BioVie, Inc. Common Stock Status update

Answer your questions. Welcome. 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'm the President and CEO of the company. Give me one minute to get my screen share up and running again. Our company has two assets: Bezzy Sperum is a novel modulator of inflammation, and BIB201, which potentially has the potential to become the first drug to treat ascites, which is a terrible end-stage liver condition. We've 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 two, we reported out on our Long COVID trial. So we will spend today mostly on these two clinical trial results. And 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 and excitingly, we planned to meet with the FDA at the end of Phase II meeting for Parkinson's and hopefully get 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.

And 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. And that's where our drug candidate, Bezzy Sperum, comes in. Bezzy Sperum is a small molecule that's orally bioavailable, so patients take two capsules a day, one in the morning and one at night. It freely crosses the blood-brain barrier, so it gets into the CNS. And it's believed to block the activation of ERK and NFB. And by blocking ERK and NFB, you block the production of TNF-alpha. So 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 JUNK. IKK and JUNK binds to the insulin receptor substrate one and two, and blocks insulin's ability to bind to that same IRS one two that thereby causing insulin resistance. So by blocking ERK and NFB, we block the production of TNF-alpha, we reduce inflammation, and we reverse insulin resistance. That's how Bezzy Sperum is believed to work. And 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 US 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're suffering from brain fog, fatigue, and post-exertional malaise. And research have tied these conditions to inflammation. That works through exactly the same mechanisms where Bezzy Sperum affects and that's the reason why we believe Bezzy Sperum has the potential to become the first therapy for Long COVID, because there is absolutely nothing that's available now. All the trials on Long COVID has failed. And first, it's 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. But 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. And we believe that Bezzy Sperum may have an impact on those conditions.

So we conducted the ADRESS-LC Phase II trial. It is a signal finding trial. That's designed to essentially identify which endpoints could show that Bezzy Sperum could work to measure how big of an impact Bezzy Sperum 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're looking for is statistical significance. Does it work or does it not work? Which 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. And in this Phase II trial, we evaluated 22 different clinical outcomes. We collect blood samples and we did all of this with the support of a 13 million dollar grant from the Department of Defense, now the Department of War. We have always known that Long COVID is very complicated heterogeneous situation, condition. So 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. And one of those ways of specifying subgroups is based upon disease severity. And which disease symptoms. So here what you find is in the trial, we had about 100 we had 112 patients with high fatigue, we have 98 with brain fog, and 70 with post-exertional malaise. And we always talk of Long COVID in those essentially involving those three symptoms. But interestingly, you see that only 15% of the patients have all three symptoms with high severity. But yet, another 35% have some combination of two symptoms, and another 35% have some combination of just one symptom. But the important thing to recognize here is that if you do not have a symptom, it's not possible for you to improve on it. So 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's 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.

So it's to the right, the Cohen's D is positive, meaning that the treatment effect favors Bezzy Sperum. But interestingly, none of these endpoints reach statistical significance of P equal 0.05 or less. And that has to do, we believe, with what we talked about here. Only if you have fatigue, so if you look at this fatigue, only this 112 patients can really improve on it, which means that the improvement for these patients, the red and the green, is zero. And so while you see some impact some effect favoring Bezzy Sperum treatment, you do not get statistical significance. Because so many of those patients, those that do not have high fatigue, do not show improvement. And that's 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. And by doing so, you see a remarkable outcome. So if you looked at patients who have high fatigue, the impact doubles. The Cohen's D doubles. And you see that patients who have statistically significant improvement on fatigue and other measures. So you see the P-values here are less than 0.5 for five measures, and you get trending improvements on another three.

So 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. So DSQ, PEM. With statistical significance. But these patients also improve on their cognitive impairment, on their brain fog. And this actually is very easy to imagine and to see. Sometimes when I, and I'm sure many of us on this call, if we wake up early in the morning, if it's too early or whatever it is, we could be groggy and so forth. So we're just not thinking clearly. So fatigue, directly affect our ability to think clearly. But for these patients who suffer from high post-exertional malaise, those patients are suffering from it all the time. And so here, by Bezzy Sperum's ability to help patients improve under fatigue, not surprisingly, they're improving on brain fog. As well. And like similarly, if you have high brain fog, you improve on brain fog. So this shows that Bezzy Sperum 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.

