Our next company today in the RedChip Biotech Investor Conference is BioVie, ticker BIVI on the Nasdaq. Presenting today will be Cuong Do, CEO and President. Cuong, are you there?
I'm here, Greg. Thank you so much. Happy to be here.
Great to see you again. We're so happy that you have been able to make it today. Will you be showing your presentation today?
I will.
Okay. Bring it on up. Make sure that's okay. Meanwhile, I will read the Safe Harbor statement. This segment 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 statements, and of course, forward-looking statements can involve risks and uncertainties. As is the case throughout our webinar today, if you have a question and you're on Zoom, click the Q&A button at the bottom of your Zoom window. A text box will appear, and you can then submit your question. Thank you very much. Cuong, I'm done. Please go ahead.
All right. Thank you, Greg. Thank you everyone for joining today. Just very quickly, my name is Cuong Do. I'm the President, CEO of BioVie. I'm a biochemist by training. I spent 17 years at McKinsey, where I helped build the healthcare practice there. Since then, I've been serial Chief Strategy Officer for companies including Merck and Samsung . I've also started three biotech companies myself, actively invest in biotech startups, serve on their boards. That's how I got to BioVie. I put in some early money into the company, sat on the board to shepherd through program in liver disease. A few years back, I came across a molecule that I was convinced would become the first truly effective drug for Alzheimer's and the first new treatment for Parkinson's in decades.
From my board seat, I orchestrated the acquisition of that asset, and at that time, the board asked me to step in to lead the company. At BioVie, we have two assets. Our lead asset is a drug called bezisterim. This is a drug that we acquired, which is a novel modulator of TNF-alpha production. In various clinical trials, it has shown that it can reduce inflammation and reverse insulin resistance. Parkinson's disease patients have seen improved muscle control. Alzheimer's patients have seen a 68% slowing of cognitive decline, and everyone experienced lower levels of DNA inflammation. Essentially, this is a modulation of the DNA of your biological aging process. I'm on my laptop, so sorry, things are moving around unexpectedly. Our second drug is BIV201, which is the legacy of startup the company.
It has the potential to be the first therapy for ascites, which is an end-stage liver disease condition that has greater than 50% mortality. We have two imminent near-term catalysts. These two will be in June this year, so just a few months away. Our top line from our long COVID trial is expected to be out before the end of summer. As I mentioned, we all know insulin resistance. Our drug candidate is bezisterim, which is orally bioavailable, so patients take a capsule in the morning and one at night. It freely crosses the blood-brain barrier, and it works through something called ERK and NF-kappaB. Essentially, it blocks the activation of ERK and NF-kappaB to prevent the production of TNF-alpha. If you don't have TNF-alpha, you prevent more inflammation. You also prevent activation of ERK and JNK, and therefore, that reverses insulin resistance.
Insulin resistance, we believe, is actually the key to many various disorders. It starts with inflammation. Your inflammation then triggers and drives insulin resistance, and insulin resistance starts to do a lot of bad things. Now, it's been known in Parkinson's disease that two things has to be present at the same time in order for Parkinson's symptoms to be present. The first is you actually need low dopamine in the brain, but the second is you actually need inflammation and insulin resistance. Most people think of Parkinson's simply as a muscle disease that's associated with an absence or a lack of dopamine, insufficient dopamine. That's part of the story, but it's not the whole story. Now, since it's been known that you need insulin resistance, people have tried for decades to essentially reverse insulin resistance in the brain, but no one's ever been able to do so. Right?
That's why the drug levodopa remains the standard of care five decades after it was first introduced. Levodopa is a great drug. It helps restore muscle control by enhancing the level of dopamine in the brain. It is a really, really good drug, but it does have several problems. One is that it actually has a short half-life. That means patients have to take it three, four, five times a day, which could be problematic overnight when you sleep, because when you wake up in the morning, you have no control of your muscles. The drug has worn off overnight. You can't get out of bed. Right, so that's one problem. The second, and perhaps the bigger problem is that Parkinson's itself is a neurodegenerative disorder.
