BioVie, Inc. Common Stock Study result

Hello, this is Craig Brelsford with RedChip Companies. Thank you for joining today's event with BioVie, which trades on the Nasdaq under the ticker BIVI. With us today is Cuong Do, President and CEO of BioVie, Joseph Palumbo, Chief Medical Officer of BioVie, and Mark Stacy, a key opinion leader and the William E. Murray Professor of Neurology, Movement Disorders Division at the Medical University of South Carolina. We will begin with a brief presentation in a moment, and then we will answer your questions. Welcome to everyone joining us today on X, 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. Team BioVie, please go ahead.

Thank you, Craig, and thank you everyone for joining today. Before I start, I would like to thank everyone who has worked so hard for so many years to get us to where we are today. Our team has worked countless hours, sometimes pulling all-nighters and so forth, weekends, to get us here. It is on their behalf that I am speaking to you today regarding this. I would also like to acknowledge two people in particular. It is Clarence Ahlem and Chris Reading, who are senior members of our team, who literally have spent decades of their life working on this to get us to where we are today. We affectionately call them the fathers of bezisterim. Craig has, I will let you read this by your leisure. But let us start with bezisterim. What is bezisterim? Bezisterim is a small molecule that is orally bioavailable.

Patients take it twice a day, a capsule in the morning, a capsule at night. It freely crosses the blood-brain barrier, and it is believed to block the activation of something called ERK and NF-κB. When you block NF-κB and ERK, you block the production of TNF-α. Therefore, what you are doing is you are breaking the continuous forward-feeding pro-inflammatory cycle that essentially is going on. By blocking NF-κB and TNF-α production, it is also believed that it is blocking the activation of something called IKK and JNK, which is essentially implicated in insulin resistance. IKK and JNK, when it is activated, binds to something called the insulin receptor substrate 1 and 2, and when it binds to IRS 1 and 2, it prevents insulin from binding there. That is the direct linkage between inflammation and insulin resistance, and that is the key to how bezisterim works.

We conducted the SUNRISE-PD phase II trial to figure out what to do to get the data that is needed to design the phase III trial. The SUNRISE-PD was designed as a short, 3-month-long study. It is a classical signal finding study to essentially identify which endpoint can we get an efficacy signal. Which endpoints have the most favorable treatment benefits? It is to measure the magnitude of this difference, to identify the populations where the drug works best for, and all of that allows us to design and size the phase III trial. That is the critical trial. That is the trial where you basically say, "What is the primary endpoint, and did you meet your statistical significance or not?" That is the thing that really matters. It is in the phase III trial. The phase II trial is signal finding.

It is trying to get us the information so that we can do that in the phase III. In this phase II trial, we evaluated a series of motor and non-motor endpoints. We created something called the Early Parkinson's Neuro-Inflammation Composite 15, which is the EPNIC-15. We will go much more detail about that as we go over the course of this presentation. We looked at the classical metrics of Parkinson's, something called the Movement Disorder Society's Unified Parkinson's Disease Rating Scale. It has three parts. Parts one deals with non-motor symptoms, part two deals with activities of daily living, part three is motor, and then you add them up to get the total score. We also looked at something called the Parkinson's Disease Sleep Scale 2. At sleep. We looked specifically at sleep because in our prior trial we saw a signal on sleep.

We also looked at quality of life using something called PDQ-39. In addition, we evaluated a series of biomarkers, and we conducted what is called a proteomic study that evaluated 380 different proteins in our blood plasma. As part of that battery, we looked at biomarkers of neurodegeneration. We will come back much more to this, but I especially love NfL, which is neurofilament light and GFAP. We looked at neuroinflammation, and we also looked at peripheral inflammation. That is what we tried to do. That is what this study was designed to do. This is what we found. We found that patients treated with bezisterim appeared to have experienced a statistically significant treatment advantage compared to those on placebo. We looked at the clinical outcomes, where we saw significant impact on the EPNIC-15.

