Annovis Bio’s AD/PD Therapy Reduces Cytotoxic Cascade in Phase IIa Trials
Annovis Bio’s therapy for Alzheimer’s disease is fast-acting and has the potential for Alzheimer’s patients to significantly improve cognition and motor function, according to data presented at the Alzheimer’s Association International Conference® 2021 (AAIC®), held July 26th through 30th.
Efficacy data from two Phase IIa studies of ANVS401 (posiphen) for cognition in Alzheimer’s disease (AD) patients and motor function in Parkinson’s disease (PD) patients, was reported at the beginning of the week. It shows a 30% improvement in cognition after 25 days of treatment.
Data regarding the cytotoxic cascade was released a few days later during a dinner symposium. It detailed significant reductions of neurotoxic protein levels and inflammation, as well as biomarkers for axonal damage, and highlighted the efficacy data.
“This trial was based on patients’ symptoms rather than the presence of tau or amyloid, which is unusual,” Priscilla Hernandez, co-founder of EZY Medical Research, told the audience. Her company enrolled 7 of the 14 patients in the AD trial and 12 of the 34 in the PD trial.
In terms of demographics, 56% of the AD patients were Hispanic, nearly 44% were Caucasian, and more than 12% were Asian. Nearly 69% were female. The average age was 71 years. In the PD trial, just over 13% were Hispanic and nearly 87% were Caucasian. The average age was 68.5 years. “Most had chronic conditions, none of which were acerbated during the trial,” Hernandez said.
The just-released data showed that treatment with ANVS401 lowered levels of neurotoxic proteins for both AD and PD cohorts. In AD, P-Tau was lowered approximately 12% and T-Tau about 11%. sAPPa and b also were lowered about 9% compared to placebo. For PD patients, the greatest reduction in neurotoxic proteins was in AB42, at 12%, followed by sAPPa at about 11%. In both patient groups, additional neurotoxic proteins were also reduced.
“What is interesting is the AB40 and AB42 ratio between AD and PD patients,” Hernandez said. (Baseline measurements used those two proteins to confirm the diagnosis of AD.) After treatment, the two were lowered significantly more in PD patients – 8 and 12% respectively – compared to about 4% in AD patients.
Neurofilament light was reduced significantly, too – about 13% in AD patients and 9% in PD patients. “This indicates improved axonal health,” Hernandez said. Improvement reductions in the levels of three inflammatory markers (YKL40, sTREM2, and GFAp) also were seen, indicating that inflammation is reduced.
“The last patient (of the additional 40) in the PD trial was treated last weekend,” she concluded. “The toxic cascade biomarker data is expected to be completed within the next two months.”
This cytotoxic cascade data is relevant, Maria L. Maccecchini, Ph.D., CEO, Annovis Bio, explained, because, “Chronic and acute brain insults lead to high levels of neurotoxic proteins, inflammation, and neurodegeneration. Those proteins impair the axonal transport system, slow synaptic transmission, and lead to inflammation, nerve cell death, and ultimately, impair patients’ cognition or movement.”
To counter that, ANVS401 attacks multiple neurotoxic proteins simultaneously, improving axonal transport, increasing synaptic transmission, eliminating inflammation, preventing nerve cell death, and enhancing cognitive and motor function.
The double-blind, placebo-controlled Phase II trial in AD for early to moderate AD showed a 4.4-point cognitive improvement, as measured by Alzheimer's Disease Assessment Scale- Cognitive Subscale 11 (ADAS-Cog11). “That’s a 30% improvement from baseline, only 25 days after treatment,” Maccecchini pointed out.
The charts presented during the symposium showed cognitive impairments levels after 25 days of treatment. For example, impairment scores dropped from just over 1 for the placebo group to about 0.75 for ADAS-Cog3 and 6, and from slightly more than 0.9 to just over 0.7 for ADAS-Cog 11. Changes in ADAS-Cog14 were notably, but less pronounced.
Wechsler Adult Intelligence Scale (WAIS) coding and symbol search tests also documented improvements. In the coding test, which measures speed in movements and thinking, AD patients experienced a 6.6-point (23%) improvement from baseline. PD patients say a 6.1-point (14%) improvement from baseline.
Additionally, using the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), PD patients treated with ANVS401 also exhibited an 18% improvement in motor function improvement.
“We have one month of data for 14 patients for AD and recruited an additional 40 for PD,” Maccecchini told BioSpace. “Before we present this to the FDA, we will conduct a two-year trial,” to assess long-term cognitive and motor function improvements.