Benzinga | Aug 5, 2021 08:14AM EDT

BioVie Announces First Patient Enrolled in Phase 3 Study of NE3107 in Alzheimer's Disease

BioVie Inc. (NASDAQ:BIVI) ("BioVie" or "Company"), a clinical-stage company developing innovative drug candidates for the treatment of neurological and neurodegenerative disorders, liver disease and certain cancers, today announced that the Company has enrolled the first patient into the NM101 Phase III clinical study testing NE3107 for the treatment of Alzheimer's Disease (AD).

The NM101 study (NCT04669028) is a potentially pivotal Phase 3, randomized, double blind, placebo-controlled, US multicenter study of NE3107 in 316 subjects with mild to moderate AD. In addition to conventional cognition, memory, functional, behavioral and imaging end points, NM101 will assess measures of glycemic control, brain glucose utilization and systems dysregulation. The mechanistic basis for the study design was recently published in a peer-reviewed article in Neurodegenerative Disease Management ( https://doi.org/10.2217/nmt-2021-0022). This study design and pathophysiology and mechanism data were also presented as Poster 55458 entitled "Rationale for an Anti-inflammatory Insulin Sensitizer in a Phase 3 Alzheimer's Disease Trial" by Christopher L Reading, PhD, BioVie's Executive Vice President for Neuroscience Research & Development at the 2021 Alzheimer's Association International Conference (AAIC), July 28, 2021. The study aims to have data readout by the end of 2022.

"NM101 is the first randomized, double blind, placebo-controlled Phase 3 trial conducted by any company to test a potentially disease modifying anti-inflammatory insulin sensitizer compound in subjects with mild to moderate AD," said Cuong Do, Chief Executive Officer of BioVie. "In prior animal studies and Phase 1 and 2 human clinical studies, NE3107 generated data supporting reduced neuroinflammation and insulin resistance, both of which are recognized as important players in AD pathology."

Neuroinflammation and insulin resistance are associated with cognitive decline associated with Alzheimer's. NE3107's potential to inhibit neuroinflammation and insulin resistance forms the basis for the hypothesis that it may impact cognitive decline in Alzheimer's patients.

Inflammation is increasingly recognized as an important mechanism in AD. Inflammation drives activation of the Extracellular Signal-Regulated Kinase (ERK) signaling molecule and Nuclear Factor kappa-B (NF?B). NF?B is the central regulator of proinflammatory cytokines and chemokines important in neurodegeneration. Furthermore, NF?B activation in the brain is triggered by Amyloid Beta (A?) and phosphorylated tau (P-tau), and by the very proinflammatory mediators that NF?B stimulates, leading to perpetual low-grade chronic inflammation.

Inflammation also triggers inhibitory phosphorylation of Insulin Receptor Substrate 1/2, leading to insulin resistance (IR) and the inhibition of insulin signaling. As insulin is the master regulator of energy and metabolism, neuroinflammation's disruption of insulin signaling is believed to contribute to AD pathology. The Mayo Clinic estimates that up to 81% of AD subjects have impaired glucose tolerance or type 2 diabetes mellitus.

NE3107 is an oral small molecule, blood-brain permeable, compound with potential anti-inflammatory, insulin sensitizing, and ERK-binding properties that may allow it to selectively inhibit ERK- and NF?B-stimulated inflammation. No major safety signals have been observed in preclinical and clinical studies to date.