Hello and welcome to Reviva Pharmaceuticals Company Webcast. My name is Ben Shamsian, Vice President at Lithium Partners, and today we welcome Dr. Lax Bhat, CEO of Reviva, who will be taking us through their slide presentation, followed by a brief Q&A discussion. Reviva Pharmaceuticals trades under RVPH on the Nasdaq. With that, let's get started. Dr. Bhat, welcome.
Thanks, Ben, for having me here. It's a pleasure to be back with your conference here. Before I begin my presentation, I would like all the viewers to go through these forward-looking statements displayed here. We are a late-stage pharmaceutical company focused on developing next-generation therapies for diseases of neurodysfunction. We have two molecules in development. Brilaroxazine is the most advanced molecule currently in development for schizophrenia. We have completed multiple trials, including a long-term safety study, one-year study in schizophrenia, altogether treated now close to 900 patients. So with this data, we believe the drug can be readily developed for beyond schizophrenia to other closely related indications such as bipolar disorder, major depressive disorder, and ADHD. So in this presentation, I mainly focus on schizophrenia indication.
That's our lead indication in all the value inflection data readouts in the next 18, 12, to 24 months, primarily focused on this indication. So before I present the high-level data, I would like to take a moment to discuss about schizophrenia and unmet need. Schizophrenia is not a single disease like most other chronic conditions. This is a disease mix of multiple symptoms. Major symptoms are highlighted here: negative symptom, positive symptom, cognitive, and then more. And then huge unmet need despite having a few drugs approved currently widely used. Globally, around 24 million people suffer from schizophrenia. Most patients, this is a lifelong treatment. So if you look at the unmet needs highlighted here, despite having multiple treatment options, around 30% of patients do not respond to currently available treatment.
And then currently available treatments are suboptimal, not only with respect to addressing the multiple symptom domains highlighted here, but also multiple side effects associated with that that lead to a combination of these two, leading to high treatment discontinuation in the short-term treatment, around 30%-45% in long run, up to 80%. And then also the relapse on treatment is also very high, around 25% of patients while taking or while on medication reported to get relapse within a year of treatment in the long run, up to 90%. So to summarize overall, the unmet needs are not only related to efficacy, suboptimal efficacy, but also side effects and tolerability. If you would like to summarize, the top two unmet needs are ability to treat negative symptoms, that's the chronic condition, and treatment adherence.
If we are able to address these two, possibly we are able to, we are addressing most of the unmet needs. We believe with the available data generated in the multiple clinical trials, our drug, brilaroxazine, addresses this unmet need to a great extent. So this is a trial design, pivotal trial we completed. This has two parts. One is acute patients treated for one month, and then stable schizophrenia patients treated for one year, collectively together around 800 patients, 850 patients. So this is the primary endpoint derived from the phase three study. As you can see here, there is a good dose response from 15 to 50, as we see here, top the short statistically significant outcome within a week, early onset of action, significant outcome, continue to improve in a progressive improvement over a period of next three weeks.
You'll see in the one year how the progressive improvement continues. I'll show you in a minute. The bottom line here is a drug has shown good efficacy and then dose dependency, dose response. Compared to placebo, we have seen around 10 points separation. This is really a robust outcome. If you would like to compare this data with the historical data, historical data in similar trial compared to placebo, the lowest efficacy, to my knowledge, seen in similar trial for Caplyta, around four points separation, and the highest shown in four weeks for olanzapine. Altogether, if you look at the historical data, this is really a differentiated product with respect to efficacy on the primary endpoint, as well as the secondary endpoints I will walk through very quickly. Now, secondary endpoints play a very critical role in the treatment of schizophrenia.
So in the interest of time, I would not go into every single secondary endpoint, but I do have a slide to show you how much the improvement we have seen in each secondary endpoint. But the one secondary endpoint I would like to highlight here that is negative symptom. This is the most critical symptom domain. Again, it is one of the most unmet needs in the efficacy standpoint. So negative symptom, not all antipsychotics approved to date show efficacy for negative symptom. We have seen consistent data from phase two to phase three. As you can see, we use two standard scales to evaluate negative symptom. One is standard negative symptom derived from total PANSS. Then the second one is Marder factor. Again, it's derived from total PANSS, but it takes into different criteria.
