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 progress of the pivotal phase III Alzheimer's trial, the status of the Parkinson's program, and additional clinical directions. We also welcome our audience to leave a question in the comment section. There's a Q&A box on your toolbar. You can leave a question during the webcast or raise your hand by using the button on the taskbar. Once it's your turn, you'll be unmuted and allowed to ask your question directly.
Without further ado, I would like to turn the call over to Dr. Maria Maccecchini.
Good afternoon, and thank you so much for attending. As Brooke already said, I would like to give you first an overview of the company, where we are with all our clinical studies, how we use the clinical studies we have done to continue our development and go into pivotal studies in Alzheimer's and in Parkinson's disease. First, the overview. Most of you may have seen this slide. It is our pipeline. As you can see, in Alzheimer's, we are in the second study, large study, which we believe that when we will read out the data, will be adequate to be the pivotal study and to actually allow us to file an NDA, one for symptomatic and one for disease-modifying. In Parkinson's disease, we have finished one large study.
At this point, we are looking at opening an open-label study for the patients that were in our previous study and for some additional patients that have deep brain stimulation. Finally, Lewy body dementia is a disease that is something between Alzheimer's and Parkinson's. Patients with Lewy body dementia exhibit the symptoms of an Alzheimer's person and of a Parkinson's person. Those three indications are the ones we are pursuing. For the rest, we will get there when we have more money. This is a very busy slide, but it actually shows how many studies we have done. We have treated way over 800 patients. Here, the first two studies show safety in healthy volunteers. The next two studies show very small biomarker studies and a little of efficacy in Alzheimer's patients. The next two studies are two small studies, one in Alzheimer's, one in Parkinson's.
We did a study, a large study, 350 studies in Alzheimer's and a 500-patient study in Parkinson's. Lately, we have done all the studies necessary to file an NDA, which is a food effect, a combination or a bridge study between the old semi-crystalline form and the new crystalline form of buntanetap, and an ADME study, which is you really give radioactive material to a human being, and you look where the radioactivity shows up, where in the body, where in the feces, where in the urine. Finally, we have the last study that we are conducting right now, which is the 760 early Alzheimer's patient study. As you can see, we have done a lot of studies, and we have a lot of understanding of our drug.
I will try to walk you through to see what we know for sure and what we do not know for sure. Let's first look at cognition and safety. This is what we believe we are sure that it's correct. I told you we have two very small Alzheimer's studies when we looked at cognition and then mostly safety. The first one on the left, the ADCS study, only treated five patients. These five patients look substantially better than their placebo counterparts. Our ADPD study only treated nine Alzheimer's patients. Again, these nine Alzheimer's patients look a lot better than the placebo. When we combine the two studies, they were both one-month studies, we see that the 14 treated patients actually show highly statistical improvement in cognition over baseline and almost over placebo.
While you can discount these studies as too small, the fact that they both, and together even more so, show efficacy over placebo is very encouraging. Since we were encouraged, we did a 350-patient Alzheimer's study. We took moderate and early Alzheimer's patients, and we did not check for plaque and tangles in the brain. What we found is that we had 40% patients that did not have Alzheimer's disease. We were able, after the fact, to figure out who had Alzheimer's disease by using the pTau217 test. It's a test in plasma that tells you and correlates really well with plaques and tangles. When we looked at early Alzheimer's patients that had Alzheimer's and were early, we see the graph on the right. All three doses show statistical significance over placebo, and the 30 mg dose is over three and a half points better than placebo.
You will see that three and a half points is a very nice improvement. You know, whenever you cherry-pick, you want to have some safety net that, in fact, you are not cherry-picking. We looked for robustness of our data by doing a Forest Plot. A Forest Plot looks at groups within your data and looks at how these groups behave. The blue square on the top is the overall outcome. That is what I just showed you, that the three and a half points improvement in cognition. We looked at age. Age makes no difference. Patients respond. We looked at APOE4 carriers. APOE4 carrier or not makes no difference. People respond. Heavy or light, people respond. Ethnicity, Hispanic, Latino or not, they respond to our drug. Gender, female or male, they respond to our drug. Then concomitant medication.
