Hello everyone, and thank you all for joining us during the Lithium Partners Fall 2025 Investor Conference. My name is Ben Shamsian, Vice President at Lithium Partners. During this Fireside Chat webcast, we welcome Reviva Pharmaceuticals, ticker symbol RVPH, on the Nasdaq. Joining us today is the company's CEO, Dr. Laxminarayan Bhat. Also joining us today is Boobalan Pachaiyappan, Senior Research Analyst with Roth, who I've asked to moderate today's Fireside Chat. Boobalan covers a wide array of biotechnology companies at Roth, including Reviva. At Roth, he's responsible for fortifying the firm's SMID Cap coverage of emerging growth companies in the healthcare sector, with a focus towards neurology, neuropsychiatry, neuromuscular disorders, and pain. Before I turn over to Boobalan, I wanted to remind everyone that Reviva management is available for one-on-one meetings throughout the conference and in upcoming weeks.
If you have not already signed up for a meeting with the company, please send me an email at shamsian@lithiumpartners.com. That's shamsian@lithiumpartners.com. With that said, Boobalan, the floor is yours.
All right, good day everybody. My name is Boobalan Pachaiyappan, Managing Director and Senior Research Analyst at Roth Capital Partners. So with me today is Dr. Laxminarayan Bhat, who is the Founder, President, and Chief Executive Officer of Reviva Pharma. For those who are unfamiliar with the story, Reviva is a late-stage biopharma that's focused on developing novel treatments for schizophrenia and a host of other diseases. So the plan for today is to engage in a virtual fireside discussing Reviva's clinical progress and business strategy. Lax, welcome to the show.
Thank you, Boobalan. Thanks, Ben, for this opportunity. Greatly appreciate it. Thank you.
Great. So before we begin the Q&A, I have a disclosure to make. As previously said, I cover Reviva Pharma, and a recommendation for the stock is buy rating, and 12 months price target is $3 per share. All right, so with formalities out of the way, let's dive deeper into the fireside. So for the ease of clarity, I've segmented this discussion into four broad topics. So first, we'll level set the discussion by talking about the company and its flagship asset, brilaroxazine, particularly the agent's mechanism of action and some of its unique differentiating attributes. And secondly, we will take a sneak peek into brilaroxazine's clinical journey, specifically highlighting some of the important data which the company has disclosed most recently in their Phase 3 RECOVER study, and also the corresponding open label extension data.
And thirdly, we will look at some of the exciting forward-looking events, specifically the potential Type C meeting with the FDA, which is slated to occur sometime in the fourth quarter of 2025. And then we will also drill down deeper whether there are opportunities for early NDA filing, which in our view is going to be an important inflection for the company's stock price. And finally, provided we have some time, we will spend some time on competitive developments in the schizophrenia landscape. There's multiple companies that are developing drugs for schizophrenia, and we've chosen to focus on at least three assets. For instance, LB Pharmaceuticals' LB-102, which is a Phase 3 ready asset, and Newron's evenamide, which is ongoing, which is in Phase 3, and Neurocrine's NBI-1117568. So this is the broad thematic that we are going to discuss today.
So, Lax, why don't we spend a couple of times discussing Reviva Pharma and then discussing some of the unmet needs in schizophrenia and explain why brilaroxazine is so unique?
Sure, thanks Boobalan. Just for those who are not very familiar with Reviva, I would like to display a few slides while we are discussing this topic. Just allow me a few seconds to display a few slides here. So Reviva is a late-stage company. We develop next-generation therapies for diseases of neuro dysfunction. Lead product is brilaroxazine, currently in the Phase 3 development for schizophrenia. We have done multiple trials, treated now close to over 900 patients. With the available data, we believe the drug can be developed beyond schizophrenia to bipolar, very closely related psychiatric conditions, bipolar, major depressive disorder, and ADHD as well. Drug has shown very good anti-inflammatory effect as measured by biomarkers, both in the animal studies as well as in clinical trials over 800 patients from two trials. So we believe this is a very well differentiated product.
Now coming to the mechanism of action, our drug targets upstream target that is responsible for causing schizophrenia's dysfunctional serotonin dopamine, and then also it addresses inflammatory targets as well, as evident by multiple pro-inflammatory cytokines as well as a neurotrophin BDNF level favorably changed during clinical trials. So with this background, I will quickly walk through key clinical data so that we can have a very good Q&A in this segment. So brilaroxazine, we have, with the safety endpoint as well as the side effects compliance, we have generated a good amount of data. Most important with respect to efficacy, it's not just on the primary endpoint. What is unmet need in the treatment of schizophrenia? There are two things efficacy standpoints. One is ability to treat negative symptoms. That is one of the challenging tasks. Second one is avoiding relapse. How do you evaluate in this?
