Annovis Publishes Phase 2/3 Alzheimer's Trial Results in Nature Portfolio

Rhea-AI Summary

Annovis (NYSE: ANVS) published Phase 2/3 results for oral buntanetap in Nature NPJ Dementia showing dose-dependent cognitive improvement in pTau217-positive mild AD patients and biomarker reductions. The randomized 12-week trial (351 patients) found buntanetap safe and well-tolerated, including in ApoE4 carriers. The company is advancing a pivotal Phase 3 in early AD (MMSE 20–28), now ~80% enrolled.

Biomarker changes included lower TDP-43, tau, NfL and reduced inflammatory markers, supporting potential disease-modifying activity; Phase 3 will evaluate effects at 6 and 18 months.

Positive

• Dose-dependent cognitive improvement in pTau217-positive mild AD
• Biomarker reductions: TDP-43, tau, and neurofilament light chain
• Reduced neuroinflammation markers: IL-5, IL-6, S100A12, IFN-γ, IGF1R
• Safety maintained in ApoE4 carriers versus non-carriers and placebo
• Pivotal Phase 3 for early AD nearing completion with 80% enrolled

Negative

• Phase 2/3 treatment duration was short at 12 weeks
• Primary cognitive benefit reported in pTau217-positive mild AD subgroup only
• Phase 3 pivotal trial results are not yet available or confirmed

News Market Reaction – ANVS

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$69.06M Market Cap

0.1x Rel. Volume

In the Apr 28 session, ANVS declined 2.12%, reflecting a moderate negative market reaction. Our momentum scanner triggered 3 alerts that day, indicating moderate trading interest and price volatility.

Data tracked by StockTitan Argus on the day of publication.

Market Context

This announcement highlights peer-reviewed Phase 2/3 Alzheimer’s results showing cognitive benefits ...

Analysis

This announcement highlights peer-reviewed Phase 2/3 Alzheimer’s results showing cognitive benefits and biomarker improvements in pTau217-positive patients, alongside confirmation that a pivotal Phase 3 trial is about 80% enrolled. In context of prior DSMB clearance and FDA alignment on Phase 3 design, the publication further supports buntanetap’s mechanism. Investors may watch upcoming 6‑ and 18‑month Phase 3 readouts as key efficacy and disease-modifying milestones.

Key Figures

Phase 2/3 sample size: 351 patients Treatment duration: 12 weeks Dose levels: 7.5 mg, 15 mg, 30 mg +5 more

8 metrics

Phase 2/3 sample size 351 patients Mild to moderate Alzheimer’s disease study

Treatment duration 12 weeks Phase 2/3 buntanetap trial

Dose levels 7.5 mg, 15 mg, 30 mg Randomized, double-blind, placebo-controlled trial

High dose tested 30 mg Showed consistent treatment effect across patient subgroups

Early AD MMSE range 21–24 pTau217-positive mild Alzheimer’s subgroup

Phase 3 MMSE range 20–28 Ongoing pivotal early Alzheimer’s trial

Phase 3 enrollment 80% Pivotal early Alzheimer’s study nearing full enrollment

Efficacy timepoints 6 and 18 months Phase 3 symptomatic and disease-modifying assessments

Previous Clinical trial Reports

5 past events · Latest: Feb 12 (Positive)

Same Type Pattern 5 events

Date	Event	Sentiment	24h Move	Catalyst
Feb 12	Phase 3 safety update	Positive	+2.5%	DSMB cleared pivotal Phase 3 Alzheimer’s trial to continue without changes.
Nov 18	Regulatory alignment	Positive	+11.2%	FDA Type C meeting scheduled for PDD and reaffirmed Phase 3 AD alignment.
Nov 06	Phase 3 progress	Positive	-2.5%	All 84 AD Phase 3 sites activated and trial 25% complete toward 760 patients.
Feb 05	Phase 3 initiation	Positive	+0.0%	Pivotal Phase 3 AD study initiated after positive Phase 2/3 data and financing.
Jul 02	PD Phase III data	Positive	+76.1%	Phase III Parkinson’s data showed dose-dependent, significant motor and cognitive gains.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Pattern Detected

Clinical trial updates have usually been received positively, with several past Alzheimer’s and Parkinson’s data releases producing double‑digit gains, though one Phase 3 progress update drew a mild negative reaction.

Recent Company History

Over the past two years, Annovis has repeatedly used clinical milestones to advance buntanetap. Prior events include DSMB approval to continue the pivotal Alzheimer’s Phase 3 (Feb 12, 2026), FDA alignment on trial design and dual NDA paths (Nov 18, 2025), and activation of all 84 Phase 3 sites with the study 25% complete (Nov 6, 2025). Earlier, the company initiated the pivotal Phase 3 and shared positive Phase 2/3 Alzheimer’s and Phase 3 Parkinson’s data. Today’s Nature Portfolio publication fits this sequence by reinforcing the scientific basis for the ongoing Phase 3 program.

