A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study of Buntanetap in Participants With Mild to Moderate Alzheimer's Disease

The purpose of this study is to measure efficacy and safety of three different doses of buntanetap/Posiphen compared with placebo in participants with mild to moderate Alzheimer's disease.
Study details include:
The double-blind treatment duration will include a screening period of up to 42 days followed by 12 weeks of treatment at home.
The study duration will be 4-5 months. There will be 4 in-clinic visits and 1 phone call.

Start Date01 Apr 2023

Sponsor / Collaborator

Annovis Bio, Inc.

NCT05357989 / CompletedPhase 3

A 6-month Prospective, Randomized, Double-blind, Placebo-controlled Clinical Trial Investigating the Efficacy, Safety, and Tolerability of Two Different Doses of Buntanetap or Placebo in Patients With Early Parkinson's Disease

The purpose of this study is to measure safety and efficacy of buntanetap/posiphen capsules compared with placebo capsules in participants with early PD.
Study details include:
The study duration will be up to 7-8 months.
The double-blind treatment duration will be up to 6 months.
There will be 5 in-clinic visits and 7 phone calls

Start Date03 Aug 2022

Sponsor / Collaborator

Annovis Bio, Inc.

[+1]

NCT04524351 / CompletedPhase 1/2

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of Posiphen® in Subjects With Early Alzheimer's Disease (AD) or Early Parkinson's Disease (PD)

Annovis is conducting a clinical study to investigate Posiphen in patients with Early Alzheimer's Disease (AD) and Early Parkinson's Disease (PD). Investigators are looking to recruit 68 patients in two parts of the study. In Part one of the study Investigators will recruit 14 AD and 14 PD patients who will either receive placebo (an inert pill which looks like the study drug) or the study drug Posiphen, both taken daily. In Part two of the study Investigators will recruit 40 PD patients who will receive different strengths of the study drug Posiphen taken daily. Patients will be required to come to the site for 3 face to face visits and have 4 phone calls, tests include but are not limited to, blood and CSF (spinal fluid) sampling, cognitive assessments, clinical examinations and laboratory safety tests. Primarily the Investigators are looking for the safety and tolerability of Posiphen, although Investigators will also evaluate the activity of Posiphen by a number of different biomarkers measuring pathway and target engagements.

Start Date14 Aug 2020

Sponsor / Collaborator

Annovis Bio, Inc.

[+1]

100 Clinical Results associated with Buntanetap

100 Translational Medicine associated with Buntanetap

100 Patents (Medical) associated with Buntanetap

Literatures (Medical) associated with Buntanetap

01 Apr 2024·SLAS Discovery

Real-time thiol detection in iPSC-derived neuron cultures using SemKur-IM, a novel fluorescent dithio probe

Article

Author: Kurfis, Jayson ; Hendrickson, Michael ; Alvarez, Roxanne ; Sem, Daniel S

Neurological disorders associated with inflammation and oxidative stress show reduced glutathione (GSH) levels in the human brain. Drug discovery efforts and pharmacological studies would benefit from tools (e.g. chemical probes) that detect changes to oxidative stress, from the perspective of physiologically-relevant reporters like cellular thiols, including GSH. To this end, we have developed a fluorescence visualization assay using iPSC-derived cortical glutamatergic neurons that were loaded with 25 μM of a novel thiol-detection fluorescent probe, SemKur-IM. This probe enables visualization of cellular thiol level changes in the neuronal somas and neurites, in response exposure to N-acetyl-cysteine (NAC). Cellular thiol redox state was observed to change, based on an increase in green fluorescence (485 nm excitation maximum; 525 nm emission maximum) due to changes in thiol levels, from 0 to 40 mM. Interestingly, prior to treatment with NAC, cells did not appear to have significant levels of reduced thiols. Our studies demonstrate the utility of SemKur-IM in the detection of thiol levels in live cells in response to chemical exposures, such as from drugs that return the cell to a healthier reduced state. An initial application to screening the effects of an Alzheimer's disease drug candidate, Posiphen, using fluorescence cell sorting is presented. Other potential applications include high throughput screening of central nervous system (CNS) drugs thought to work by affecting cellular redox state in neurons.

