NX-5948 demonstrated robust clinical activity with objective responses observed in 7 of 9 (77.8%) evaluable Waldenstrom’s patients in the ongoing Phase 1a/1b clinical trial
Responses are durable and deepen over time with two patients on treatment for greater than one year
Data were presented at the 12th International Workshop on Waldenstrom’s Macroglobulinemia (IWWM-12)
SAN FRANCISCO, CA, USA I October 19, 2024 I Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with cancer and inflammatory diseases, today announced the presentation of clinical data from its ongoing Phase 1a/1b clinical trial of NX-5948, an orally bioavailable, brain penetrant degrader of Burton’s tyrosine kinase (BTK), in patients with relapsed/refractory Waldenstrom’s macroglobulinemia (WM) at the 12th International Workshop on Waldenstrom’s Macroglobulinemia (IWWM-12) which is being held in Prague, Czech Republic October 17–19, 2024.
“We are encouraged by the emerging positive data from NX-5948 in patients with Waldenstrom’s macroglobulinemia, which add to the previously disclosed robust clinical activity observed in patients with chronic lymphocytic leukemia,” said Paula G. O’Connor, M.D., chief medical officer of Nurix. “These data support our decision to advance NX-5948 into the ongoing Phase 1b expansion cohort in patients who have previously received at least one prior line of therapy including a BTK inhibitor and patients presenting with Bing-Neel syndrome, a rare form of WM with central nervous system involvement where NX-5948’s ability to penetrate the brain may offer a distinct advantage.”
The data presented at IWWM-12 included previously reported safety findings for all patients in the Phase 1a dose escalation study treated with NX-5948 at doses ranging from 50 mg to 600 mg once daily by oral administration regardless of diagnosis (n=79) based on an April 17, 2024 data cut. NX-5948 demonstrated a tolerable safety profile, and the safety profile for patients with WM was consistent with the safety profile for the overall population (WM patient safety data not shown separately).
New data from an October 10, 2024 data cut include the baseline characteristics of the first 13 patients with WM enrolled across both the Phase 1a and Phase 1b portions of the trial, clinical response assessments in 9 response-evaluable patients, and duration on study for all 13 patients. Among the 13 WM patients, the median age was 74 years and the median number of prior lines of therapy was 3. All 13 patients previously had been treated with both BTK inhibitors (BTKi) and chemotherapy/chemo-immunotherapy. Three patients (23.1%) had received prior treatment with the non-covalent BTKi pirtobrutinib, and one patient (7.7%) had received prior treatment with a BCL2 inhibitor. Baseline mutation status in MYD88 and CXCR4 was captured from patient records, and eight patients (61.5%) had mutations in MYD88, and two patients (15.4%) had mutations in CXCR4. Among the nine patients who were evaluable for response, seven patients (77.8%) had an objective response and two patients experienced stable disease (22.2%). All seven responses were observed at the first assessment at 8 weeks, and five remain on treatment with two patients on treatment for longer than one year. Responses were observed in patients regardless of their baseline mutations in MYD88 and CXCR4.
Two illustrative cases studies of patients treated with NX-5948 were presented. The first case study is a patient with baseline MYD88 and CXCR4 mutations and four prior lines of therapy, including autologous bone marrow transplantation and ibrutinib, who demonstrated a rapid response observed at the first assessment and remained on study at the time of the October 10, 2024 data cut with greater than one year of treatment (currently in cycle 16; 28 days per cycle). NX-5948 treatment resulted in deepening of response over time as measured by reduction in serum IgM levels, a key biomarker of clinical response in WM patients. The second case study is a patient with baseline MYD88 mutation and three prior lines of treatment, having most recently progressed while on zanubrutinib. This patient also experienced a rapid response at the first assessment with decreasing IgM through treatment which was ongoing in cycle 15 at the time of the October 10, 2024 data cut.
The IWWM-1 presentation is available in the Scientific Resources section of Nurix website in the Posters and Presentations section.
About NX-5948
NX-5948 is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK. NX-5948 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Nurix has previously reported that NX-5948 is highly potent against a range of tumor cell lines that are resistant to current BTK inhibitor therapies, an important consideration in heavily pretreated CLL/SLL patient populations. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022).
About Waldenstrom’s Macroglobulinemia
WM is a rare, slow growing type of non-Hodgkin’s lymphoma that is characterized by the replacement of normal bone marrow cells by malignant lymphocytic cells that produce monoclonal IgM. This replacement leads to anemia, bleeding, and impaired immune function, while the elevated IgM levels may cause neurologic symptoms. In the United States the annual incidence rate is approximately 3 per million or between 1,000 to 1,500 newly diagnosed patients per year. Recommended first-line treatments including chemoimmunotherapy and BTK inhibitor therapy. There are no therapies approved to treat patients after BTKi. Additional therapeutic options are needed.
About Nurix
Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative small molecules and antibody therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer, inflammatory conditions, and other challenging diseases. Leveraging extensive expertise in E3 ligases together with proprietary DNA-encoded libraries, Nurix has built DELigase, an integrated discovery platform, to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. Nurix’s drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin-proteasome system to selectively decrease or increase cellular protein levels. Nurix’s wholly owned, clinical stage pipeline includes targeted protein degraders of Bruton’s tyrosine kinase, a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B, an E3 ligase that regulates activation of multiple immune cell types including T cell and NK cells. Nurix is headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com.
