Hello, welcome to the Life Sciences Investor Forum. On behalf of OTC Markets and our co-host, Zacks Small-Cap Research, we are very pleased you've joined us. The next presentation of the day is from Reviva Pharmaceuticals. Please note you may submit questions for the presenter at any time. You can also view a company's availability for one-on-one meetings by clicking "Book a Meeting." At this point, I am very pleased to welcome Dr. Lax Bhat, Founder, President, and Chief Executive Officer of Reviva Pharmaceuticals, which trades on the OTCQB Venture Market under the symbol RVPH. Welcome, Lax.
Lily, thanks for having me here. I really appreciate this opportunity to present here, as well as a opportunity to interact with investors in this conference in the next two to three days. Before I begin my presentation, I would like to display forward-looking statements here. I encourage all the viewers to review these forward-looking statements. We are a late-stage pharmaceutical company based in California. We are focused on developing novel therapies for CNS and immune-related conditions. Currently, we have two molecules in development. The focus of today's presentation is the lead molecule, brilaroxazine. Brilaroxazine comes with established efficacy and safety, as of today, with treating close to 900 patients. Based on the available data, we believe the drug can be developed beyond schizophrenia to bipolar, major depressive disorder, and ADHD as well.
As you can see, the psychiatric space, schizophrenia, bipolar, major depressive disorder, and ADHD collectively surround a $40+ billion market. Schizophrenia alone, close to currently around $10+ billion. By 2033, it is expected close to a $15 billion market. Before I quickly walk through a few important clinical data of brilaroxazine coming from pivotal studies we completed in a little over 400 patients in the double-blind study, as well as in the long-term, an additional another 400, close to 450 patients. Before I walk through those data, I would like to have a very brief overview of schizophrenia disease itself, some of the data points where you can connect how important is this developing new therapies for schizophrenia indication. Also I will give you a very brief snapshot of mechanism of action of our drug. Schizophrenia is a very large indication globally.
Over 24 million people suffer, U.S. alone, close to four million people. It is primarily caused by dysfunctional neurotransmitters, dopamine, serotonin functions. Of course, dysfunction in dopamine, serotonin also imbalances other neurochemicals. Primarily, dopamine, serotonin are the key neurochemicals implicated. Despite having few treatment options, around 30% patients do not respond to or partially respond to currently available treatment. Those who respond on treatment, if you look at some of the points highlighted here, around 30% patients, they get relapse in one year. Around 90% patients, they get relapse over five years. Discontinuation rates are very high. This gives you a kind of an idea how big is the market, patient population, and unmet need. Now, coming to the mechanism of action, primarily it is caused by dysfunctional dopamine, serotonin in the brain.
If you look at the mechanism of our drug, it directly modulates dopamine and serotonin functions. Most important thing is here, the ability to modulate 5-HT2B and then dopamine D4, 5-HT7, besides key receptors D2 and then 5-HT2, it makes a difference compared to other treatment options. Especially the 5-HT2B, they are implicated in multiple symptom domains associated with schizophrenia, besides the neuroinflammation. I will walk through the clinical data addressing our drug, major symptom domains, as well as neuroinflammation. This is the phase III trial design. This trial had a successfully completed trial. It had two parts. First part is a double-blind trial in the 411 patients. It is a global trial with the two doses, 15 and then 50, compared to placebo.
Patients were rolled over to one-year treatment, one year treatment, and the new patients also enrolled with the similar characteristic of disease severity to evaluate the efficacy, safety, and compliance, not only in the hospitalized patients in the first part, but also to evaluate long-term outcome, safety, efficacy, and then compliance in the schizophrenia patient population. Quickly coming to the data. If you look at here, this is the primary endpoint, PANSS. PANSS is the scale, positive and negative symptom scale, used as a primary endpoint. This has been a historically, over close to 30 years, PANSS is considered with all the approved antipsychotics as a primary endpoint. It is easy to compare with this data, historical data of approved antipsychotics. If you look at here, where the two doses, the top dose showed statistically significant improvement in four weeks of treatment.