11 Feb 2022·ACS Pharmacology & Translational Science

In Silico and Ex Vivo Analyses of the Inhibitory Action of the Alzheimer Drug Posiphen and Primary Metabolites with Human Acetyl- and Butyrylcholinesterase Enzymes

Article

Author: Furqan, Tiyyaba ; Hasan Mahmood, Muhammad Sibte ; Greig, Nigel H. ; Batool, Sidra ; Kamal, Mohammad A. ; Tweedie, David

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Ongoing research to develop AD treatments has characterized multiple drug targets including the cholinergic system, amyloid-β peptide, phosphorylated tau, and neuroinflammation. These systems have the potential to interact to either drive or slow AD progression. Promising agents that simultaneously impact many of these drug targets are the AD experimental drug Posiphen and its enantiomer phenserine that, currently, are separately being evaluated in clinical trials. To define the cholinergic component of these agents, the anticholinesterase activities of a ligand dataset comprising Posiphen and primary metabolites ((+)-N1-norPosiphen, (+)-N8-norPosiphen, and (+)-N1,N8-bisnorPosiphen) were characterized and compared to those of the enantiomer phenserine. The "target" dataset involved the human cholinesterase enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Binding interactions between the ligands and targets were analyzed using Autodock 4.2. The computationally determined inhibitory action of these ligands was then compared to ex vivo laboratory-measured values versus human AChE and BChE. While Posiphen lacked AChE inhibitory action, its major and minor metabolites (+)-N1-norPosiphen and (+)-N1,N8-bisnorPosiphen, respectively, possessed modest AChE inhibitory activity, and Posiphen and all metabolites lacked BChE action. Phenserine, as a positive control, demonstrated AChE-selective inhibitory action. In light of AChE inhibitory action deriving from a major and minor Posiphen metabolite, current Posiphen clinical trials in AD and related disorders should additionally evaluate AChE inhibition; particularly if Posiphen should be combined with a known anticholinesterase, since this drug class is clinically approved and the standard of care for AD subjects, and excessive AChE inhibition may impact drug tolerability.

01 Feb 2021·Alzheimer's & DementiaQ1 · MEDICINE

Targeting increased levels of APP in Down syndrome: Posiphen‐mediated reductions in APP and its products reverse endosomal phenotypes in the Ts65Dn mouse model

Q1 · MEDICINE

Article

Author: Overk, Cassia ; Chen, Xu‐Qiao ; Pearn, Matthew L. ; Salehi, Ahmad ; Nguyen, Phuong D. ; Maccecchini, Maria ; Mobley, William C. ; Kleschevnikov, Alexander M.

AbstractObjectiveRecent clinical trials targeting amyloid beta (Aβ) and tau in Alzheimer's disease (AD) have yet to demonstrate efficacy. Reviewing the hypotheses for AD pathogenesis and defining possible links between them may enhance insights into both upstream initiating events and downstream mechanisms, thereby promoting discovery of novel treatments. Evidence that in Down syndrome (DS), a population markedly predisposed to develop early onset AD, increased APP gene dose is necessary for both AD neuropathology and dementia points to normalization of the levels of the amyloid precursor protein (APP) and its products as a route to further define AD pathogenesis and discovering novel treatments.BackgroundAD and DS share several characteristic manifestations. DS is caused by trisomy of whole or part of chromosome 21; this chromosome contains about 233 protein‐coding genes, including APP. Recent evidence points to a defining role for increased expression of the gene for APP and for its 99 amino acid C‐terminal fragment (C99, also known as β‐CTF) in dysregulating the endosomal/lysosomal system. The latter is critical for normal cellular function and in neurons for transmitting neurotrophic signals.New/updated hypothesisWe hypothesize that the increase in APP gene dose in DS initiates a process in which increased levels of full‐length APP (fl‐APP) and its products, including β‐CTF and possibly Aβ peptides (Aβ42 and Aβ40), drive AD pathogenesis through an endosome‐dependent mechanism(s), which compromises transport of neurotrophic signals. To test this hypothesis, we carried out studies in the Ts65Dn mouse model of DS and examined the effects of Posiphen, an orally available small molecule shown in prior studies to reduce fl‐APP. In vitro, Posiphen lowered fl‐APP and its C‐terminal fragments, reversed Rab5 hyperactivation and early endosome enlargement, and restored retrograde transport of neurotrophin signaling. In vivo, Posiphen treatment (50 mg/kg/d, 26 days, intraperitoneal [i.p.]) of Ts65Dn mice was well tolerated and demonstrated no adverse effects in behavior. Treatment resulted in normalization of the levels of fl‐APP, C‐terminal fragments and small reductions in Aβ species, restoration to normal levels of Rab5 activity, reduced phosphorylated tau (p‐tau), and reversed deficits in TrkB (tropomyosin receptor kinase B) activation and in the Akt (protein kinase B [PKB]), ERK (extracellular signal‐regulated kinase), and CREB (cAMP response element–binding protein) signaling pathways. Remarkably, Posiphen treatment also restored the level of choline acetyltransferase protein to 2N levels. These findings support the APP gene dose hypothesis, point to the need for additional studies to explore the mechanisms by which increased APP gene expression acts to increase the risk for AD in DS, and to possible utility of treatments to normalize the levels of APP and its products for preventing AD in those with DS.Major challenges for the hypothesisImportant unanswered questions are: (1) When should one intervene in those with DS; (2) would an APP‐based strategy have untoward consequences on possible adaptive changes induced by chronically increased APP gene dose; (3) do other genes present on chromosome 21, or on other chromosomes whose expression is dysregulated in DS, contribute to AD pathogenesis; and (4) can one model strategies that combine the use of an APP‐based treatment with those directed at other AD phenotypes including p‐tau and inflammation.Linkage to other major theoriesThe APP gene dose hypothesis interfaces with the amyloid cascade hypothesis of AD as well as with the genetic and cell biological observations that support it. Moreover, upregulation of fl‐APP protein and products may drive downstream events that dysregulate tau homeostasis and inflammatory responses that contribute to propagation of AD pathogenesis.

