MYD88

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) Oct. 19, 2024 -- 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. 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). 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. 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. The content above comes from the network. if any infringement, please contact us to modify.

A test that looks for genetic hallmarks of brain cancers in samples of cerebrospinal fluid can decrease the time to diagnosis and eliminate the need for invasive brain biopsies for some patients. Experts in neurosurgery, cancer and pathology worked together to develop a rapid, genotyping test that can detect key mutations associated with brain cancers from samples taken during a lumbar puncture. A test that looks for genetic hallmarks of brain cancers in samples of cerebrospinal fluid can decrease the time to diagnosis and eliminate the need for invasive brain biopsies for some patients. Mass General Brigham experts in neurosurgery, cancer and pathology worked together to develop a rapid, genotyping test that can detect key mutations associated with brain cancers from samples taken during a lumbar puncture. The team evaluated the technique known as TetRS (Targeted Rapid Sequencing) among 70 patients admitted to Massachusetts General Hospital with new central nervous system (CNS) lesions of unknown origin. The test detected mutations in samples from 42 percent of patients with tumors, including cases of primary and secondary CNS lymphoma, glioblastoma, and gliomas. Results are published in Blood. "Unlike other forms of cancer that might get diagnosed at an outpatient center, most brain tumors and spinal cord tumors get diagnosed in the hospital, where patients often present with rapidly progressive deficits. This means that speed is of the essence," said corresponding author Ganesh Shankar, MD, PhD, a neurosurgeon and neurosurgical director of biospecimen banking for the Department of Neurosurgery at Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system. "Because of the test we've developed, patients are now being diagnosed and treated without brain biopsies, which has also resulted in decreased time to diagnosis from 10 days to 2 days." Shankar traces the origins of TetRS back almost a decade, to a time when researchers identified a handful of genes that were mutated in certain forms of brain cancer. In a paper published in 2015, the team showed that genetic mutations could be detected in tissue samples removed during surgery. The team further optimized TetRS and showed in 2021 that they could use the same approach on cerebrospinal fluid. The new study puts TetRS to the test in the real world, where patients may present to the Emergency Department with an abnormal lesion that could be from a tumor or could be from something else. The research team wanted to ensure that TetRS could help lead to an accurate diagnosis faster, without leaving any room for a false positive result. Shankar and colleagues designed TetRS to look for genetic signatures unique to brain cancer, including mutations in the MYD88, TERT promoter, IDH1, IDH2, BRAF and H3F3A genes. The team evaluated samples from 70 patients, 33 of whom were eventually diagnosed with neoplasms (abnormal tissue that can be benign or malignant). TetRS alone diagnosed six of the patients and, when combined with conventional methods, diagnosed an additional eight patients, for a total sensitivity of 42 percent. For the other 37 patients who were not diagnosed with neoplasms, TetRS returned zero false positives, for a specificity rate of 100 percent. Using the rapid genotyping test eliminated the need for surgical brain biopsies for seven patients and significantly accelerated time to treatment for them, from an average of 12 days down to an average of 3 days. The authors note that larger studies are needed to determine whether their findings are broadly applicable and what the clinical impact of earlier diagnosis and treatment will be for patients. TetRS has been implemented as a clinically available test across Mass General Brigham, and Mass General Brigham Pathology has received and evaluated patient samples from MGH, Brigham and Women's Hospital and many other sites around the country. "By working together across pathology, neuro-oncology and neurosurgery teams, we've developed an innovative, collaborative way to improve patient care," said co-author Deborah Forst, MD, of the Mass General Cancer Center. "The ability to rapidly detect tumor-related molecular variants in patients' spinal fluid samples has allowed us to promptly draw diagnostic conclusions through less invasive testing and to initiate individualized and potentially life-saving chemotherapies in rapid fashion." Authorship: In addition to Shankar, Mass General Brigham authors include first author Mihir Gupta, Joseph D. Bradley, Elie Massaad, Evan J. Burns, N. Zeke Georgantas, Garrett E. Maron, Julie M. Batten, Aidan Gallagher, Julia Thierauf, Naema Nayyar, Amanda Gordon, SooAe S. Jones, Michelle Pisapia, Ying Sun, Pamela S. Jones, Fred G. Barker 2nd, William T. Curry, Rajiv Gupta, Javier M. Romero, Nancy Wang, Priscilla K. Brastianos, Maria Martinez-Lage, Deborah A. Forst, Brian V. Nahed, Tracy T. Batchelor, Lauren L. Ritterhouse, Justin T. Jordan, Jorg Dietrich, Daniel P. Cahill, Jochen K. Lennerz and Bob S. Carter. Additional authors include Kensuke Tateishi, Florian Iser, Tobias Kessler, and Matthew Meyerson. Disclosures: Cahill and Shankar hold a patent pertaining to the use of peptide and locked nucleic acids as utilized in this study during the amplification of target DNA sequences (patent #US20170369939A1). Funding: This work was supported by grants from the National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (1K08NS107634-01A1), The Darwin Project, the Brian D. Silber Memorial Fund, and National Cancer Institute (5U01CA230697).

