BioVie Inc. (BIVI) Earnings Call Transcript & Summary

Hello, everyone, and welcome. This is Paul Kuntz with RedChip Companies. I want to thank everyone for joining today's event with BioVie. BioVie trades on the NASDAQ under the ticker BIVI. With us today, we have Cuong Do, President and CEO of BioVie. We will begin with a brief presentation in a moment and then we open up the event for your questions. You can submit your questions at any time by using the Q&A tool at the bottom of the Zoom window. Before we begin, please allow me to read the safe harbor statement. This call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements pertaining to future financial and/or operating results, along with other statements about the future expectations, beliefs, goals, plans or prospects expressed by management constitute forward-looking statements. Any statements that are not historical facts should also be considered forward-looking and, of course, forward-looking statements involve risks and uncertainties. With that, I will now turn the webinar over to BioVie's President and CEO, Cuong Do. Please go ahead.

Thank you, Paul. Thank you, everyone, for joining today and good afternoon. I'd like to give us an update and a bit of a recap of where we stand over the course of the year. Just a reminder, we have 2 assets in the company. Our lead asset is a drug called bezisterim, formerly known as NE3107. It is a novel inhibitor of TNF alpha and in clinical trials that's been shown to be able to reduce inflammation and the associated insulin resistance. Our Parkinson's patients have seen improved muscle control in our earlier Phase II trial. Alzheimer's patients have experienced a 68% slowing of cognitive decline after just 6 months of treatment, and everyone has experienced lower levels of DNA methylation, essentially a modulation of the biological aging process. We can go into some of this later as part of the Q&A, if you like. Our second drug candidate that we don't spend enough time discussing is BIV201. This is essentially the origins to company. This drug is being developed for ascites, which is late-stage end-stage liver disease. It's a condition that have over 50% mortality rate within 12 months, right? So it's a horrible condition, then we'll spend a little bit of time discussing today. Before we go into each one of these, I'd like to give a bit of a status update, so a timing update and outlook for what to expect over the course of next year. First is our Parkinson's trial. We are currently conducting a Phase IIb in Parkinson's, as you know, and we'll go into greater detail on that program in a minute. But the update is that program is now almost fully enrolled. We are almost complete with enrollment and we expect a full enrollment by the end of this year. And this is a 3-month treatment duration trial, which puts us in a position to expect to have top line data readout in May 2026. So Parkinson's is nearly fully enrolled, we expect full enrollment by the end of the year, top line data readout in 2026. In addition, we are currently conducting a Long COVID trial. Enrollment in this trial is accelerating. As of now, almost all of our clinical sites are fully up and running and active. I believe that only one academic site is still in the late stages of getting ready. We expect full enrollment of this trial in late February. And as such, we expect top line data readout in summer of 2026. As the trial proceeds, we accumulate -- we monitor what's going on with the subjects on a daily, weekly basis. First off, we have to monitor for safety, just to make sure that there's nothing crazy that's going on. And there's been no safety concerns in what we see so far. So blinded data is accumulating on a daily basis. And we would expect to have sufficient blinded data in late first quarter to be able to start to see if there are any patterns on the efficacy side of the equation. And what we're hoping to see, of course, is a spreading, a spread to start to develop, right? We hope to see that those -- a group of people who are getting better and then there's a different group of people who are getting worse or not improving. If there's a beginning to be of a spread, that starts to give us a signal that the drug may be doing something and that may give us a sense of what to expect when the data becomes fully unblinded, right? I underscore May here because when data is blinded, there are still many things that could go wrong, right? But if there's no spreading patterns and so forth, that gives us a different thing to start thinking about versus when there's a spread in the pattern of the data that we start to see. And lastly, on our ascites program, you may recall that we terminated the trial early so that we can engage the FDA in a conversation on what it would take to move to Phase III and register the trial. As of now, we have received all feedback that we need to move into Phase III from the FDA. And since we already have orphan and fast-track designation, we only need one Phase III trial to be completed and to register the drug. And that's up now. We are exploring partnering and other funding options that we hope to give a further update in the first half of next year, right? So that's the quick update. Now let's go into deeper a bit. As you know, we believe that inflammation is the root of all things that start to go wrong in the body, and it really starts with TNF alpha. TNF alpha is considered to be the master regulator of inflammation. When you have TNF alpha it drives the release of a bunch of cytokines, chemokines and other things that leads to a pro inflammatory inflammation cycle, which has been implicated by a number of these diseases that you see here, right? And once you have TNF alpha and inflammation, it drives something called IKK and JNK, which leads to insulin resistance, which, of course, is associated, implicated in diabetes, metabolic diseases and Parkinson's. We'll come back and discuss Parkinson much more, right? TNF alpha draw also drives something called DNA methyltransferases 3A and B which drives DNA methylation, which essentially is playing with the biological aging process. And it turns out that our drug candidate affects inflammation in just the central node and involving ERK