Key Terms

pTau217, adas-cog11, mmse, apoe4, +3 more

7 terms

pTau217 medical

"Study analyses revealed statistically significant, dose-dependent improvements in cognition, as measured by ADAS-Cog11, in pTau217 biomarker-positive patients"

ptau217 is a specific form of the brain protein tau that carries a small chemical tag at a particular spot (position 217) and can be measured in blood or spinal fluid as a signal of Alzheimer’s disease. It matters to investors because a reliable early signal — like a smoke alarm for brain changes — can speed drug trials, enable earlier diagnosis and create markets for tests and treatments, affecting the value of biotech and diagnostic companies.

adas-cog11 medical

"dose-dependent improvements in cognition, as measured by ADAS-Cog11, in pTau217 biomarker-positive patients"

A 11-item cognitive test used in Alzheimer’s clinical trials to measure thinking, memory, language and orientation skills; higher scores typically indicate worse impairment. Think of it as a standardized report card that tracks whether a patient’s cognitive abilities are declining, stable, or improving over time. Investors watch ADAS‑Cog11 results because changes on this scale are often used by researchers and regulators to judge a drug’s effectiveness and can strongly influence trial outcomes, approval chances and a company’s valuation.

mmse medical

"patients with mild AD (MMSE 21–24). Moreover, at the 30 mg dose, buntanetap"

The Mini-Mental State Examination (MMSE) is a short, standardized test doctors use to measure basic memory, attention, language and thinking skills, typically scored numerically to indicate cognitive function. Investors should care because MMSE scores are often used to define who can join clinical trials, assess whether a drug or device changes cognition, and influence regulatory decisions and market potential—think of it as a quick health meter that helps determine a treatment’s effectiveness and target patient group.

apoe4 medical

"safety was also assessed in ApoE4 carriers, the most genetically at-risk population for AD"

APOE4 is a specific version of the APOE gene that increases the risk of developing Alzheimer’s disease and can influence how people respond to certain treatments. For investors, APOE4 matters because its prevalence in patient groups can shape clinical trial results, regulatory decisions and market size for therapies—like knowing a neighborhood’s weather pattern affects how many umbrellas a seller should stock.

tdp-43 medical

"Biomarker analyses further revealed reductions in neurotoxic proteins TDP-43 and tau, in the markers of neuroinflammation"

TDP-43 is a protein inside cells that helps regulate how genetic instructions are used; when it misfolds or accumulates into clumps in brain or spinal cord cells, it is linked to neurodegenerative conditions like ALS and some dementias. For investors, TDP-43 matters because it is a clear biological target for diagnostics and therapies—detecting or stopping its abnormal behavior could change patient care and create commercial value, similar to fixing a faulty part in a complex machine.

neurofilament light chain medical

"as well as in the marker of neurodegeneration, neurofilament light chain (NfL), pointing to potential disease-modifying activity."

Neurofilament light chain is a protein released into cerebrospinal fluid and blood when nerve cells are damaged, acting like a measurable “leak” that signals injury to the brain or spinal cord. For investors, it matters because rising or falling levels can serve as an objective readout in clinical trials and disease monitoring, helping assess whether a drug or therapy is slowing nerve damage and reducing development or commercial risk.

randomized, double-blinded, placebo-controlled medical

"The Phase 2/3 study (NCT05686044) was a randomized, double-blinded, placebo-controlled trial evaluating three doses"

A randomized, double-blinded, placebo-controlled trial is a clinical study where participants are assigned by chance to receive either the experimental treatment or an inactive dummy (placebo), and neither the participants nor the researchers know who receives which until the study ends. This design reduces bias and chance effects—like flipping a coin and keeping the result hidden—so investors can trust the study’s evidence about a drug’s effectiveness and better assess regulatory, approval and commercial risk.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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Add on Google Not now

• Buntanetap improved cognition in pTau217-positive early AD patients
• The drug reduced neurotoxic proteins as well as biomarkers of neuroinflammation and neurodegeneration
• Buntanetap was safe and well-tolerated, including in ApoE4 carriers
• Phase 2/3 findings support ongoing pivotal Phase 3 study in early AD, with 80% patients enrolled to date
  
  

MALVERN, Pa., April 28, 2026 (GLOBE NEWSWIRE) -- Annovis Bio, Inc. (NYSE: ANVS) (“Annovis” or the “Company”), a Phase 3 clinical-stage biotechnology company developing the investigational oral therapy, buntanetap, for neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), today announced a new publication titled “Buntanetap treatment in mild to moderate Alzheimer’s disease: phase 2/3 study” in a peer-reviewed journal Nature NPJ Dementia.