As the disease progresses, as more and more dopaminergic neurons die, you actually need to take higher and higher doses of levodopa to get the same effect. Therein lies the problem. As you give the higher doses, it causes something called levodopa-induced dyskinesia, which is the uncontrollable tremors that you see in Parkinson's patients who have. When you have the dyskinesia, all you need to do is back the dose and wait for it to pass. As you back off the dose, it's muscle. It's a terrible situation that Parkinson's patients have. It's a condition that we believe bezisterim can address, because in our preclinical trials in rodents and in marmosets or non-human primates, we found that bezisterim alone is equally effective as levodopa in restoring muscle mass. Now, that's a huge statement in and of itself.
That means that no drug has been able to match levodopa. When we started using combinations, using bezisterim in combination with levodopa, you saw a synergistic effect. You saw maximum results. What got us at all is that at the end of the study, we sacrificed the monkeys' brains. We found that those that were treated with the bezisterim levodopa retained twice as many neurons as those treated with just levodopa alone, suggesting that there's a neuroprotective property to the drug, which to us is not at all surprising because we know that bezisterim first aids insulin resistance. That means there's greater glucose that's available to neurons. We also know that bezisterim enhances blood flow to the brain. That just means greater oxygen availability. When you have more glucose and oxygen available, that bodes well for better neuronal health.
Based on that, we enrolled 40 moderate Parkinson's patients. We essentially did in humans the same study that we did in monkeys. We essentially found exactly the same thing. We found that those that were treated with the combination, as shown here, saw better muscle control than those treated with just levodopa alone, as shown in red. We also found that about a third treated with the combination, all of their muscles first thing in the morning, their muscles were considered to be in on state first thing in the morning. This phase IIa trial establishes human proof of concept. You can use bezisterim in combination with levodopa to restore muscle control, to enhance muscle control for moderate to severe Parkinson's patients. It essentially gives us the first half of what we want to do in Parkinson's.
We are now conducting a phase IIb trial that aims to establish the second half, namely use bezisterim alone with Parkinson's patients at a much earlier stage in their disease. We have enrolled 60 Parkinson's patients early in their disease. All 60 of these patients need to go with the therapy for the first time to address their symptoms. We've randomized half to just bezisterim and then the other half to a placebo. What we're trying to show in this trial is that those treated with bezisterim, essentially bezisterim can help those patients address both their muscle control as well as their non-motor symptoms, non-motor being things such as anxiety, mood, depression, substance. This trial is fully enrolled.
Hey, Cuong. This is Greg. Sorry to interrupt. We did cut your video hoping that that would help. You're very hard to understand and we are thinking maybe you can hold the microphone closer to your mouth.
Let me do that. I hope this is better.
That's much better. I can hear already. Continue that way please. Thank you very much.
OK. The last patient is coming in for his or her last visit on May 1st, which means that we should be in a position to have top-line data readout by the end of June. When fully developed, we believe this could become the first new therapy for Parkinson's in over five decades. We believe this could become the first treatment to potentially delay the progression of the disease, namely delay the neurodegeneration. We believe this could become a $3 billion-$5 billion annual sales opportunity in the U.S. alone.
With that, let me move on to our trial in long COVID. You may be asking yourself, what does long COVID have to do with Parkinson's and Alzheimer's? To be honest, we had no idea when we started this journey. Our experts clued us in on it. I've had COVID three times now, as I'm sure many people on this call. I and many on this call are among the lucky majority, because when we got the infection, our immune systems kicked in and fought off the virus, and afterwards, our immune system got back to normal, our body got back to normal, and life moved on. This is the reason why the world has essentially just forgotten about COVID, right? Because life moved on.
Unfortunately, for 17 million Americans, that is not the case because they continue to suffer from the lingering aftereffect of the infection that shows up as brain fog, fatigue, and malaise. 3 million Americans have it so badly that they have had to quit or change their jobs simply because they cannot keep up with the physical demands of the job. Many of them are on disability. Within the last couple of years, researchers have tied those long COVID symptoms to inflammation that works through exactly the same mechanisms that bezisterim affects. Essentially, for these 17 million people, after the virus has been fought off and been killed off, they still have small fragments of what's called the envelope proteins and the spike protein continuing to linger and circulate in their body.
