Preclinical Innovation

点击翻译按钮获取中文摘要

The TRND program was initiated in May 2009, establishing infrastructure and six pilot projects. Through subsequent rounds of public solicitation for new collaborative proposals, a robust portfolio of projects has been developed. Collaborators represent academia, non-profit organizations, small and large biotechnology businesses, and government labs. Upon adoption into the TRND portfolio, a joint project team develops a research project plan and agrees to critical milestones and timelines that must be reached. A project that successfully meets these milestones will be supported scientifically and financially until it can be adopted by an outside organization to complete development and approval by the FDA for marketing. As TRND is a data-driven and milestone-dependent program, projects that fail to meet agreed-upon milestones in a timely fashion are discontinued. Projects adopted for collaboration (in order of solicitation / adoption) include: Pilot Phase: 1. Niemann-Pick Type C1 Disease, a rare disease 2. Hereditary Inclusion Body Myopathy, a rare disease 3. Giardiasis, a neglected disease (project completed) 4. Schistosomiasis, a neglected disease (project discontinued) 5. Sickle Cell Disease, a rare disease (project completed) 6. Chronic Lymphocytic Leukemia, a rare disease (project discontinued) Two solicitations in FY 2011: 1. Duchenne Muscular Dystrophy, a rare disease (2 different projects; one discontinued) 2. Fragile X Syndrome, a rare disease (project discontinued) 3. Cryptococcal Meningitis, a neglected disease 4. CBF Leukemia, a rare disease 5. Neonatal Herpes Simplex Virus, a rare disease 6. Pulmonary Alveolar Proteinosis, a rare disease 7. Fibrodysplasia Ossificans Progressiva, a rare disease 8. Schistosomiasis, a neglected disease 9. Creatine Transporter Defect, a rare disease One solicitation in FY 2012: 1. Retinitis Pigmentosa, a rare disease (2 different projects; one completed) 2. Hypoparathyroidism, a rare disease 3. LEOPARD Syndrome, a rare disease One solicitation in FY 2013: 1. Hemoglobinopathies, a rare disease 2. Lassa Fever, a neglected disease 3. Malaria, a neglected disease Within two years of initiation, four projects (Aes-103 for Sickle Cell Disease; Auranofin for Chronic Lymphocytic Leukemia; Cyclodextrin for Niemann-Pick Type C; and DEX-M74 for Hereditary Inclusion Body Myopathy) yielded successful IND applications to the FDA, and first in-human clinical trials were initiated in all four. One pilot project (Giardiasis) successfully completed its project milestones, while another pilot project (Schistosomiasis) was discontinued for failure to meet preclinical milestones. A third pilot (Chronic Lymphocytic Leukemia) was discontinued for failure to meet clinical milestones. Two projects adopted in FY 2011 (Duchenne Muscular Dystrophy; Fragile X Syndrome) were discontinued from the TRND portfolio. The Duchenne Muscular Dystrophy partner is now able to carry out future steps without further TRND support, whereas the Fragile X Syndrome project was discontinued due to realignment of the collaborators business strategy. Two projects have been successfully de-risked and adopted by outside biopharmaceutical partners (Aes-103 for Sickle Cell Disease; a small molecule for Retinitis Pigmentosa). The development of therapeutics for these rare or neglected indications continues to involve resources in the following areas, performed and/or provided by TRND: 1. Medicinal Chemistry Optimization 2. Pharmacokinetics / Pharmacodynamics 3. Toxicology 4. Dosing 5. Formulation 6. Regulatory Support 7. Project Management In FY 2014, three new BrIDGs projects were initiated. These projects include a small molecule combination therapy for cardiac arrest-induced acute brain injury, a peptide mimetic therapy for beta thalassemia, and a recombinant protein therapeutic for Acute Radiation Syndrome. Other ongoing BrIDGs projects support the development of potential therapies for Aromatic L-Amino Acid Decarboxylase Deficiency, Alzheimers Disease, Anemia of Inflammation, Atherosclerosis, Chronic Pain, Epilepsy, Fibrodysplasia Ossificans Progressiva, Hyperinsulinism, Hypoparathyroidism, Peritoneal Cancer, Niemann-Pick C Disease, Metabolic Disorder, Multiple Sclerosis, Osteoarthritis, Spinal Cord Injury and Traumatic Brain Injury. Upon completion of agreed upon in-kind studies, projects related to therapies for Chronic Dry Eye and Rheumatoid Arthritis were discontinued. The Chronic Dry Eye project led to an IND filing by the BrIDGs collaborator, Parion Sciences. In January 2014, BrIDGs solicited applications for new projects. Over seventy pre-application calls were held and awards are expected in September 2014.