and NF-kappa B. It's been known for decades now that ERK plays 2 very different roles in virtually every cell in our body. The first involves insulin signaling. Insulin goes through a series of steps involving insulin substrate receptor 1 and 2 IRS 1 and 2, and eventually activates ERK for all of its cellular growth repair and regeneration activities. This is known as homeostatic ERK. But ERK is also involved in inflammation, right? So different extracellular signals such as cytokines, chemokines, who enter the body will activate MEK and activate ERK. When ERK is activated, which then that incurs activate NF-kappa B and triggers the production of TNF alpha. When you have TNF alpha, it creates a forward-feeding pro inflammatory cycle that leads to more inflammation. So it's obvious what you want to do. You want to block inflammatory ERK, but not touch homeostatic ERK. Unfortunately, that is much easier said than done because dozens of teams have tried over the years, but they all failed. All of those drug candidates failed due to toxicity because no one was able to create a selective enough inhibitor of just inflammatory ERK. It was touching insulin signaling as well. And whenever you touch insulin signaling, you're going to create toxicity problem. And that's where bezisterim comes in, right? And to be frank, we did not set out to do this. We got lucky, right? We just had our eyes open when we observed this effect. It turns out that bezisterim blocks the activation of ERK and NF-kappa B, as you can see here. And when you block the activation of NF-kappa B and ERK, you do not have the production of TNF alpha, right? And when you do not have TNF alpha, you do not have insulin resistance, right? As I mentioned before, insulin resistance is triggered by TNF-alpha, activating ERK and NF-kappa B. It is triggered by the insulin substrate receptor 1 and 2. It turns out that naturally insulin binds insulin substrate receptor 1 and 2 on a tyrosine residue, which then goes through this natural process here. But when you have inflammation, JNK and NF-kappa B also activate and it binds to the IRS 1 and 2 on the serine residue, right? So when the serine residue is activated and occupied, it blocks the tyrosine site and insulin is not then able to bind into the tyrosine site. And that's how you have insulin resistance, right? It's inflammation, activating JNK and IKK, activating the serene site and IRS 1 and 2, which then creates insulin resistance. And by bezisterim's ability to block NF-kappa B and thus the production of TNF alpha, it's believed that we're actually alleviating the activation of JNK and IKK. We're opening up -- we're freeing up the serine site, opening up the tyrosine cytokine. So I know that's a lot of science and a lot of mechanism there, but that's critical to understand how the drug works. And I have to first turn to Parkinson's. Two things need to be true at the same time for a person to develop Parkinson's symptoms. And this has been known for decades. The first is that you need to have low dopamine levels in the brain and then the second is you need neuro inflammation and the associated insulin resistance in the brain. If you're somehow able to reverse the insulin resistance in the brain, the brain is then able to make use of whatever level of dopamine that's there and help to restore muscle control. So people have tried for a long time and tried lots of different ways, lots of crazy things as well to try to reverse insulin resistance in the brain, including this study, which used inhaled insulin just to try to get more insulin through the nose up into the brain so that you can free up more glucose. And it works. If you're able to get enough inhaled insulin up into the brain, you create more glucose and the brain then is able to make use of the dopamine that's there. That's what you see here. But of course, that's not a very practical thing -- solution to use, right. Inhaled insulin to treat Parkinson's. It's not a very recognized solution. And nothing else has been very practical. And as a result, the drug levodopa remains the standard of care for treating Parkinson's over 5 decades after it was introduced, right? Now levodopa is a great drug. It is a really, really good drug in restoring muscle control, and that's why it remains a standard of care. But there are a few problems associated with levodopa. The first is that it has a short half-life. Such that Parkinson's patients end up having to take it every 3, 4 hours or so which then becomes a real problem overnight when you go to sleep, right. When you go to sleep, levodopa wears off, so that in the morning, you're rigid, your muscle is rigid, you can't get out of bed. So that's one problem associated with levodopa. The second is that the effect of the drug wanes over time. So the longer you take the drug, the higher the dose you need to have just to get that effect. But as you get into higher and higher doses because of something called levodopa-induced dyskinesia, which is the tremors that you see many Parkinson's patients have. And when you have the dyskinesia, all you can do is to cut back on the levodopa dose and wait for the dyskinesia to pass. But as you cut back on the levodopa, you lose muscle control and you are rigid, right? So it's a terrible, terrible situation that Parkinson's patients have faced, right? And that's why that we believe that bezisterim may play a role in addressing this problem. In our preclinical research, we found that in mice and rodents, and in nonhuman primates, in monkeys. We found that bezisterim was equally effective as restoring muscle control as bezisterim. Now that is a huge statement right? Because over the decades, nothing has been able to equal levodopa in its restoration of muscle control. But here, we found that bezisterim alone was equally effective as levodopa in restoring muscle control in rodents and in monkeys. And what we also found is when you use it in combination, when you give bezisterim in the combination of levodopa, you saw a synergistic effect. We saw a significant -- a statistically significant improvement in muscle control when used in combination, right? So this is a disease score, so a lower score is better. The other thing we found is that when we use it in combination, we saw a reduction of dyskinesia. This is a very complicated chart to read, right? So when those monkeys that were given a placebo and levodopa right? So levodopa alone, as shown in the thin green line here, you see many abnormal involuntary movements. So very many tremors, right? So the distribution skews to the right, but when you give bezisterim and levodopa, you see that the distribution skews all the way to the left. It dramatically reduced the incidence of dyskinesia. And what got most people, all of us, very excited is that at the end of the study when we sacrificed the monkeys and looked at their brains. We found that those that were treated with bezisterim retained twice as many dopaminergic neurons as those that were in control, suggesting that there is a neuroprotective property to the drug. And this to us is not at all surprising, right? Because we know that bezisterim reverses insulin resistance, which means that there is greater glucose availability in the brain. We also know from various imaging studies and other ways that bezisterim enhances blood flow to the brain, which means there's greater oxygen availability in the brain. So when you have greater oxygen and glucose availability, it only bodes well for better neuronal health, right? So this was terrific work that, frankly, we were pointed in this direction by funding that was provided by the Michael J. Fox Foundation. So we're grateful to them and they continue to help us for our trial today. So based upon this research, we wanted to go into the clinic. And so we enrolled 40 moderate-to-severe Parkinson's patients and essentially replicated in human patients, a study that we did in monkeys, right? So what we did is we gave half the patients placebo and levodopa, essentially just levodopa alone, as shown in red here. And we get the other half, bezisterim and levodopa. So the combination is shown in blue. And after 28 days of treatment, we saw that those that we treated with the combination experienced a greater than 3-point advantage on the Part III score or the muscle or motor score of unified Parkinson's disease rating scale. Now that's a clinically meaningful difference. But if you look at patients who are younger than 70 years old, which is about half the population that was in this trial, that difference was somewhere between 4 and 5 points. Now that's a big difference that you do not see very often. But the other thing that was very terrific to see has to do what's called the morning on symptoms. As I mentioned before, levodopa wears off overnight. So this happens every day in life and have been in this trial. In this trial, patients would come into our sites, they would take their evening medications and go to bed. And then first thing in the morning before they take their morning medication, we would measure the muscle control again. And what we found is that none of the patients that were given to placebo and levodopa, so just levodopa alone. None of those patients have their muscles in the on state, none of them could move, none of them could get out of bed. So their muscles were considered to be in the off-state, but about 1/3 of the patients that were given the combination of bezisterim and levodopa had their muscles in the on state, right? And this was an unexpected statistically significant finding, right? This was a small trial, so we did not expect statistical significance on this, but we had statistical significance, partly all driven despite the magnitude of the impact that bezisterim has. So this gives us human proof of concept that you can use bezisterim and levodopa to help moderate and severe Parkinson's patients improve their muscle control, and it establishes the first half of what we want to show in Parkinson's. We are -- right, which is you can use bezisterim and levodopa in combination to help moderate-to-severe Parkinson's patients. We are now embarked in the middle of another trial to establish the second half of what we want to show, which is bezisterim can be used as monotherapy. So it can be used alone earlier in the disease progression, right? So we are now enrolling 60 patients in a trial of Parkinson's patients who needs to go on to treatment for the first time to treat their disease symptoms. Half of patients will be enrolled, it will be randomized to placebo, and then the other half will be randomized to just bezisterim alone. This trial will run for 3 months and what we're hoping to show is that those patients that are treated with bezisterim will have a slowing of their loss of muscle control, right? Whereas we believe that those on placebo will have greater muscle loss -- motor control loss, right? And the other thing is that we expect -- we think what may happen is that a greater proportion of patients that are in the placebo arm may need to drop out of the study as well so that they can go on to levodopa, right? This is a short and small study. It is only 3 months long. It's only 60 patients large. In many ways, we do not expect to see statistical significance in the Part III score here because it's an exploratory study. And what we're hoping to see is the magnitude of the impact at the Part III score so that we can power the Phase III study. But we are fairly confident that when we'll see statistically significant changes in many of the component pieces that lead that contribute to the Part II score, the Part III score and the various other endpoints that we are doing. So this trial is almost fully enrolled, right? And we expect this to be fully enrolled by the end of the year. We expect to have data coming out of this trial in the May time frame of next year that would allow us to power the 2 Phase III trials that we would expect to run. The Phase III program will have 2 parts to it. The first part would demonstrate symptomatic relief, right? So that would be a short 3, possibly 6-month study to demonstrate that we could give symptomatic relief to new, to patients who need to go on to therapy for the first time. But we will continue to follow these patients in an open-label study for another year in anticipation of demonstrating disease modification, right? And when taken in totality, we believe that this would allow bezisterim hopefully to become the first newly -- the first new therapy for Parkinson's patients in over 5 decades. The first new therapy that would be able to restore muscle function in a manner that's equal to or better than levodopa, and also could be used in combination with levodopa for more severe patients in the disease -- with the disease. When fully developed, we believe this could represent a $3 billion to $5 billion annual sales opportunity in the United States alone, right. With that, let me move on to our work in Long COVID, right? And you may think and ask the question, why Long COVID, what does Long COVID have to do with Alzheimer's and Parkinson's. And the short answer is really very little, except the mechanism of action, and it's also CNS related. Long COVID is defined as having persistent symptoms, at least 3 months after the infection has been beaten, but many of us have moved on. The world has moved on, believing that Long COVID -- believing that COVID has been beaten. It's behind us. But the reality is thousands of patients are still getting infected with COVID every single day in the U.S. right now, right? And 17 million Americans are currently suffering from Long COVID symptoms, primarily brain fog, fatigue and malaise. And roughly 3 million of these Americans have the conditions so severely that they have had to quit or change their job simply because they can no longer keep up with the physical demands of the job, right? There are people who have difficulty staying out of bed for more than 2 or 3 hours, right? Or people who just cannot focus and have the cognitive function that they used to, right, 3 million. And this is part of the reason why there are so many large Long COVID centers out there, particularly at academic medical sites, right? We did not know any of this, right, until some of the experts we were working with turned us on to it, right? We were really focused on Alzheimer's and Parkinson's. But what the experts really turned us on to is that within the last couple of years, researchers have tied Long COVID symptoms to inflammation. And it's really working through 2 things: the spike protein and the envelope proteins. What happens is that for these 17 million and perhaps even more Americans even after we have beaten the infection, you could have fragments of the spike protein and the envelope protein continuing to circulate around in your bloodstream, in your body. And as a result, the body's immune system believes that there's still an infection. So it's constantly mounting an immune response. And as such, it's creating inflammation, okay? Because the spike protein is working through the pathway TLR4 or toll-like receptor 4 and then the envelope protein is working TLR2, both TLR2 and 4 is a couple of steps upstream from the activation of ERK and NF-kappa B. And that's the reason why we and many other experts out there believe that there's good reason to believe that bezisterim may be able to block the activation and the production of TNF alpha and block inflammation for these patients. We were made about known -- we were alerted to this by our experts. And they also told us of the various grant programs that were available out there. So we applied for a grant and we were given a $13 million grant to fully fund an exploratory trial in Long COVID, right? This grant allows us to enroll over 200 patients. Half of the patients will be given placebo and the other half will be given bezisterim twice a day. And as of now, this trial is enrolling very rapidly. Acceleration -- the enrollment is accelerating. We have one academic site that is still in the final stages of getting activated. And as such, we expect this to be fully enrolled by the end of February, which puts us in a position to have top line data readout in the summer time frame. To be fully transparent, we do not know what to expect in this trial. We have no preclinical studies to give us a hint. There are no preclinical models of Long COVID that's reliable in this arena. So we do not know what to expect. But mechanistically, we know that this makes sense. But the other thing that we do know is that there are a good number of patients out there who do not qualify for this trial. For example, you may not qualify because of the age, right? And you may not live near one of our sites. So over the years, we also have had -- we have also supported something called investigator-initiated trials. Where we would support various researchers who may have a plausible theory as to how bezisterim may contribute to addressing a need that their patient may have. And as such, we have supported trials in traumatic brain injury, ALS and so forth. We've had some researchers come to us asking for support for their patients in Long COVID. So we've had several patients supported through this. And through those IITs, all the patients have gotten better, right? All the patients in these investigator-initiated trials have gotten better in their cognition and their malaise and fatigue. We know of 1 patient who frankly was just not able to stay up for more than 2 to 3 hours at a time. This was a very accomplished person who was older in age, but thus could not qualify for a trial. And just could not stay up and rarely left his house. He got so well that he was able to go on vacation this past summer, right? And we basically -- he and his clinician are very happy with his progress. His various endpoints, the scores that we measure in this, it's all improving, and his clinician is preparing a case study right now that we hope to publish relatively soon, just to tell the world on how this one particular patient is improving, right? So that is a sample of one. But if that sample, coupled with some of the blind data -- blinded data that we're beginning to see in this trial continues to develop the way that we think it would develop. We believe that there's a very good chance that we may see statistically significant improvement for patients in either fatigue and/or brain fog. So we're looking at all combinations of fatigue alone, cognitive functions alone or the combination of the two. And if should we see that results, statistically significant result in either of those -- in any of those combinations. One thing that we're working towards right now is a conversation with the FDA