MAP4K

-- New development candidate, NTX-452, a non-covalent WRN inhibitor, demonstrated significant tumor regression and complete responses at low oral doses in MSI-H tumor models refractory to immunotherapy and chemotherapy -- -- Company plans to initiate clinical trial of NTX-452 in first half of 2025 -- BOSTON--(BUSINESS WIRE)-- Nimbus Therapeutics , LLC (“Nimbus Therapeutics” or “Nimbus”), a biotechnology company that designs and develops breakthrough medicines for patients through its powerful computational drug discovery engine, announced that it is presenting preclinical data on its new development candidate, NTX-452, a novel Werner syndrome helicase (WRN) inhibitor, at the 36 th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, taking place October 23-25, 2024 in Barcelona, Spain. WRN is a helicase required for DNA replication and DNA repair and is a validated target for tumors with microsatellite instability (MSI). MSI is a phenotypic consequence of defective mismatch repair (dMMR) and occurs in various tumor types, including colorectal, gastric and endometrial cancers. Inhibition of WRN activity has the potential to induce synthetic lethality in MSI-high (MSI-H) tumors. Using a structure-based drug design approach, Nimbus developed highly potent and selective covalent and non-covalent inhibitors of WRN, and has selected a novel non-covalent inhibitor, NTX-452, as the clinical candidate. In a poster (abstract #356) titled “Preclinical Characterization of NTX-452, a Potent, Selective and Highly Efficacious WRN Inhibitor for the Treatment of MSI-H Tumors,” Nimbus is presenting new data from preclinical assays and several tumor models that support the potential of the company’s non-covalent WRN inhibitor as a treatment for MSI-H tumors. Key findings from the preclinical studies include: NTX-452 demonstrated potent and selective inhibition of WRN activity with favorable drug-like properties. The compound showed synthetic lethality in MSI-H tumor cells, triggering a DNA damage response that suppressed cell viability and promoted cell death. Treatment with NTX-452 at low doses in vivo exhibited a robust pharmacodynamic response, resulting in tumor regression across multiple MSI-H cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) tumor models, including established models for colorectal, gastric and endometrial cancers. Significant tumor regression and complete responses were observed at low oral doses in MSI-H models refractory to immunotherapy and chemotherapy. “These compelling preclinical results for NTX-452 further highlight the significant potential of our WRN inhibitor as a promising therapeutic approach for patients with MSI-H tumors, many of whom fail to respond to or eventually relapse with current standard of care therapies including immune checkpoint inhibitors,” said Peter Tummino, Ph.D., Chief Scientific Officer of Nimbus. “Our novel non-covalent approach to WRN inhibition, coupled with the robust efficacy demonstrated across diverse tumor types and treatment settings, positions our program for potential best-in-class status. We are particularly encouraged by the low doses required to achieve robust anti-tumor activity in preclinical models, which may translate to an improved benefit-risk pro the clinic.” The preclinical pro NTX-452 suggests several potential advantages in the treatment of MSI-H tumors, including: The non-covalent mechanism may offer more durable on-target activity, and a greater safety window compared to covalent inhibitors. High potency and favorable pharmacokinetic properties indicate the potential for target levels of efficacy at lower doses. Broad efficacy across treatment-naïve, chemotherapy-pretreated, and immunotherapy-pretreated models suggests potential utility in both early-stage and advanced disease settings. Activity in multiple MSI-H tumor types, including those with diverse genetic alterations, indicates potential broad applicability across dMMR/MSI-H cancers. Nimbus is advancing NTX-452 with plans to enter the clinic in the first half of 2025. About Nimbus Therapeutics Nimbus Therapeutics is a clinical-stage, structure-based drug discovery company developing novel small molecule medicines designed to act against well-validated but difficult-to-drug targets implicated in multiple human diseases. The company advances promising research based on a unique strategy that combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus’ pipeline includes a clinical-stage HPK1 inhibitor for the treatment of cancer (NCT05128487), as well as a diverse portfolio of preclinical programs focused on cancer, including the WRN program, autoimmune conditions, and metabolic diseases. The company is headquartered in Boston, Mass. To learn more about Nimbus, please visit . Contacts Media Cindy Fung, PhD Nimbus Therapeutics cindy.fung@nimbustx.com

Genentech has entered into an agreement with Regor Pharmaceuticals to acquire its next-generation CDK inhibitors for the treatment of breast cancer. The deal includes an upfront payment of $850 million, with additional payments contingent on the achievement of development, regulatory, and commercial milestones. Genentech will handle clinical development, manufacturing, and commercialization worldwide. Regor will continue to manage two ongoing phase 1 trials to their completion and will focus on advancing other assets in oncology, metabolic diseases, and autoimmune disorders that are not part of this acquisition. In addition to its CDK inhibitor portfolio, Regor has other leading assets including RGT-075, a GLP-1 receptor agonist with potential applications for obesity and related conditions, and RGT-419B, a CDK4 inhibitor showing promise for treating advanced breast cancer resistant to standard therapies. The company also explores immune-modulatory drugs like HPK1 inhibitors for cancer immunotherapy.