While there's no active infection, their immune system is tricked into thinking there is one, so it's constantly mounting an immune response. As the immune system is active, it is producing a lot of TNF-alpha. Right? That's the belief in what's really triggering a lot of the long COVID symptoms. We did not know any of this. It was our experts who clued us in. They also told us about a grant program that we applied to, and we've received a $13 million grant to support a exploratory trial. In fact, we are the only organization, company, nonprofit, only organization of any kind, that has received a grant to explore whether a therapeutic can help address these CNS symptoms of long COVID.
With the grant, we are enrolling 100 patients into the trial, where half will be given bezisterim, and then the other half will be given placebo. We're exploring a number of different cognitive and physical attributes as well as biomarkers as well. This trial is rapidly enrolling right now because most of the long COVID centers associated with academic medical centers in the country are working with us, places like Yale, Mount Sinai, Mayo Clinic, Stanford, UCSF. They're all working with us because, frankly, we're the only game in town. We have the only therapeutic that's being tested for long COVID. This trial should be fully enrolled by the end of this month, which then puts us in a position to have top line data readout by the end of this year. I must tell you, we get to see the blinded data as they come in.
We don't know who's on drug or who's on placebo. Right? We are seeing an encouraging pattern of some people getting better. In fact, some are telling us they're back to normal. Their thinking is clear. Their activity level is back to normal. Frankly, there are a bunch of people who are just not getting better or slightly getting worse. If that unblinds the perfect way, if those who are getting better are on drug, when we unblind the study, the community will be in for a great day because this could become the first therapy for long COVID. If we see that at the end of the summer, we'll go to the FDA in the fall to have a conversation with them about Accelerated Approval or perhaps an Emergency Use Authorization as well.
If that happens, we believe we would be in a strong position for partnering opportunity or frankly, a take out by larger companies, because we know companies are eyeing the study, looking at this. We believe this could become a $10 billion annual sales opportunity in the U.S. alone, annual sales. We are the rare health tech microcap company that has plenty of cash to last towards the end of the year. We have two imminent data readout. Right? Unfortunately, we are lumped in with all of the other companies where no one understands our story. Our current market cap is only $10 million, trading half our cash. Any way you want to discount these two drugs will lead you to a valuation that's substantially higher than our current market cap. That's the reason why I believe we are woefully undervalued.
I believe we represent a terrific buying opportunity for investors who have 6-12-month investment horizon. I say this not because only I'm the CEO of the company, I'm also one of the largest shareholders in the company. I just recently crossed the 5% threshold between my direct holdings, my options, and my warrants. All right, so with that, let me stop it here to see if you have any questions. Right? I'll stop the share, and maybe I can go back on camera, and then I'll take any questions you may have.
Thank you, Cuong. We already have several questions in. How should investors think about bezisterim? As a pipeline of indications or as a platform drug with broad applicability across inflammatory and neurodegenerative conditions?
That's a great question. The way that I think about bezisterim itself as a single molecule is that it's a starting point for a bunch of CNS-related conditions. Because think of it this way, neural inflammation and insulin resistance affect all parts of the brain. For one patient, the affected lesion could be in one part of the brain that leads to Parkinson's. For other patients, it could be in a part of the brain that could lead to Alzheimer's. For some, it could be both, or it could be traumatic brain injury, ALS. Everything in the brain is affected by neural inflammation and insulin resistance. Over time, we'll explore additional CNS indications. We also have sister molecules to bezisterim that do not cross the blood-brain barrier.
We look forward to the opportunity to develop some of those molecules for other indications. This together as a family of molecules is a broad platform, but in bezisterim alone is a single molecule that has applicability across different CNS indications. Thank you for the question.
Thank you, Cuong. From your perspective, what is the most compelling piece of data that gives you confidence heading into the next phase of development?
