Nurix Therapeutics Presents Data from Studies of Its Targeted Protein Degraders in B Cell Malignancies and Initiates Expansion of NX-2127 Phase 1b Trial in Diffuse Large B Cell Lymphoma and Mantle Cell Lymphoma Indications
15 Jun 2023
Phase 1PROTACs
Initiation of NX-2127 Phase 1b expansion cohort in patients with diffuse large B cell lymphoma (DLBCL) was informed by a rapid and sustained complete response; Phase 1b expansion cohort also initiated in patients with mantle cell lymphoma (MCL)
Clinical biomarker data from Phase 1a trial of NX-5948 demonstrate rapid, robust, and sustained degradation of Bruton’s tyrosine kinase (BTK) and support ongoing investigation of B cell malignancies
NX-5948 crosses the blood brain barrier and catalyzes robust and efficient degradation of BTK, improving survival in an intracranial patient-cell-derived preclinical model of central nervous system (CNS) lymphoma
SAN FRANCISCO, CA, USA I June 14, 2023 I Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with hematologic malignancies and solid tumors, today announced the presentation of clinical and preclinical data from its targeted protein degradation programs, NX-5948 and NX-2127, which are being evaluated in ongoing Phase 1 clinical trials in patients with relapsed/refractory B cell malignancies. These data are being presented at the 17th International Conference on Malignant Lymphoma (ICML) which is being held June 13-17, in Lugano, Switzerland.
“The positive data emerging from our two targeted BTK degrader clinical programs are guiding our strategy on how best to deploy each drug candidate’s strengths and have informed our decision to initiate Phase 1b dose expansion for NX-2127 in patients with DLBCL and MCL where this drug has been well tolerated and has shown promising activity,” said Robert J. Brown, M.D., executive vice president and head of early clinical development at Nurix. “The observed rapid and sustained complete response with NX-2127 as a once daily oral single agent therapy in a relapsed/refractory patient with DLBCL supports our decision to advance this program into a Phase 1b expansion cohort. This exciting result is consistent with our findings in other non-Hodgkin lymphoma indications such as mantle cell lymphoma.”
Both orally available compounds are efficient degraders of BTK, a key therapeutic target in the treatment of B-cell malignancies including primary CNS lymphoma. Limitations of current covalent and non-covalent BTK inhibitorsBTK inhibitors include the susceptibility to mutational escape as a basis for resistance. Recent evidence also suggests certain resistance mutations are catalytically inactive yet maintain the ability to drive cell growth through a putative scaffolding function of the protein. Nurix’s BTK degraders have the potential to address these limitations of BTK inhibitorsBTK inhibitors and provide a new therapeutic option for patients.
“The significant preclinical activity demonstrated in an aggressive, patient-derived CNS lymphoma model conducted in the laboratory of Dr. James Rubenstein at UCSF provides strong support for the inclusion of primary CNS lymphoma patients in our ongoing NX-5948 clinical trial,” said Gwenn Hansen, chief scientific officer of Nurix. “We remain enthusiastic about NX-5948's differentiated profile, including potent and sustained BTK degradation, activity against treatment-emergent BTK mutations, and the ability to cross the blood brain barrier. Further updates from both programs are anticipated in the second half of 2023.”
Details of the ICML Presentations
NX-2127 Clinical Trial Update
Nurix is announcing plans to initiate two new Phase 1b dose expansion cohorts in the ongoing Phase 1a/1b clinical trial of NX-2127 in patients with relapsed or refractory B-cell malignancies. The new cohorts include patients with relapsed or refractory DLBCL who have failed at least two prior lines of therapy and patients with relapsed or refractory MCL who have failed at least two prior lines of therapy. The expansion protocol provides for treatment with once daily oral NX-2127 at a dose of 300mg. The decision to open a DLBCL and MCL expansion cohort was informed by emerging clinical activity in the Phase 1a dose escalation including the rapid, robust, and prolonged clinical response observed in the DLBCL patient described in the IMCL presentation.
About NX-2127
NX-2127 is a novel bifunctional molecule that degrades BTK and cereblon neosubstrates Ikaros (IKZF1) and Aiolos (IKZF3). NX-2127 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Additional information on the ongoing clinical trial can be accessed at www.clinicaltrials.gov (NCT04830137).
About NX-5948
NX-5948 is an investigational, orally bioavailable, small molecule degrader of BTK that, unlike NX-2127, has been designed to lack cereblon immunomodulatory activity. NX-5948 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022).
About Nurix Therapeutics, Inc.
Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of small molecule therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer 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 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 T cell activation. Nurix is headquartered in San Francisco, California. For additional information visit
http://www.nurixtx.com.
SOURCE: Nurix Therapeutics
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