And then, what's our data here? So if you look at negative symptom from two double-blind trials as well as in the long-term study, we have seen consistent efficacy, robust efficacy for negative symptom. And then that is further supported by biomarker. That is something very differentiated to my knowledge. Secondly, durable efficacy. That's very hard to see in the currently available treatment options. So historical data clearly indicate in the over one-year treatment, around 25% to over 25% patients discontinue, anywhere around 25%-50%. In the long run, over five years, historical data clearly indicate that around 80% patients have one or multiple relapse episodes. In our study, over one-year treatment, we have seen hardly any patient got relapse in the study. That's clearly an indication that a sustained durable efficacy, in other words, it's a broad spectrum efficacy.
Secondly, side effects profiles are very robust, good profile. Motor side, hardly any motor side effect in over one-year treatment, less than 1%. And then, endocrine side effects and motor side effects, metabolic side effects, cardiac side effects are all comparable to placebo, except in patients' slight elevated weight gain over one year, around 1.2 kg. And then again, these are not dose-dependent. Otherwise, it is very clean profile. And then, good treatment adherence reported across the doses, and then they are all further supported by biomarkers. This is the summary of all the trials completed. We believe we met statutory requirement for filing NDA. We are reaching out to FDA for guidance, for feedback for filing NDA, so we expect to have FDA feedback sometime later this year in December. This will be a major value inflection point for us. This is the primary endpoint in Phase 3.
As you can see, robust data, dose dependency, top dose showing 10 points separation from placebo. We evaluated multiple secondary endpoints, seven secondary endpoints besides primary endpoint, to my knowledge. This we have seen robust efficacy, broad spectrum efficacy with the statistical significant outcome on every single secondary endpoint besides primary. And then further supported by biomarkers. Speech biomarker is a digital biomarker as well as multiple blood-based biomarkers. Similarly, over one-year treatment, we have seen consistent efficacy, all three doses, dose-dependent and time-dependent efficacy. These are very convincing to our knowledge for the sustained durable efficacy. So lastly, again, primary and then key secondary endpoints, including biomarkers, evaluated in hospitalized patients. They're also evaluated in the long-term study. They are consistent and time-dependent, what we have seen in the hospitalized patients, very durable efficacy.
Lastly, if we would like to compare the data generated to date with the historical data, there are two graphs shown here. The left-hand side one is a primary endpoint based on the effect size for multiple antipsychotics. We have seen really robust data. Second one is a top five antipsychotics in 2024 efficacy data. Compared to our data, you can see again, brilaroxazine, our data generated to date, clearly outstanding compared to historical data. So with this, I would like to answer any questions you may have, and our analyst here may have additional questions on the data and as well as outlook. Thanks, Boobalan.
Yeah, if you could bring the slides to the foreground, that will be helpful.
Okay.
Yeah, because some of my questions are related to slides. I just wanted to tell the audience that brilaroxazine's clinical journey has been very well executed to date. But in a nutshell, as Lax just quickly traveled through several slides, a Phase 1 study was conducted in 24 healthy volunteers, a 1b study in 32 patients. And then after that, there was a well-controlled placebo Phase 2 study, 234 patients. And then a Phase 3 study, which is RECOVER I, in 411 patients, and a Phase 3 study, which was done in 446 patients. Lax, you probably generated, I don't know, maybe several gigabytes of data. But in the interest of time, let's just discuss the primary endpoint first, especially the PANSS total score, which is your primary endpoint in both RECOVER I and RECOVER open label extension study.
So can you maybe elaborate more on how brilloroxazine impacted PANSS total in RECOVER and RECOVER II, and how does this score reflect when you compare it with some of the approved antipsychotics?
Sure. This is a PANSS Positive and Negative Symptom Scale, is a primary endpoint for all the drugs approved over 25 years. This is the PANSS scale data for the Phase 3, and then our data generated here comparable to Phase 2. As you can see here, the gray bar is for placebo, and then purple bar for treatment arm, two treatment arms. The dotted line is for 15 milligram low dose, and then a strong bar is for a high dose, 50 milligram. So the good dose dependence with the early onset of action with the efficacy, statistically significant efficacy within a week, that's very important in this patient population. The hospitalized patient, early onset of action is very critical. It improved over a period of four weeks, and then as you can see with the 10-point separation from placebo.