So, FDA considers Marder factor is a standard scale for evaluating efficacy for negative symptom. As you can see here, we have seen early onset of action for negative symptom, statistically significant outcome, progressive improvement at the end of four weeks. Another point to be noted here, negative symptom in the Marder factor also evaluates efficacy for depression, hostility, disorganized thoughts. These are all very closely related to negative symptom. Disorganized thoughts to a great extent reflective of cognitive improvement. Depression is another chronic condition. Altogether taken Marder factor data, this is a robust data for negative symptom. Further to support that, we have evaluated this one on the speech latency, a vocal biomarker that is kind of specific to or more relatable to negative symptom. This is an enrichment approach. We have this manuscript already been accepted for publication. It should be in print soon.
So the data generated here for the vocal biomarker, the speech pattern in schizophrenia patients, especially negative symptom, is unique. The machine can identify in a millisecond level. We utilized the technology and then identified severe negative symptom patients, 229 patients out of 411 patients enrolled. We have seen robust efficacy in those 229 patients with our treatment. Efficacy is almost double compared to the total patient population that further supports strong efficacy for negative symptoms. Now, this is about the hospitalized patients. So what is also important is in the long run, because this is a lifelong treatment, if the efficacy is not durable enough or sustained enough, so then the patients will discontinue medication or on while treatment, they get relapse and end up in hospital. If you look at the data here, all three doses show really a good progressive sustained efficacy over one year.
As you can see, efficacy dose dependent from 16-point improvement for the 15 milligram to 19-point improvement for the 50 milligram. Especially if you look at the last two bullet points, the patients rolled over from hospitalized acute treatment patients to one-year completer. We have seen almost a 50-point reduction in PANSS score. They are almost recovered patients. Overall, to summarize here, a progressive, durable, sustained efficacy in this patient population. This is really a good outcome to our knowledge. Another point to be noted here, as I mentioned, on treatment, historical data shows about 25% of patients get relapse or near relapse, increase in symptom. We don't see that one here. In our case, hardly less than 1% of patients showed the relapse of symptom or close to relapse.
This is really compared to other historical data, very robust outcome, robust efficacy, sustained efficacy over a period of one year. Now, to summarize the data, here is a very busy slide. Sorry for that, but if you look at here, the first column with the purple subtitle, that is for the hospitalized patients, acute patients, the efficacious dose 15 milligram showed not only the primary endpoint, but every single pre-specified secondary endpoint showed statistically significant outcome, especially CGI. If you look at, 78% patients showed over one-point improvement, and that led to good safety and then efficacy led to around 16% dropout versus 22% dropout. Historical data is around 30%-45%, 42% in similar trial. Now, coming to the one-year treatment, we put the breakdown data for 300 patients completed six months and then 159 patients completed one year. As you can see here, progressive improvement in efficacy.
Again, it is durable over one year, and then if you look at the last column here, that is the data for rollover patients. Again, not only for the primary endpoint, every single endpoint showed really robust sustained improvement, so discontinuation rate in the one-year treatment is around 36%. Again, this is 50% less compared to historical data, 80% reported for other approved antipsychotics. In the last column, we have highlighted multiple biomarkers. In the interest of time, I would not go into it, but again, all these biomarkers shown here, we have seen improvement over placebo or the baseline in the right direction. To summarize here, strong, durable efficacy seen not only in acute patients, but also stable patients treated over one year. Most important thing is progressive durable efficacy sustained over one year.
You can consider this durable efficacy as less than 1% report of relapse or near relapse symptoms in the long-term treatment in 446 patients. This is really a good outcome to my knowledge. So besides efficacy, tolerability is also very important because it is a lifelong treatment in most patients. So we have seen a good safety profile, well tolerated. There is no drug-related serious adverse event reported in treatment over a period of one year. Most common side effects are headaches, sleep disturbances. These are very common in this patient population. Again, these common side effects also around 5% or less than 5%. Only sleep headache and sleep disturbances are around 7%. That is, again, compared to historical data, it's a very lower end. Motor side effect often we see in this patient population with widely used antipsychotics.
Here, we have seen hardly less than 1% of one or two patients, very mild motor side effect that we believe pre-existing condition. But otherwise, it's very clean profile, except a mild or a benign weight gain of around 1-1.5 kilo weight gain over a period of one year. We have seen no other concern in this. Again, this weight gain, we believe, not related to the drug. Often, if it is related to the drug, we expect to see increase in lipid profile or change in blood sugar. However, we don't see change in blood sugar. They are comparable to baseline or placebo. Whereas in lipid level, we have seen decrease in lipid, cholesterol decrease, LDL decrease. These are all good signs, not indicating that mild weight gain, what we have seen related to mechanism of action.