Clinical Outcomes of ALSFRS-R, Slow Vital Capacity, and Plasma Neurofilament Light to be Evaluated in Placebo Digital Twins of Study Participants Dosed with Prosetin NEW YORK, Sept. 26, 2024 /PRNewswire/ -- ProJenX, Inc., a clinical-stage biotechnology company developing novel therapies targeting biologically defined pathways for the treatment of amyotrophic lateral sclerosis (ALS) and other debilitating brain diseases, today announced its partnership with Unlearn to augment PRO-101, its Phase 1 clinical trial of prosetin—a brain-penetrant, MAP4 kinase (MAP4K) inhibitor—with Unlearn's advanced generative artificial intelligence (AI) technology. Unlearn, a pioneering technology company innovating machine learning to revolutionize medical research, will implement its ALS-Digital Twin Generator (ALS-DTG) to produce digital twins of PRO-101 clinical trial participants living with ALS to evaluate the clinical outcomes of ALSFRS-R, Slow Vital Capacity, and plasma neurofilament light over a 52-week open-label extension. Digital twins will act as placebos of participants dosed with prosetin. Unlearn's ALS-DTG is an advanced machine-learning generative model trained on patient-level data to generate probabilistic forecasts of future health outcomes, known as digital twins, for individual clinical trial participants. At the start of a trial, baseline data are collected from all participants. The ALS-DTG uses these data to forecast longitudinal clinical placebo outcomes, biomarkers, and labs—regardless of the participant's randomization assignment. Digital twins help address key challenges in clinical development and are delivered through Unlearn's Platform. "ProJenX and Unlearn's collaboration aims to extract valuable insights that will help us expedite clinical trials and more efficiently evaluate prosetin in individuals living with ALS," said Stan Abel, president and CEO at ProJenX. "Digital twins provide the opportunity for us to compare participants with ALS who are dosed with prosetin to their digitally generated placebo versions of themselves based on their baseline measurements. In PRO-101, this collaboration will enhance our interpretation of the effects of prosetin on ALS patients to support a more efficient and data-driven clinical development program." "With hundreds of thousands of people affected by ALS, the need to accelerate research that can transform treatment for this debilitating and paralyzing disease has never been more pressing," said Steve Herne, CEO of Unlearn. "ProJenX is making significant strides in this area, and we are confident that our collaboration will continue to support their efforts to develop impactful therapies that improve the lives of patients everywhere." About PRO-101 PRO-101 is a hybrid phase 1 clinical trial designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of prosetin in healthy volunteers and patients with ALS. Parts 1a and 1b, which have been completed, consisted of a randomized, double-blind, placebo-controlled, dose-escalating study to evaluate the safety, tolerability, and pharmacokinetics of single ascending and multiple doses of prosetin in healthy volunteers. Parts 1c and 1d will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of prosetin in ALS patients. For more information about PRO-101, contact [email protected]. About ProJenX ProJenX is a clinical-stage biotechnology company developing novel, brain-penetrant, targeted therapies to address untreatable brain diseases, with an initial focus on ALS. ProJenX was created out of a long-term research collaboration between Project ALS and researchers at Columbia University to rapidly develop and commercialize its lead therapy candidate, prosetin, for people living with ALS. At the heart of ProJenX's approach is an innovative, patient-specific, cell-based drug discovery platform that can be leveraged for research and drug development for ALS and other debilitating brain diseases. For more information, visit projenx.com. About Unlearn Unlearn is a pioneering AI company with a product-driven focus, dedicated to transforming medicine by eliminating trial and error. Our Platform harnesses the power of digital twins—advanced computational models of patients—to empower pharmaceutical and biotech companies to overcome critical challenges in clinical development. For more information, please visit or follow @UnlearnAI on Twitter/X and @unlearn-ai on LinkedIn. SOURCE ProJenX WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED