| Drug Candidate | Target (Delivery) | Therapeutic Area | Discovery | IND enabling | Phase 1 | Phase 2 | Phase 3 | |
|---|---|---|---|---|---|---|---|---|
| Clinical Pipeline | ||||||||
| NX-2127 Degrader | BTK + IKZF | B-cell malignancies |
| |||||
| NX-5948 Degrader | BTK (Oral) | B-cell malignancies and autoimmune disease |
| |||||
| NX-1607 Inhibitor | CBL-B (Oral) | Immuno-oncology |
| |||||
| DeTIL-0255 Cell Therapy | Adoptive cell therapy with ex vivo CBL-B inhibition | Gynecologic malignancies |
| |||||
| Drug Candidate | Target (Delivery) | Therapeutic Area | Discovery | IND enabling | Phase 1 | Phase 2 | Phase 3 | |
| Discovery Pipeline | ||||||||
| Wholly Owned | Multiple targets* | Undisclosed |
| |||||
| Gilead Sciences | 5 targets | Undisclosed |
| |||||
| Sanofi | 5 targets | Undisclosed |
| |||||
| Candidate / Target | Phase |
|---|---|
| Clinical Pipeline | NX-2127 Degrader BTK + IKZF | Phase 1 |
| NX-5948 Degrader BTK (Oral) | Phase 1 |
| NX-1607 Inhibitor CBL-B (Oral) | Phase 1 |
| DeTIL-0255 Cell Therapy Adoptive cell therapy with ex vivo CBL-B inhibition | Phase 1 |
| Discovery Pipeline | Wholly Owned Multiple targets* | Discovery |
| Gilead Sciences 5 targets | Discovery |
| Sanofi 5 targets | Discovery |
Degraders and inhibitors of multiple targets including E3 ligases, T cell kinase, hematology & oncology drivers, and viral proteins
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 (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 different drug candidates.
| Drug Candidate | Target (Delivery) | Therapeutic Area | Discovery | IND enabling | Phase 1 | Phase 2 | Phase 3 | |
|---|---|---|---|---|---|---|---|---|
| Clinical Pipeline | ||||||||
| NX-2127 Degrader | BTK + IKZF | B-cell malignancies |
| |||||
| NX-5948 Degrader | BTK (Oral) | B-cell malignancies and autoimmune disease |
| |||||
| NX-1607 Inhibitor | CBL-B (Oral) | Immuno-oncology |
| |||||
| DeTIL-0255 Cell Therapy | Adoptive cell therapy with ex vivo CBL-B inhibition | Gynecologic malignancies |
| |||||
| Drug Candidate | Target (Delivery) | Therapeutic Area | Discovery | IND enabling | Phase 1 | Phase 2 | Phase 3 | |
| Discovery Pipeline | ||||||||
| Wholly Owned | Multiple targets* | Undisclosed |
| |||||
| Gilead Sciences | 5 targets | Undisclosed |
| |||||
| Sanofi | 5 targets | Undisclosed |
| |||||
| Candidate / Target | Phase |
|---|---|
| Clinical Pipeline | NX-2127 Degrader BTK + IKZF | Phase 1 |
| NX-5948 Degrader BTK (Oral) | Phase 1 |
| NX-1607 Inhibitor CBL-B (Oral) | Phase 1 |
| DeTIL-0255 Cell Therapy Adoptive cell therapy with ex vivo CBL-B inhibition | Phase 1 |
| Discovery Pipeline | Wholly Owned Multiple targets* | Discovery |
| Gilead Sciences 5 targets | Discovery |
| Sanofi 5 targets | Discovery |
NX-2127 (BTK + IKZF 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.
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 cereblon immunomodulatory 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.
Our initial Phase 1 trial of NX-5948 is for patients with B-cell malignancies who have failed prior treatments.
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 Candidate | Target (Delivery) | Therapeutic Area | Discovery | IND enabling | Phase 1 | Phase 2 | Phase 3 | |
|---|---|---|---|---|---|---|---|---|
| Clinical Pipeline | ||||||||
| NX-2127 Degrader | BTK + IKZF | B-cell malignancies |
| |||||
| NX-5948 Degrader | BTK (Oral) | B-cell malignancies and autoimmune disease |
| |||||
| NX-1607 Inhibitor | CBL-B (Oral) | Immuno-oncology |
| |||||
| DeTIL-0255 Cell Therapy | Adoptive cell therapy with ex vivo CBL-B inhibition | Gynecologic malignancies |
| |||||
| Drug Candidate | Target (Delivery) | Therapeutic Area | Discovery | IND enabling | Phase 1 | Phase 2 | Phase 3 | |
| Discovery Pipeline | ||||||||
| Wholly Owned | Multiple targets* | Undisclosed |
| |||||
| Gilead Sciences | 5 targets | Undisclosed |
| |||||
| Sanofi | 5 targets | Undisclosed |
| |||||
| Candidate / Target | Phase |
|---|---|
| Clinical Pipeline | NX-2127 Degrader BTK + IKZF | Phase 1 |
| NX-5948 Degrader BTK (Oral) | Phase 1 |
| NX-1607 Inhibitor CBL-B (Oral) | Phase 1 |
| DeTIL-0255 Cell Therapy Adoptive cell therapy with ex vivo CBL-B inhibition | Phase 1 |
| Discovery Pipeline | Wholly Owned Multiple targets* | Discovery |
| Gilead Sciences 5 targets | Discovery |
| Sanofi 5 targets | Discovery |
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 Candidate | Target (Delivery) | Therapeutic Area | Discovery | IND enabling | Phase 1 | Phase 2 | Phase 3 | |
|---|---|---|---|---|---|---|---|---|
| Clinical Pipeline | ||||||||
| NX-2127 Degrader | BTK + IKZF | B-cell malignancies |
| |||||
| NX-5948 Degrader | BTK (Oral) | B-cell malignancies and autoimmune disease |
| |||||
| NX-1607 Inhibitor | CBL-B (Oral) | Immuno-oncology |
| |||||
| DeTIL-0255 Cell Therapy | Adoptive cell therapy with ex vivo CBL-B inhibition | Gynecologic malignancies |
| |||||
| Drug Candidate | Target (Delivery) | Therapeutic Area | Discovery | IND enabling | Phase 1 | Phase 2 | Phase 3 | |
| Discovery Pipeline | ||||||||
| Wholly Owned | Multiple targets* | Undisclosed |
| |||||
| Gilead Sciences | 5 targets | Undisclosed |
| |||||
| Sanofi | 5 targets | Undisclosed |
| |||||
| Candidate / Target | Phase |
|---|---|
| Clinical Pipeline | NX-2127 Degrader BTK + IKZF | Phase 1 |
| NX-5948 Degrader BTK (Oral) | Phase 1 |
| NX-1607 Inhibitor CBL-B (Oral) | Phase 1 |
| DeTIL-0255 Cell Therapy Adoptive cell therapy with ex vivo CBL-B inhibition | Phase 1 |
| Discovery Pipeline | Wholly Owned Multiple targets* | Discovery |
| Gilead Sciences 5 targets | Discovery |
| Sanofi 5 targets | Discovery |
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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