So that's the reason why we believe this is not related to drug. It is possibly related to diet in this patient population. The next one is endocrine side effect. We see with the most widely used antipsychotics, imbalance of prolactin hormone, thyroid hormone that often leads to sexual side effect. We don't see that one here. Most importantly, prolactin level reduced and then reduced to a normal level in four to six weeks that maintained over a period of one year. That's very important. Some of the widely used antipsychotics in the short term, in the hospitalized patients, we have seen decrease in prolactin. However, in the long-term treatment, prolactin increased. So why it is important, prolactin increase can lead to patients will have difficulty in recovering negative symptom depression. And often we see sexual side effect increase in prolactin.
We don't see increase in prolactin, rather prolactin decreased and maintained the normal healthy subject's prolactin level. Maintaining prolactin also have an improvement or an impact on thyroid hormone. We haven't seen any hypothyroidism overall. Rather, we have seen improvement in thyroid hormone, while most widely used antipsychotics are known to cause hypothyroidism. These are all good attributes that we have seen over a period of one year. Lastly, by treating 900 patients, we don't see any cardiac side effects. Typically, in the medical term, we call it as QTc prolongation. We don't see with our drug. Again, GI side effects like acute constipation or a chronic constipation, nausea, and other things are below 1%, let's say, noise, I would say. There is no drug-induced liver injury reported.
Liver injuries are quite common in this patient population with some of the widely used existing therapies, possibly compounded by substance abuse in this patient population. So we don't see that one here. These are all good attributes. Lastly, to compare the data generated to date with the widely used antipsychotics, if you look at the right-hand side shown here, top five drugs in 2024 highlighted here, and then compare to these top five drugs as well as additional three drugs, they have over $1 billion in sales, each one of them. Our drugs, certainly on the primary endpoint, showed comparable to or better than these antipsychotics. And then lastly, if you look compare, this is one of the antipsychotics very closely related to our drug, Caplyta, that got approved by Johnson & Johnson early last year. It's a very mega acquisition in the industry.
If you compare the historical data with our data, we believe our data certainly very well differentiated compared to Caplyta. Now, lastly, we have completed, to summarize here, multiple trials required for filing an NDA, and as we recently announced last month, we had a pre-NDA meeting with the FDA, and we submitted all the data generated to date required for filing NDA to FDA, and the FDA reviewed the data, and then we received the feedback. The FDA recommended to do additional phase three study, one phase three study. Successful completion of this phase three study would meet the requirement for filing an NDA for schizophrenia, so summarized here, the trial design that's very similar to what's already successfully completed, RECOVER trial, only change is a low dose, 15 milligram will be replaced by mid-dose 30 because both 15 and 30 showed good efficacy in the long-term trial.
We believe 30 milligram would show statistically significant outcome. Top dose is same as last completed trial. FDA has already reviewed the protocol, and we are in a process of preparing for initiating the second trial. So we expect to initiate the study in early Q2, and then complete the study in mid of 2027, and then anticipate submitting NDA in Q4 2027. So we have currently about a little over $12 million cash in the bank. And in the process, as we announced, we need to raise additional at least around $50 million to complete the second study and submit NDA by Q4 2027. So we will update the progress in the next couple of weeks with respect to raising capital as well as initiation of the second trial. So thanks for your time and interest in Reviva.
Happy to answer any questions you may have.
Thank you, Dr. Bhat, for that. If you could just add a little bit on the latest pre-NDA meeting with the FDA, what are some of in having another trial? What are some of the positives there in terms of having another trial? Your data has been great, but talk about this.
Yeah. Historically, drugs got approved, the two or more phase three trials conducted on. Again, statutory requirement is two randomized trials and one long-term safety study so we completed those trials. Again, the agency would review the data, and then they recommend as appropriate so we reached out to FDA with the full dataset generated to date and then we requested FDA guidance on filing NDA requirement. FDA reviewed the data as we announced. There is no negative comment about our data.
Rather, I would say, to our knowledge, data look good. Otherwise, often the FDA with the pre-NDA meeting, we would get feedback on the data. So to my knowledge, there is no disagreement or a negative comment on the data generated to date. However, the FDA said they strongly recommend doing a second trial for filing an NDA. So if we can successfully complete a second trial, that would meet the requirement for filing an NDA. That is what we are currently preparing to initiate the second trial. So we hope we will be able to start to raise capital in the next few weeks and then start the second trial soon.
Okay. Well, thank you. Thank you for your time, Dr. Bhat, and thank you, everyone, for watching. If you have any questions or would like to schedule a meeting with Reviva Pharmaceuticals, please send me an email at shamsian@lithiumpartners.com. That is shamsian@lithiumpartners.com.
We have additional presentations and fireside chats coming up next, so please stick around for more. Thank you, everyone, and have a great rest of the day.
Thanks again, Ben. Thank you all for attending this.