The efficacy with the early onset of action started in the first week itself, started separating with a significant improvement, continued to improve at week four. This is a great improvement compared to historical data. The low dose, it took a week more to start efficacy. It is understandable because some patients are very high, acutely ill patients, they take a week more to respond to the drug. That is the only reason. Otherwise, if you look at the low dose also started separating from placebo at the end of day 28. Overall, 10-point separation from placebo on the primary endpoint is a really robust data. Historical data, if you look at most widely used blockbuster drugs, showed in similar trial anywhere four-point separation to eight-point separation. Having 10-point separation makes this drug anywhere around a 30% to over 50% better than some of the widely used antipsychotics.
What makes difference in the treatment outcome compared to other options available? Primary endpoint is an approval criteria, not necessarily that this is a criteria used for evaluating how good is the drug. To evaluate that drug, how good is the drug to treat schizophrenia patients and then get to the remission in these patients, the secondary endpoints are key because schizophrenia is not a single disease, rather it is a mix of multiple symptoms. Quite heterogeneity we see in schizophrenia patients. That is why multiple secondary endpoints always good to look at it, and then they give a good information about the drug, and then broad-spectrum efficacy. Negative symptom is one of the most important endpoints we evaluate. As you can see on the multiple factors, there are two scales used for negative symptom.
On both scales, we have seen robust efficacy with our drug compared to placebo as well as the historical data. The last column showed the biomarker. This is a digital biomarker used as a voice pattern in schizophrenia patients. They are unique in this patient population. Voice pattern is used as a digital marker. As you can see here, patients with a significant negative symptom identified in this trial, those patients responded robust efficacy in our drug. Magnitude of efficacy in those patients is much higher than overall patient population. This is a clear indication that drug not only has good efficacy overall on the primary endpoint, but also it addresses the key unmet need in addressing the major symptom domain, negative symptom. This data shows the data in the overall efficacy in over one-year treatment period.
As you can see, all three doses in one-year treatment with the 446 patients is a very consistent, progressive, and durable over one year. When I say durable over one year, this is very important. Historically, without any exception, most drugs approved in the market, they showed over 20% relapse on treatment in similar trial. We have seen hardly 1% relapse in this trial. That shows the efficacy is very robust, durable, sustainable over one year. This is a very important data. We have seen the dose-dependent efficacy here from 15%, 30%- 50%. Here is the summary of the data. The first one, I already talked about the primary endpoint in the four weeks trial as well as in the long-term one-year trial. The first column is just for viewers to compare the phase II data as well.
phase II data was kind of identical to successfully completed phase III double-blind trial. Collectively together, it is around 800+ patients. Data is very consistent in four weeks trial as well as in the one-year trial. The magnitude of efficacy increases from four weeks to one year, as you can see. Very consistent data from individual secondary endpoints as well. This is really a good data. Compared to compliance or treatment discontinuation is one of the major unmet need in the treatment. If patients can't take medication because of the side effect or drug not working in them, they can't get better. Continuing on treatment is extremely important.
As you can see here from the phase II as well as phase III and four weeks trial, we have seen 12%-16% discontinuation for the efficacious dose versus historical data for approved drug, around 30%-42%. It's almost over 50% better than any other antipsychotics approved to date. Also, this is better than placebo. Even in the one-year treatment, historical data is anywhere around 60%-80%. We have seen 36% dropout, again, in a one-year treatment as well. This is 50% less compared to historical data. Overall, we have seen a very consistent, good efficacy, robust efficacy, not only on the total overall, but also individual secondary endpoints as well as we have seen the biomarker outcome as well. Just to summarize here in the interest of time, I would not go into the biomarker data.
In the biomarker data, we evaluated inflammatory markers in the study. Neuroinflammation is real in almost every single schizophrenia patient as well as depression, bipolar patients. Our drug has shown a good improvement in multiple neuroinflammatory, pro-inflammatory markers. That's a good indication that the good efficacy, what we have seen that complements the reduction in inflammation should translate into better efficacy. That's what we have seen. Just to summarize here in the interest of time, I'll quickly summarize here. Drug has shown good efficacy and a broad-spectrum efficacy in the multiple major symptom domains. Most importantly, over one-year period, we have seen around less than 1% patients got relapsed on treatment. This is a confirmation that drug has a durable, sustainable efficacy. The side effects profile, often with other widely used antipsychotics, we see motor side effect, weight gain, cardiac side effect.
