Annovis Bio Inc (ANVS)

Agreed. So far, your estimation of 5% every two weeks has been spot on...so we should have full enrollment by the end of June. Having said that, I should emphasize that timing is not as important as the quality of the patient population that is enrolled in the trials.

According to the January 28th webinar, Annovis is following the same inclusion/exclusion process that was used by Eisai and Eli Lilly...which is why, according to the CEO, that it is taking longer than they had anticipated. Think about that for a minute...Esai and Eli Lilly have the only two AD drugs that received FDA approval for disease modification. So, rather than creating a new type of P3 study - like Anavex did - Annovis is playing it smart and duplicating what has already proven to be acceptable in the eyes of the FDA.

The CEO also said that the patients that had p-tau and other (AD) proteins in their blood samples are the ones that had the best results to their drug...which is another reason why I'm confident that they will be successful in reaching their endpoints.

Below is a very good article on why clinical trials have failed in the past. Enjoy.

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Why Do So Many Alzheimer's Clinical Trials Fail?
Written by RJ Tesi, MD, CEO and chief medical officer, INmune Bio

Since 2003, 98% of Alzheimer’s disease (AD) treatment clinical trials have failed, showing a disappointing 2% success rate (aducanumab included). While clinical trials are difficult in and of themselves, AD is a complicated disease, and there are common issues across these particular trials that have caused so many failed attempts.
There are also ways to manage the issues with AD clinical trials and move forward with successful ones. Understanding why AD clinical trials fail and how to best mitigate those failures is vital to the future of AD clinical success. Here are three primary reasons why so many AD clinical trials fail, as well as ways to improve the chance of success.


1) Recruiting the right participants is difficult.

Enrollment of elderly patients with dementia is challenging because it involves the patient’s whole family. Because the evaluation period to determine eligibility for participation in the trial is long and complicated, a patient cannot simply walk in and sign up. They must undergo 30 to 60 days of testing before eligibility is determined. This testing includes cognitive testing and neuroimaging tests such as positron emission tomography (PET) scans and Magnetic resonance imaging (MRI). These tests often happen at different locations over the course of several days. This requires a commitment by the patient, the caregiver, and often the extended family.

Another barrier to recruitment is that while placebo groups are essential for trials, they are off-putting to patients and their families. A patient may undergo one or two months of evaluation to determine eligibility for the clinical trial only to end up in the placebo arm. Even more daunting is that many trials last 18 months or longer. If a patient is assigned to the placebo group, their disease worsens for a year and a half and, at the end, the patient may be too sick to participate in another trial. The sheer possibility of being on placebo makes patients and their families hesitant to enroll. However, it is important to note that the placebo group is necessary in these clinical trials as they ensure accuracy.

Almost all clinical trials in patients with AD are looking for patients with early AD. Yet, in general, patients are diagnosed late in their disease state and are often too far along to participate in a clinical trial. A 2019 study found “diagnostic and care pathways hindered identifying patients with mild-moderate AD, with a lack of up-to-date patient records and data access problems affecting screening.” Early diagnosis starts with the patient inquiry of concern but requires the patient’s medical team to act on that concern. In the past, due to lack of effective therapies, there was little reason for the patient to ask and even less for the physician to act. This is a slowly changing issue, as people learn more about managing the disease and some treatments are becoming available, but more education around the importance of an early diagnosis is needed.

Everyone from the patient to the payer needs to understand the problem can only be solved with their help. A clinical trial is only possible with the right participants in the right stage of their disease with a supportive family or caretakers to help the patient through the process. Providing proper screenings that are rapid, easy and convenient, and diagnoses early is an important first step to solving this issue.


2) Typical trial design is plagued with shortcomings.

There are many issues with how Alzheimer’s clinical trials were designed, including poorly chosen primary clinical outcome measures, insufficient accounting for potential AD subtypes, and the too-late administration of therapeutic interventions.

AD is defined as cognitive decline in patients with amyloid in their brain. This inclusion criteria assumes amyloid is causing a person’s cognitive decline. The standard assumption is that decreasing amyloid will then change the course of the disease. Thus, the 30-year quest to eliminate amyloid has been successful — the current therapies remove amyloid. Unfortunately, the success in removing amyloid did not result in dramatic improvements in cognition.

Preclinical data and human experience now confirm amyloid plays only a small part of the cognitive decline in patients with AD. This focus on decreasing amyloid as the primary clinical outcome measure has been proven to be misplaced, and clinical trial leaders now need to look for other outcome measures that will have a larger impact on stopping cognitive decline.

Another issue has been the old-fashioned trial design used in AD clinical trials. Most AD trials are “all comer” trials. That is, if you carry the diagnosis of AD, you are eligible. Oncology gave up “all comer” trial design two decades ago because it was proven not to work. For example, in breast cancer, if you have a drug that is meant for HER2 positive breast cancer but include all patients with breast cancer, your results will have limited success due to the population not being the right fit. If you only enroll patients with HER2 positive breast cancer, the results will be stronger, even with a smaller trial because you are targeting the correct patient population. The need for personalized and precision treatments has been recognized. In cancer, enrichment criteria are used to match the patient’s disease with the drug’s mechanism of action. As a result, trials are smaller and more successful so that many drugs get approved in oncology faster at lower cost.

The old-fashioned trial design assumed that AD is just one disease. AD is complicated; it is more than a single disease, and the role of amyloid is minimal. The same can be said for tau, which is a protein that is released by dying neurons in the brain. Some believe that tau must be a cause of AD because it is present in the brains of those with AD. However, tau appears when cells die, they do not cause cell death. Clinical trials need to match the patient's specific disease with a therapy, a precision medicine approach that is already standard in oncology. Why is it not done with AD?

