inhibitor Portfolio
NX-1607 CBL-B (Oral) Immuno-oncology

 

DeTIL-0255 CBL-B (ex vivo) Tumor infiltrating lymphocytes

 

LIGASE-INH2 Undisclosed Immuno-oncology

 

Drug CandidateTarget (Delivery)Therapeutic AreaDiscoveryLead OptimizationPreclinicalPhase 1Phase 2Phase 3
Partners and Subsidiaries
DeCART CBL-B and others (ex vivo) Chimeric antigen receptor T‑cells (CAR-T)

 

Gilead Sciences 5 targets Undisclosed

Undisclosed Progress

 

Sanofi 5 targets Undisclosed

Undisclosed Progress

 

Candidate / TargetPhase
Protein Degradation Chimeric Targeting Molecule (CTM) Portfolio
NX-2127
BTK + IMiD Activity (Oral)
Phase 1
NX-5948
BTK (Oral)
Preclinical
KINASE-CTM3
Undisclosed
Lead Optimization
COVID-CTMs
3 targets
Discovery
Ligase Inhibitor Portfolio
NX-1607
CBL-B (Oral)
Phase 1
DeTIL-0255
CBL-B (ex vivo)
Preclinical
LIGASE-INH2
Undisclosed
Lead Optimization
Partners and Subsidiaries
DeCART
CBL-B and others (ex vivo)
Lead Optimization
Gilead Sciences
5 targets
Undisclosed Progress
Sanofi
5 targets
Undisclosed Progress

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

BTK Degraders

Bruton’s tyrosine kinase (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 non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and B-cell mediated autoimmune diseases such as graft versus host disease (GVHD).

The FDA and global regulatory agencies have approved several inhibitors of 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.

We have developed two unique and functionally distinct BTK degraders that harness cereblon, an E3 ligase active in hematopoietic cells. Cereblon itself is the target for a class of drugs known as immunomodulatory imide drugs (IMiDs), including Revlimid (lenalidomide) and Pomalyst (pomalidomide). We have designed two BTK degraders with and without IMiD activity, creating two functionally different drug candidates.

BTK
Drug CandidateTarget (Delivery)Therapeutic AreaDiscoveryLead OptimizationPreclinicalPhase 1Phase 2Phase 3
Protein Degradation Chimeric Targeting Molecule (CTM) Portfolio
NX-2127 BTK + IMiD Activity (Oral) B-cell malignancies

 

NX-5948 BTK (Oral) B-cell malignancies and autoimmune disease

 

KINASE-CTM3 Undisclosed T-cell malignancies and autoimmune disease

 

COVID-CTMs 3 targets Anti-viral

 

Drug CandidateTarget (Delivery)Therapeutic AreaDiscoveryLead OptimizationPreclinicalPhase 1Phase 2Phase 3
Ligase Inhibitor Portfolio
NX-1607 CBL-B (Oral) Immuno-oncology

 

DeTIL-0255 CBL-B (ex vivo) Tumor infiltrating lymphocytes

 

LIGASE-INH2 Undisclosed Immuno-oncology

 

Drug CandidateTarget (Delivery)Therapeutic AreaDiscoveryLead OptimizationPreclinicalPhase 1Phase 2Phase 3
Partners and Subsidiaries
DeCART CBL-B and others (ex vivo) Chimeric antigen receptor T‑cells (CAR-T)

 

Gilead Sciences 5 targets Undisclosed

Undisclosed Progress

 

Sanofi 5 targets Undisclosed

Undisclosed Progress

 

Candidate / TargetPhase
Protein Degradation Chimeric Targeting Molecule (CTM) Portfolio
NX-2127
BTK + IMiD Activity (Oral)
Phase 1
NX-5948
BTK (Oral)
Preclinical
KINASE-CTM3
Undisclosed
Lead Optimization
COVID-CTMs
3 targets
Discovery
Ligase Inhibitor Portfolio
NX-1607
CBL-B (Oral)
Phase 1
DeTIL-0255
CBL-B (ex vivo)
Preclinical
LIGASE-INH2
Undisclosed
Lead Optimization
Partners and Subsidiaries
DeCART
CBL-B and others (ex vivo)
Lead Optimization
Gilead Sciences
5 targets
Undisclosed Progress
Sanofi
5 targets
Undisclosed Progress

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

NX-2127 is an oral small molecule that combines the activity of a targeted BTK degrader with the therapeutic activity of the immunomodulatory imide drug (IMiD) class. IMiDs such as Revlimid (lenalidomide) and Pomalyst (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 IMiD activity will have enhanced therapeutic benefit in patients suffering from a variety of B-cell malignancies.

Preclinical data support the activity of NX-2127 in tumor models harboring either wild-type BTK or BTK with mutations conferring clinical resistance to FDA approved agents. Studies in non-human primates 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 and autoimmune disease)

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. Unlike NX-2127, our other BTK degrader, NX-5948 lacks IMiD activity 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.

We anticipate starting clinical development of NX-5948 in 2021. Our initial Phase 1 trial will be in hematologic malignancies, with potential future studies in autoimmune diseases.

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

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 Adoptive Cell Therapy.

