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Further look at earlier Phase 1b study by ADCS unveils confirmatory data
MALVERN, Pa., April 01, 2024 (GLOBE NEWSWIRE) -- Annovis Bio, Inc. (NYSE: ANVS), a clinical-stage drug platform company developing novel therapies for neurodegenerative diseases, today announced the publication of new data from an earlier study supporting buntanetap as a translational inhibitor of amyloid precursor protein (APP) in patients with early Alzheimer’s Disease (AD).
Buntanetap is an oral molecule that selectively binds to an iron-responsive element in the mRNA of APP and other neurotoxic proteins and inhibits their translation. Through this mechanism, buntanetap was shown to decrease the production of amyloid beta (Aβ), a key hallmark in AD. This study, which was finished in 2021, aimed to assess pharmacodynamic effects of buntanetap on the translation of APP mRNA by employing Stable Isotope Labeling Kinetics (SILK). SILK measures the translation, steady state, and degradation of a protein in the cerebrospinal fluid (CSF) and is able to detect subtle protein changes, which cannot be measured in normal CSF sampling. Here, SILK was used to measure the kinetics of APP in early AD patients and to quantify Aβ40 in CSF.
In this randomized, double-blind, placebo-controlled study, participants received oral buntanetap (1x60, 2x60 and 3x60 mg per day or placebo) up to a 25-day period. At the end of the study, patients were catharized in the lumbar spine for 36 hours to accommodate the total time it takes for APP to be synthesized, processed into Aβ, and degraded. A total of 15 patients completed the study. Notably, the analysis of adverse events demonstrated no dose-dependent effect of buntanetap compared to placebo, affirming the drug’s safety and tolerability. Furthermore, multiparameter modeling of APP kinetics provided additional evidence for dose-dependent lowering of APP production by buntanetap. A model that included the pre-drug lumbar CSF concentration as a covariate showed statistical significance between the placebo and 120, 180 mg per day buntanetap groups, suggesting a drug effect on lowering APP production. In general, buntanetap lowered the rate of translation, the maximum concentration (Cmax), lengthened the Tmax, and decreased the area under the curve (AUC). It is important to note that the results were not statistically significant (other than the difference between placebo and 120 and 180 mg mentioned above) due to a very small number of patients; however, the demonstrated trend fully mirrors the mechanism of action of buntanetap as a translational inhibitor of APP.
Buntanetap (formerly known as Posiphen or ANVS401) attacks neurodegeneration by inhibiting the formation of multiple neurotoxic proteins - amyloid beta, tau, alpha synuclein, and TDP43 - thereby improving synaptic transmission, axonal transport and neuroinflammation. Dysregulation of these pathways has been shown to be the cause of nerve cell degeneration and ultimately death. By attacking these pathways, buntanetap has the ability to reverse neurodegeneration in Alzheimer’s Disease.
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This press release contains "forward-looking" statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The Company advises caution in reliance on forward-looking statements. Forward-looking statements include, without limitation, the Company's plans related to clinical trials. These statements involve known and unknown risks, uncertainties and other factors that may cause actual results to differ materially from those implied by forward-looking statements, including regarding patient enrollment, the effectiveness of buntanetap and the timing, effectiveness, and anticipated results of the Company's clinical trials evaluating the efficacy, safety, and tolerability of buntanetap. See also additional risk factors set forth in the Company's periodic filings with the SEC, including, but not limited to, those risks and uncertainties listed in the section entitled "Risk Factors," in the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the SEC. All forward-looking statements in this press release are based on information available to the Company as of the date of this filing. The Company expressly disclaims any obligation to update or alter its forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable law.
Maria Maccecchini, Ph.D.