ENDECE Neural announced today the presentation of new, pre-clinical evidence that the company’s lead compound, NDC-1308, induces remyelination and increases forelimb grip strength in a validated animal model of demyelination. As presented in a poster session at the 2014 annual meeting of the Society for Neuroscience in Washington, D.C., the improvements with NDC-1308 therapy are linked to the drug’s unique ability to repair the myelin sheath of demyelinated axons (nerve fibers).
The data, presented by Steven H. Nye, Ph.D., Vice President of Discovery at ENDECE Neural, suggest that the remyelinating properties of NDC-1308 may benefit patients with secondary progressive multiple sclerosis (SPMS). ENDECE Neural has announced plans to initiate non-clinical investigational new drug (IND)-enabling studies of NDC-1308 and a first-in-humans Phase 1 clinical trial in 2015.
“We continue to be encouraged by the reproducible pre-clinical data generated for NDC-1308,” said Dr. Nye. “In addition to our previous knowledge about its mechanism of action, we now conclusively demonstrate the ability of NDC-1308 to repair the damaged myelin sheath in a cuprizone mouse model of demyelination. The grip-strength findings are especially encouraging, as this test may be translated to the clinic for measuring functional improvement in MS patients. We look forward to initiating clinical trials of this promising compound.”
Dr. Nye and colleagues reported that NDC-1308 induced significant remyelination in several brain regions using the cuprizone model of demyelination, in which the neurotoxicant cuprizone was used to remove the myelin sheath from the axons of mice. In addition, prophylactic treatment with NDC-1308 delayed the onset of clinical symptoms of MS in an experimental autoimmune encephalomyelitis (EAE) mouse model of brain inflammation while preserving neuronal cells, suggesting that it also exerts a neuroprotective activity. Chronic treatment with NDC-1308 was well-tolerated by the studied animals, suggesting it can be safely administered.
“All research to date indicates that NDC-1308 is ready to advance to IND-enabling and clinical studies,” commented James G. Yarger, Ph.D., Chief Executive Officer of ENDECE Neural. “The IND-enabling program has been designed to determine the safety and toxicity of NDC-1308 and appropriate starting doses for initiating Phase 1 studies in humans. We look forward to continuing the momentum from the pre-clinical studies as we enter the clinic with NDC-1308.”
NDC-1308 is a novel chemical entity designed to address the damage to the myelin sheath that occurs in patients with secondary progressive MS (SPMS), a common later phase of the disease that follows relapsing-remitting MS (RRMS). NDC-1308 is being developed for potential use either alone or in combination with other MS therapeutics that slow the progression of the disease. By dramatically up-regulating key genes in pathways leading to oligodendrocyte progenitor cell (OPC) differentiation and myelin synthesis, NDC-1308 appears to induce restoration of the lost myelin sheath that is believed to cause the devastating symptoms of MS. NDC-1308 is a small molecule that readily crosses the blood-brain barrier, allowing it to reach the tissues in the brain and spinal cord where promoting myelin production is needed. NDC-1308 works by inducing differentiation of OPCs into mature oligodendrocytes, cells that synthesize and maintain the myelin sheath. ENDECE Neural discovered NDC-1308, and owns the intellectual property surrounding the compound.
About ENDECE Neural
ENDECE Neural is a private biotechnology company at the forefront of developing therapies to repair and potentially reverse damage caused by devastating neurological diseases such as MS. A wholly owned subsidiary of ENDECE LLC, ENDECE Neural was founded in 2011 to focus on the development of what could be the first drug capable of repairing the myelin sheath of demyelinated nerve axons in patients with MS. The company is leveraging decades of accumulated knowledge about how activation of estrogen receptors in a specific manner affects gene regulation. Researchers at ENDECE Neural have identified small-molecule compounds that upregulate key genes in pathways involved in promoting myelin sheath synthesis. ENDECE Neural is developing NDC-1308, which appears to directly induce OPCs to differentiate into mature oligodendrocytes that restore the depleted myelin sheath in rodent models. ENDECE Neural discovered and owns the intellectual property surrounding its compounds, and the company’s management team has a track record of successfully taking products from the laboratory through FDA approval and commercial release.