All these things we have seen here, very clean profile. Motor side effect, we don't see motor side effect here with our drug in the phase III. They are less than 1%, very mild, versus 5%-16% side effects, what we see with the widely used drug. There is no clinically meaningful weight gain. Yes, we have seen from in the development study around a 1.5 kilo weight versus placebo. Even with the long run, one-year treatment, we have seen anywhere around a 1.2-1.5 kilo weight gain. This is very benign. Even with the healthy individuals can gain 1-1.5 or more in the normal course. We don't believe this is a drug causes weight gain. Rather, it is a diet-caused weight gain. We don't see any hormonal imbalance, especially with other widely used antipsychotics.
We do see hormonal imbalance, such as a prolactin, thyroid imbalance, leading to sexual side effect and various other cardiometabolic issues. We don't see that one here. In fact, the hormone prolactin, what we see imbalance in most schizophrenia patients enrolled in the trial or in the real world, we see imbalance in prolactin. In our study, the imbalanced prolactin came to normal stage in the four weeks of treatment. It maintained over a period of one year. That means the efficacy is sustained over a period of one year, and then maintaining prolactin level over one-year treatment. This is a remarkable data to my knowledge. The next is a cardiac side effect, liver injuries. These are other bothering side effects with some of the widely used antipsychotics. We don't see that by treating over 900 patients.
We don't see the liver injury we call typically in the medical term called DILI, drug-induced liver injury. There is no report of DILI so far in treating over 900 patients. There is no clinically meaningful cardiac side effect or in other words, in the medical term, we call QTc , also gastrointestinal side effect often see with other drugs, we don't see here. This is a very encouraging safety profile as well. Compared to other approved antipsychotics, this drug has shown really good efficacy. Here, the left-hand side, the top eight antipsychotics, they capture over 90% of the market. On the right-hand side showed top five antipsychotics, they capture around 80% of the market in 2024. These are the top five antipsychotics. Even now in 2020, they are the top five antipsychotics.
Compared to this, our data is certainly very well differentiated in all respect. This is the last slide I have with respect to the data. Comparing our data with CAPLYTA. CAPLYTA is an approved drug for schizophrenia and bipolar and major depressive disorder. It was acquired by Johnson & Johnson last year for $14.9 billion. If you look at our phase III data and CAPLYTA, certainly the magnitude of efficacy in all the count, whether it is a primary or secondary endpoint or the safety or the compliance, in all respect, we believe this is a much better data. Again, this is not a head-to-head comparison in the same trial. It's the comparison with the historical data. Data, it say in all count, this is very consistently better to our knowledge. Lastly, now this is the summary of all the studies done, clinical trial.
We believe for the NDA submission, we need to do one more phase III study. That's the last column highlighted here. That is identical to already successfully completed first phase III study. It say we expect to start the second phase III study later this year, in Q3, and a top-line data anticipate in early Q1 2028, potential NDA in 2028. The reason for delay, primarily is, as we announced recently, we are in a process of switching the drug product to increase the commercial exclusivity patent life up to 2046. We are currently putting the package for U.S. FDA concurrence. We hope to have FDA feedback and concurrence in the next few weeks. Right after that, we plan to start the second phase III study. This is what I wanted to share with all the investors.
Before I wrap up, I would like to highlight top two questions often I get from investors. One, how much cash you have, how long it takes, the cash runway. We have currently around $20 million cash, it would take us into Q2 next year. The second question what we often get is, what's the upcoming major milestone or the milestones in the near term and long term? The major milestone what we are expecting FDA concurrence for extending the commercial exclusivity up to 2046 with the new form of brilaroxazine, what we are planning to introduce in the phase III and to NDA. That we expect FDA concurrence in the next few weeks. That's the major catalyst.
Right after that, we start the second phase III, in the next 12 months, the significant progress we anticipate with the phase III study, top-line data in early 2028, Q1, and NDA, as highlighted here, in Q2 2028. Overall, we feel we remain very confident about the future prospects of the company, that we believe there's a great potential for the growth, with the upcoming milestone, especially the clinical data generated to date. We are happy to answer any questions. As I mentioned at the beginning, we are available to interact with the investors on one to one. Our investors can directly contact us for our investor relations. We are happy to answer any questions you may have. Thank you all.
Thanks for the Life Sciences Investors Forum for giving us this opportunity to present Reviva and then interacting with the investors in this forum. Thank you all.