101

News (Medical) associated with Buntanetap

22 Oct 2024

·www.globenewswire.com

Annovis to Highlight Buntanetap's Alzheimer's Research Progress with Presentations at CTAD 2024

MALVERN, Pa., Oct. 22, 2024 (GLOBE NEWSWIRE) -- via IBN – Annovis Bio Inc. (NYSE: ANVS) ("Annovis" or the "Company"), a late-stage clinical drug platform company developing transformative therapies for neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), today announced it will present two scientific posters at the 17th Clinical Trials on Alzheimer’s Disease (CTAD) conference. The event will be held from October 29 to November 1, 2024, in Madrid, Spain. Dr. Maria Maccecchini, President and CEO of Annovis Bio, will present the following posters: Poster LP023 Title: Efficacy of Buntanetap in Early AD and APOE4 Phase 2/3 Alzheimer’s Patients. Date: Tuesday, October 29, 3:00 PM – Wednesday, October 30, 5:00 PM (CET). Poster LP074 Title: Biomarker Data Showed Buntanetap Reduced Neurotoxic Proteins, Improved Axonal Integrity, Reduced Inflammation, and Neuronal Functions in Alzheimer’s Clinical Studies. Date: Thursday, October 31, 7:15 AM – 5:00 PM (CET). The posters will be available on Annovis’ website following the conclusion of the conference. About CTAD 2024 CTAD 2024 brings together leaders from the Alzheimer’s research community, including pharmaceutical companies, academic research centers, and patient advocacy groups. The conference serves as a platform for discussing innovative avenues for the treatment of Alzheimer’s disease. For more information about the conference, please visit the CTAD Website. About Annovis Bio, Inc. Headquartered in Malvern, Pennsylvania, Annovis Bio Inc. is dedicated to addressing neurodegeneration in diseases such as AD and PD. The company’s innovative approach targets multiple neurotoxic proteins, aiming to restore brain function and improve the quality of life for patients. For more information, visit www.annovisbio.com and follow us on LinkedIn, YouTube, and X. Investor Alerts Interested investors and shareholders are encouraged to sign up for press releases and industry updates by registering for Email Alerts at https://www.annovisbio.com/email-alerts. Additionally, we invite you to explore our updated investor website, which provides comprehensive access to company news, financial reports, and other key information. Forward-Looking Statements 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. These statements include, but are not limited to, the Company's plans related to clinical trials. Forward-looking statements are based on current expectations and assumptions and are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Such risks and uncertainties include, but are not limited to, those related to 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. Additional risk factors are detailed in the Company's periodic filings with the SEC, including those listed in the "Risk Factors" section of the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. All forward-looking statements in this press release are based on information available to the Company as of the date of this release. The Company expressly disclaims any obligation to update or revise its forward-looking statements, whether as a result of new information, future events, or otherwise, except as required by law. Contact Information: Annovis Bio Inc. 101 Lindenwood Drive Suite 225 Malvern, PA 19355 www.annovisbio.com Investor Contact: Scott McGowan InvestorBrandNetwork (IBN) Phone: 310.299.1717www.annovisbio.com/investors-relations IR@annovisbio.com