Well, I guess a few things. One is in multiple clinical trials so far, we have seen bezisterim essentially demonstrate efficacy signals. We've seen reduction of inflammation, we've seen an impact in insulin resistance, we've seen improvement in muscle control, we've seen improvement in cognition, right? There are multiple signs that gives us confidence that there's an efficacy signal, is point one. Point number two is that we do look at the blinded data across the Parkinson's and the long COVID trial. We're seeing an encouraging pattern of some people getting better and some people getting worse or not improving at all. The pattern we see would be suggestive that this is something going on with this drug. Lastly, in all of the clinical trials so far, the drug has shown to have a quite safe profile.
The number one reported side effect has been a mild headache that disappears after a day, reported by about 8% of patients. We have signals of efficacy, we have signs of safety, and you want those two things when we unblind, and we are quite optimistic that as we unblind, we'll see the results that we're seeking.
Cuong, at what inflection point do you see BioVie becoming attractive to larger pharmaceutical partnerships?
Well, we've had a number of conversations with larger pharma companies over the years, and the feedback from them has been consistent. They like the molecule, they like the mechanism. They just want us to go and do the trials and come back and talk to them when we have the data. I get it. I've been on their side of the table, right? The world out there is littered with promising molecules that fail in phase III. In big pharma, no one has ever been fired by playing it safe. I get it. We'll go and do the hard work to demonstrate that it works. At that point in time, we'll re-engage with the companies that we've spoken to over the years and essentially get them re-engaged and looking at the data.
I think there is a chance, a good chance, that we'll be able to create a feeding frenzy, positive data coming out of the Parkinson's trial. Namely, this could be the first new therapy in Parkinson's in over five decades. It could be the first therapy that could demonstrate disease modification, right? Likewise, with long COVID, this could be the first therapy for long COVID, period.
Beyond clinical readouts, Cuong, what other milestones should investors be tracking as indicators of progress?
Well, unfortunately, we are now in an industry of show me. show me the data. we've been working for a lot of years now to conduct these two clinical trials, and we are very much looking forward to and reliant on these two clinical readouts. we do have another molecule in BIV 201 to treat ascites. Ascites is end-stage liver disease, and when the body gets to this point, the liver is so scarred that it's no longer able to process fluid the way that it normally does. that fluid accumulates in the abdomen, right, and there's no therapy for it. the only thing that you could do right now is stick a large bore needle into the abdomen and physically remove all that fluid.
Since nothing has been done to address why the fluid accumulates in the first place, those patients are back in the hospitals every week or two to get another 5-10 L removed. Frankly, the only objective to treating these patients is to try to keep them alive for as long as possible so they may qualify for a liver transplant. Since there are not enough livers to go around, it's a condition that has over 50% mortality rate within a year. Our drug candidate, BIV201, is essentially a solution for that. In a phase IIa trial, we demonstrate that it's safe. There was no drug related SAEs. We were then in the midst of a phase IIb trial to demonstrate efficacy.
Halfway through the trial, we decided to stop, terminate the trial, because by then we already had enough data to show that those on treatment had greater than 50% reduction of ascites fluid buildup. Due to the high mortality, we thought that the only ethical thing to do is to stop the trial and engage the FDA in a conversation about what it would take to register the drug. Since we already have Fast Track and Orphan Designation, we only need one phase III trial to get the drug registered. At this point, we have received all the feedback that we need from the FDA to proceed. We just need to raise $25 million.
That's why for those that are observant and following us, you may have seen that we have filed an S1 with the SEC to take a new company public, a company called Option Therapeutics. Our intention is to drop BIV201 into Option Therapeutics, essentially spin off a portion of the company to raise $25 million to initiate that clinical trial. We're just waiting for market conditions to improve or to get to a point where it would allow us to go and raise $25 million. That's another thing to be looking out for in terms of how we're making progress.
Cuong, what probability of success do you assign to your long COVID program, and how should investors think about it within your overall valuation?