Drug CandidateTarget (Delivery)Therapeutic AreaDiscoveryLead OptimizationPreclinicalPhase 1Phase 2Phase 3
Protein Degradation Chimeric Targeting Molecule (CTM) Portfolio
NX-2127 BTK + IMiD Activity (Oral) B-cell malignancies

 

NX-5948 BTK (Oral) B-cell malignancies and autoimmune disease

 

KINASE-CTM3 Undisclosed T-cell malignancies and autoimmune disease

 

COVID-CTMs 3 targets Anti-viral

 

Drug CandidateTarget (Delivery)Therapeutic AreaDiscoveryLead OptimizationPreclinicalPhase 1Phase 2Phase 3
Ligase Inhibitor Portfolio
NX-1607 CBL-B (Oral) Immuno-oncology

 

DeTIL-0255 CBL-B (ex vivo) Tumor infiltrating lymphocytes

 

LIGASE-INH2 Undisclosed Immuno-oncology

 

Drug CandidateTarget (Delivery)Therapeutic AreaDiscoveryLead OptimizationPreclinicalPhase 1Phase 2Phase 3
Partners and Subsidiaries
DeCART CBL-B and others (ex vivo) Chimeric antigen receptor T‑cells (CAR-T)

 

Gilead Sciences 5 targets Undisclosed

Undisclosed Progress

 

Sanofi 5 targets Undisclosed

Undisclosed Progress

 

Candidate / TargetPhase
Protein Degradation Chimeric Targeting Molecule (CTM) Portfolio
NX-2127
BTK + IMiD Activity (Oral)
Phase 1
NX-5948
BTK (Oral)
Preclinical
KINASE-CTM3
Undisclosed
Lead Optimization
COVID-CTMs
3 targets
Discovery
Ligase Inhibitor Portfolio
NX-1607
CBL-B (Oral)
Phase 1
DeTIL-0255
CBL-B (ex vivo)
Preclinical
LIGASE-INH2
Undisclosed
Lead Optimization
Partners and Subsidiaries
DeCART
CBL-B and others (ex vivo)
Lead Optimization
Gilead Sciences
5 targets
Undisclosed Progress
Sanofi
5 targets
Undisclosed Progress

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

NX-1607 is an oral, small molecule CBL-B inhibitor. In 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 as monotherapy or in combination with other complementary therapies such as anti-PD-1 antibodies. A Phase 1 clinical trial of NX-1607 as a single agent therapy in multiple oncology indications is ongoing.

Drug-enhanced Cell Therapy Programs

Adoptive Cell Therapy

Nurix is pioneering applying targeted protein modulation to adoptive cell therapy.  Our lead cell therapy program applies a CBL-B inhibitor, NX-0255, to a cancer patient’s T cells outside the body (ex vivo) to enhance their tumor-killing ability when returned to the patient as an autologous cell therapy. Inhibiting CBL-B has several beneficial effects that enhance adoptive T cell therapy, including stimulation of IL-2 secretion, increased T cell proliferation, reduced T cell exhaustion, and a skewing of the phenotype of the T-cells for improved clinical outcomes.

Drug CandidateTarget (Delivery)Therapeutic AreaDiscoveryLead OptimizationPreclinicalPhase 1Phase 2Phase 3
Protein Degradation Chimeric Targeting Molecule (CTM) Portfolio
NX-2127 BTK + IMiD Activity (Oral) B-cell malignancies

 

NX-5948 BTK (Oral) B-cell malignancies and autoimmune disease

 

KINASE-CTM3 Undisclosed T-cell malignancies and autoimmune disease

 

COVID-CTMs 3 targets Anti-viral

 

Drug CandidateTarget (Delivery)Therapeutic AreaDiscoveryLead OptimizationPreclinicalPhase 1Phase 2Phase 3
Ligase Inhibitor Portfolio
NX-1607 CBL-B (Oral) Immuno-oncology

 

DeTIL-0255 CBL-B (ex vivo) Tumor infiltrating lymphocytes

 

LIGASE-INH2 Undisclosed Immuno-oncology

 

Drug CandidateTarget (Delivery)Therapeutic AreaDiscoveryLead OptimizationPreclinicalPhase 1Phase 2Phase 3
Partners and Subsidiaries
DeCART CBL-B and others (ex vivo) Chimeric antigen receptor T‑cells (CAR-T)

 

Gilead Sciences 5 targets Undisclosed

Undisclosed Progress

 

Sanofi 5 targets Undisclosed

Undisclosed Progress

 

Candidate / TargetPhase
Protein Degradation Chimeric Targeting Molecule (CTM) Portfolio
NX-2127
BTK + IMiD Activity (Oral)
Phase 1
NX-5948
BTK (Oral)
Preclinical
KINASE-CTM3
Undisclosed
Lead Optimization
COVID-CTMs
3 targets
Discovery
Ligase Inhibitor Portfolio
NX-1607
CBL-B (Oral)
Phase 1
DeTIL-0255
CBL-B (ex vivo)
Preclinical
LIGASE-INH2
Undisclosed
Lead Optimization
Partners and Subsidiaries
DeCART
CBL-B and others (ex vivo)
Lead Optimization
Gilead Sciences
5 targets
Undisclosed Progress
Sanofi
5 targets
Undisclosed Progress

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 planned to start in the second half of 2021.

DeCART (drug-enhanced chimeric antigen receptor T cells)

Nurix has established a subsidiary, DeCART, focused on drug-enhanced CAR T therapies for hematological and solid tumors. DeCART was founded by Nurix and world-renowned physician and scientist Dr. Carl June, in collaboration with his colleagues from the University of Pennsylvania.
Visit DeCART