On top of Aricept and Namenda, which are the current standard of care, people respond. Interestingly enough, if they are on antidepressants, they respond really well. If they take no concomitant medication, they also respond. Finally, black and white. Every group we looked in early Alzheimer's responds to buntanetap. That gave us some belief or some strong belief that the drug actually works in that population. Safety, it was important for us to show that buntanetap is safe, especially in APOE4 carriers, because the two novel approved drugs, Leqembi and Kisunla, have high side effect profiles in APOE4 carriers. We looked at all concentrations and placebo. We looked at carriers and non-carriers, and there is absolutely no difference between placebo, carriers, and non-carriers. Our drug is safe no matter what genetic makeup the patients have. Let's look what else.
In what other group we have seen cognitive improvement, and that is in Parkinson's. In Parkinson's, in the whole ITT population, what you see on the left is that the population placebo gets a little worse, and the two treated groups actually do not. However, when we specifically look at the Parkinson's patients that are cognitively impaired, we see a huge improvement from minus 1.7 to a little better than baseline. It really shows that our drug improves cognition in Parkinson's patients. Again, we wanted to see the robustness of our data. Again, we did a Forest Plot. Here we looked what else do these mildly cognitive-impaired Parkinson's patients respond to. What we saw is that they respond to every single one of the Parkinson's scales. UPDRS is a Parkinson's scale, has four parts. They respond to part one, part two, part three, part four, CGIS.
Then below, response is on the right, not on the left. You see that they respond to WAIS coding. Of course, to MMSE, that's how we selected them, and then to PGIC. Again, we feel very confident that this is not cherry-picking, that these patients that are cognitively impaired and have Parkinson's actually do respond to our drug. Again, safety. We wanted to see if the two doses and placebo have the same safety profile, and they do. We have shown consistently that our drug works in cognition independent of Alzheimer's and Parkinson's, and it is safe independent in Alzheimer's and Parkinson's. Let's see how we use the data I just showed you to move into a pivotal phase III study. What we learned is that it works in early Alzheimer's. We selected patients by MMSE over 20.
High numbers of MMSE are better, low numbers are worse. MMSE 21 to 28 spans the gamut from early and mild. If they have that MMSE, then we look to whether they are really Alzheimer's patients. We do the pTau217 test in plasma. We do a volumetric MRI that actually is the baseline for us to then continue the study. Let's see on how we look at efficacy for symptomatic and efficacy for disease modification. For symptomatic, we look at ADAS-Cog13 and ADCS IADL. This is what the FDA told us to do. For disease modification, we choose biomarkers that may show disease modification and then volumetric MRI.
The biomarkers we have so far chosen, and we may increase the number as more biomarkers in plasma become available, are inflammatory ones like GFAP, are nerve health ones or nerve distress ones like neurofilament light, are pTau217 and brain-derived tau. As I said, as they become available, we will do more biomarkers. Volumetric MRI we do because we want to know whether the brain shrinks or not. In Alzheimer's, over 18 months, the brain shrinks substantially. If we see no shrinkage, it means that our drug protects nerve cells from dying. I need to point out here that this screening process with the three steps takes a minimum or takes eight weeks, sometimes a little bit more.
That is important when we go to recruiting because it takes a long time between when you have a patient that has the correct MMSE and then have that patient into going randomization because they have gone through the pTau217, through the plasma biomarkers, and through the volumetric MRI. This is the study we proposed to the FDA, and we are conducting right now. It is a 6/18 month study, which means that we actually have an analysis of the data at six months and then one at 18 months. As I just mentioned, we are looking for MMSE. We are looking for pTau217, and the primary endpoints are ADAS-Cog13 and ADCS IADL plus volumetric MRI and biomarkers. We are allocating 380 patients to placebo and 300 to buntanetap, a total of 760 patients. This is a more schematic diagram of the study. We started the six-month arm.
By next summer, we should have treated 760 patients for six months. By fall, we will have the readout of the six-months data. The patients remain blinded. They continue the study for an additional 12 months. In summer of 2027, we should have treated 760 patients for 18 months and then open the blind. When the data actually confirms or negates that the drug is disease-modifying, file an NDA. The FDA cleared us for this study, and we are actually conducting it. This is our target. The target is 100 sites. We think we're going to open about 90, sorry. We want to screen 1,500 patients and randomize 760 to fulfill the patients we need. Recruitment is about a year, and the study is 18 months. The dose is 30 mg and placebo. This is where we are today.