The Phase 2/3 study (NCT05686044) was a randomized, double-blinded, placebo-controlled trial evaluating three doses of buntanetap (7.5 mg, 15 mg, and 30 mg) over 12 weeks in 351 patients with mild to moderate AD. The study demonstrated that buntanetap was safe and well-tolerated across all disease stages and dose levels. Notably, safety was also assessed in ApoE4 carriers, the most genetically at-risk population for AD, with no increase in adverse events compared to non-carriers and to placebo. Given buntanetap's distinct mechanism of action, the drug was also well-tolerated when taken alongside approved symptomatic therapies, allowing patients to maintain their existing medication regimens without the need for discontinuation.

Study analyses revealed statistically significant, dose-dependent improvements in cognition, as measured by ADAS-Cog11, in pTau217 biomarker-positive patients with mild AD (MMSE 21–24). Moreover, at the 30 mg dose, buntanetap demonstrated a consistent treatment effect across all analyzed patient groups when stratified by age, body mass index, sex, ethnicity, ApoE4 carrier status, and concomitant medication use, with favorable effects versus placebo observed across each of these groups.

Biomarker analyses further revealed reductions in neurotoxic proteins TDP-43 and tau, in the markers of neuroinflammation, including IL-5, IL-6, S100A12, IFN-γ, and IGF1R, as well as in the marker of neurodegeneration, neurofilament light chain (NfL), pointing to potential disease-modifying activity. Importantly, the same trends were observed in plasma samples from patients with moderate AD, further supporting buntanetap's mechanism of action.

"The publication of these results in a peer-reviewed journal marks an important step in the scientific validation of buntanetap," said Cheng Fang, Ph.D., Senior Vice President, Research & Development. "The data reinforce what we have seen across multiple studies: buntanetap addresses the underlying pathology of AD with a safety profile that supports its use in a broad, genetically diverse patient population. The treatment effect we observed in biomarker-confirmed early AD patients provides strong scientific rationale as we advance our drug candidate through a pivotal Phase 3 study."

Buntanetap is currently being investigated in a pivotal Phase 3 clinical trial enrolling pTau217 biomarker-positive patients with early AD (MMSE 20–28) (NCT06709014). The trial is designed to replicate and extend the findings of the Phase 2/3 study, evaluating the efficacy of buntanetap at 6 and 18 months, measuring symptomatic and potential disease-modifying benefits, respectively. The study is nearing full enrollment, with 80% of patients already enrolled.

About Annovis
Headquartered in Malvern, Pennsylvania, Annovis Bio, Inc. (NYSE: ANVS) is a Phase 3 clinical-stage biotechnology company developing treatments for neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). The Company's lead drug candidate, buntanetap (formerly posiphen), is an investigational once-daily oral therapy that inhibits the translation of multiple neurotoxic proteins, including APP and amyloid beta, tau, alpha-synuclein, and TDP-43, through a specific RNA-targeting mechanism of action. By addressing the underlying causes of neurodegeneration, Annovis aims to halt disease progression and improve cognitive and motor functions in 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.

Forward-Looking Statements
This press release contains forward-looking statements under the Securities Act of 1933 and the Securities Exchange Act of 1934, as amended. Actual results may differ due to various risks and uncertainties, including those outlined in the Company’s SEC filings under “Risk Factors” in its Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. The Company undertakes no obligation to update forward-looking statements except as required by law.

Contact Information:
Annovis Bio Inc.
101 Lindenwood Drive
Suite 225
Malvern, PA 19355
www.annovisbio.com

Investor Contact:
Alexander Morin, Ph.D.
Director, Strategic Communications
Annovis Bio
ir@annovisbio.com

FAQ

What did Annovis (ANVS) report about buntanetap efficacy in the April 28, 2026 publication?

Buntanetap showed dose-dependent cognitive improvement in pTau217-positive mild AD patients. According to the company, the randomized 12-week Phase 2/3 trial (351 patients) found statistically significant ADAS-Cog11 benefits at higher doses in biomarker-confirmed early AD.

Is buntanetap safe for ApoE4 carriers according to Annovis (ANVS)?

Yes—buntanetap was well-tolerated in ApoE4 carriers with no increased adverse events versus non-carriers or placebo. According to the company, safety was consistent across doses and when used with approved symptomatic AD therapies.

Which biomarkers did Annovis (ANVS) report buntanetap affected in the Phase 2/3 study?

Buntanetap reduced TDP-43, tau, NfL and several inflammatory markers including IL-5 and IL-6. According to the company, plasma and CSF biomarker analyses showed declines suggesting potential disease-modifying activity.

How does the Phase 3 Annovis (ANVS) study build on the Phase 2/3 findings and what is its enrollment status?

The Phase 3 will evaluate bunatnetap at 6 and 18 months for symptomatic and disease-modifying effects. According to the company, the pivotal trial is near full enrollment, with about 80% of patients enrolled.

Did Annovis (ANVS) report buntanetap working across demographic and concomitant medication subgroups?

Yes—at the 30 mg dose buntanetap showed a consistent treatment effect across age, sex, BMI, ethnicity, ApoE4 status, and concomitant medication use. According to the company, favorable effects versus placebo were observed across those subgroups.