Awardees are poised to advance healthcare innovations within five years to improve patient care in oncology, gastroenterology and more AURORA, Colo., Jan. 18, 2024 /PRNewswire/ -- The University of Colorado Anschutz Medical Campus announced the grant awards for the Anschutz Acceleration Initiative, a program focused on advancing cutting-edge healthcare innovations poised to reach patients within three to five years. The initiative was made possible by a $50 million gift from The Anschutz Foundation, a longtime philanthropic campus partner focused on bringing the innovative work at CU Anschutz to the forefront of patient care. "The Anschutz Foundation has championed the people and programs that drive innovation here," said CU Anschutz Chancellor Donald M. Elliman. "As a result, we have become recognized locally, nationally and internationally as leaders in healthcare innovation." The CU Anschutz faculty, whom the Anschutz Acceleration Initiative will fund, represent a range of expertise that spans disciplines including oncology, dermatology, gastroenterology, ophthalmology, pharmacology, dental medicine, and more. They were chosen through a rigorous scientific review by an external committee of experts, which assessed the degree to which proposed projects fit the initiative's intent: to rapidly advance medical treatments and health innovations poised to impact patients directly within the next few years. The grant recipients are: Project: Immunomodulatory Therapy for Down Syndrome Principal investigator (PI): Joaquin Espinosa, PhD | Professor, Pharmacology & Executive Director, Linda Crnic Institute for Down Syndrome Espinosa and team are working to pave the way for the first immunomodulatory therapy for children with Down syndrome. Assuming positive results, their work could launch a new age of therapeutic development to improve the quality of life and extend the lifespan of millions of individuals affected by this condition. Project: Implementation of Personalized Skin Cancer Screening: Using Genetic and Clinical Risk Factors to Identify a High-Risk Subgroup PI: Maryam Asgari, MD, MPH | Professor and Chair, Dermatology Leveraging established expertise in developing skin cancer polygenic risk scores (used for stratification and prediction of disease risk), Asgari and team will test a skin cancer screening risk prediction tool that combines genetic and clinical risk factors to identify individuals at high risk for skin cancer among study participants. The results of this research are likely to impact patient care in the next five years by identifying a high-risk subgroup for which skin cancer screenings could yield clear, direct benefits, including reduction in morbidity and mortality. Project: Making Personalization the Standard Through Rapid Design, Implementation, Testing and Maintenance PIs: Dan Matlock, MD | Professor, Geriatrics & Director, Colorado Program for Patient Centered Decisions (plaid shirt) Russell Glasgow, PhD | Research Professor, Family Medicine & Director, ACCORDS Dissemination and Implementation Science Program (glasses) This comprehensive, patient-centered personalization program will develop patient-centered decision support tools across various clinical domains, with a strong emphasis on rapid and rigorous development, sustainable processes and equity in engagement. Initially, the team will embark on four distinct projects: primary care for patients with multiple chronic conditions; specialty care – carotid stenting decision aid; tertiary care – heart transplant decision aid; and late life care for patients with dementia. Project: Multimaterial 3D Print Processing of Antimicrobial and Antifungal Dental Prosthetics PI: Jeffrey Stansbury, PhD | Senior Associate Dean for Research and Professor, Craniofacial Biology Stansbury and team plan to enhance affordability of dentures for patients most in need, while significantly raising the clinical value and performance of dentures for denture wearers. Their goal is to bring together several already demonstrated materials-based technologies that, when combined and used with innovative printing processes, will