The National Cancer Institute (NCI) awarded a $607,634 Project Grant (CFDA 93.395 - Cancer Treatment Research) to Mayo Clinic Jacksonville (a nonprofit corporation) for a research project titled "Generating Synthetic Lethality in Glioblastoma with a First-in-Class Non-Muscle Myosin II Inhibitor." The project aims to investigate the use of a novel small molecule inhibitor, MT-125, to target the non-muscle myosin II (NMII) isoforms in glioblastoma, a highly aggressive form of brain...
This $399,669 federal Project Grant awarded by the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) aims to establish the feasibility of commercializing a personalized and multi-targeted adoptive T cell therapy (ATCT) for glioblastoma (GBM), the most common and deadly primary brain tumor. The key products or services to be delivered under this grant include: Evaluating the ability of the applicant's Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) platform to...
This federal Project Grant award from the National Cancer Institute's Cancer Treatment Research program (CFDA 93.395) provides $417,858 to Brigham & Women's Hospital Inc. to develop novel cellular therapies for glioblastoma (GBM), a highly malignant brain tumor. The research aims to engineer mesenchymal stem cells (MSCs) to release bi-specific T cell engagers (BiTEs) targeting GBM antigens EGFR/EGFRvIII and IL13Rα2, and co-express IL-12 and PD-1 inhibitors to enhance T cell potency and...
This Project Grant award from the National Cancer Institute (CFDA 93.394 - Cancer Detection and Diagnosis Research) provides $609,749 to the University of North Carolina at Chapel Hill to develop a novel combination therapy for the treatment of glioblastoma multiforme (GBM), the most aggressive form of brain cancer. The key products/services to be delivered include: Developing an injectable, biodegradable hydrogel scaffold that can accommodate high concentrations of induced neural stem cells...
The National Cancer Institute (NCI) awarded a $1,881,613 Project Grant under the Cancer Treatment Research program (CFDA 93.395) to The General Hospital Corporation, doing business as Massachusetts General Hospital (MGH), to conduct research on improving immunovirotherapy for glioblastoma, a fatal brain cancer. The project aims to determine if combining an oncolytic herpes simplex virus engineered to express IL-12 with inhibitors of the adenosine pathway can synergistically enhance the...
This federal Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides funding for the preclinical development of an EYA2 tyrosine phosphatase inhibitor as a potential therapeutic for medulloblastoma, the most common malignant brain tumor in children. The $399,709 award to Sieyax, Inc. (a woman-owned small business) will support two primary objectives: 1) Optimizing the synthesis and evaluating the drug metabolism, pharmacokinetics, and toxicity...
This federal Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $1,200,000 to Creative Biotherapeutics LLC, a biotechnology research firm, to develop a novel biologic therapy to eradicate brain cancer and brain metastases. The project aims to target the extracellular glucose-regulated protein 78 (eGRP78), which is upregulated in drug-resistant recurrent brain cancers and promotes tumor growth, immune evasion, and stem cell formation. The...
This Project Grant award of $633,656 from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) federal grant program aims to improve immunogene therapy for glioblastoma (GBM), an aggressive brain cancer. The research focuses on two key questions: 1) whether the timing of administering immune checkpoint inhibitors (ICI) in relation to intratumoral interleukin-12 (IL-12) immunogene...
This federal Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, supports research focused on developing an encapsulated stem cell-based oncolytic virus therapy for glioblastoma (GBM), the most lethal primary brain tumor. The $420,251 award to Brigham & Women's Hospital Inc., a subsidiary of Partners Healthcare System Incorporated, aims to...
This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $665,000 to support the development and clinical testing of MT-601, a novel multi-tumor associated antigen (MTAA)-specific T-cell therapy for the treatment of non-Hodgkin lymphoma (NHL). The key objectives of this project are to manufacture the MT-601 product and conduct a Phase 1 clinical trial evaluating its safety and efficacy in NHL patients who have relapsed after prior CD19...