Finally, the cognitive scales used in most AD clinical trials have been designed for testing patients with moderate and severe AD, even though clinical trials enroll patients with mild cognitive impairment (MCI) or mild AD. Therefore, the cognitive scales are not “fit for purpose” in determining cognition in patients with early AD. For instance, many trials use ADAS-Cog13, a cognitive test designed for patients with moderate-severe disease. The “13” stands for the number of tests in the scale. For patients with early AD (MCI and mild AD), nine of the 13 elements of the ADAS-Cog evaluation are at “ceiling effect.” A ceiling effect happens when too large a percentage of participants achieve the highest score on a test, this results in the measurement losing its value. Since these tests are meant for patients with a more advanced disease, they are not useful for testing patients with early AD. Thus, the ADAS-Cog13 is really an ADAS-Cog4 (13 tests minus nine tests at ceiling effect equals four valid tests). This is not good enough.

The second issue with cognitive testing is subtle but easy to understand. None of the standard cognitive measurement scales can demonstrate cognitive improvement. That is, they only show stable or worsening cognition. This is a major statistical disadvantage if a therapy actually makes patients better. As researchers are striving to make patients better, not just slow their decline, we need better measures.


3) Scientific approaches for treating AD are outdated.

One of the biggest issues that AD clinical trials have faced is the overreliance on treatments targeting amyloid protein that has given, at best, modest success. At least five other causes of neurodegeneration — neuroinflammation, mitochondrial dysfunction, lysosomal dysfunction, insulin resistance, and lipid abnormalities — drive the disease. Each may work alone, but they most likely work in concert with amyloid. Amyloid is only part of the problem.

Traditionally, researchers viewed nerve cell dysfunction and death (neurodegeneration) as the cause of AD. Now, we understand synaptic function is a key part of the disease. While you cannot “fix” a dead nerve cell, you can repair synaptic dysfunction. Repairing synaptic dysfunction is now a target for the treatment of AD.

More recently, demyelination has been identified as a critical pathology in patients with AD. Myelin pathology is no longer under the exclusive purview of multiple sclerosis. Surprisingly, demyelination may be one of the earliest pathologies in AD. Finally, the number of cells involved in the disease is increasing beyond nerve cells. Microglia and astroglia, the immune cells of the brain, and oligodendrocytes that produce myelin are recognized as major players in the disease and are “drug targets.” This rapidly changing landscape converts simple AD, once thought of as a disease of amyloid, into a complicated disease. There will be no silver bullet.

Given the complexity of AD, researchers must realize monotherapy may not be good enough; complex diseases need complex therapies. The remarkable advances in cancer therapy come from using new drugs in innovative combinations. Combination therapy for treatment of cancer, cardiovascular disease, pulmonary disease, autoimmune diseases, and other complex diseases is the rule. AD will be no exception.

We at INmune Bio believe neuroinflammation is the future target of Alzheimer’s treatment. Cognitive decline is the sum of synaptic dysfunction and nerve cell death, and neuroinflammation is what causes both synaptic dysfunction and nerve cell death. Stopping neuroinflammation solves both problems. Repairing synaptic dysfunction is the most important and fastest strategy to “fix” cognitive decline. Targeting neuroinflammation also will help other strategies work better. [This is exactly what Annovis' drug, Buntanetap, is supposed to target.]


The Real Failure Is When You Stop Trying

Even though so many AD clinical trials have failed, much of the failure has been caused by the industry itself. We must design better and smarter clinical trials in AD. The need is great and the aging population is growing. AD patients and their caregivers and families deserve the best we can give.

By exploring other causes of neurodegeneration and synaptic dysfunction, we can design modern trials utilizing all the best practices that have been successful in the development of drugs for other deadly diseases. Oncology drug development should be our model — the system works. As this new trial implementation begins, there is new hope for ending this devastating disease.



About The Author:
RJ TesiRJ Tesi, MD, is the cofounder and CEO of INmune Bio, a publicly traded clinical-stage biotechnology company developing therapies that target the innate immune system to fight disease. INmune Bio has two product platforms that are both in clinical trials, the DN-TNF product platform and the Natural Killer Cell Priming Platform, which includes INKmune™. From November 2011 to May 2015, Dr. Tesi was CEO, president, and acting chief medical officer of FPRT Bio Inc., a development-stage biotech company formed to develop XPro1595 for the treatment of neurodegenerative disease and other inflammatory diseases.



https://linklock.titanhq.com/analyse?url=https%3A%2F%2Fwww.clinicalleader.com%2Fdoc%2Fwhy-do-so-many-alzheimer-s-clinical-trials-fail-0001&data=eJxVjLEOgjAURb8GtkcKQpGhg4PuhsX18Shp42trWpTg1wsmDiZ3uufcS0q29VTJppGlOE75qND78LJpsKGg4HKn-lYO5_5O3fXW5UnNmjmGNasFBv4qUTkk0kTGerv3_w9PZeb5kbLDKasuW5ZlKYg3lZBZ46jjrm1gDLRjs8IYIAVw6FdAfhttnY6Q4LeCOVrkBBNaBiFE-QG-gkO7

Let's just hope they announce the trial is fully accrued over the next week. Their pace of patient accrual seems to have been steady - even if it is taking much longer than they initially guided.

Exactly five years ago today, Annovis hit their all-time high of $139/share based on a positive study that I listed below. Since then, Annovis has conducted a total of 14 studies...and treated more than 1,200 patients. And, as far as I know, there were absolutely no safety problems from using the drug in all 14 studies.