We have selected 84 sites. Fifty-two are open. We have screened to date 220 patients. We have had 88 screen failures, which is a screen failure rate of 38%. Now, the data I need to explain is that we have enrolled 760 patients, but only 11 are on drug. That is because of the eight-week delay. The 760 just started or are somewhere in the eight-week piece, and the 11 are actually on drug. Nobody has discontinued, and nobody, of course, has completed. I have shown this before. It is a nice diagram that shows the difference between disease symptomatic, disease modifying, and what we know about our drug and what we do not know. The green line is the natural disease progression. Patients get worse over 18 months by about 5.5 points. That is an average.
If you treat them with Aricept, which is a symptomatic drug, they will get better for three to six months by about one and a half points. Then they get below baseline. They get worse. Eventually, they look just like patients that were never treated. They go back to natural disease progression. The blue line is Leqembi and Kisunla. These two drugs do not improve cognition. What they do, they slow the progression. In fact, they slow the progression by 30%. The blue line actually has a slope that is slower and flatter than the green line. The further you go in treating these patients, the more the distance between the natural disease progression and the disease modification. On top, the purple line, that is us. The solid line is what we know.
At one and three months, we are over three and a half points better than baseline, which is two and a half times better than Aricept, the standard of care. After that, the line gets open because we really do not know how it is going to progress. It could stay as we have depicted here. That is our hope. Because you may notice that it has the same slope as Kisunla and Leqembi, which means it is disease modifying, but at the high, much higher level because it improves cognition to get started by three and a half points. Now, of course, it does not have to do that. It could come down. If we are really lucky, it could stay even higher. But, you know, I mean, do not hope for too much. But there is a reality that it could come down and just be symptomatic.
Now, even if it was just symptomatic, I want to point out that short term, it would increase cognition two and a half times better than the standard of care, which is nothing to sneeze at. Now let's go to Parkinson's disease. As I was telling you, in Parkinson's, the best result we have was really not in the UPDRS, which is the Parkinson's scale. It was in cognition. In order to minimize our risk of doing an incorrect study, we decided to be conservative and do a study in Parkinson's patients that have cognitive decline. They are two groups. They are grouped under Lewy body dementia, but there is dementia with Lewy bodies and Parkinson's disease dementia. The patients we have in our study and we have analyzed are actually most likely Parkinson's disease dementia patients.
We proposed two studies to the FDA, one for DLB and one for PDD. Again, we are using 30 mg. We showed them the design. We were expecting a response by last week. The response we got was we're overworked and understaffed, and we'll get to it. We don't know when. We don't have a response. Realistically, I don't expect them to be terribly negative because there are no drugs for Lewy body dementia. There are no guidelines for Lewy body dementia. We probably have the absolute best data in Parkinson's disease dementia cognition. I don't see any problem for them to say yes. Also, a lot of you want to know when do we do the open label extension study. Yes, we again have asked the FDA. We have actually not asked.
We have submitted a protocol, and we expect them to approve the protocol. That is expected by later this month, so maybe in a few days because there is not that much left in a month. Let me show you what we sent to the FDA and what we hope we are going to get. Here you see Parkinson's disease dementia and dementia with Lewy bodies. The lowest hanging fruit for us is Parkinson's disease dementia. With 300 patients, we can do a pivotal study and actually get statistically significant data if we use the same patients we found in our Parkinson's disease study. That is, once we have the money, the most likely for us to actually conduct. We also asked for the open label extension. Here there is a little something different.
We will, of course, ask, or we will invite all the patients that have already been in one of our Parkinson's studies. We also decided to include patients with DBS. The reason is that patients with DBS are routinely left out of clinical studies because nobody knows how they respond to drugs since they have electrical stimulation in the brain. Since this is an open label study, we can take the risk that they do not respond. This study will have between 500 and 700 patients, half of them or as many as want to come from the previous Parkinson's studies, and the other half or as many as we can get that have DBS. That is it. Thank you very much. I'm open for questions.
Thank you, Dr. McCarthy, for that comprehensive update on the company's progress.