So 10-point separation, how good is the data? With the 14 drugs got approved over the last 40 years, last drug got approved to market is Cobenfy. So in a four-week trial, the highest separation from placebo reported around 8.4 olanzapine. The lowest separation reported for approved antipsychotics in similar trial is for Caplyta, to my knowledge. That's around the four-point separation. So having a 10-point separation consistent in the Phase 2 as well as in the Phase 3, two randomized trial, this is, to my knowledge, clearly robust and then anywhere 20%-50% better than historical data reported for other trials. So this is really robust data. And then this is further supported by key secondary endpoints. To my knowledge, secondary endpoints are very important, especially negative symptom, general psychopathology. They are reflective of long-term outcome treatment, what you can evaluate in the double-blind trial.
Okay. And then you comprehensively evaluated several secondary endpoints. But if investors have to focus on, can you maybe comment on one or two endpoints where you can clearly say, okay, so brilloroxazine unequivocally works in schizophrenia patients, especially those who have DRS symptoms?
Sure. Negative symptom is one of the major unmet need with respect to efficacy because it's chronic in nature, and then due to chronic in nature, before these patients recognized, end up in hospital, possibly many months and years ahead, negative symptom started, so it's a chronic in nature due to chronic condition, high inflammation these patients experience, and then it is very hard to treat unless a drug address negative symptom. Patients may feel some stability and short-term treatment, but they will have difficulty in recovering. To a great extent, they will experience relapse and end up in hospital again. That's called relapse, so relapse symptoms and then negative symptom, these are two major unmet need. Relapse historical data, if you look at around a 25% discontinuation in short-term treatment to one year, and then in long-term up to 80%.
We hardly see any patients relapse even in over one-year treatment. That is really good overall broad spectrum efficacy, sustained efficacy. When I say negative symptom, out of 14 drugs got approved, only six to seven drugs showed consistently from the two randomized trial, consistent efficacy, significant efficacy. But the remaining drug showed mixed efficacy based on the commercial data available. Only those drugs showed significant efficacy to the two randomized trial could make it to over $500 million sales, and then, in other words, they are reflective of widely used antipsychotics in the market. Our drug showed consistently from the two randomized trial, strong negative symptom efficacy, and then further supported by biomarkers. We believe this is one of the major unmet need, and then our drug addressed unequivocally to our knowledge compared to historical data for other approved antipsychotics.
All right, great. And then in that context, I wanted to get some additional thoughts on the disadvantages of targeting dopamine pathway because the general dogma is that dopamine pathway, if you target it, is going to lead to a host of side effects, for instance, extrapyramidal symptoms and cognitive and negative symptom worsening, hormonal imbalances, and some blunted effects. But we are not seeing any EPS in your studies, right? So what explanation you can provide for that?
Yes. This is a very good point, Boobalan. Often we carry what is observed without going into scientific rationale. And then what is observed becomes a historic milestone. I would like to point out here, to our knowledge, yes, the EPS is a dopamine targeted, but not all dopamine targeted are same. Historically, we have seen, if you look at the journey of antipsychotics from the typical antipsychotics, they are fewer dopamine antagonist with less serotonin-rich activity. And then newer antipsychotics reduce significantly the extrapyramidal symptoms. But still, they carry that dogma, what you mentioned, called motor side effect. So what we are learning, especially I will give you the example of our study. So if a drug has serotonin-rich activity that is known to cause, known to mitigate neuroinflammation in these patients, to a great extent, that can mitigate or reduce extrapyramidal symptoms.
And then second thing is dopamine partial agonist are known to significantly mitigate. So in our drug, in our trial, if you look at the Phase 2 study, based on the historical data, we protocol what other companies used. We allowed everyone in the trial. There is no exclusion criteria with the pre-existing motor side effect. And then they are taking medication to treat motor side effect. By doing so in the trial, there is no way a clinician can assess whether drug caused a motor side effect or the pre-existing condition caused a motor side effect. So motor side effects are it's a it's not a continuous. It is intermittent. So with the 20-minute assessment, physicians cannot assess. So in the Phase 2 study, we allowed all the patients with the pre-existing motor side effect, uncontrolled motor side effect.
They were on medication to treat motor side effect, and then we reported around 5%-10% motor side effect. However, in the Phase 3, we uncontrolled motor side effect, we excluded in the Phase 3. The reason for that is to evaluate whether drug is causing motor side effect because antipsychotics are not treatment for motor side effect. It is not a Parkinson's medication. This is a clear differentiation for the expectation, so in the Phase 3, we did not see any motor side effect. Hardly one patient showed motor side effect that is less than 1%. That means we did not our drug do not cause motor side effect even after treating over one year. This is the clear differentiation. With other side effects such as endocrine side effect, we have seen improved prolactin level, thyroid level. They are very hard to maintain with the currently available treatment.
