Annovis Bio, Inc. Investor update

date and answer questions from the audience. Before we begin, I would like to remind everyone that today's call may include forward-looking statements. These 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. For more information on the risks and uncertainties related to Annovis Bio's business, please refer to the forward-looking statements and the company's latest SEC filings. To guide us through today's presentation, I am pleased to introduce our speaker, Dr. Maria Maccecchini, the founder, President, and CEO of Annovis Bio. Today's presentation will address the current progress of Alzheimer's and Parkinson's clinical programs, including the pivotal phase III Alzheimer's trial, the upcoming open label extension for AD, and the ongoing open label extension for PD. The presentation will also cover clinical and corporate milestones anticipated in the coming months.

During the webcast, we welcome our audience to leave a question in the comments section, the Q&A box, or raise hand by using a button in the task bar. Once it's your turn, you'll be unmuted and allowed to ask your question directly. Now without further ado, I will turn the call over to Dr. Maria Maccecchini. So all over to you, Dr. Maria.

Good afternoon, and thanks a lot for joining us. This is a really good time in our life because it feels like we are almost there. Let me tell you what almost there means. We have 42 million outstanding shares, and we are the only company that has a drug that works in Alzheimer's and Parkinson's. We still have $19 million in the bank, so we're not totally desperate, and we are in late-stage development. The most important thing that we're going to be discussing today is that we have the pivotal phase III Alzheimer data read out in March. It's coming up. The pipeline hasn't changed a lot other than we have added open label studies to Alzheimer's and to Parkinson's disease. In terms of the combination, some of you sometimes ask me, we really don't have money to do that.

What we are doing is additional combinations in mice to figure out why these combinations work and to better understand the brain. Because if we can better understand the brain, we can actually treat it better. This is our patent portfolio. I told you we are working on combinations, and if you look at the very top, you have cancer combinations, statin combinations, and how our drug works with all these other drugs. This right now is more in the research stage, but we are publishing, and we are obviously filing patents. I wanted to spend a minute talking about our people. I usually just say we are a young, aggressive, very hardworking team. We are. But I do want to point out that while we are small, we are doing a really fantastic job. Cheng Fang is our Chief Scientific Officer.

She is probably the most innovative person in the world in terms of biomarkers, not because other people don't know more, somebody may know more, but because she's really actually using them in our studies, and that is unusual. Most people don't measure half the biomarkers she does. She is also really fantastic in designing our studies. We have heard from a number of PIs and KOLs that our studies are fantastic. Eve has been running our regulatory group for over 15, 16 years. While she seems alone here, she actually has nine people reporting to her, and she has touched every single aspect of regulatory. We just started filing the NDA. We started putting in the modules for the NDA, so we will be ready next year to file it. Sarah is a fantastic organizer. She is running clinical studies.

She is running three CROs and over 50 people. We could never do this study without her. Mike, well, he is doing three large batches. He has run our CMC since inception. Our drug is 99.999% pure, and we are at the registration batch study. Hui Liu is running statistics together with three other groups. So again, she has a lot of people. I want to point out Alex, who is our do everything boy. He wrote the history of buntanetap. If you haven't read it, you should really read it. He just wrote a paper on AI and how Alzheimer drugs go into the brain. Alex is also our Director of Strategic Communication. As I said, he is very multifaceted. He's setting up our AI in-house. While you see these people here, behind this group, we have over 30 people.

I've told you before several times that our drug inhibits more than one neurotoxic aggregated protein. It does. Because it does, it can be used in Alzheimer's and in Parkinson's disease. I've also told you that in order to develop a drug, it takes more than one study. It takes an enormous amount of studies. In fact, we have treated to date over 1,600 patients. We have finished 13 studies and are in two large studies. One is the pivotal Alzheimer's study we are talking about, one is the open label Parkinson's. Altogether, we will end up with maybe 1,700 or 1,800 patients by the time we file the NDA. Let's go to the study everybody wants to know everything about. You know we're fully enrolled. We enrolled much better than expected.