MT-125 FOR THE THERAPEUTIC TREATMENT OF GLIOBLASTOMA - PROJECT SUMMARY AN AREA OF SIGNIFICANT UNMET NEED IS THE TREATMENT OF GLIOBLASTOMA (GBM), AN AGGRESSIVE, FAST-GROWING AND LETHAL BRAIN CANCER THAT REPRESENTS 48% OF ALL MALIGNANT BRAIN TUMORS. UNTREATED, GBM IS FATAL WITHIN THREE MONTHS, AND DUE TO ITS HIGH RATE OF RECURRENCE AND INVASIVE NATURE, THE CURRENT STANDARD OF CARE, CONSISTING OF SAFE MAXIMAL TUMOR RESECTION, RADIATION THERAPY AND CHEMOTHERAPY, ONLY EXTENDS SURVIVAL FOLLOWING INITIAL DIAGNOSIS TO ONE YEAR. INVASION AND PROLIFERATION, ALSO KNOWN AS GO AND GROW, ARE DEFINING PHENOTYPES OF GBM, AND GBM CELLS DO ONLY ONE OR THE OTHER. HOWEVER, BLOCKING INVASION STIMULATES PROLIFERATION AND VICE VERSA, IMPLYING THAT AN IDEAL THERAPEUTIC NEEDS TO BLOCK BOTH GO AND GROW SIMULTANEOUSLY. EXTENSIVE GENETIC INTERVENTIONS HAVE SHOWN THAT SIMULTANEOUS DISRUPTION OF TWO NON-MUSCLE MYOSIN II (NMII) MOLECULAR MOTORS (NMIIA AND IIB) MEET THESE CRITERIA. HOWEVER, THE TRANSLATIONAL POTENTIAL OF THIS RESEARCH HAS BEEN LIMITED BY THE LACK OF A CLINICALLY SAFE, CNS-PENETRANT NMII SMALL MOLECULE INHIBITOR. FOLLOWING EXTENSIVE MEDICINAL CHEMISTRY EFFORTS TO OPTIMIZE SELECTIVITY FOR SAFETY AND TOLERABILITY, MT-125 WAS IDENTIFIED. MT-125 IS A WELL-TOLERATED, DUAL SMALL MOLECULE INHIBITOR OF NMIIA AND IIB WITH A HIGH DEGREE OF BRAIN PENETRANCE, A REQUIREMENT FOR AN EFFECTIVE GBM THERAPEUTIC. PRECLINICAL IN VITRO AND IN VIVO STUDIES SHOW THAT MT-125 BLOCKS THE GO AND GROW PHENOTYPES AND EXTENDS SURVIVAL. DUE TO ITS UNIQUE MODE OF ACTION, MT-125 ALSO SYNERGIZES WITH EXISTING FDA-APPROVED TREATMENTS, PRESENTING A PATH TO A POTENTIALLY CURATIVE TREATMENT. THE OVERARCHING GOAL OF THE CURRENT PROPOSAL IS TO READY MT-125 FOR RAPID ENTRY INTO IND-ENABLING STUDIES. THIS WILL BE ACHIEVED THROUGH SEVERAL ACTIVITIES. PHASE I WILL FOCUS ON CONFIRMATION OF PRECLINICAL EFFICACY WITH A CLINICALLY VIABLE ROUTE OF ADMINISTRATION, IN VITRO STUDIES OF SYNERGY BETWEEN MT-125 AND ADDITIONAL EXISTING FDA-APPROVED TREATMENTS, AND IN VITRO SAFETY PROFILING, PRE-FORMULATION STUDIES AND DEMO BATCH SCALE-UP OF MT-125. QUANTITATIVE MILESTONES FOR TRANSITION TO PHASE II ARE DETAILED IN THE APPLICATION. IN PHASE II, IN VIVO EFFICACY TESTING WILL BE PERFORMED ON THE MOST PROMISING SYNERGY COMBINATIONS IDENTIFIED IN PHASE I, AS WELL AS A NON-GLP DOSING SAFETY STUDY, GLP SYNTHESIS, AND FORMULATIONS DEVELOPMENT WITH POLYMORPH SCREENING. THE COMMERCIALIZATION PLAN DETAILS THE GBM MARKET, AS WELL AS MYOSIN THERAPEUTICS' CLINICAL AND REGULATORY STRATEGY FOR RAPID ADVANCEMENT OF MT-125 TO THE CLINIC.