This Project Grant award from the National Center for Advancing Translational Sciences (NCATS), under the CFDA 93.350 National Center for Advancing Translational Sciences program, provides $489,500 to support research on developing a potential prophylactic intervention for Familial Platelet Disorder with Associated Myeloid Malignancy (FPDMM), a rare genetic disorder. The grant will fund studies to investigate how a small compound called Repsox may correct both the platelet defects and leukemic...
This Project Grant award of $601,169 from the National Heart, Lung, and Blood Institute (CFDA 93.837 - Cardiovascular Diseases Research) supports research by the University of Virginia to investigate the molecular basis for the progression of myeloproliferative neoplasms (MPNs), a group of hematologic malignancies characterized by overproduction of myeloid cells. The research aims to elucidate how the JAK2V617F mutation and deficiencies in the PTPN1 tumor suppressor gene cooperate to promote...
The National Cancer Institute (NCI), under the Cancer Treatment Research program (CFDA 93.395), has awarded a $683,472 Project Grant to the University of Cincinnati to advance pharmacodynamically directed targeted therapy for acute myeloid leukemia (AML). The 5-year project aims to transition the DHODH inhibitor HOSU-53 into clinical trials, starting with a Phase 1 trial in 2025 to evaluate the compound's pharmacokinetics, pharmacodynamics, and ability to eliminate specific AML cell clones....
This $299,790 Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) supports the development of novel allosteric modulators of the thrombin receptor, protease-activated receptor 1 (PAR1), called Parmodulins, for the treatment of sickle cell disease (SCD). The project aims to identify optimized Parmodulins with improved potency and oral activity, and confirm their efficacy in mouse models of SCD, including...
The National Cancer Institute awarded a $378,674 Project Grant (CFDA 93.395 - Cancer Treatment Research) to The University of Texas MD Anderson Cancer Center (MD Anderson) to develop a small-molecule inhibitor of the EIF2AK1 protein kinase. The goal is to overcome ineffective erythropoiesis, or impaired red blood cell production, in patients with myelodysplastic syndromes (MDS) characterized by mutations in the SF3B1 gene. This novel therapeutic approach aims to address the severe anemia and...
This Project Grant award from the National Institutes of Health (NIH) Research Infrastructure Programs (CFDA 93.351) provides $270,428 to TEO Therapeutics Incorporated, a small disadvantaged business, to develop a biomimetic platform for more efficient pharmaceutical drug development in oncology. The key products and services to be delivered include: Refining and testing a proof-of-concept hardware product line for a Shell-Free Quail Xenograft Assay, optimizing throughput and assessing...
This Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) is focused on conducting definitive (GLP) toxicity and toxicology studies for a novel small molecule therapy to protect against cardiotoxicity in triple negative breast cancer (TNBC) patients. The $1,000,000 award will support the development and commercialization of this novel, safe, and effective therapy that synergizes with anthracyclines, such...
The National Center for Advancing Translational Sciences (NCATS) awarded a $407,792 Project Grant (CFDA 93.350) to Nostopharma LLC, a woman-owned small disadvantaged business, to develop a novel localized treatment for Fibrodysplasia Ossificans Progressiva (FOP), an ultrarare genetic disease. The project aims to create extended-release formulations of Hedgehog pathway inhibitors, such as arsenic trioxide, encapsulated in immunomodulatory nanoparticles for intramuscular administration. The goal...
Novelmed Therapeutics, Inc. was awarded a $1,599,495 Project Grant from the National Heart, Lung and Blood Institute of the Department of Health and Human Services. The grant falls under the Cardiovascular Diseases Research program (CFDA 93.837), which supports heart and vascular research. Novelmed will use the funding to develop a novel disease-modifying treatment for paroxysmal nocturnal hemoglobinuria (PNH). The company's lead drug candidate selectively inhibits the alternative pathway of...
This $1,398,552 Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) supports Avantgen Inc., a San Diego-based biotechnology company, in conducting preliminary IND-enabling studies for a novel antibody therapy targeting the Jagged-1 pathway in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The key products and services to be delivered under this grant include cell line development, early chemistry and manufacturing controls (CMC)...