At the end of the year, so December 31st, is the last person last visit for the six-month study. Then we have to clean the data, lock the data, analyze the data, and in March of 2027, we will present at ADPD. The data, we don't have a choice. Since all this is organized, in March, we will present the top-line data. That data, the six months data, filing an NDA at that point, puts us into a $7 billion generic market. That market consists of Aricept, Namenda, and Exelon. As I said, it's a 30-year-old market, it's generic, and in spite of that, just in the U.S., we're selling $7 billion worth of drug. Study will continue for an additional 12 months, and then in March of 2028, we will have the top-line data for the 18-month, disease-modifying readout.

Now, that market is estimated to be $100 billion, and we do want to be part of that market. How does the statistics for this study look to date? The study was started in January of 2025, and I'm giving you data up to July of 2026. Last year, in 12 months, we recruited 200 patients. That was slow. We really sped up, and this year we recruited 662 patients until the end of July. The screen failure rate is 67%. That compares favorably to the existing anti-amyloid drugs like Leqembi, Kisunla, and aducanumab. They had a 70%-80% screen failure rate. So we are a little better, but not much. The dropout rate, however, is fantastic. We only have an 8% dropout rate. If we compare that to the amyloid drugs, they have a 20%-30% dropout rate.

And we have no drug-related serious adverse events. This is good statistics. If we keep this 8% dropout rate, we will actually finish the study with about 790 patients, which is plenty. Maybe a little bit more detail about the study we are doing now. We had very stringent inclusion criteria. Just like in our previous studies, we first relied on the PI's analysis of does this person have Alzheimer's or not? However, we also measured the MMSE. It had to be over 20 and below 29. We measured p-tau to make sure they had Alzheimer pathology. And we did MRI, A, to see whether the brain was healthy, but B, also to give a baseline as to the volume of the brain. The primary endpoints for both the six and the 18 months are ADAS-Cog 13 and ADCS-ADL.

That is exactly what the FDA asked us to do. This is exactly what we do. At 18 months, we have added secondary endpoints, volumetric MRI and p-tau217, to show disease modification. And then we will do biomarkers. And we have seen in biomarkers in a number of studies, that I'll show you a little later, that our drug consistently lowers inflammation. And that is very important because you do not want to have inflammation in your brain independent of what disease you have. The planned open label, which will continue once the patients have reached 18 months. We don't expect that many patients because an 18-month study is a long study, and adding to that two years is really long for the patients to be continuously monitored. But we open it up to whoever wants to.

Now, from an FDA point of view, an open label study really only counts for safety. However, for us, we can see how the patients that were on placebo do once they come off placebo and go on drug, how the patients that have been on drug progress or stay the same. And so the open label will give us indication on whether the disease continues to go downhill or stays the same, and how it differs from the patients that were on placebo and the patients that were on drug. And now I'm taking a step back because I told you what study we are doing. But why are we so sure that the study we are doing actually is going to work?

The reason we are so sure that the study we are doing is actually going to work is because we are basing it on the previous study that unfortunately only worked in a subgroup. In the previous study, we were not half as selective in how we put people into the study. We relied on the PI to tell us whether the person had Alzheimer's. It turns out a lot of patients didn't. We didn't do p-tau. We didn't do MRI. Our MMSE was too advanced. The endpoints per se were correct. There was nothing wrong with them. In that study, we did look at three doses, and of course, we had placebo. The ITT, intent to treat population, did not show statistical improvement in cognition.

However, when we then took a subgroup that consisted of p-tau217 positive patients, which are patients that actually had amyloid in the brain and were confirmed to have Alzheimer's disease, and we looked at the three doses, we saw that 30 mg, the pink bar, is by far the best. The study we are doing now are the patients that are identical to the patients in this pink bar. If we look at the patients in the pink bar, we don't just see that they improved in cognition, but they improved in inflammation. They improved in five different inflammatory factors, and they improved in neurofilament light. The reason I'm highlighting neurofilament light is that the FDA has approved neurofilament light as a biomarker for ALS. Actually, if you show an improvement in neurofilament light in ALS, you get approval.