18 Oct 2024

·www.globenewswire.com

FDA Clears Annovis to Launch Pivotal Phase 3 Alzheimer’s Studies, Paving the Way to NDAs

Oct. 15, 2024 -- via IBN – Annovis Bio Inc. (NYSE: ANVS) (“Annovis” or the “Company”), a late-stage clinical drug platform company developing transformative therapies for neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), announced today the successful outcome of the End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) on October 10, 2024. During the meeting, the FDA granted clearance to proceed with pivotal Phase 3 studies, based on the Company's Phase 2/3 clinical data showing symptomatic improvement in early AD patients. Annovis and the FDA have now aligned on a development path for buntanetap towards the filing of New Drug Applications (NDAs), one for short-term and one for long-term efficacy. The Phase 3 program will investigate buntanetap in patients with early AD and will consist of two trials: a 6-month study aimed at confirming buntanetap’s symptomatic effects and an 18-month study designed to demonstrate potential disease-modifying effects. While the Company plans to run both studies, the completion of a well-designed and well-executed 6-month trial may be sufficient to support an NDA filing, potentially within one year of the study’s initiation. Additionally, the FDA raised no concerns about the Company’s data on buntanetap’s safety, including liver enzymes, drug interactions, dose selection, pharmacokinetics, and population pharmacokinetics and confirmed that development can proceed using the new crystal form of buntanetap. “We are now ready to move into the highly anticipated Phase 3 stage,” said Maria Maccecchini, Ph.D., Founder, President, and CEO of Annovis Bio. “Our priority is to bring the treatment to patients as early as possible, and we are committed to ensuring the next clinical trial is executed at the highest standards to attain an expedited NDA submission. Our team is already preparing for trial initiation early next year and will continue to keep you updated as we advance towards our goal.” Headquartered in Malvern, Pennsylvania, Annovis Bio Inc. is dedicated to addressing neurodegeneration in diseases such as AD and PD. The company’s innovative approach targets multiple neurotoxic proteins, aiming to restore brain function and improve the quality of life for patients. For more information, visit www.annovisbio.com and follow us on LinkedIn, YouTube, and X. The content above comes from the network. if any infringement, please contact us to modify.

NDA

03 Oct 2024

·www.globenewswire.com

Annovis Bio Inc. (NYSE: ANVS) Leading Way in Development of Safe, Effective Drugs for Neurodegenerative Diseases

NEW YORK, Oct. 03, 2024 (GLOBE NEWSWIRE) -- NetworkNewsAudio – Annovis Bio Inc. (NYSE: ANVS) announces the availability of a broadcast titled, “Transforming Alzheimer’s Treatment: Innovative Combinations to Boost Cognition.” To hear the AudioPressRelease, please visit: The NetworkNewsAudio To view the full editorial, please visit: https://nnw.fm/ZIUid Annovis Bio Inc. is at the forefront of the movement to develop new safe and effective drugs for neurodegenerative diseases, including AD. The company has long pursued the goal to improve the health of nerve cells and, in the process, improve cognition in neurodegenerative disorders. The company’s lead drug candidate, buntanetap, has completed late-stage AD and PD clinical trials and was shown to be efficacious in both indications. Earlier this year, Annovis announced promising results from its phase 2/3 clinical trial of buntanetap as an oral therapy for early AD. The study involved 353 patients and assessed buntanetap’s efficacy on top of standard of care medications as well as its safety. About Annovis Bio Inc. Annovis Bio, headquartered in Malvern, Pennsylvania, is dedicated to addressing neurodegeneration in diseases such as Alzheimer’s disease (“AD”) and Parkinson’s disease (“PD”). The company’s innovative approach targets multiple neurotoxic proteins, aiming to restore brain function and improve the quality of life for patients. For more information, about the company, please visit www.AnnovisBio.com. NOTE TO INVESTORS: The latest news and updates relating to ANVS are available in the company’s newsroom at https://ibn.fm/ANVS http://nnw.fm/ANVS About NetworkNewsWire NetworkNewsWire (“NNW”) is a specialized communications platform with a focus on financial news and content distribution for private and public companies and the investment community. It is one of 60+ brands within the Dynamic Brand Portfolio @ IBN that delivers: (1) access to a vast network of wire solutions via InvestorWire to efficiently and effectively reach a myriad of target markets, demographics and diverse industries; (2) article and editorial syndication to 5,000+ outlets; (3) press release enhancement to ensure maximum impact; (4) social media distribution via IBN to millions of social media followers; and (5) a full array of tailored corporate communications solutions. With broad reach and a seasoned team of contributing journalists and writers, NNW is uniquely positioned to best serve private and public companies that want to reach a wide audience of investors, influencers, consumers, journalists and the general public. By cutting through the overload of information in today’s market, NNW brings its clients unparalleled recognition and brand awareness. NNW is where breaking news, insightful content and actionable information converge. For more information, please visit https://www.NetworkNewsWire.com Please see full terms of use and disclaimers on the NetworkNewsWire website applicable to all content provided by NNW, wherever published or republished: https://www.NetworkNewsWire.com/Disclaimer NetworkNewsWireNew York, NY www.NetworkNewsWire.com 212.418.1217 Office Editor@NetworkNewsWire.com NetworkNewsWire is powered by IBN