Like you mentioned, we will now move to the Q&A portion of the webcast. I already see some hands up there. Thank you so much. First of all, we are going to address some questions that have come in written, and then we will address the questions live that I see people raising their hands for. Let's get started with a few questions that we have written. Question one, Dr. McCarthy, if the AD data are positive, when do you expect the drug to be on the market, and how long does it take for the FDA to approve it?
It's a difficult question because I was telling you that we will open the blind for very few people next summer, analyze the data, have something in fall, and if it's good, file an NDA. The FDA is changing.
On one hand, they're saying that they want to make approval faster, especially for drugs that are safe, especially for drugs that have a huge unmet need. There is a possibility that we get fast tracked. There is also a possibility that overworked and understaffed is still a reality. I really don't know. If everything goes as planned, it would be about a year after we have the data. Fall of 2027 for symptomatic and fall of 2028 for disease modifying.
Thank you, Maria. All right, next question. Will there be an open label extension after the 18-month completion of AD study?
Yes, absolutely. After the Alzheimer's study, we will attach the open label. Yes.
Perfect. All right, we'll move to the next question. I see more coming in as we speak.
Is it possible to begin the regulatory submission process while the planned 18-month confirmatory trial is still ongoing?
I hope so. As I just said, it's not 100% clear where the FDA is going. But yes, McCarthy says so. Yes. Let's hope he is right. McCarthy is the new director of the FDA. Commissioner, I think, is the name.
Perfect. Thank you for that. All right, moving on to the next question that we have here. Do you have a set date for Parkinson's clinical trials, including open label?
We are desperately, and I really mean with all my strength and every minute I can dedicate, looking for money. Okay. Right now, I haven't really totally given up on open label this year, but we need to raise money, and it has been very difficult.
Okay, thank you.
When do you anticipate full enrollment for AD trial, and how long after that will it take to obtain meaningful results?
We hope to be done by the end of the year. Remember, I said we have so many patients screened, but only so few in the clinic. In eight weeks, 60% of those will be actually on drug. The beginning has been painful because, A, not all your sites are open, and B, it takes eight weeks to recruit somebody. Then you have 40% failure on top of that. We really hope to be done by year-end and then treat for six months.
Perfect. Okay. We're going to answer one more question before going to live, Mike. What is the funding status for all these anticipated programs?
I just said I'm trying very, very hard. Yes.
Good. Okay. I saw several hands.
We're going to open the floor for live questions now. Thank you, Maria. I see Jason McCarthy. You can feel free to open your microphone. All right, you're live, Jason.
Maria, thanks for taking the question. A question about the MRI approach that you had mentioned, and I think I caught it right. You're looking at MRI and imaging of the brain to show symptomatic modifications at six months, or is this for disease modification over 18 months? And if so, do you need to correlate that to specific biomarkers, and can it fluctuate with water content and kind of all of the above? Can you just elaborate a little bit more on that?
I think it's all of the above. We just had a meeting with KOLs. The trouble is that PET has been approved.
P2017 has been approved, but as a biomarker, not to show disease modification. So PET has been approved as a biomarker and for disease modification. P2017 has only been approved as a biomarker. When we finish and show the difference between P2017 here and P2017 there, and brain-derived tau here and brain-derived tau there and neurofilament light here and neurofilament light there, if we see a difference, which we believe we do because we saw it in our other studies, and can then also combine them with volumetric MRI and of different parts of the brain because it is not just the ventricle, it is a whole bunch of different parts. I am not an expert at that. We hope that is good enough. The FDA has not told us it is not good enough. In terms of PET, there is a precedent. In terms of what they are doing, there is not.
As far as the ongoing phase three Alzheimer's program, do you expect the 38% screening failure rate to continue at that rate? Kind of what are some of the key elements that are driving those fails? Is it very specific and defined inclusion criteria and exclusion criteria? Is it comparable to other large-scale trials or you just can't compare to their different drugs, different inclusion criteria, etc.?
Our calculation and our expectation was 50%. The 38% corresponds very, very nicely with the pTau ratios that we saw in our phase two three. Interestingly enough, we actually don't have that, we don't have that many pTau and MMSE, a few MMSEs, but we also have a lot of kidney and liver and kidney failure people.
We exclude them for something that's unrelated, but I'm told you don't want to have kidney failure in your study.
Got it.
