BioVie Status update

Answer your questions. Welcome to YouTube, LinkedIn, and other social media platforms. To submit your question, we invite you to join us on Zoom. Use the link provided. Once in Zoom, click the Q&A button at the bottom of your window and type your question into the text box. 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 fact should also be considered forward-looking statements. Of course, forward-looking statements involve risks and uncertainties. Cuong, please go right ahead.

Good morning, everyone. Thank you for joining today. My name is Cuong Do. I am the President and CEO of the company. Give me 1 minute to get my screen share up and running again. Our company has 2 assets. Bezisterim is a novel modulator of inflammation, and BIV201, which potentially has the potential to become the first drug to treat ascites, which is a terrible end-stage liver condition. We have had a very exciting August and September. About 45 days ago, we reported out on our Parkinson's phase II trial, and just within the last week or 2, we have reported out on our Long COVID trial. We will spend today mostly on these 2 clinical trial results. As we look forward to the remainder of this year, we have a lot more data to analyze from the trial, so we will provide additional clinical updates.

Excitingly, we plan to meet with the FDA in an end-of-phase II meeting for Parkinson's, and we expect to get formal feedback from the FDA on our Parkinson's phase III design, by the end of the year, perhaps even by Thanksgiving time. We believe that inflammation is a starting point for a lot of things that go wrong in the body, particularly starting with TNF-alpha. When you have the production of TNF-alpha, which is considered to be the master regulator of inflammation, it leads to a lot of the bad things that you see on this page. That is where our drug candidate bezisterim comes in. Bezisterim is a small molecule that is orally bioavailable, so patients take 2 capsules a day, 1 in the morning and 1 at night.

It freely crosses the blood-brain barrier, so it gets into the CNS, and it is believed to block the activation of ERK and NF-kappa B. By blocking ERK and NF-kappa B, you block the production of TNF-alpha. Essentially, when you have TNF-alpha, it leads to a forward-feeding pro-inflammatory cycle, so it just creates more inflammation. When you have TNF-alpha, it activates something called IKK and JNK. IKK and JNK binds to the insulin receptor substrate 1 and 2, and blocks insulin's ability to bind to that same IRS1/2, thereby causing insulin resistance. So by blocking ERK and NF-kappa B, we block the production of TNF-alpha, we reduce inflammation, and we have reversed insulin resistance. That is how bezisterim is believed to work. You can see the impact of that first in Long COVID. This is a trial that we reported out on just the last couple of weeks.

Long COVID affects a large population. There are up to 20 million adults in the U.S. that are affected with long COVID. Nearly 4 million have it so badly that they are considered to be disabled. They can no longer keep up the physical demands of the jobs because they are suffering from brain fog, fatigue, and post-exertional malaise. Research has tied these conditions to inflammation that works through exactly the same mechanisms where bezisterim affects. That is the reason why we believe bezisterim has the potential to become the first therapy for long COVID, because there is absolutely nothing that is available now. All the trials on long COVID have failed. First, it is important to recognize that long COVID is not the same as COVID. COVID is the infection caused by the virus. Many of us have had it.

Many of us have been able to ward it off, and life just resumes. Life goes on. Unfortunately, for the 20 million Americans who have long COVID, they continue to suffer from these different conditions, and it lingers for years after the initial infection. We believe that bezisterim may have an impact on those conditions. So we conducted the ADDRESS-LC phase II trial. It is a signal finding trial that is designed to essentially identify which endpoint could show that bezisterim could work, to measure how big of an impact bezisterim could afford patients that are on drug, and to identify the patients that can benefit from this drug. All of this is needed so that we can design the phase III trial.

The phase III trial is really the critical trial where you have to have a single endpoint or a few endpoints, and all you are looking for is statistical significance. Does it work or does it not work with statistical significance? That is a phase III trial that we now will plan. This phase II trial gives us the information to do so, the planning. In this phase II trial, we evaluated 22 different clinical outcomes. We collect blood samples, and we did all of this with the support with a $13 million grant from the Department of Defense, now the Department of War. We have always known that long COVID is a very complicated heterogeneous situation, condition. At baseline, we had 203 patients enrolling in our trial.

