BioVie Inc. announced positive results from two Phase 2 trials assessing NE3107's potential in Parkinson's Disease (PD) and Alzheimer's Disease (AD). Enhanced motor control shown in Parkinson's trial: The NM201 study (NCT05083260) is a double-blind, placebo-controlled, safety, tolerability, and pharmacokinetics study in Parkinson's disease (PD) participants treated with carbidopa/levodopa and NE3107. 45 patients with a defined L-dopa “off state” were randomized 1:1 to placebo:NE3107 20 mg twice daily for 28 days.

This trial was launched with two design objectives: 1) the primary objectives are safety and a drug-drug interaction study as requested by the FDA to demonstrate the absence of adverse interactions of NE3107 with levodopa; and 2) the secondary objective is to determine if preclinical indications of promotoric activity and apparent enhancement of levodopa activity can be seen in humans. Both objectives were met. Before study commencement and at multiple points throughout the 28-day trial, patients who did not receive PD medications for at least 8 hours overnight were observed using the Unified Parkinson's Disease Rating Scale (UPDRS) first thing in morning (hour 0).

Patients were then given medication and observed again using UPDRS at 1, 2, 3, 4, and 8 hours after drug administration. Part 3 of the UPDRS instrument assessed motor control. Patients treated with NE3107 and levodopa saw improvements of part 3 score on Day 28 compared to Day 0 that is 3+ points better than those treated with levodopa alone at the 2- and 3-hour marks.

This level of superiority is considered by PD experts to be clinically meaningful. Patients younger than 70 years old treated with NE3107 and levodopa experienced improvements that are roughly 6 points better than levodopa-treated alone. Patients younger than 70 years old represented roughly one-half of study participants.

After 28 days of treatment, 63.6% of patients treated with levodopa alone experienced >30% improvement from Day 0 at the two-hour mark compared to 80% for NE3107+levodopa-treated patients and 88.9% of NE3107+levodopa patients under 70 years old. This pattern is also observed for other time periods. There were no drug-related adverse events Additional Positive Alzheimer's Data Presented at CTAD: The Phase 2 trial (NCT05227820) enrolled a total of 23 patients – 18 patients with Mini-Mental State Examination (MMSE) scores greater than or equal to 20 (i.e., mild cognitive impairment [MCI] to mild AD) and 5 patients with MMSE <20 (i.e., moderate AD) – in an open-label, single arm study.

The trial measured changes in cognition through verbal and visual test procedures, changes in biomarkers of Alzheimer's disease and inflammation that can be measured in both cerebral spinal fluid (CSF) and serum samples, and changes in functional magnetic resonance imaging in patients before and after treatment with 20 mg of NE3107 twice daily for 3 months. Topline results were released on September 7, 2022, and Dr. Sheldon Jordan (the Principal Investigator) and his team presented additional data through a platform presentation at the Clinical Trial in Alzheimer's Disease (CTAD) annual conference, held in San Francisco, CANovember 29 to December 2, 2022. These data showed the following among patients with MMSE>=20 (i.e., mild cognitive impairment and mild AD): Patients demonstrated enhanced cognition after three months of treatment with NE3107 compared to baseline as measured using multiple rating scales Improvement of 2.2 point on the modified ADAS-Cog12 scale (p=0.0173), equating to 21.1% (p=0.0079) change compared to baseline.

Among only responders, the improvement was 3.7 points (p=0.0003) equating to 36.2% (p<0.0001) compared to baseline Improvement of 0.11 (p=0.0416) on the Clinical Dementia Rating scale (CDR), equating to 19.4% (p=0.0416) change from baseline Improvement of 0.07 points (p=0.0094) on Alzheimer's Disease Composite Score (ADCOMS) Patients improved in daily function as evidenced by an increase in the Global Rating of Change scale2: +2.67 (p<0.0001) as observed by clinicians; +2.08 (p=0.0012) as reported by the patients; and +1.69 (p=0.0011) as reported by study partner. Improvements in inflammation (reduction in TNFa) correlated with improvements in cognition (R=0.59, p=0.0259) Patients experienced a reduction of CSF phospho-tau levels of -1.66 pg/mL (p=0.0343) and the ratio of p-tau to Aß42 by -0.0024 (p=0.0401). Among responders, the reduction in p-tau was -3.22 pg/mL (p=0.0027) and the ratio of p-tau to Aß42 was 0.0040 (p=0.0144) 18 of 22 patients with abnormal baseline scans showed improvement in one or more brain regions as seen from advanced functional MRI studies MCI and mild AD subjects with abnormal scans that improved after 3 months treatment also saw a -0.068 points improvement in their ADCOMS scores (p=0.0258).