sometime later next year about an emergency use authorization for an accelerated approval. Because there are many, many patients out there, 13 million -- 17 million patients affected, 3 million very severely. So the unmet medical need is very high. There are no approved therapy for this condition. So patients really have nothing to help them, right? And that's why the emergency use pathway is there, right? And we are eagerly working and eyeing that pathway as a possibility of what may unfold next year as we unblind the study next summer. So with that, let me stop here and be mindful of time, let me move very quickly on to ascites, which is end-stage liver disease. Ascites is condition that you get to when the liver has been very, very scarred. By this point, you've gone through fibrosis, cirrhosis and so forth and the liver has been so scarred that it is no longer able to process fluid the way it normally does. And the kidney is also implicated at this point in time. So as such, fluid accumulates in the abdomen, right? And since there's no therapy for this, the only solution is to stick a large needle into the abdomen and physically remove the fluid, right? And since nothing has been done to address why the fluid accumulates in the first place. These patients are back in the emergency room at the hospital every 1 or 2 weeks to get another 5 to 10 liters of fluid removed. So you can just imagine the strain that this puts on to the body. This is just not water, right? This is -- think of it as serum, so there's protein. There's lots of other things that are in, nutrients that are in this fluid. So these patients end up being malnourished and many other things, right? And so frankly, the only treatment objective at this point in time is to try to keep the patient alive for as long as possible so that they may qualify for a liver transplant. And since there are not enough liver transplant to go around the mortality rate in this condition is over 50% in 12 months. So it's a horrible condition where there's no current therapy. We believe that our drug candidate, BIV201 may be that first therapy. It is a novel formulation of a drug called terlipressin. Terlipressin is a very, very potent vasal constructor that was first approved in Europe in the mid-80s, right? It's -- first of all, it's a peptide. So it has to be refrigerated. It's very potent. So you only need 2 milligrams of this drug. So how it works is that you would measure 2 milligrams and put it into an IV bolus and you give it to the patient, which then causes a severe constriction of virtually all the blood vessels in your body. And this was first approved to treat a condition called bleeding esophageal varices, which is a complication from ascites, whereby the patient is just bleeding out, right? So terlipressin represents the last chance a clinician has to try to stop the bleeding and prevent the patient from bleeding out, and you would use it despite the fact that this creates a big blood spike of the drug, which then creates all kinds of side effects. You'll put up with side effects if you can try to keep the patient alive. So this has been used abroad for a very long time. So we know that the drug works. But it was not approved in the U.S. up until very recently because of this dramatic severe side effect, right? And what we do instead is we take the same 2-milligram. Through a novel formulation, we're able to put it into a continuous infusion pump, keep it and use it at room temperature instead of having to be refrigerated. We can use that at room temperature, cook it up to a portable infusion pump and drip it into patients slowly over the course of the day. We conducted a Phase IIa starting to evaluate safety, and we found no drug-related safety concerns. We then moved on to a Phase IIb trial to try to measure the magnitude of therapeutic impact here. So how much can we actually affect the efficacy side? We intended to enroll 30 patients, but after just 15 patients, we already had statistically significant data to show that those completing treatment saw a 50-plus percent reduction worth of ascites fluid, with just the treatment. Whereas those on standard of care saw no change, right? And in fact, one patient did not have to go back for another paracentesis, right? And since the mortality rate is so high here, we concluded that the only ethical thing for us to do as a company is to stop the study early and to engage the FDA in a conversation to see what it would take for us to go into Phase III trial to get this drug registered. And since we already have orphan and fast track designation, we only need to complete 1 Phase III trial to get this registered. As of now, we have received all the feedback we need from the FDA to proceed with this program, right? And we are in conversations and exploring various partnering and other funding opportunities to launch this program. We hope to give a further update in the first half of next year as to when this program could be launched. And from funding, from the moment we have funding, we believe this drug could be on the market in as short as 3 years, right, because we only have one trial to conduct. But this is a complicated trial. This will be a global trial that will be led out of Europe by our principal investigator out of Italy, who is the most experienced person in this field. All right. So let me just stop here and summarize. BioVie has 2 drug candidates. Bezisterim is currently in the clinic for Parkinson's and Long COVID. The Parkinson's trial is expected to be fully enrolled by the end of this calendar year. As such, we expect to have top line data readout by May of 2026. Our Long COVID trial is currently enrolling. We expect that to be fully enrolled by the end of February, which puts us in a position to have top line data readout by the summertime. And in addition to that, our liver disease program or ascites program has received all the feedback we need from the FDA to proceed. We are now exploring funding options, and we hope to start that program sometime next year, and we'll give additional feedback and update in early part of -- the first half of next year. With that, and being mindful of time, let me open it up for any questions that you may have. Thank you very much.