SOURCE: Nurix Therapeutics
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NX-5948 demonstrated robust clinical activity with objective responses observed in 7 of 9 (77.8%) evaluable Waldenstrom’s patients in the ongoing Phase 1a/1b clinical trial
Responses are durable and deepen over time with two patients on treatment for greater than one year
Data were presented at the 12th International Workshop on Waldenstrom’s Macroglobulinemia (IWWM-12)
SAN FRANCISCO, CA, USA I October 19, 2024 I Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with cancer and inflammatory diseases, today announced the presentation of clinical data from its ongoing Phase 1a/1b clinical trial of NX-5948, an orally bioavailable, brain penetrant degrader of Burton’s tyrosine kinase (BTK), in patients with relapsed/refractory Waldenstrom’s macroglobulinemia (WM) at the 12th International Workshop on Waldenstrom’s Macroglobulinemia (IWWM-12) which is being held in Prague, Czech Republic October 17–19, 2024.
“We are encouraged by the emerging positive data from NX-5948 in patients with Waldenstrom’s macroglobulinemia, which add to the previously disclosed robust clinical activity observed in patients with chronic lymphocytic leukemia,” said Paula G. O’Connor, M.D., chief medical officer of Nurix. “These data support our decision to advance NX-5948 into the ongoing Phase 1b expansion cohort in patients who have previously received at least one prior line of therapy including a BTK inhibitor and patients presenting with Bing-Neel syndrome, a rare form of WM with central nervous system involvement where NX-5948’s ability to penetrate the brain may offer a distinct advantage.”
The data presented at IWWM-12 included previously reported safety findings for all patients in the Phase 1a dose escalation study treated with NX-5948 at doses ranging from 50 mg to 600 mg once daily by oral administration regardless of diagnosis (n=79) based on an April 17, 2024 data cut. NX-5948 demonstrated a tolerable safety profile, and the safety profile for patients with WM was consistent with the safety profile for the overall population (WM patient safety data not shown separately).
New data from an October 10, 2024 data cut include the baseline characteristics of the first 13 patients with WM enrolled across both the Phase 1a and Phase 1b portions of the trial, clinical response assessments in 9 response-evaluable patients, and duration on study for all 13 patients. Among the 13 WM patients, the median age was 74 years and the median number of prior lines of therapy was 3. All 13 patients previously had been treated with both BTK inhibitors (BTKi) and chemotherapy/chemo-immunotherapy. Three patients (23.1%) had received prior treatment with the non-covalent BTKi pirtobrutinib, and one patient (7.7%) had received prior treatment with a BCL2 inhibitor. Baseline mutation status in MYD88 and CXCR4 was captured from patient records, and eight patients (61.5%) had mutations in MYD88, and two patients (15.4%) had mutations in CXCR4. Among the nine patients who were evaluable for response, seven patients (77.8%) had an objective response and two patients experienced stable disease (22.2%). All seven responses were observed at the first assessment at 8 weeks, and five remain on treatment with two patients on treatment for longer than one year. Responses were observed in patients regardless of their baseline mutations in MYD88 and CXCR4.
Two illustrative cases studies of patients treated with NX-5948 were presented. The first case study is a patient with baseline MYD88 and CXCR4 mutations and four prior lines of therapy, including autologous bone marrow transplantation and ibrutinib, who demonstrated a rapid response observed at the first assessment and remained on study at the time of the October 10, 2024 data cut with greater than one year of treatment (currently in cycle 16; 28 days per cycle). NX-5948 treatment resulted in deepening of response over time as measured by reduction in serum IgM levels, a key biomarker of clinical response in WM patients. The second case study is a patient with baseline MYD88 mutation and three prior lines of treatment, having most recently progressed while on zanubrutinib. This patient also experienced a rapid response at the first assessment with decreasing IgM through treatment which was ongoing in cycle 15 at the time of the October 10, 2024 data cut.
The IWWM-1 presentation is available in the Scientific Resources section of Nurix website in the Posters and Presentations section.
About NX-5948
NX-5948 is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK. NX-5948 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Nurix has previously reported that NX-5948 is highly potent against a range of tumor cell lines that are resistant to current BTK inhibitor therapies, an important consideration in heavily pretreated CLL/SLL patient populations. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022).
About Waldenstrom’s Macroglobulinemia
WM is a rare, slow growing type of non-Hodgkin’s lymphoma that is characterized by the replacement of normal bone marrow cells by malignant lymphocytic cells that produce monoclonal IgM. This replacement leads to anemia, bleeding, and impaired immune function, while the elevated IgM levels may cause neurologic symptoms. In the United States the annual incidence rate is approximately 3 per million or between 1,000 to 1,500 newly diagnosed patients per year. Recommended first-line treatments including chemoimmunotherapy and BTK inhibitor therapy. There are no therapies approved to treat patients after BTKi. Additional therapeutic options are needed.
About Nurix
Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative small molecules and antibody therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer, inflammatory conditions, and other challenging diseases. Leveraging extensive expertise in E3 ligases together with proprietary DNA-encoded libraries, Nurix has built DELigase, an integrated discovery platform, to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. Nurix’s drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin-proteasome system to selectively decrease or increase cellular protein levels. Nurix’s wholly owned, clinical stage pipeline includes targeted protein degraders of Bruton’s tyrosine kinase, a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B, an E3 ligase that regulates activation of multiple immune cell types including T cell and NK cells. Nurix is headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com.
SOURCE: Nurix Therapeutics
Post Views: 2,983