This is what. To compare with others, Leqembi and Kisunla and also Presenumab or Gantenerumab, they had 80% screen fail.
Got it. This is more of a broad current, I used to call it current events question. Have the changes at FDA in leadership and departures in certain departments at FDA had any potential impact on Alzheimer's or Parkinson's drug development that you can anticipate? I know the change that occurred just last week with Brassard coming in, he was very against the Aducanumab approval in 2021, I think it was, and issues with some other drugs that were controversially approved.
The interesting thing is that I was down at the FDA meeting and I actually talked to McCarthy and I talked to Jacqui. What I postulated is that Alzheimer's disease is being evaluated the same, whether it is a biologic or whether it is a drug. I do not think it is fair that if you have a biologic, you have to jump through less hoops, especially since biologics have more side effects than if you have an oral drug. They both agreed. They said they are considering doing a neurodegenerative group that specifically looks at diseases that take a long time, take long studies, and where we are starting to look predominantly at disease modification. Now, Jacqui Lapp, I have no clue what is going to happen. I do not know.
Got it. Great. Thanks for taking the questions.
Thank you so much, Jason. All right, next, we will hear from Michael Gopes.
You are live. Mike, you could just turn on your microphone. Michael, there you go.
Thank you. Maria, good to see you. Question on the phase three trial you've entered on Alzheimer's. Just looking backwards on the last trial you did, you were much better on the symptomatic improvement than the current drug Aricept. You said you'll see if there's going to be disease modification as you go further out 18 months. I wondered if you could just clarify, the current drugs that show that disease modification over a short period of time have a totally different mechanism and treat the disease after it's already affected the brain, is my understanding. Your drug treats it, pre-solves some of the issues in the proteins in the brain.
If you could just clarify between your drug and the drugs on the market and if it's better, whether you expect to see a better result?
Yes, I definitely expect to see a better result. The short studies we did show a better result. The reason is that in the brain of an Alzheimer's and/or a Parkinson's patient or an ALS person or a Huntington's person, there is more than one neurotoxic aggregating protein. Pharma, Leqembi, and Kisunla, they are targeting a beta, which is plaque. They're not targeting anything else. If you look at the brain of these people, they have plaque, they have tangles, they have alpha-synuclein, they have Lewy bodies, and they have TDP-43. If you look, they probably may have some prions. There were some studies about that, but they have not been reproduced.
If you just remove one neurotoxic aggregating protein, you still have the others. Just think if you have four killers, you kill one. The other three still kill you. That is the beauty of our drug. It inhibits them all. Okay, that was my question. Are you seeing biomarkers on all of the proteins in the brain that have shown improvement with buntanetap? In animals, yes. In humans, not all of them have been discovered in the brain, in the blood, sorry. In brain of animals, we can reduce every single one of the proteins I showed you. In CSF in humans, we have seen a reduction in a lot of these proteins. In plasma, it is hard to do. We only have A beta-42. We only have brain-derived tau. We have some taus, some pTau's. There is not much else.
But you're showing improvement in more of these than any other drug on the market or at this point?
I don't know because I cannot really compare apples and oranges. See, Kisunla and Leqembi have shown that they reduce plaque. I don't see plaque. I measured P217. And P217 is supposedly correlated with plaque. When I have the six and the 18-month study, I will know if it goes down and it correlates with plaque. Right now, it's an assumption.
Okay, thank you.
Thank you very much, Michael. All right, we'll move to Don Tice. You're welcome to open up your microphone, Don.
Okay, can you hear me?
Yes, you're live.
Okay, my question is, for someone who has not participated in or completed any of your previous Annovis trials, when do you expect to have another clinical trial available for brand new participants?
You put me in a tough spot. I would like to do all the studies that are needed to get this drug approved for any indication it may be working on. I don't know. As I just presented to you, you're going to go for the low-hanging fruit. Number one, we have no money for Parkinson's studies. Okay, let's be very clear about that. I'm not going to do a study for which I have no money. What I presented, though, is that the first study we will do in Parkinson's is the low-hanging fruit, which is cognition. If you don't belong to the Parkinson's disease dementia patients, you're not going to be in that one. Now, if the stock goes up, if we can raise an additional $70 million, I'll do that study.
Okay, thank you very much.