Great. Thank you for a great presentation, Cuong, as always. We are, as Cuong just said, going to open up the event for questions. [Operator Instructions] What company manufactures levodopa?

Levodopa is currently a generic drug. It has been on the market for quite some time, right? So that is generic. Many manufacturers make it.

And our next question, how can somebody in Virginia get into the Parkinson's study?

It may be too late right now. But the Parkinson's trial actually has a very innovative design and a very unique design, whereby we send patient -- nurses out to see the patients. One thing you should know is that Parkinson's is actually a very difficult trial to conduct because by the mere fact that a person is going into a clinical site, that person thinks that he or she is going to get better treatment, and that may trigger a placebo effect, right? And many trials have failed or have seen less stellar results simply because of this placebo effect. To avoid that placebo effect, we did 2 things in the innovative design for current trial. One of those is that we send patients out to their homes. So that we can actually keep everything as constant and as stable as possible. And when the nurse goes out to the house, everything is videoed, right? And all the videos, both from the in-home visits as well as those from our in site visits are then centrally rated by a team of 3 expert reviewers. That way, we try to keep everything constant for the patient, and we keep everything consistent across all the sites, all the patients because we have the same 3 people reviewing. I give that context because you can go to our website, there's a place that you can contact. You can put in a contact to see if you may qualify. And if you qualify, we can send a nurse out to your home in Virginia or anywhere else in a contiguous 48 states in the U.S. But as I said, we are very close to full enrollment right now. So you need to hurry and there's no guarantee that there's still time to qualify for the trial. Hopefully, that answered your question.

And our next question, do you think you have an open-label extension on the current Phase II Parkinson study?

We are currently not planning on an open-label extension. But again, in the design of the trial, we do have a data monitoring committee that is unblinded to the data as we go along. And it may be very possible for any number of reasons that data monitoring committee may come back to us and may recommend doing an open-label extension of the trial, particularly if there is -- if the patients are getting benefit from a treatment, it would be a shame to discontinue treatment that those patients are benefiting. So we may consider an open label, but that really depends on the data monitoring committee.

Thanks, Cuong. And couple of related questions there. Are any Alzheimer's trials under consideration? And where does the Alzheimer's program fit with the Parkinson's trial.