Right now, I don't believe anybody gives us any credit for long COVID, so right now I don't think we're being valued for long COVID. This, frankly, is the program that I'm most bullish on. In our current trial, as I look at the blinded data, I see a pattern of separation to indicate that there is activity going on. I hope that holds up as we unblind the trial. We also see lots of other encouraging signs around long COVID, and we believe that even if we focus on the 3 million Americans who have a very severe form of long COVID, whereby they're on disability or no longer able to work, this could become a $10 billion annual sales drug in the U.S. alone. This could be our biggest-selling drug in the near term.
This is 3 million Americans with severe long COVID compared to 1 million Americans with Parkinson's. I think this is actually the company's most exciting indication.
Cuong, as you just pointed out again, Parkinson's is currently your most advanced near-term catalyst. Now, what should investors understand about the significance of that upcoming phase IIb top-line data expected in the second quarter?
Yep. The key point to a phase II trial is for us to have really just get two numbers. One is called the magnitude of therapeutic impact, so how much better are treated patients on various endpoints compared to those that are on placebo? How well does the drug work? The second thing that we're looking for is the standard deviation, so essentially the variation around that impact number. We need those two numbers to power the phase III trial that we then would need to conduct to register the drug. That's really the importance of this trial. When we report top-line data readout, we will discuss the various motor and non-motor endpoints, and we will give everyone a sense of how well does the drug work compared at those endpoint for those that are treated compared to those on placebo.
Now, the magnitude of the impact is important. The variation is also important because that allows us the power to phase III trial. Soon thereafter, we will give some guidance on how large the phase III trial will need to be. We estimate, based upon what we know now, that that trial could be three to 500 patients large. We think it could be on the smaller end, but time will tell as we get the data.
Thank you, Cuong. How important are correlations between clinical outcomes and biomarkers like TNF-alpha and low tau for de-risking future trials?
Well, at the end of the day, the FDA likes biomarkers. If there's a biomarker that we can point to that is highly correlated to the progression of the disease that's recognized by the FDA, that's great. Unfortunately, there are few of those biomarkers that's recognized by the FDA. Thanks to the work by the Michael J. Fox Foundation, who also supported our work, by the way, they have shown that the alpha-synuclein represents a biomarker that could be used as a marker of the progression of Parkinson's disease. They are doing a lot of the hard work to validate that biomarker, and we wish them the best of luck, and we are absolutely behind them on that. We are also advocating three different biomarkers. One is DNA methylation. We believe that is actually perhaps the leading biomarker for age-related neurodegeneration.
All of our trials, we're looking at DNA methylation, and over time, we're hoping to get the FDA to recognize the importance of that as well.
We have a minute and a half left, Cuong. Would you like to close with some final thoughts, maybe the value proposition? Once again, tell us in a minute, why should anyone be interested in BioVie?
Well, BioVie is a rare pharmaceutical, small biotech company that has multiple shots on goal. In bezisterim, we have a novel modulator of TNF-alpha. It is currently in the clinic for two indications. One is for Parkinson's. Our Parkinson's trial is going to be reading out before the end of June. This could become the first new therapy in Parkinson's since levodopa was introduced over five decades ago, and it could become the first therapy that could modify the progression of the disease. This represents a $3 billion-$5 billion annual sales run-rate in the U.S. Bezisterim was also in the clinic for long COVID, an indication that currently has no therapy. In fact, the long COVID trial is expected to read out before the end of the summer, and this could become a greater than $10 billion annual sales product in the U.S. alone.
I believe that we are woefully undervalued, and any way you want to look at these two indications, you will get to a valuation that's substantially higher than our current $10 billion market cap. We're trading at half our cash, and we have two imminent near-term catalysts. I believe we represent a terrific investment opportunity for those who have a 6-12-month planning horizon. With that, I thank you so much for your time today, and please do your research on our company.
Thank you very much, Cuong. If you would like more information about BioVie, write us at bivi@redchip.com, and of course, you can always call us at 1-800-RED-CHIP. Thank you, Cuong Do, BioVie. Next up, we've got Vin Singh, the Chairman of the Board and CEO of BullFrog AI, BFR-