We saw that 283 out of the 380 proteins we looked at moved towards a direction that is beneficial, that has been shown by others to slow the progression of disease. We looked at different metrics of neurodegeneration, and those moved in a very beneficial manner. Of course, we looked at various measures of inflammation. We also saw that while bezisterim appeared to have an effect across the trial population, we also found that our hypothesis that patients who have higher inflammation at the start of the study would be the ones that benefit the most and would respond the fastest, and that is exactly what we found. Those with higher inflammation at baseline experienced statistically significant advantages over placebo across all clinical measures that we looked at, including UPDRS parts one, two, and three, and the total score, as well as EPNIC-15. I will share more of that as we go along.

The biomarker results also suggest that bezisterim may be slowing neurodegeneration over time. This is a big deal if we can show this, and certainly this is something, a hypothesis that we would be testing as we move into phase III registrational trial. Lastly, but not least, bezisterim continues to demonstrate a very safe profile. It was well-tolerated. The safety profile was very similar to placebo. Before I go into deeper, let me set the context for why these data are so important. First of all, we know that Parkinson's is a progressive neurodegenerative disease. Once you have it, the brain's cells will continue to die, neurodegeneration will continue to happen. Right now, the community largely view Parkinson's as a motor disease, characterized by low dopamine levels in the brain, which then leads to muscle disorders and slowing of motor symptoms.

Unfortunately, it misses all the non-motor symptoms right now. Since that is such an important part of this, I am going to dive deeper into non-motor, and we will spend a lot of time on non-motor discussions. We found this chart in a great journal article. So frankly, we just liberally borrowed it. We copied and pasted it here. The green at the bottom discusses non-motor symptoms. Non-motor symptoms include things such as sleep disorders, depression, cognitive slowing, GI symptoms, and a lot of constipation. The important thing to note here is that many of these non-motor symptoms exist for years, many, many years before the actual diagnosis of the motor symptoms. These non-motor symptoms continue to worsen, and some patients would say it is the non-motor symptoms that could be worse than the actual motor symptoms themselves.

Once it is diagnosed, somewhere along the way, patients will get put onto therapy, and the current standard of care for Parkinson's treatment is levodopa, which is a great drug that has been around for over five decades. But treatment with levodopa and similar drugs also create their own treatment complications as well. The thing to note about this chart is that it all heads upwards. The disease continued to progress. Things always get worse. It never changes. It never gets better. That is where we believe is the big unmet need. What we are trying to do with bezisterim and the unmet need that we are trying to address is conceptually depicted on this chart. The dashed line at the top, think of it as the top line on this chart. The disease, if untreated, will continue to progress.

Then as you get put onto levodopa, what you are doing is that you are shifting that curve down because you are addressing the motor symptoms of the disease. Right? So, you are shifting this curve down. But since nothing has been done to address the underlying reason for the disease progression, disease continues to progress. What we are trying to do is, and we believe the big unmet need in the community, is something that changes that trajectory, something that can slow the progression and essentially bend that curve. Right? As I move on, let me ask that my others are in the panel. Mark and Taryn, I am not sure why you are on the panel. If you can just take yourself off camera, right, and mute yourself as well. Thank you. Joe as well. Okay. So we know that bezisterim works on inflammation.

The neuroinflammation hypothesis essentially goes something like this: It is peripheral inflammation that is activated by TNF-α and NF-κB, as I showed before, essentially leads to neural inflammation and oxidative stress, ER stress, and so forth in the CNS, which then leads to neuronal loss, which then leads to clinical progression. That is the hypothesis for what is really going on, right? This hypothesis is partly associated with a term called type 3 diabetes. That was coined by Dr. Suzanne de la Monte from Brown, who is also one of our scientific advisors. She believes, and we totally believe, and many other people believe in her thesis, that neural degeneration has an underpinning metabolic reason that essentially starts with insulin resistance, and insulin resistance is caused by inflammation.

What we did in this trial is, again, it is a signal finding study that is very short and very small, all aimed at getting us the data to design the phase III trial. In this trial, we looked at four different things. The first is inflammation. This is really our primary endpoint, is inflammation. Does bezisterim have an impact on inflammation? We also looked at what is happening with biomarkers associated with the disease. The third thing is we spent a lot of time looking at neuronal injury, things such as neurofilament light and GFAP. NfL and GFAP are known biomarkers of neurodegeneration, so they naturally increases in our blood samples as neurodegeneration progresses. And we are asking the question, can bezisterim have an impact on the progression of, and the release of NfL and GFAP? And of course, we look a lot at clinical scales.