The Alzheimer's program right now is on hold. You may recall that we conducted an Alzheimer's trial a couple of years back and when we unblinded the data, we found that those treated with bezisterim for 6 months saw a 68% slowing of cognitive decline compared to placebo, right? And the #1 reported safety concern was a mild headache reported by fewer than 8% of patients, right? And that mild headache disappeared after a day. And to give you context between those -- for those numbers. You may also note that there are 2 drugs currently on the market to treat Alzheimer's. These are known as antibodies to the amyloid plaques. And as a class, these drugs have been able to demonstrate a 30% slowing of cognitive decline after 18 months of treatment. And that's part of the reason why clinicians question whether or not there's a real therapeutic benefit at all with these drugs, 30% slowing of cognitive decline after 18 months of treatment compared to bezisterim slowing of 68% of slowing of cognitive decline after just 6 months of treatment. In addition, the monoclonals have significant concerns about safety. Particularly around brain swelling and brain bleeding. And that's why these patients have to be monitored by PET scans. Now I get these numbers, not to mean, not to imply a head-to-head comparison has been conducted. No head-to-head comparison has been conducted. These are just results that have been reported by various studies out there, right, that they are the best that we can have at this point in time to try to draw any kind of comparative -- comparisons. But the problem we ran into then is that we had a problem whereby we had to exclude patients from 15 clinical sites who did not properly follow a protocol. And by excluding those patients, we missed our statistical significance, right? We are convinced that drug works, but we just missed on statistical significance 2 years ago. So we have every intention of redoing that trial. So what we are doing now is waiting until such time as funding becomes available and we will restart the trial at that point in time. Funding could come from a partner, but it could come from when we have positive results from Parkinson's and Long COVID that may create a catalyst for us to go and raise some additional funding as well. Hopefully, that answered your question.

Thanks, Cuong. And next question, have you had any discussions about partnering with a large pharma company to help fund more accelerated trials?

That's a great question. We've had a good number of conversations with big pharma companies, larger -- big pharma, right? And we know that a number of them are very intrigued with this mechanism and they're waiting for data. They were waiting for the data that we hope to have had 2 years ago. And when we missed on statistical stats, they basically wished us well, urged us to redo the study, and they'll be waiting for us when the data completes. And I get it. I've been on their side of this table, right? The world out there is littered with promising molecules in Alzheimer's that failed in Phase III. And in big pharma, no one has ever been fired for playing it safe. You only can get fired for playing -- for essentially going out on a limb and losing, right? So that's why big pharma like to play it safe. And they eventually will overpay and so forth, but that's okay. So it's really -- the onus is now on us to go and do the Phase III in Alzheimer's. If we get positive statistically significant data from this Phase II trial, there may be an opportunity for engagement with big pharma, but more likely, we'll probably need to go and do the phase III trial in Parkinson's ourselves as well. But if we get statistically significant data in Long COVID and guidance from the FDA for how -- for emergency authorization, I think, that is we will be high target for a takeout or a partnering conversation at that point in time.

And our next question, given the changes at the FDA, are you concerned that there will be any delays in obtaining the approvals you need to move forward?

That is always the risk, right? But maybe we are experiencing an anomaly or frankly, what we are experiencing may not be the kind of stuff that makes headlines. But what we're experiencing right now is timely engagement with the FDA. We have not seen any meaningful delays in our conversations with the FDA on the trials that we are conducting or have been in discussions with them, right? So we're hopeful that, that will keep up.

Thank you, Cuong. And back to the previous Alzheimer's drug trial, did you ever take legal action against the testing centers that disrupted the trial?

Great question. This actually ties into the conversation about funding for Alzheimer's drugs. All -- many investors have asked me to basically unleash the lawyers, go after the 15 sites and get compensation that could be used to help support the next Alzheimer's trial. And we will do that. We have not done it so far. The approach that we have taken is to support the FDA and the DOJ, the Department of Justice in investigating these sites. We know that the FDA has set up investigators to the sites that have been the most active enrollers of patients in our trials. We know that the FDA has been handing out 483 citations, which basically says that you failed to adhere to the protocol and did not conduct a trial in the, right? And we're just waiting for them to take the appropriate next step and render their findings. Because the -- they have far more investigative power than we do. So we'll give them a little bit more time in hopes that they will make their findings public at such time, we will initiate our steps, but we only have so much patients. So we will rethink how long we wait for the FDA and we'll give you more guidance on that over the course of the first half of next year.

Thank you, Cuong. And I think we have somebody with their hand raised. We'll get to you in one moment. Another question we had. You've been talking to major pharma companies for the liver ascites drug for quite some time. Why have there not been any takers?