Clinical Result

100 Deals associated with Buntanetap

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15317

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 3	US	Annovis Bio, Inc.	01 Apr 2023
Parkinson Disease	Phase 3	EU	Annovis Bio, Inc.	08 Feb 2023
Young onset Parkinson disease	Phase 3	PL	Annovis Bio, Inc.	03 Aug 2022
Young onset Parkinson disease	Phase 3	ES	Annovis Bio, Inc.	03 Aug 2022
Young onset Parkinson disease	Phase 3	US	Annovis Bio, Inc.	03 Aug 2022
Young onset Parkinson disease	Phase 3	IT	Annovis Bio, Inc.	03 Aug 2022
Young onset Parkinson disease	Phase 3	DE	Annovis Bio, Inc.	03 Aug 2022
Young onset Parkinson disease	Phase 3	HU	Annovis Bio, Inc.	03 Aug 2022
Cognitive Dysfunction	Phase 2	US	Annovis Bio, Inc.	26 May 2009
Lewy Body Disease	Phase 2	-	Annovis Bio, Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05357989 (Biospace) Manual	Phase 3	Parkinson Disease	-	Buntanetap	(bygmbqefab) = 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 abrdrtovom (lrotawxfuj ) View more	Positive	02 Jul 2024
				Placebo
GlobeNewswire Manual	Not Applicable	Alzheimer Disease	-	Buntanetap 15mg	(ynctqxjqly) = wqwnllfkpd fhivbshhjp (irowpbvbja )	Positive	11 Jun 2024
				Placebo	(ynctqxjqly) = qkleldivlc fhivbshhjp (irowpbvbja )
NCT05686044 (Biospace) Manual	Phase 2/3	Alzheimer Disease	325	Buntanetap 7.5 mg	(dvendjiwzo) = eudvnaejtv frijebzbze (dwbktbcnsq, 0.87)	Positive	29 May 2024
				Buntanetap 15 mg	(dvendjiwzo) = zblooubtiv frijebzbze (dwbktbcnsq, 0.81)
NCT05686044 (Biospace) Manual	Phase 2/3	Alzheimer Disease	107	Buntanetap	(eudhcifkig) = hxidaqmngm egihilhllz (yfibairuea )	Positive	30 Oct 2023
NCT04524351 (CTgov)	Phase 1/2	Young onset Parkinson disease \| Alzheimer Disease	75	Posiphen (Posiphen, 80mg (Parkinson's Participants))	yubhfjuymd(vthmxcwxgc) = xfitvkhlbf lfkqeduawa (btynphaqnf, tsyhqivwng - nbwzcizuso) View more	-	28 Feb 2023
				Posiphen (Posiphen, 40mg (Parkinson's Participants))	yubhfjuymd(vthmxcwxgc) = furopziham lfkqeduawa (btynphaqnf, xeietgghip - mdhrozxsfy) View more
NCT02925650 (CTAD2022)	Phase 1	Mild cognitive disorder CSF Aβ42/40	19	Posiphen	lavroqeifl(goghduvrzc) = 8/19 participants reported headache either during CSF sampling (4),after the procedure (3), or both (1). 5 had blood patches with rapid resolution of headache. oxmwjpaubo (eohjdgjwog )	-	03 Dec 2022

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