BioVie Inc. announced data from two presentations at the Advanced Therapeutics in Movement and Related Disorders Congress® (ATMRD Congress) held June 21-25, 2024 in Washington, D.C. Presentations include a first look at the protocol design of the upcoming SUNRISE-PD Phase 2 trial of bezisterim (NE3107) in patients with early Parkinson's disease along with an encore presentation of detailed results from the Company's Phase 2a trial of bezisterim adjunctive to carbidopa/levodopa (C/L) in patients with Parkinson's disease. Protocol Design of SUNRISE-PD: A Phase 2, Placebo-Controlled Study of Bezisterim in Early Parkinson?s Disease: The presentation Assessment of Bezisterim (NE3107) in Patients with Early Parkinson?s Disease: A Phase 2, Placebo-Controlled Study outlined the study protocol of the Company?s upcoming SUNRISE-PD Phase 2 trial evaluating bezisterim in patients with Parkinson?s disease who have had minimal exposure to C/L treatment but in need of symptomatic therapy for motor symptoms. SUNRISE-PD will be a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial with a hybrid decentralized design that will last 20 weeks from the initial screening phase to the safety follow up. During the 12-week double-blind phase, around 60 patients will be randomized 1:1 to receive either bezisterim 20 mg or placebo twice-daily.

Objective Primary: Evaluate the efficacy of bezisterim in the treatment of motor symptoms of PD; Endpoint: Change in MDS-UPDRS Part III score at week 12 (centralized ratings); Secondary: Evaluate the impact of bezisterim on non-motor symptoms of PD and on overall symptoms of PD as assessed by the clinician; Endpoint: Change in the MDS-UPDRS Part I and Part II scores at week 12; Percent of subjects with any improvement as measured by the CGI-I at week 12; Percent of subjects with any improvement as measured by the CGI-S at week 1. Exploratory: Assess the effects of bezisterim treatment on other aspects of PD; Endpoint: Change in MDS-UPDRS combined and sub-domain scores; Evaluate the effect of bezisterim on Patient Reported Outcomes; Endpoint: Change in PDQ-39 response; Change in PDSS score; Evaluate the effect of bezisterim on discontinuation events for worsening of PD; Endpoint: Proportion of subjects discontinuing from the study due to worsening of PD; Time to discontinuation due to worsening of P;D Assess the effect of bezisterim on epigenetics associated with biological age and alpha synuclein gene methylation, Endpoint: Change in DNA methylation up to week 12; Assess the effect of bezisterim on plasma biomarkers of inflammation and pharmacodynamics, Endpoint; Change in plasma biomarkers of inflammation up to week 12; Assess the effect of bezisterim on circulating biomarkers and correlations between biomarkers and clinical endpoint changes, Endpoint: Change and percent change from baseline in pre-specified exploratory biomarkers and the correlation between biomarkers and clinical endpoints at week 12; Assess population PK and E-R relationships for efficacy and safety of bezisterim, Endpoint: PK and E-R assessments for efficacy and safety where data permit; Safety: Assess the safety and tolerability of bezisterim, Endpoint: Treatment-emergent adverse events; Vital signs; Electrocardiograms; Clinical laboratory values; Physical exam; C-SSRS. As part of the trial, patients may participate either completely from their home or at a clinical site. At-home participants will be visited by study nurses who will complete study assessments with the assistance of a neurologist who will attend the visit remotely by video.

If the results of the study are positive, then participants may be eligible to enter a longer-term, open-label safety study at a future date. Phase 2a Data Reinforce Potential of Bezisterim to Improve Motor and Non-Motor Symptoms of Parkinson?s Disease: An encore presentation, Improvement of Motor and Non-Motor Symptoms with Bezisterim (NE3107) Adjunctive to Carbidopa/Levodopa in Patients with Parkinson?s Disease: A Phase 2a, Placebo-Controlled Study, suggested improvements in both motor and non-motor symptoms with bezisterim adjunctive to C/L. These findings were presented last month at the XXIX World Congress on Parkinson?s Disease and Related Disorders hosted by the International Association of Parkinsonism and Related Disorders (IAPRD) in Lisbon, Portugal. Patients treated with bezisterim and C/L experienced superior improvements on the Disorder Society Unified Parkinson?s Disease Rating Scale (MDS-UPDRS) Part III at 2- and 3-hour marks when compared to placebo.

In patients younger than 70 years old (~50% of the total patient population) the advantage for bezisterim-treated patients was -4.7 points. Furthermore, 30% of bezisterim-treated patients experienced improvement in their ability to move, having Part III scores prior to their first morning dose of C/L that were equal to or better than Part III scores associated with their being in the ?ON? state after C/L treatment at the start of the study, whereas none of the placebo patients had the similarly improved morning Part III scores.

The difference was statistically significant (p=0.02). Bezisterim-treated patients experienced a significant improvement of -2.4 points for the sleep/fatigue domain of the Non-Motor Symptom Scale (NMSS) in Parkinson?s disease, whereas placebo patients experienced a worsening of +1.0 points (p=0.0159). Sleep/fatigue domain improvements correlated with motor score improvements (r=0.51; p=0.0259).

More patients on bezisterim had improvements in the NMSS sleep/fatigue domain, while more patients on placebo worsened. Bezisterim-treated patients experienced an improvement of -0.89 on the urge to move legs/restlessness in legs whereas placebo patients experienced a worsening of +0.99 (p=0.0321).