Thank you, Don.
Okay, Antoine Romanos, we'd like to hear from you. You're welcome to turn on your microphone. Antoine Romanos. Okay, you're live.
Hi, Maria. Thank you for the call. My question is about the pivotal phase three study that in the chart I saw that so far you've only enrolled 11 patients out of the 760, and you're projecting to be able to have full enrollment by the end of the year, which is five and a half, six and a half months from now. How do you see us achieving that?
That's what I was trying to explain, that there are 760 patients screened. And somehow they're stuck between the eight weeks. Actually, I'm not sure that number is correct, but there are 280 patients screened that are stuck between those eight weeks, which means that in the next eight weeks, we will have over 200 more patients.
Next.
Why are they stuck?
Because it takes eight weeks between when we say hi, and we have done all the tests to know that they're early Alzheimer's disease.
Got it. Basically, enrollment's on track, and you do not foresee any issue with getting to 760 patients by the end of the year?
We are a little slower than I hoped, okay? We have been picking up quite nicely in the last month. Yes, I think we'll be there.
Got it. Thank you.
Thank you very much, Antoine. All right, we'll hear from Christy Castro. You're welcome to turn on your microphone, Christy.
Hi, thank you for taking my question. I've heard from a couple of actual participants with Parkinson's disease in the past, and they have said they had such great improvement.
Those of us who have Parkinson's disease have been waiting for the new recruits, those of us who are new to get in, like the previous person asked about. It sounds like it is going to be quite a ways down the road. Being hopeful, I am wondering in the future, what would be the soonest timeframe that you think could be possible for it to be approved for all of us with Parkinson's disease to go through our doctors and receive this drug? Are we talking five years, 10 years if everything works out? I know you do not have a question.
I hope not, okay. I hope not, but then I have been kind of optimistic a lot. Let's say, or let's assume that the six-month Alzheimer's data is good. I really believe it is because we are replicating the previous study to a T.
If the previous study, that group worked as well as I showed you, and the Forest Plot proves that it was not cherry-picked, then the present study at six months should work. The stock will go up. We can raise money. People say, "Why can't you raise money if your company is worth $50 million?" Because I cannot. I can raise 20% of who we are. I cannot raise 200% of who we are. It is just not possible. Yes, let's say that symptomatic works, we can raise $100 million, and then we can do the Parkinson's study. Since we are not doing the studies, we are talking to the FDA ongoing to get things in line for when we can do the study. It should not take that long to do it, then maybe six months later.
Okay, thank you.
I wanted to know what is on the market.
On the market, it would be three years after we start the Parkinson's study.
Okay, okay. All right. If we include that Parkinson's study, it could take a year or two, then we're talking probably five years or so. Thank you for giving us a realistic timeline on that.
Yes.
Thank you, Christie. Appreciate it. All right, we'll hear from Greg Gallo. You're welcome to turn on your microphone, Greg. You're live now.
Hey, Maria. Hi. What I was wondering is when we, I think I heard you first talk, it was $10 million in funding you were requiring. Now it's $70 million?
No, no, no, no, no. Different studies. Okay. Open label, $10 million a year. I was saying an 18-month full-fledged Parkinson's study that shows symptomatic and disease modification. Different studies.
$70 million. Let me ask you one thing, Maria.
Can we lobby our state and local government officials to provide funding? They're taking all this funding away from all these institutions. Couldn't some of that be rerouted to you? And have you also went to investment firms to see whether there's any money available there?
Yes. Yes to all of the above. Yes.
Okay. I know you're trying. We'll have to hope that you're successful.
Or open black market in Africa, something like that.
Okay. Thank you.
Thank you, Greg. All right, we'll hear from Dennis Beckman. Dennis, you're welcome to turn on your microphone. You're live now.
Thanks very much. First of all, I'm really pleased to hear you including some DBS people in your study. How do you recruit people for your open label DBS cohort? We talk to PIs and universities that do DBS. And Chang, I think she's on the call.
She actually has really good contacts, and we have started to talk to them. They're very happy to give it to their patients because DBS patients just are always left out.
Indeed, that's true. Who is that person you were talking about?
Chang Feng. She works for Annovis. She has the contacts with the PIs with the DBS sites.
Thank you.
