Annovis Bio Inc. announced new data from its Phase III PD study demonstrating that buntanetap is safe and effective in improving motor and non-motor activities and improving cognitive functions in patients with early Parkinson's disease. Background: Parkinson's is a very heterogeneous disease. Key Findings from the Study: Buntanetap stops cognitive decline in all enrolled patients (MMSE 20-30) and improves cognition in patients with mild dementia (MMSE 20-26): Findings: In the entire enrolled population, placebo group demonstrated cognition deterioration throughout the study, whereas all treatment groups (10mg and 20mg buntanetap) maintained baseline levels, indicating a statistically significant effect of the drug in stopping cognitive decline.

In patients with mild dementia, as measured by MMSE 20-26, cognition deteriorated at a faster pace in the placebo group compared to those treated with 10mg buntanetap. Moreover, treatment with 20mg buntanetap showed significant improvement in cognition compared to placebo. Background: Inclusion criteria for enrollment included MMSE scores between 20-30, and MMSE scores were measured again at the end of the study as an exploratory endpoint.

This allowed to determine changes in cognition in the entire enrolled population as well as in patients with cognitive decline. Most PD patients had normal cognitive functioning, and just 12% showed cognitive decline as measured by MMSE 20-26. These patients declined by 1.5 MMSE points in the placebo group but did not decline at all and even improved when treated with buntanetap.

This data aligns with its AD cognition data, where patients with MMSE>20 responded well to buntanetap, showing statistically significant cognitive improvement in early AD patients. Buntanetap improves motor and non-motor PD-related functions in patients with a diagnosis of over 3 years: Findings: Patients with a diagnosis of less than 3 years showed minimal or no deficits in MDS-UPDRS Part II, making it challenging to measure improvement and assess treatment effectiveness. However, in patients diagnosed with PD for longer than 3 years (MH>3), with measurable declines in MDS-UPDRS Part II, 20mg buntanetap significantly improved MDS-UPDRS Part II, Part III, Part II+III, and Total scores compared to placebo and baseline.

Background: Longitudinal studies from Parkinson?s Progressive Markers Initiative (PPMI) cohorts have shown that Parkinson patients? self-evaluation of their activities of daily living (MDS-UPDRS Part II) are relatively intact in the early disease stages. They have also shown that MDS-UPDRS Part II deteriorates at a much slower pace compared to the physician-scored motor evaluation (MDS-UPDRS Part III (Holden et al.

2017). Buntanetap improves motor and non-motor PD-related functions in patients with Postural Instability and Gait Difficulty (PIGD): Findings: PIGD patients treated with buntanetap showed significant improvements in MDS-UPDRS Part II, Part III, Part II-III, and Total scores. The disease in this patient group progresses faster than in other PD patients.

Its data showed that PIGD patients respond better to buntanetap and improve further than other Parkinson?s patients. Background: Parkinson?s is a very heterogeneous disease. Patients diagnosed with PIGD are considered to have faster disease progression (Jankovic et al.

1990 & Stebbins et al. 2013) than patients with no postural and gait issues. This observation provided with the rationale to evaluate whether PIGD patients, who are at risk of faster decline, would benefit from buntanetap.

Safety Profile: Buntanetap maintained a consistent safety profile across all participants, with no significant differences between early and advanced PD patients confirming its previous AD data. FDA and Endpoint Clarification: Recent questions regarding the primary and secondary endpoints in MDS-UPDRS scores warrants additional explanation. Initially, Annovis chose MDS-UPDRS Part II+III as the primary endpoint.

However, based on FDA feedback, MDS-UPDRS Part II alone was deemed more appropriate for reflecting clinically relevant changes (Goetz et al., 2023). Consequently, the company adjusted its primary endpoint to MDS-UPDRS Part II, with MDS-UPDRS Part III as a key secondary endpoint. The results met both primary and secondary endpoints in the specified subgroups.