Great question. I wish I had a good answer to that, too. There is one midsized pharma company that is the most logical partner for us to work with on this program. But unfortunately, they have been held up by their own internal changes, management changes, mergers and so forth. But luckily, that is now behind them. And hopefully, management is able to focus a bit more on some other things beyond the internal challenges. We know that the scientists in those -- in that company really likes this program. We've been in discussion with the scientists for years, and they really want to work with us, but they have never been able to get this thing up and get the attention and support of management. And now that, that is behind us. We're hoping to essentially get this elevated in management to initiate those conversations. The companies that have shown much greater interest, unfortunately, are smaller companies. And they, like us, have had to go through a very difficult fundraising environment, right? And we need to raise $25 million to really initiate this next phase. And for small companies, raising $25 million to supportive program that you're going to partner on has been a tall order, and that's the reason why all these companies have been trying to raise the funds and have not been able to raise the funds to come back to us to initiate this program.

Thank you, Cuong. And we're going to go to Mike, you can help me here to let -- [ Mike Samuels ], you have a question here.

Cuong, a quick question. In the past couple of years, we've been doing these tests. We've had multiple reverse splits, multiple money raising. Currently, do we have enough funds on hand to get us through how far?

Yes, great question. Thanks for that. As of now, we have sufficient cash to go to 4Q of next year towards the tail end of 2026, right, which is plenty of runway to allow us to have the 2 data readouts that I mentioned before. The Parkinson's readout is expected in May, the Long COVID readout is expected in the summer, right? We do not anticipate needing to raise cash between now and those readouts. I can never say that we will never do it. Somebody comes to me with an offer that cannot give up, cannot refuse, I'll consider it, right? But at this point in time, we are not considering nor are we actively trying to seek additional funding. We have sufficient cash to go beyond the 2 catalysts that we expect for next year.

Thank you, Cuong. And coming up on an hour now. So I think we will just try to wrap things up here. Just sort of a final question. What milestones should investors expect over the next 12 months?

We have a good number of milestones coming up and this is part of the reason why I believe BioVie represents a terrific investment opportunity for investors who have a 12- to 18-month planning horizon. We have a Parkinson's trial that is almost fully enrolled. That trial is expected to read out in May, which will provide a catalyst at that point. Our Long COVID trial is expected to be fully enrolled in February, which puts us in the position to have top line data readout in the summer. We also have an ascites program that is frankly the most derisked program I've seen in my career of developing drugs, right? And we are exploring a number of funding opportunities that may be able to allow us to start that trial sometime next year. Any one of those 3 programs will create significant upside for shareholders and put the numbers on to these. Parkinson's, we believe, could become a $3 billion to $5 billion annual sales opportunity in the U.S. alone for bezisterim. Long COVID, if you just take 10% of the 3 million Americans who suffer from the most severe form of Long COVID. This could become a multi-tens of billions of dollars drug as well. And the ascites drug could be easily $1.5 billion to $2 billion annual sales drug. In any way you want to discount, risk adjust these drugs. It will lead you to a value that is significantly more than our current market cap of $10 million to $15 million. We unfortunately have been left for dead and essentially been ignored just like many other micro-cap biotech companies. We are trading, our market cap is less than half our cash, right? And that's the reason why we spend a lot of time trying to tell the market about our story, and we try to prepare everybody for the catalysts that are coming in 2026. So 2 major data readouts in 2026. That would hopefully provide catalyst for our share price in our stock. With that, I thank you very much for your time this afternoon. If you are a current investor, thank you for your support. We hope that next year will be a pleasant one for our shares, right? And the -- for those that are not shareholders, really study what we do and considering -- weigh the facts. And we hope that you fully get to understand our story. There was a question we did not get around to as to why there has not been more insider buying. The reality is I have participated and bought every time that the lawyers have allowed me to do so, right. I am a strong believer in this drug, not only because I'm the CEO, right? I'm putting my money where my mouth is. At one time, I was one of the largest shareholders in the company as well. But because I have nonpublic material information, I often cannot invest and buy more shares, right? And that is the same with much of the management team. All right. So with that, I thank you for your time. I wish you a great day. Thank you very much. Bye-bye.

Thank you, Cuong. And for our audience, if you do -- for more information on BioVie, you can always give us a call here at RedChip at 1-800-REDCHIP or you can e-mail us at [email protected], which is the ticker symbol [email protected]. And of course, you can also visit the redchip.com website to the BioVie page at biviinfo.com. There you can actually view and download the investor presentation, fact sheet. You can also sign up for news alerts to stay abreast of all the developments as they happen. With that, I want to thank all of our attendees for their time today. And again, thank you, Cuong, for once again joining us, and we look forward to having you back.

Thank you. Have a good day.