BioVie Reveals Bezisterim's Epigenetic Impact on Inflammation and Aging at Aging Research Meeting

Bezisterim appears to possess broad properties pertinent to inflammation and conditions related to aging. Patients treated with bezisterim experienced a 2 to 4-year advantage in age deceleration compared to placebo. The drug modulated DNA methylation of pro-inflammatory genes and seemed to encourage the transition of M1 pro-inflammatory to M2 anti-inflammatory macrophages. Additionally, bezisterim was linked to a 1.5 to 2.3-fold enrichment in gene control for numerous genes in pathways tied to neurodegenerative disorders and biological processes.

A recent presentation at the 11th Aging Research and Drug Discovery Meeting (ARDD 2024) in Copenhagen highlighted the effects of bezisterim on biological age, Alzheimer's epigenetics, and neurological assessments. Christopher L. Reading, BioVie’s Senior Vice President of the Alzheimer’s Disease Program, detailed the clinical data, emphasizing bezisterim’s potential to affect the biological aging process and chronic low-grade inflammation.

BioVie’s President and CEO, Cuong Do, pointed out that the data provide a comprehensive understanding of bezisterim's gene-level impact on inflammation and disease. Notably, patients treated with bezisterim showed a significant age deceleration advantage when measured by various biological clocks: 3.68 years on the SkinBlood Clock, 4.77 years on the Inflammation Age Clock, 5.0 years on the Hannum Age Clock, 1.92 years on the GrimAge Clock, and 3.71 years on the PhenoAge Clock. These results suggest that bezisterim might be the first drug candidate to exhibit an ability to modulate DNA methylation and age deceleration in diseases.

DNA methylation is a process where methyl groups are added to DNA, affecting gene function. The presentation explained how bezisterim modulates DNA methylation, impacting several areas. Specifically, bezisterim appears to support the transition of macrophages from a pro-inflammatory M1 state to an anti-inflammatory M2 state, crucial for managing inflammation. In clinical trials, bezisterim-treated patients did not show a correlation between the monocyte clock and observed monocyte cell levels, unlike placebo-treated patients.

Additionally, bezisterim has the potential to modulate pro-inflammatory genes coding for molecules like ERK, MAP3K8, NFκB, TNFα, and IL6, which are involved in inflammatory pathways. Modulating these genes could lead to reduced production of inflammatory factors. The Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping showed that bezisterim is associated with a significant enrichment in pathways linked to Alzheimer’s, Parkinson’s, ALS, Huntington’s disease, and other biological processes involving cellular senescence and apoptosis.

Bezisterim (NE3107) is an orally bioavailable, blood-brain barrier-permeable insulin-sensitizer that is also anti-inflammatory. Unlike some other treatments, it is not immunosuppressive and has a low risk of drug-to-drug interactions. It has shown potential in reducing symptoms of long COVID, such as fatigue and cognitive dysfunction, by modulating the activation of NFκB and inflammation. 

BioVie has conducted Phase 3 trials for bezisterim in Alzheimer's disease (AD), showing improved cognition and biomarker levels. Phase 2 studies for Parkinson's disease (PD) demonstrated significant improvements in motor control when bezisterim was used in combination with levodopa, with no drug-related adverse events reported.

BioVie Inc. is a clinical-stage company focused on developing innovative drug therapies for neurological and neurodegenerative disorders and advanced liver disease. The company’s candidate, bezisterim, targets inflammatory activation linked to neuroinflammation and insulin resistance, pivotal in AD and PD treatment. Another candidate, BIV201, is being evaluated for treating ascites due to chronic liver cirrhosis.

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