If you haven't already watched the last two videos in their video library, I strongly encourage you to do so. You'll learn why I believe Annovis will easily hit their primary endpoints for the 6-month and 18-month P3 pivotal trials...which should send their SP beyond $139/share. https://www.annovisbio.com/video-library

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ANVS stock is rocketing higher today, thanks to some optimistic results in its ongoing clinical trial

https://investorplace.com/2021/05/anvs-stock-the-huge-news-sending-annovis-bio-rocketing-200-today/

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Annovis Bio Announces Positive Phase 2 Data - ANVS401 Improves Cognition in Alzheimer's Disease - Patients' Cognition Improved 3.3 Points on ADAS-Cog11

Berwyn, Pennsylvania--(Newsfile Corp. - May 21, 2021) - Annovis Bio Inc. (NYSE American: ANVS), a clinical-stage drug platform company addressing Alzheimer's disease (AD), Parkinson's disease (PD) and other neurodegenerative diseases, today announced new results from a double-blind, placebo-controlled study of ANVS401, its lead drug candidate for the treatment of AD and PD. Patients treated with ANVS401 for 25 days showed statistically significant cognitive improvement as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11). The 11-part test is one of the most frequently used tests to measure impaired cognition in clinical trials for AD.

Dr. Maria L. Maccecchini, CEO of Annovis Bio, explained: "We previously reported that ANVS401 significantly increased speed, coordination and motor function in PD patients in this trial. We set up this study to measure the toxic cascade leading to nerve cell death and loss of function and its reversal in AD and PD. Since the study was powered to investigate changes in biomarker levels, not to demonstrate efficacy, we believe these results are that much more impactful."

Efficacy

From baseline to 25 days in the ANVS401-treated group, ADAS-Cog11 improved by 4.4 points, a statistically significant improvement of 30% (p=0.04).

Additionally, the ANVS401-treated group compared to placebo group at 25 days showed an improvement of 3.3 points, or 22% (p= 0.13).

This is the first double-blind, placebo-controlled study that shows cognitive improvements in AD patients as measured by ADAS-Cog and functional improvements in PD patients as measured by the Unified Parkinson's Disease Rating Scale (UPDRS).

"The results from the first cohort of 14 AD and 14 PD patients, show that the drug is effective in both diseases," stated Dr. Maccecchini. "Seeing efficacy in both patient populations supports our hypothesis that the impairment of axonal transport, the information highway of the nerve cell, affects nerve cells in the same way in both diseases. The toxic cascade in neurodegeneration begins with high levels of neurotoxic proteins, which impair axonal transport, increase inflammation and eventually lead to nerve cell death and permanent loss of cognition and function."

Axonal Transport

High levels of neurotoxic proteins lead to impaired axonal transport, which is responsible for the communication between and within nerve cells. By inhibiting the translation of multiple neurotoxic proteins, ANVS401 improves axonal transport, reduces inflammation, protects nerve cells from dying and leads to better cognition and function.


Figure 1

To view an enhanced version of this graphic, please visit:
https://orders.newsfilecorp.com/files/7656/84812_dddd92333490aadb_001full.jpg

[The picture in the link above is very powerful! It shows before and after results using Buntanetap]

On the left (Figure 1) there are three pictures of axonal transport through an axon (arm) of a nerve cell. The first picture shows the axon of a normal healthy nerve cells: the black dots depict information packages which flow smoothly from the left to the right. In the middle is the arm of a sick nerve cell. The information packages stop, then move, then stop again. At the bottom, the same sick nerve cell is treated with ANVS401 and the information flow is re-established. This shows in a very visual way, how normalizing axonal transport increases the flow and re-establishes normal function.

Comparison to Other Studies

In 2019, Biogen reported the data from its EMERGE study, a double-blind, placebo-controlled large phase 3 study and showed an improvement of 1.4-points in ADAS-Cog13 over one year.

In February 2021, Cassava reported in an open-label phase 2 study a 1.6-point improvement in ADAS-Cog11 over six months.

With ANVS401 in a double-blind, placebo-controlled study, Annovis Bio is reporting statistically significant improvements in ADAS-Cog11; specifically, a 4.4-point improvement, when the same people are measured at baseline and 25 days later. We also see a 3.3-point improvement when at 25 days we compare placebo to treated in less than one month. While we do not know how ANVS401 will affect cognition after more than one month of treatment, the present results show promise that the drug may improve or stop the course of AD.

Safety

The safety profile of ANVS401 in the interim analysis was consistent with prior safety data that shows it to be safe at 80 mg once a day in humans. There were no adverse events that could have been ascribed to the drug treatment.

Interim Analysis

Annovis Bio's ongoing Phase 2a study is designed to treat a combined total of 68 patients for four weeks with the Company's lead compound, ANVS401. The first 14 PD plus 14 AD patients, whose data are reported here, have finished treatment and their biomarkers are being measured. Recently, Annovis Bio reported the results of the measurement of inflammation in the first 14 PD patients using four biomarkers. The last 40 patients are being treated with different doses to determine the optimal dose. The study compares, in both patient populations, how nerve cells die by measuring all the steps in the toxic cascade leading to nerve cell death and how ANVS401 reverses the toxic cascade and recovers normal brain and body function.

Next Steps

The cerebral spinal fluid and plasma samples of the 14 PD and 14 AD patients who completed treatment are continuing to be analyzed to measure the reversal of the toxic cascade with additional data expected to be reported in the next two months. The full study data, including a dose ranging analysis in 40 PD patients, is anticipated in July or August of this year.