And this is the reason why our experts and all of the experts in the field are so excited about this. Because there's been dozens of trials that have all failed to demonstrate impact on any endpoint. Whereas here, Bezzy Sperum, this is the first trial that has been able to show that have an impact not on one, but on all three of the neurosymptoms of Long COVID. This is the reason why all 12 of our PIs or advisors all 12 out of 12 that we have spoken to so far and polled strongly recommend that we move quickly to phase three because this is the first thing that has worked for these patients in the community. A remarkably consistent Bezzy Sperum continues to show that it's a very safe drug. There was zero serious events and so forth. And the safety profile is incredible because in this population, virtually everybody is taking one or more other kinds of medications. So 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. So this gives us great excitement that Bezzy Sperum 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 and based upon when we have the totality of the data, we will then ask for a meeting with the FDA and end of phase two meeting with the FDA later on this year to go and discuss our plans for phase three for Long COVID. So with that, let me excuse me one sec. With that, I'd like to move on to Parkinson's. Parkinson's is known as a progressive neurodegenerative disorder. That leads to problems with both motor and non-motor symptoms. And there are no disease-modifying therapy out there. So there's great unmet need for a new medication that can address motor and non-motor symptoms and hopefully modify the progression of the disease. And when we talk about non-motor symptoms, I'll ask you to focus on the green part at the bottom of this chart that we found in a great article. So we just shamelessly copied and pasted it here. When we talk about non-motor symptoms, we're talking about sleep disorders, depression, cognitive impairment, lots of GI problems and constipation. And these symptoms often show up for years before a patient is actually diagnosed with the motor symptoms.

And when you have the motor symptoms diagnosed, sooner or later, you will go on to a drug called levodopa or a similar drug to help address the motor symptoms, to help you improve your muscle control. But those drugs eventually lead to other complications. And as you can see over time, the progression of the disease only heads in one direction. It only heads up. What we believe is there is the need and the potential to change that, to conceptually display what we mean. If you look at the dashed line, this is directly what happens to a patient's symptoms if it goes untreated. It just continues to get worse over time. But as you go on to levodopa to address the motor symptoms, you're addressing the motor symptoms. So you're shifting that curve down. But since nothing has been done to address the underlying progression of the disease, it continues to progress at the same pace, but at just a lower level. And what we believe is needed is for a therapy that bends that curve, that changes the slope of that curve. And we believe that Bezzy Sperum has the potential to do so. That's why we conducted the Sunrise PD trial.

Where we looked at four different things. We looked at inflammation, biomarkers of inflammation, because that's how we're convinced Bezzy Sperum works. We conducted a proteomic study looking at different plasma proteins of inflammation and CNS disease. We looked at a lot of neuronal injury and we looked a lot at clinical outcomes. And in our entire trial of 57 patients, what we see is that patients treated with Bezzy Sperum do not worsen as quickly as patients that are treated with placebo. And the way to read this chart is that a positive a bigger positive number is greater progression. So you see that those that are treated with Bezzy Sperum shown in blue do not worsen as quickly as those that are treated with placebo. But we do not see statistical significance at this gross level of 57 patients. In the whole population. But again, we know that patients who have inflammation or have higher disease burdens are the ones that will respond most quickly and most profoundly. And that's why we pre-specified with the FDA before we unblinded the data that we unblinded the data. So what we found is that patients that have high inflammation as shown by high-level baseline levels of platelets, you see that those treated with Bezzy Sperum not only slowed the progression, we saw a reversal, an improvement of something called the unified Parkinson's disease rating scale that comes in three parts.

Part one is the non-motor, part two is the activities of daily living skills, and part three is motor symptoms. Part three is what is the endpoint that the FDA has used historically to approve Parkinson's drugs. They've also used the total score and so here, either part three or total, you see that we win statistically. So we have statistical significance showing that Bezzy Sperum treated patients improve on treatment. But you also see that we win on part one, which is the non-motor endpoint, as well as the activities of daily living. So this is the reason why we believe that Bezzy Sperum has the potential to become the first drug to address both the motor and the non-motor symptoms. Of the disease. And of course, you may know that the non-motor symptoms are considered to be the biggest unmet medical need in the Parkinson's population at this point. We also created something called the Epnic 15, which puts together motor, non-motor, and all of those endpoints into a single measure, Epnic 15. Let me focus your attention to the left chart. And here on the Epnic 15, an improvement is a smaller number, a negative number. And here you see, if you focus on the left side of this chart, you see that the majority of the patients that improved are those that are treated with Bezzy Sperum.

As shown in blue. And those that are stable, that did not change, are those majority are treated with Bezzy Sperum. The fact that you did not improve or did not worsen is a win in our part. In our mind, because we believe that we prevented these patients from worsening. Conversely, if you look on the right-hand side, most of the patients that have worsened were on placebo. So you see very, very big statistical significance here when you look at this metric. Another way of looking at the data is you see that 25% of the patients treated with Bezzy Sperum meaningfully improved compared to just 4% of those that were treated with placebo. Conversely, only 14% of those treated with Bezzy Sperum meaningfully worsened compared to 46%. So when we look at the totality of this data, we conclude that Bezzy Sperum treatment helped patients meaningfully and statistically significantly improved on both their motor and non-motor symptoms. Thereby positioning Bezzy Sperum to potentially become the first drug to address both motor and non-motor symptoms. In Parkinson's. Let me move on to look at biomarkers. We looked at 380 different biomarkers in what's called a proteomic study. In that battery, there were seven Parkinson-specific biomarkers.