significantly advance the potential application of the field of 3D printing for dentistry. Project: MyD88 Platform for Enhancing Cellular Cancer Immunotherapy PI: Eduardo Davila, PhD | Professor, Medical Oncology The Davila laboratory, in collaboration with multiple stakeholders, is developing a novel methodology to enhance all forms of cellular immunotherapy including a more universal form of cell therapy referred to as tumor-infiltrating lymphocyte (TIL) therapy. The goal is to develop good manufacturing practices, technology and methodology to reduce production times, reduce the number of cells that need to be administered, lessen costs, and generate more effective cellular immunotherapy products. Project: Oculomics as a Biomarker for Comprehensive and Non-Invasive Patient Health Assessment PI: Jayashree Kalpathy-Cramer, PhD | Professor, Ophthalmology Kalpathy-Cramer and team are developing a multidisciplinary project by bringing AI-assisted ophthalmic imaging outside of ophthalmology to improve patient health and clinical outcomes, meet quality metrics and reduce health system costs, and further advance the field of oculomics. The successful completion of this ambitious goal would make oculomics a mainstream, non-invasive and cost-effective tool for the assessment of patient health. Project: Retinal Transplant to Restore Vision in Patients with Macular Degeneration PI: Valeria Canto-Soler, PhD | Associate Professor, Ophthalmology & Director, CellSight Canto-Soler and team have developed two products to address the needs of patients with geographic atrophy (GA) – an advanced form of dry age-related macular degeneration or AMD. The potential impacts of these products are enormous, as approximately 2 million Americans with GA would be immediately eligible for experimental retinal transplantation to restore vision, thus having a profound effect on their quality of life. Project: Targeting Protein Translation Elongation to Treat Cancer Patients PI: Antonio Jimeno, MD, PhD | Professor, Medical Oncology An interdisciplinary team will target fusion proteins to treat patients with head and neck cancers. With the use of a synthetic small molecule called SVC112 that uses a new and unique mechanism of action, the team now has a clear line of sight from discovery to generate preclinical data to de-risk and ready SVC112 for the clinic. Project: Transforming Gastrointestinal Cancer Care from Inpatient Surgery to Outpatient Endoscopy by Enabling Third Space Endoscopy PI: Steven Edmundowicz, MD | Professor, Gastroenterology & Medical Director, Digestive Health Center Edmundowicz and team are developing minimally invasive, highly specialized endoscopy procedures that have the potential to supplant one-third of conventional surgical gastrointestinal (GI) interventions and transform GI cancer care. They intend to bridge the gap between conventional tools and advanced procedures by using the Ancora™ platform that leverages CU's patented Pillar balloon in an interventional overtube to reduce dependence on expert free-hand skill and enable more repeatable and predictable procedures. To read more about the initiative and the awardees, visit the Anschutz Acceleration Initiative website. About the University of Colorado Anschutz Medical Campus The University of Colorado Anschutz Medical Campus is a world-class medical destination at the forefront of transformative science, medicine, education and patient care. The campus encompasses the University of Colorado health professional schools, more than 60 centers and institutes, and two nationally ranked independent hospitals - UCHealth University of Colorado Hospital and Children's Hospital Colorado - that treat more than two million adult and pediatric patients each year. Innovative, interconnected and highly collaborative, the University of Colorado Anschutz Medical Campus delivers life-changing treatments, patient care and professional training and conducts world-renowned research fueled by over $704 million in research grants. For more information, visit . Contact: Julia Milzer, [email protected] SOURCE University of Colorado Anschutz Medical Campus