Following completion of the Phase 2a trial, Annovis Bio will request a meeting with the FDA to present the results of the trial and its chronic toxicology study in animals. Annovis Bio believes today's data and prior clinical results support the potential advancement of ANVS401 into late-stage studies, which the Company is targeting in late 2021, assuming successful completion of its ongoing Phase 2a study.

https://finance.yahoo.com/news/annovis-bio-announces-positive-phase-120100640.html?fr=sycsrp_catchall&guce_referrer=aHR0cHM6Ly9zZWFyY2guYW9sLmNvbS9hb2wvc2VhcmNoP3E9YW5ub3ZpcytiaW8rbmV3cyttYXkrMjElMkMrMjAyMSZmcj1hb2wtd2VibWFpbC1zZWFyY2hib3g&guce_referrer_sig=AQAAAIicwZR24OtphPivot6qQcAxs-nxVqZaori8sJn2M-CL5IEEFHTQbQZvzZm256fV5zsD3ySDMib7LLZstTwdKwMqQY8z2B_QtX5H8Mp2jwRXP5eHlIDiUCKDJ1hMVK3wYnOlwvl3alE9uKBrkftSYa2vJTVCbUo1GugK2zojYphD&guccounter=1

Interesting. Thanks for the info!

IMO, this is good news because it sets things up for a short squeeze.

I base that upon the high interest rate available to those of us willing to loan our shares to short sellers. Yes, I do think price will get a boost upon full enrollment, but I don't think it will be that much, and I believe it will be short lived.

What makes you think that the "shorts are after this"?

Remember, they added almost 8 million shares to the float (see my post from May 20th below), so the SP should be around $1.55 due to the added dilution.

Follow up question: Do you think that the SP will get a boost once they announce full enrollment for their pivotal P3 trial?

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abew4me

Wednesday, May 20, 2026 4:27:05 PM

Post# 775

This is NOT supposed to happen. We should've dropped 20% in value today because of the additional shares from the $15M financing. Instead, we increased in value by over 5%!!!

Prior to the financing, we had ~40M shares in the float. When you add another 7.9 MM shares, that dilutes the overall float by 20%.

So now our MC stands at $80M...which is extremely undervalued for a biotech company that is going to announce a TLR for their P3 Alzhiemer's trial in 1Q 2027.

What does all of this mean? It just reaffirms Jim Cramer's prediction: The first one with a pill, wins!

Another Alzheimer’s drug candidate enters testing category :

https://investorshub.advfn.com/stock-market/USOTC/cytodyn-qb-CYDY/stock-news/98720904/cytodyn-announces-first-patient-dosed-in-phase-2a

Shorts are after this; combine that with data readout not expected until Q1 2027, and there is nothing to support the price. It's a good time to buy...if you believe study results will be positive.

Just broke through the $2 resistance level with good volume. If we can close above $2 today, we'll have a shot at testing the $2.40 level again.

Lacey...those are the same questions that I had when I first started researching Annovis' drug, Buntanetap.

You'll have to go to their website and start reading the News Releases (or watch their videos) to catch up on everything.

https://www.annovisbio.com/press-release

https://www.annovisbio.com/video-library

Lacey...those are the same questions that I had when I first started researching Annovis' drug, Buntanetap.

You'll have to go to their website and start reading the News Releases (or watch their videos) to catch up on everything.

https://www.annovisbio.com/press-release

https://www.annovisbio.com/video-library

How does Annovis drug compare to anavex's drug? Does it score better? Does it meet endpoints? Were there a lot of dropouts?

I see your point...

I could have worded it differently:

I agree, 250,000 shares is a significant amount for one individual trade. This happens with all securities at any given point in time but not that unusual when a ticker is in a period of "very high above average daily volume" in my humble opinion. I appreciate you pointing it out and as for investors here, very noteworthy "especially occuring during an uptick" in price

Just keeping it real as I believe there will be many wow moments for this anvs journey in the very near future...

LOL. Nice try!

The issue isn't what the percentage of institutional ownership is (or will be), it is the amount purchased on the open market. (Read your own words below!)

Quote: "It's not that unusual of a buy (250,000) when there are 7,895,000 newly issued shares hitting the market."

And btw, if we get to $20 - $30 per share, I'll be living on the beach somewhere in the Virgin Islands!

Ha yourself, lol...
Lets see how the institutional ownership percentage changes on the next report. It currently stands at just under 17%

But keep up the great "wow" cheerleading and watching every second the stock trades, lol, lol, lol

What are you going to be like when we get to $20, $30, ha ha...

I'm saving my "wow" for if the Knicks sweep the Cavs, and of course if/when, as we all believe, for stellar trial results, and for if the trial fills by the end of June and for if my dream scenario plays out... as for intraday trading, I'll leave that "wow" one for you, lol

Enjoy the holiday weekend!

Quote: "It's not that unusual of a buy (250,000) when there are 7,895,000 newly issued shares hitting the market."

LOL...that's one of the most ridiculous statements I have ever read!

Just because a company issues 7.9 million new shares onto the market, doesn't mean that institutions will start buying large chunks of 250,000 shares on the open market.

Canaccord agreed to buy those shares directly from the company...and will now resell them in accordance with the agreement with Annovis. (Click the link below for full details)

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UNDERWRITING
Subject to the terms and conditions set forth in the underwriting agreement, dated May 20, 2026, between the Company and Canaccord Genuity LLC (the “underwriter”), the Company has agreed to sell to the underwriter, and the underwriter has agreed to purchase from the Company, the number of securities set forth opposite its name below.

http://archive.fast-edgar.com/20260520/ABB2I22C8Z22GJZA22T92ZZZHMNR72R2Z282/

It's not that unusual of a buy (250,000) when there are 7,895,000 newly issued shares hitting the market. Lets see how the institutional ownership percentage changes on the next report. It currently stands at just under 17%

ps - you seem to like that word, "wow"..., lol

The latest buys were from the COB..., the CEO bought shares late last year.
All of the purchase amounts were significant.

Always a good sign when the ceo of a biopharma buying stock instead of issuing themselves cheap option compensation.Always

Test

Wow...someone just bought 250,000 shares of ANVS in one transaction!