We have always known that patients that have high inflammation or high symptom burden are the ones that are most likely to respond most quickly and most profoundly. So we always pre-specify certain subgroup populations with the FDA before we unblind the study. We did exactly that here. One of those ways of specifying subgroups is based upon disease severity, right? Which disease symptoms. Here what you find is in the trial, we had 112 patients with high fatigue, we have 98 with brain fog, and 70 with post-exertional malaise. We always talk of long COVID essentially involving those three symptoms. Interestingly, you see that only 15% of the patients have all three symptoms with high severity, right? Yet, another 35% have some combination of two symptoms, and another 35% have some combination of just one symptom.

The important thing to recognize here is that if you do not have a symptom, it is not possible for you to improve on it. Here you see 112 patients with high fatigue. That means all of these patients that are red and in green do not have fatigue, and therefore they have no room to improve. That is a critical thing to keep in mind as we go through the data. Because here, as you look at what happens on the results for all 203, you see that on 21 out of the 22 endpoints treatment, you see a favorable treatment effect. It is to the right. The Cohen's d is positive, meaning that the treatment effect favors bezisterim. But interestingly, none of these endpoints reach statistical significance of p equal 0.05 or less. That has to do, we believe, with what we talked about here.

Only if you have fatigue, if you look at this fatigue, only this 112 patients can really improve on it, which means that the improvement for all these patients, the red and the green, is zero. While you see some impact, some effect favoring bezisterim treatment, you do not get statistical significance you have because so many of those patients, those that do not have high fatigue, do not show improvement. That is the reason why we pre-specify in our submissions to the FDA that we will look at different subgroups based upon the symptoms they have and severity. By doing so, you see a remarkable outcome. If you look at patients who have high fatigue, the impact doubles. The Cohen's d doubles. You see that patients have statistically significant improvements on fatigue and other measures.

You see the p values here are less than 0.5 for five measures, and you get trending improvements on another three. You need to have fatigue to be able to improve on fatigue with statistical significance. Similarly, if you look at patients who have high post-exertional malaise at the start of the trial, those patients improve on post-exertional malaise, the DSQ-PEM, with statistical significance. But these patients also improve on their cognitive impairment, on their brain fog. This actually is very easy to imagine and to see. Sometimes when I, and I am sure many of us on this call, if we wake up early in the morning, if it is too early or whatever it is, we could be groggy and so forth. We are just not thinking clearly. Fatigue directly affect our ability to think clearly.

For these patients who suffer from high post-exertional malaise, those patients are suffering from it all the time. Here, by bezisterim's ability to help patients improve under fatigue, not surprisingly, they are improving on brain fog as well. Similarly, if you have high brain fog, you improve on brain fog. This shows that bezisterim has the ability to help patients improve on all three of these symptoms, of fatigue, malaise, and brain fog, but you need to have the symptom to begin with in order to improve. This is the reason why our experts and all of the experts in the field are so excited about this. Because there has been dozens of trials that have all failed to demonstrate impact on any endpoint.

Whereas here, bezisterim, this is the first trial that has been able to show to have an impact, not on one, but on all three of the neural symptoms of Long COVID. This is the reason why all 12 of our PIs and our advisors, all 12 out of 12 that we have spoken to so far and polled strongly recommend that we move quickly to phase III because this is the first thing that has worked for these patients in the community. Remarkably, consistent, bezisterim continues to show that it's a very safe drug. There was zero serious events and so forth. The safety profile is incredible because in this population, virtually everybody is taking one or more other kinds of medications.

The last thing you want is to add to this mix a drug that potentially could have drug-drug interaction or lead to other problems, and we just did not see any of that in this trial. This gives us great excitement that bezisterim could become the first therapy for Long COVID, and we're still waiting for some additional biomarker data to come back from the labs in the next 45 days or so. We will analyze that and give additional readouts at that time. Based upon we have the totality of the data, we will then ask for a meeting with the FDA and end the phase II meeting with the FDA later on this year to go and discuss our plans for phase III for Long COVID. With that, let me-- Excuse me one second. With that, I'd like to move on to Parkinson's.