Thank you very much, Dennis. All right, Brendan Duffy, you're welcome to turn on your microphone.
Great. Hello, Maria. I have Parkinson's. I was in your study. I was not taking the medication. Surprisingly, I felt amazingly better because the placebo effect is so powerful. My question to you is, there was some time ago I saw that study you did on the axons, how the speed of the axons was greatly increased. Is there any additional information you can share about that?
Because I found that to be particularly interesting.
We didn't really do any more axonal transport. However, what we have tried to do in humans, where you can't really look at how fast a nerve cell fires, we have looked at biomarkers in CSF that show how well a nerve cell lives and works and produces. In humans, we see an improvement in nerve cell health. Realistically, I don't know exactly how that helps. In animals, we know it is about axonal transport.
Thank you.
Thank you very much, Brendan. Good luck. Thank you. I see Greg raised his hand again. You're welcome to open up your mic, Greg. Greg Gallo.
I just had one other thought. I know a lot of us, maybe a lot of people, don't know how they became Parkinson's or Alzheimer's susceptible.
I know in my case, and this is why I say the government again, that they ought to be lobbied. I used a solvent, and I talked to a doctor, I know in Australia, actually stopped to see us last year. And the stuff I used at work, he called it nasty stuff. It claws your gut. I believe when you get to be my age or 60, 65-ish, your blood-brain barrier cannot fight off the bad stuff anymore. That is when not everybody is that way, but that is when Parkinson's starts. I imagine Alzheimer's in some people. That is why I was saying before the government ought to be funding this because they failed us.
That is blaming the environment, blaming chemicals, blaming shots to the head. A lot of things make us susceptible to neurodegeneration. You are 100% correct.
Chemicals contribute more to Parkinson's than to Alzheimer's. Hits to the head contribute more to Alzheimer's than to Parkinson's. Certain hits, just like football players or boxers, contribute to chronic traumatic encephalopathy. The reality is that you eat too many carrots. Were you protein insufficient? You eat too many carrots, you do not get protein. It seems like, oh, and then there are all the reasons about infections with viruses, with bacteria. They are all true. Every single one of them is true. There are so many things that can injure the brain. You are correct that whoever did it should pay for it. They are going to get away with it not. You know why? There are so many things that cause Alzheimer's and Parkinson's. There are so many things that cause MS.
Plus the simple fact that you breathe air, it causes something that it's really hard to prove. You see the lawsuits that are going on about Roundup, they're going to go on forever.
Yeah. A bunch of us used to use a solvent for a rubber cleaner when things were electromechanical called Fedron. It was nasty stuff. As I said, I talked to this doctor that's a neuroresearcher, also happens to be a toxicologist is what I was looking for. Okay, I think I know the path I want to take here.
Which is?
Contact local officials and government officials and start lobbying them to funnel some of this money they're saving to worthwhile causes.
Thank you. I really would appreciate that. Because sometimes I think that more money goes to pharma. Lilly gets grants of $60 million-$70 million for its studies.
I do not.
Right.
Does not Lilly have more money than I do?
It is not fair.
Yeah, but if I say that, we are never going to get anywhere. It is just called keep going.
Yeah. Okay, Maria. Thank you.
Thank you, Greg. Okay, we have time for maybe one or two more questions. Thank you so much for your hands, everyone. Let us hear from Robert Braun. You are welcome to turn on your microphone, Robert.
Maria, appreciate this Q&A session. My main question is, for us long-time investors, that is really what I have been since 2021. We want to know what we can do to help in this. We know there is a financing issue. Is there anything that you want the general public to know of something that we can do to potentially help?
Investing, obviously, is the only way to get the stock up so we can raise more money.
I really believe that the drug works. I showed you a lot of studies. There is not one study we did where we had the opposite effect. You can look at everybody else. When their studies do not work, they do not work. We are just putting one foot in front of the other. The market will get better. Raising money will get better. We will have better data. Somebody will stop shorting us someday, sometime, and we will be okay. Okay.
Thank you. Appreciate it.
Thank you, Robert. Dick Sundram, you are welcome to open your microphone. You are live.
I am Maria.
Yep.
Can you hear me?
Yes, I do.
I just basically want to thank you for everything you have done. I think the question I was going to ask, the last few people have kind of covered it.