More Insider Purchases by the Chairman of the Board.

Approximately 75,000 shares bought yesterday!


http://archive.fast-edgar.com/20260521/ALB2M22C8Z22H2ZK22T32WZZKUOPH2R2Z282/

If you click the link below, you'll see a chart that shows us at a major inflection point...the 20-Day Moving, the 50-Day Moving Average, and another resistance level from the highs. This is because we've had two very strong (green candle) days with above-average volume.

Tomorrow could push us right through the $2.40 resistance level and challenge the 200-Day Moving Average at $2.62.

Let's see what happens. Cheers!

https://finviz.com/quote?t=ANVS&ty=c&ta=1&p=d

Once Annovis announces full enrollment in their pivotal P3 AD trial, I believe we'll get a pretty good pop to the upside.

Since we are back above the $2 resistance level (which is now considered to be a support level), our runway is once again clear to challenge the $2.40 resistance level. But frankly, we could blow right through that level if they announce full enrollment.

Remember, they have already announced that they've stopped accepting applications for the screening process...so they have enough people to choose from.

I'm on record as predicting full enrollment by June 30th...but it could easily happen before that date.

Get your shares now because once they announce full enrollment, you'll be kicking yourself for not buying sooner.

This is NOT supposed to happen. We should've dropped 20% in value today because of the additional shares from the $15 MM financing. Instead, we increased in value by over 5%!!!

Prior to the financing, we had ~40 MM shares in the float. When you add another 7.9 MM shares, that dilutes the overall float by 20%.

So now our MC stands at $70 MM...which is extremely undervalued for a biotech company that is going to announce a TLR for their P3 Alzhiemer's trial in 1Q 2027.

What does all of this mean? It just reaffirms Jim Cramer's prediction: The first one with a pill, wins!

Sheesh...we're already trading above the financing price of $1.90. That's pretty impressive!

Let's see if it can hold up until the end of the day.

Annovis Announces Pricing of $15.0 Million Public Offering of Common Stock and Accompanying Warrants

MALVERN, Pa., May 20, 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 the pricing of an underwritten public offering of 7,895,000 shares of its common stock and accompanying warrants to purchase up to 7,105,500 shares of common stock. The combined offering price of each share of common stock and accompanying warrant is $1.90. Each warrant will be exercisable for one share of common stock at an exercise price of $2.25 per share of common stock, will be exercisable immediately following the issue date and will expire six years after the date of issuance.

All of the shares of common stock and the accompanying warrants are being offered by Annovis. The shares of common stock and the accompanying warrant will be issued separately but can only be purchased together in the offering.

Before deducting the underwriting discounts and commissions and other offering expenses, Annovis expects to receive total gross proceeds of approximately $15.0 million, excluding potential proceeds from the exercise of the warrants. The offering is expected to close on or about May 21, 2026, subject to the satisfaction of customary closing conditions.

Canaccord Genuity is acting as the sole bookrunner in the offering.

Annovis intends to use the net proceeds from the offering for the continued clinical development of its lead compound buntanetap in clinical studies for Alzheimer’s disease (AD) and Parkinson’s Disease (PD) and for working capital and general corporate purposes.

The shares and the accompanying warrants are being offered by Annovis pursuant to an effective shelf registration statement on Form S-3 (No. 333-276814) previously filed with the Securities and Exchange Commission (SEC) on February 1, 2024 and declared effective by the SEC on February 12, 2024. A final prospectus supplement and accompanying prospectus describing the terms of the offering will be filed with the SEC. When available, copies of the final prospectus supplement and the accompanying prospectus relating to this offering may be obtained from: Canaccord Genuity LLC, Attention: Syndication Department, One Post Office Square, 30th Floor, Boston, Massachusetts 02109, or by email at prospectus@cgf.com. Electronic copies of the final prospectus supplement and accompanying prospectus will also be available on the SEC’s website at http://www.sec.gov.

This press release does not constitute an offer to sell or the solicitation of an offer to buy the securities, nor shall there be any sale of the securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state or other jurisdiction.

The Press Release doesn't indicate the price yet. We should know something tomorrow morning.

Annovis Bio Launches Proposed Stock, Warrant Offering; Shares Fall
05:02:14 PM ET, 05/19/2026 - MT Newswires

Annovis Bio Inc (ANVS) said on Tuesday it launched a proposed underwritten public offering of common stock and accompanying warrants to purchase common stock.

The company said the shares and warrants will be issued separately but can only be purchased together in the offering.

Annovis said it plans to use net proceeds for continued clinical development of lead compound buntanetap in a Phase 3 Alzheimer's disease study, along with working capital and general corporate purposes.

Annovis shares fell about 19.1% in after-hours trading.

https://www.annovisbio.com/press-release/annovis-announces-launch-of-proposed-public-offering-of-common-stock-and-accompanying-warrants

http://archive.fast-edgar.com/20260519/ABBZIQ2C8Z22GZZ222T92ZZZHMNRZ2V2XV82/

What is the price of the offering?

Yes. I happen to agree with Jim Cramer when he said: The first one with a pill, wins!

IMO, Annovis is definitely in the lead to be the first company to be approved for a once-a-day oral pill to treat AD...and PD!