THROMBOPOIETIN TARGETING IN MYELOPROLIFERATIVE NEOPLASMS - PROJECT SUMMARY/ABSTRACT TREATMENT OF PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS (MPNS) IS LIMITED TO PALLIATIVE AND CYTOREDUCTIVE AGENTS THAT MITIGATE PROLIFERATIVE BLOOD COUNTS AND THEIR EFFECTS. SMALL MOLECULE SELECTIVE TYROSINE KINASE (JAK1/JAK2) INHIBITORS WERE ALSO SHOWN TO PROVIDE MODEST PATIENT BENEFIT, INCLUDING REDUCED SYMPTOMATOLOGY AND IMPROVED QUALITY OF LIFE. DESPITE THE AVAILABLE THERAPIES, SURVIVAL REMAINS POOR IN PATIENTS WITH ADVANCED FORMS OF MPN, AND SOME PATIENTS INEVITABLY BECOME REFRACTORY TO ALL AVAILABLE THERAPIES. CONSEQUENTLY, THERE IS AN UNMET MEDICAL NEED FOR A NEW DRUG THAT CAN SAFELY MITIGATE MPN SYMPTOMS AND, IDEALLY, ALSO ALTER THE LONG-TERM COURSE OF THE DISEASE. TO ADDRESS THIS IMPORTANT NEED, WE PROPOSE TO DEVELOP AND INVESTIGATE THE THERAPEUTIC POTENTIAL OF ARONORA'S PROPRIETARY DRUG CANDIDATE AB062, A THROMBOPOIETIN CONJUGATE ANTISENSE OLIGONUCLEOTIDE (THPO-ASO), TO BE USED ALONE OR IN ADDITION TO OTHER DRUGS, AS A NOVEL THERAPEUTIC FOR CHRONIC MYELOPROLIFERATIVE DISORDERS. OUR THPO-ASO INHIBITS HEPATIC THROMBOPOIETIN GENE TRANSCRIPTION IN BOTH MURINE AND PRIMATE MODELS, REDUCES SERUM THROMBOPOIETIN (TPO) LEVELS, AND RESULTS IN DOSE- DEPENDENT REDUCTION OF TPO CONCENTRATION-DEPENDENT DOWNSTREAM CELLULAR EFFECTS. WORK BY OUR CO- INVESTIGATORS AND OTHERS HAS SHOWN THAT TPO DEPRIVATION PREDOMINANTLY RESULTS IN DEPLETION OF CERTAIN TPO-DEPENDENT MUTANT JAK2 CARRIER MPN STEM CELLS WHILE SPARING HEALTHY BONE MARROW PROGENITORS. TARGETING THPO/MPL/JAK2 AXIS ALSO MITIGATES THE MPN PHENOTYPE IN MURINE MPN MODELS, INCLUDING REDUCTION IN PROLIFERATIVE BLOOD COUNTS AND SPLENOMEGALY. THESE OBSERVATIONS SUPPORT OUR HYPOTHESIS THAT THPO-ASO COULD FAVORABLY ALTER THE NATURAL TRAJECTORY OF CERTAIN MPNS. OUR OBJECTIVE FOR PHASE I OF THIS SBIR FAST-TRACK PROJECT IS TO CONFIRM THAT MURINE THPO-ASO TREATMENT ALONE [OR IN COMBINATION WITH THE JAK2 INHIBITOR, RUXOLITINIB,] CAN IMPROVE DISEASE OUTCOMES IN A TRANSGENIC MURINE MPN MODEL. UPON REACHING THIS MILESTONE, WE WILL EXTEND THESE STUDIES INTO PHASE II BY: 1) EVALUATING MURINE THPO-ASO IN A MURINE MPN TRANSPLANT MODEL THAT WILL ALLOW US TO ASSESS THE EFFECTS OF THPO-ASO ON THE MALIGNANT CLONAL BURDEN, 2) EVALUATING THE REVERSIBILITY OF THPO-ASO AND ASSESS FOR SYNERGY WITH THE JAK INHIBITOR RUXOLITNIB, AND 3) SCREEN FOR AND MANUFACTURE AB062, A DRUG-CANDIDATE ASO THAT TARGETS HUMAN THPO. POSITIVE RESULTS WILL JUSTIFY FURTHER COMMERCIAL DEVELOPMENT, AND WILL HELP SUPPORT AN INVESTIGATIONAL NEW DRUG APPLICATION FOR EVALUATING AB062 IN PATIENTS WITH ADVANCED MYELOPROLIFERATIVE DISORDERS WHO ARE IN DESPERATE NEED OF NEW AND INNOVATIVE THERAPIES.