I was just kind of wondering what patients and the public in general could do to help. I guess the answer is just hope we can get our congressmen and our government to funnel more money to you guys so that I think what you're doing is wonderful. I just wanted to basically thank you for what you're doing. When I've sent you emails asking you questions, you respond so promptly. I just think it's great. I just want to thank you.
You know, I honestly care about patients. I am in this because I really want to protect nerve cells from dying. If nerve cells don't die, you don't have the symptoms. If nerve cells stay alive, if they keep firing correctly, we can actually get rid of all neurodegenerative diseases. That's what they're in it for. Look, I'm getting old, okay?
I'm going to hang in until it's done.
Okay. Appreciate that. Thank you again.
Thank you, Dick. Okay, we'll take one more question from Justin Higgins. You're welcome to turn on your microphone, Justin.
Can you hear me okay?
Yes. You're live.
Fantastic. Thank you. I want to follow up a little bit on what Robert was saying. I joined you on your last call. I posed a question to you in that call. I'm hoping that we can make some progress on this call. The question I presented to you last time was, there's plenty of people on these calls, myself being one of them. I've actually made quite a bit of money on your stock in the last three months because I've been buying it at an unrealistically low level. It's done very well for me.
It's gone from $1.10 to, I think it was $3 and change this morning. And there's a lot of other people like that. Now, maybe their overall cost basis is underwater or not, but they are continuing to build their positions. As we build these positions, they can become uncomfortable at some times when we don't see progress, especially from the pharmaceutical world. My first question is, the conversations you've been having, are you having them with investment-oriented companies, or are you having any direct conversations with pharmaceutical companies? If it is the latter, would you be willing to discuss who those companies are offline, not on this call, obviously, because it's a public call?
We did both. I mean, right now I'm talking to banks.
Last year, when we had the data, most of the data I showed you, we actually, Mark White, who is a board member but was doing marketing advisor, he helped me. And he contacted 41 companies. All the big ones. They all took a phone call. They pretty much all said, "We do not know if it is disease-modifying or symptomatic. We do not care about another symptomatic drug. It is two and a half times better. We do not know if it is two and a half times better. It could just be a fluke that it is that good. So come back when you have more data.
" Okay. That basically is what I expected you to say.
The only real way you're going to make progress with those larger pharmaceutical companies is if we're able to set up meetings where we can convince the management of those companies that your data is better than it's been presented. Would you say that you've had some trouble presenting your data in the past?
It's not better than we presented it. We have studies that show very clearly that we have three and a half points improvement. And that receptor has one and a half to two. I didn't invent that. That's the way it is. It's one study, one large study and two tiny studies. What if we have better, the data is better than reality. When we reproduce it, we're worse than that recept.
If you want, I mean, I'm happy to talk to you about how to present it better because we were pretty much rejected. Basically, we were told, "Show us more data."
That's fair enough. There are lots of ways to skin a cat, as they say. I think progress can be made there. My last question is, I wanted to make sure that I had this correct because I asked this question the last time, and some investors that I work with also said, "We're not sure if that is what she meant." In the last previous study, there were some endpoint misses, okay? We understand why those misses are there. You explained that very well. It took a while to get it all out, but it's been out there now. Your stock took a pummeling because of those misses, and that's pretty obvious.
Now, my understanding of the six-month endpoint that you are presenting is you are doing what large pharmaceutical companies do when they have endpoint failures in their studies. You are teeing up what you believe has already proven to work in the prior study. Is that correct?
100% correct. Yes.
So the odds of the six-month study going very well would be more likely than not likely because of the endpoint development and the design of the study itself.
Yes. I would give it 99%. Okay. Give it 99%.
That's great. Thank you, Maria, for that. I really appreciate it. I'll be buying lots and lots of your stock. Can't wait to buy more.
Thank you.
Thank you, Justin. And thank you, everyone, for your insightful questions. Sorry that we're not able to take more at this time, but you're always able to contact later.
Thank you all for participating in today's webcast. We will close our Q&A section for now. We truly appreciate your engagement and your interest in Annovis Bio. As a reminder, a replay of today's webcast will be available on our website shortly. Thank you once again for joining us. Thank you, Maria. Have a great day, everyone.
Thank you very much and goodbye.