It was a P3. Their drug was effective for all of the participants...but the placebo group also had an improvement with their cognitive tests. They were puzzled by this anomaly and found that many of the participants in the P3 study were not suffering from cognitive decline but were admitted to the trial anyway. (See below)

Beyond Perfection: How Mistakes Shape Path to Approval

https://events.reutersevents.com/pharma/article/beyond-perfection-how-mistakes-shape-path-to-approval

After you're finished reading that article, you can read the company's release of the P3 results below. (And btw, after they released the results of the P3 data, there was a slew of insider buying all the way up to $4+ per share)

http://archive.fast-edgar.com/20251208/ALBZM22D8C22H9ZZ2R2B2ZZZKUONZ2Q2ZB72/
30,000 shares at $4.34
15,000 shares at $4.24

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Annovis Reports New Biomarker Data Linking Amyloid Co-Pathology to Accelerated Cognitive Decline in Parkinson's Patients

- Buntanetap significantly improves cognition in all Parkinson’s patients, with those exhibiting Alzheimer’s co-pathology showing a three-times greater response

- New data demonstrate reductions in plasma biomarkers pTau217, total tau, and brain-derived tau following buntanetap treatment

- Findings support buntanetap's potential to address cognitive decline in Parkinson's disease, show disease-modifying efficacy, and inform future clinical development


MALVERN, Pa., Nov. 17, 2025 (GLOBE NEWSWIRE) -- Annovis Bio, Inc. (NYSE: ANVS) (“Annovis” or the “Company”), a late-stage clinical drug platform company pioneering transformative therapies for neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), today announced new data demonstrating the impact of amyloid co-pathology on cognitive outcomes in Parkinson's patients and the therapeutic efficacy of buntanetap in this population.

In the Company’s Phase 3 study in early PD (NCT05357989), buntanetap halted cognitive decline across the overall patient population, with the greatest improvement observed in those with mild dementia. Further analysis revealed that approximately 25% of them exhibited amyloid co-pathology and experienced more pronounced cognitive decline over the course of the study, which was counteracted and reversed by buntanetap.

These findings reinforce a central principle long championed by Annovis: neurodegenerative diseases rarely occur in isolation. Instead, multiple neurotoxic proteins—those implicated in both Alzheimer’s and Parkinson’s—drive cognitive and functional decline. Addressing this complexity requires therapies capable of targeting several toxic proteins simultaneously, which is precisely what buntanetap does.

As anticipated, buntanetap treatment led to significant cognitive improvement in Parkinson’s patients with amyloid co-pathology. This response was further supported by measurable reductions in pTau217, total tau, and brain-derived (BD) tau – well-established biomarkers of neurodegeneration used in AD. Together, these findings indicate that buntanetap is actively modulating the underlying drivers of cognitive deterioration, ultimately broadening the population of patients who may benefit from treatment.

"What we see is that Parkinson's patients who experience cognitive decline also have Alzheimer's pathology, and our drug helps them," commented Cheng Fang, Senior VP, Research & Development. "These data are the first of its kind—no one has previously looked into treatment effects in Parkinson's patients with amyloid co-pathology. The findings integrate seamlessly with our growing body of clinical evidence, distinguishing buntanetap as a promising therapeutic candidate for cognitive improvement across multiple neurodegenerative diseases."

The full biomarker data will be presented at the Clinical Trials on Alzheimer's Disease (CTAD) conference in San Diego, December 1-4, 2025. Additional details regarding the presentation will be announced closer to the conference date via a separate news release.

About Annovis
Headquartered in Malvern, Pennsylvania, Annovis is dedicated to addressing neurodegeneration in diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The Company is committed to developing innovative therapies that improve patient outcomes and quality of life. For more information, visit www.annovisbio.com and follow us on LinkedIn, YouTube, and X.

It’s a failed P3.

Annovis is running an OLE for PD? what was the results of thie initial trial? Was the initial trial a P2 or P3?

Amazing that with a shot on goal set for early 2027, the market cap here is only about $70 million. Meanwhile AVXL is listing and taking on water, CEO dumped, no trials at all, and the market cap is about 4x ANVS. Seems ANVS is the better chance to make money in the next year or so. Management seems capable.

It's always nice when a person's technical analysis works out...as it did with the post below. Once ANVS broke through the $2 resistance level, the price shot up to exactly $2.40.

We are now testing the $2 level again...but this time, it is a support level. Let's see if it holds.

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abew4me

Thursday, April 30, 2026

Post# 744

Strong close today at $1.97. It's important that we closed above $1.92 because that's the selling price that was offered to finance the $10 MM package a few weeks ago.

Closing above that price gives us a runway to the next resistance level...which is $2.00. If we can close above $2.00 with good volume, we should be clear to the next resistance level...which would be $2.40.

All comments are just my opinion.

abe

Excellent post.

"If buntanetap secures FDA approval strictly for symptomatic effects (e.g., improving cognitive function in Alzheimer's or motor function in Parkinson's without a proven disease-modifying, neuroprotective label), the potential market capitalization can be evaluated through a few key lenses:
1. The Market Pricing of Symptomatic vs. Disease-Modifying Labels
Symptomatic treatments generally command lower valuation multiples than true disease-modifying therapies (like anti-amyloid antibodies) because they do not halt the underlying pathology. However, given the massive size of the Alzheimer's and Parkinson's patient populations, a clean symptomatic drug with a favorable safety profile can still achieve blockbuster or near-blockbuster status."

Fully agree with this assessment! (Extra emphasis on the exclamation point!!!) lol

test

Predicting the exact market capitalization for a clinical-stage biotechnology company like Annovis Bio (\bm{ANVS}) upon a regulatory approval is speculative, as the market's reaction depends on several dynamic variables.
Currently, Annovis Bio has a micro-cap valuation fluctuating between $65 million and $75 million, with approximately 28.5 million to 34 million shares outstanding (following recent dilutive capital raises, such as their $10 million offering in April 2026).
If buntanetap secures FDA approval strictly for symptomatic effects (e.g., improving cognitive function in Alzheimer's or motor function in Parkinson's without a proven disease-modifying, neuroprotective label), the potential market capitalization can be evaluated through a few key lenses:
1. The Market Pricing of Symptomatic vs. Disease-Modifying Labels
Symptomatic treatments generally command lower valuation multiples than true disease-modifying therapies (like anti-amyloid antibodies) because they do not halt the underlying pathology. However, given the massive size of the Alzheimer's and Parkinson's patient populations, a clean symptomatic drug with a favorable safety profile can still achieve blockbuster or near-blockbuster status.
2. Standard Biotech Valuation Multiples
If buntanetap is approved, analysts will model its peak sales based on market penetration, pricing, and insurance coverage.
• Conservative Peak Sales: If buntanetap achieves modest adoption, generating an estimated $250 million to $500 million in peak annual revenue.
• Valuation Multiples: Approved, commercial-stage biotechs with growing revenues typically trade at a price-to-sales (\bm{P/S}) multiple of 3x to 5x peak sales.
• Implied Market Cap: This standard framework implies a post-approval valuation range of $750 million to $2.5 billion.
3. Comparing the Valuation "Infection Point"
For a micro-cap company (~$70M) to transition to an approved asset owner, the valuation multiplier is often dramatic. A leap to a $1 billion to $2 billion market cap represents roughly a 15x to 30x return from current levels. This is a common trajectory for small biotechs successfully crossing the finish line into a multi-billion dollar market, though it is often accompanied by further dilutive financing to build out a commercial sales force or manufacturing infrastructure.
Ultimately, while an approval for symptomatic benefits is a massive milestone that could easily lift Annovis into the $1B+ club, the exact cap will depend on the final FDA label, the drug's safety data compared to existing treatments, and whether they partner with a major pharmaceutical firm for commercial distribution.

Poat away until your heart's content Abe, lol

Let's see how your guess of full enrollment by the end of June works out. I'm rooting for you to be right.

lol

I'm not looking for your approval for anything that I post.

This is an open board.

Full enrollment as per yesterdays company guidance will be summertime....

Whether that is the end of June, sometime in early July, July, or even early August, enrollment is going very very well and the trial will fill very very soon.

Once again, your enthusiastic prediction (exclamation point) could be interpreted as cheerleading unless you have a better window into the trial than the company.

Brava if Maria pr's this in early summer. As investors, we should applaud when mgmt over delivers. On this note, ok, I will applaud your "guess", this one time.

Here's another way of explaining it...

Annovis has two enrollment lists: The first list is for the screening process. (Also known as the inclusion/exclusion process) These applicants have not been enrolled into the trial...because we don't know if they meet the criteria that we've set. It may take 100 applicants to find 20 patients that meet the criteria. This is the enrollment list that the Press Release is referring to.

The second list is for those patients that have met the criteria and are now enrolled into the trial.

Hope that helps.
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Screening: On May 15, 2026, Annovis closed enrollment to new participants after reaching a sufficient number of patients in screening to meet the trial's enrollment goal.

NO. They said that they closed the enrollment for new participants for screening. (See below) There's an inclusion/exclusion process that screens out a certain number of the enrolled applicants for the trial.
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Screening: On May 15, 2026, Annovis closed enrollment to new participants after reaching a sufficient number of patients in screening to meet the trial's enrollment goal.

They said they have stopped screening new patients as the number of patients screened is adequate.

Once again, we added another 5% in two weeks for the enrollment of the P3 AD trial. We now stand at 85% enrolled.

If this pace continues, we should have full enrollment by the end of June!

Annovis Provides Corporate Updates and Reports First Quarter 2026 Financial Results

- Phase 3 AD trial: 85% of patients enrolled; full enrollment on track in summer 2026

- PD open-label extension (OLE) study: 40% of patients enrolled; full enrollment on track in fourth quarter 2026

- New Drug Application (NDA) for buntanetap as a symptomatic treatment for AD is expected in early 2027 and as a potential disease-modifying treatment in early 2028

Malvern, PA, May 15, 2026 -- 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 provided business updates and reported financial results for the first quarter ended March 31, 2026.

"We saw strong momentum across both our AD and PD programs in the first quarter," said Maria Maccecchini, Ph.D., President and CEO of Annovis. “Our Phase 3 AD clinical trial achieved significant enrollment growth, keeping us firmly on track to complete randomization of patients in summer 2026 and deliver first top-line results in early 2027. Simultaneously, we launched a PD OLE study and have been encouraged by the robust interest from both returning and new patients. This year is pivotal: we expect to generate substantive clinical data across both indications that will anchor our regulatory path toward an NDA submission for buntanetap."


Clinical highlights

Alzheimer’s disease – pivotal Phase 3 trial (NCT06709014)

- Enrollment: 85% of patients enrolled.

- Screening: On May 15, 2026, Annovis closed enrollment to new participants after reaching a sufficient number of patients in screening to meet the trial's enrollment goal.

- Safety: Annovis received a positive recommendation from the Data and Safety Monitoring Board (DSMB) regarding the drug’s safety at 6 months, supporting seamless continuation of the study.

- Study design: The pivotal Phase 3 AD trial is recruiting early AD patients positive for pTau217 plasma biomarker. The study is designed to evaluate buntanetap's symptomatic effect at 6 months and its potential disease-modifying effect at 18 months.


Parkinson’s disease – OLE study (NCT07284784)

- Enrollment: 40% of patients enrolled.

- Skin biomarker: The PD OLE study is implementing a biomarker test measuring levels of phosphorylated alpha-synuclein and nerve cell fiber density via skin biopsy.

- Digital biomarker: Annovis entered into a partnership with NeuroRPM to integrate an AI-powered digital biomarker, enabling continuous, real-world assessment of motor functions in response to buntanetap.

- Study design: The PD OLE study is designed to evaluate buntanetap's safety and long-term efficacy over the period of 36 months in participants from prior Annovis’ trials as well as in new patients who had deep brain stimulation (DBS) surgery.

Corporate highlights

Publications
- Annovis published a byline article in The Scientist, tracing the 170-year scientific history of buntanetap, from the origins of its predecessor compound to its mechanism of action and key events that shaped the drug’s clinical development.

- Annovis announced a peer-reviewed publication of the Phase 2/3 AD clinical trial results in Nature NPJ Dementia, available open access, demonstrating a dose-dependent cognitive improvement and biomarker reductions in patients treated with buntanetap.

Presentations
- Cheng Fang, Ph.D., SVP, R&D, presented two posters at the AD/PD2026 conference, highlighting clinical data which support buntanetap's treatment effect in PD with a particular focus on cognition and biomarker findings as well as an update on the ongoing pivotal Phase 3 AD trial.

- Maria Maccecchini, Ph.D., President and CEO, presented at Fierce Biotech Week 2026 in Boston, delivering a talk titled "The Multi-Protein Reality of Alzheimer's Disease: What the Science Has Known for Decades and What the Field Has Yet to Accept," making the scientific case for targeting multiple neurotoxic proteins in AD and presenting buntanetap's clinical evidence of cognitive and biomarker improvements.

Patents
Annovis secured a U.S. patent, covering prevention and treatment of neurological injuries arising from brain infections through the administration of buntanetap or related compounds.

Upcoming milestones

- Phase 3 AD study: Annovis expects to reach full enrollment in summer 2026. The symptomatic data readout is anticipated approximately 6 months after the last patient is dosed. The disease-modifying data readout is anticipated 18 months after the last patient is dosed.

- PD OLE study: Annovis expects to complete enrollment for the PD OLE study in the fourth quarter of 2026.

- NDA pathway: Based on the Phase 3 AD study outcomes, Annovis plans to engage with the FDA regarding a regulatory NDA submission for buntanetap as a symptomatic treatment for AD in early 2027 and as a disease-modifying treatment in early 2028.

Financial results

Annovis’ cash and cash equivalents totaled $14.2 million as of March 31, 2026, compared to $19.5 million as of December 31, 2025. This excludes gross proceeds from its recent $10.0 million registered direct offering on April 10, 2026. Annovis had 28.5 million shares of common stock outstanding as of March 31, 2026.
Research and development expenses for the three months ended March 31, 2026, were $16.7 million compared to $5.0 million for the three months ended March 31, 2025.
General and administrative expenses for the three months ended March 31, 2026, were $1.3 million compared to $1.3 million for the three months ended March 31, 2025.
Annovis reported a $0.63 basic and diluted net loss per common share for the three months ended March 31, 2026, compared to a $0.32 basic and diluted net loss per common share for the three months ended March 31, 2025.

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.

‍

Annovis CEO to Present on Multi-Protein Model of Alzheimer's Disease at Fierce Biotech Week 2026

MALVERN, Pa., May 07, 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 that Maria Maccecchini, Ph.D., President and CEO, will present at Fierce Biotech Week 2026 taking place in Boston, May 12-14, 2026.

-‍ Title: "The Multi-Protein Reality of Alzheimer's Disease: What the Science Has Known for Decades and What the Field Has Yet to Accept" [This is a MUST WATCH]

- Presenter: Maria Maccecchini, Ph.D., President and CEO

- Date: Wednesday, May 13, 2026

- Time: 1:40 PM - 2:05 PM

- Location: Picasso 4&5

The presentation will trace the scientific foundation for understanding AD as a disease driven by multiple neurotoxic aggregating proteins and examine the historical gap between that evidence and the field's reliance on a single-protein approach. Dr. Maccecchini will make the case supporting the importance of the full spectrum of neurotoxic proteins – including amyloid, tau, alpha-synuclein, TDP-43, and more – in disease progression, which are not only backed by decades of scientific data but also represent a promising path forward for the AD drug development.

"Alzheimer's disease has never been a one-protein problem, and overreliance on amyloid as the sole driver of the disease has come at a cost, hindering progress for alternative therapeutic candidates," said Maria Maccecchini, Ph.D., President and CEO. "Annovis’ program is built exactly on the premise that simultaneous reduction of the overexpression of several aggregating proteins interrupts the toxic cascade and improves the health of nerve cells. Our lead drug buntanetap, a translational inhibitor of these proteins, has already shown meaningful clinical benefits supported by encouraging biomarker data, and is now in a pivotal Phase 3 clinical trial."

The presentation will be followed by a Q&A discussion and is open to all participants.

Fierce Biotech Week 2026 brings together leaders across R&D, clinical development, business development, and communications to confront the industry's most pressing challenges, from capital strategy and pipeline advancement to partnership formation and commercialization. With more than 100 biotech CEOs and founders, over 500 companies, and 15 top global pharmaceutical organizations represented, the event is built for the leaders driving consequential decisions.

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.

If we can close over the $2.40 resistance level with good volume, we can expect a little resistance at $2.75-ish...and then another major resistance level at $3.00.

Breaking through the $3 level has been tough over the past five months, but usually breaks when you hit on your third try...which is exactly what were about to do once we get to that point.

test

If you read my post from April 30th, you'll see that my T/A was spot on!

Once we broke through $2 we had a runway right up to $2.35 today! (almost hit $2.40!)

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abew4me

Thursday, April 30, 2026 4:25:09 PM

Post #744

Strong close today at $1.97. It's important that we closed above $1.92 because that's the selling price that was offered to finance the $10 MM package a few weeks ago.

Closing above that price gives us a runway to the next resistance level...which is $2.00. If we can close above $2.00 with good volume, we should be clear to the next resistance level...which would be $2.40.

All comments are just my opinion.

abe