Our drug has shown sustained improvement. Also, metabolic side effects, except a benign weight gain that we believe not related to mechanism. There is no significant change in blood sugar level. In fact, lipid level reduced compared to baseline. These are all good profile. Most importantly, we don't see any cardiac side effect by treating over one year in this patient population. No drug-induced liver injury. These are all compared to the historical data very well differentiated safety and tolerability profile.
All right. So I wanted to briefly touch upon discontinuation, right? Because in real-world setting, patients taking antipsychotics, up to 80% of patients would take antipsychotics to discontinue the treatment within the first year, they switch over to new medication and whatnot. But in your case, I think in your open label study, the treatment discontinuation rate is 35%. So why is it so low with your drug versus approximately 50%-80% in real-world antipsychotics? What causes your drug to be more acceptable by the patients?
So often when we look at the discontinuation rate, and then we have to clearly dissect why patients discontinue. So when we run a one-year trial, there are various factors contributing to discontinuation. The most important factors contributing, that is a historical data, if you look at on treatment, around 25% patients caught relapse symptoms. They end up in hospital. That's the cost for discontinuation, anywhere 60%-74% patients reported discontinuation in similar trial. In our trial, we have seen altogether 35% patients discontinuation. In that, hardly any patient discontinued because of relapse. So this is a very important criteria for a sustained efficacy. The second one is with the standard of care, discontinuation related to motor side effect. We hardly seen motor side effect that further reduced the discontinuation.
And then we still see discontinuation because often patients stay in over one year because of the various personal reasons as well. Patients discontinue because in a trial, we expect patients to report periodically for a scale assessment. So many patients can't comply with that, and then they discontinue. There's also a cause for discontinuation. But the point I would like to make, the key discontinuation factors, what we are seeing, the historical data like a relapse and then motor side effects, we don't see with our drug. And then other side effects are very benign compared to historical data. In other words, I would put it together, a benign side effect profile or a superior side effect profile here, plus a good durable efficacy that has resulted in lowest discontinuation reported today in similar trial compared to historical data.
All right. So let's focus on some of the next steps you're planning to do. So you guided publicly that there's going to be a Type C meeting with the FDA, which is most likely going to occur in fourth quarter 2025. You're calling it pre-NDA. So I'm just using the word Type C in a broader sense. So can you discuss your preparations and some of the key items you wanted to discuss with the FDA? Because your clinical program is very well thought and wonderfully executed, and then you're hoping that the agency will somehow allow you to file NDA at an early based on existing data. So can you elaborate more on that?
Sure. This is a regulatory meeting. Again, what our understanding, what we publicly announced as well in our last earnings release, the statutory requirement for filing an NDA is two randomized trials with the comparable outcome and then one long-term safety study. So if you look at our data here, the Phase 2 and then Phase 3, they are four-week trials. And then both efficacy for the primary endpoint and key secondary endpoints like positive symptom, negative symptom, CGI, general psychopathology, these are all comparable both in the Phase 2 and then Phase 3. So to our knowledge, these are the critical endpoints required for approving an antipsychotic to market. We believe we met. Lastly, the long-term safety study with the one-year, there is a very clear guidance for 300 patients completed for six months and then 100 patients completed for one year.
We reported with the one-year study, 303 patients completed for six months, 159 patients completed one year, 59 patients more than what is needed. And then safety data, it is compared to historical data. When I say historical data, ours is in a broader sense, serotonin dopamine target. There is historical data for other 13 drugs to compare how good is our data. So based on the historical data as well as the data generated here in 446 patients or in this long-term safety, so a reasonable judgment can be made about the outcome. We have a really good outcome. So based on this, we believe we met statutory outcome. We are requesting FDA Type B meeting, but it is up to the agency to consider whether it is a Type B meeting or C.
But regardless of the category, we expect to have FDA feedback path forward for NDA sometime in December. That is, we believe, a major outcome for the company.
Is it possible you can bring in Caplyta example? Because in Caplyta, for instance, Intra-Cellular, they had only one successful Phase 3 study, and then they eventually got it approved because they have a well-controlled Phase 2 and then the open- label extension. So what lessons you can get from Caplyta that actually bodes favorably in your approach?
Yes. That is a Caplyta example is the most relevant example to us, even though we haven't done the second Phase 3 study. But Caplyta was approved in 2019 based on one successful study and then one successful Phase 3, four-week trial. So that is comparable to our data here. Data in the sense regulatory standpoint, four-week trial, and the Phase 2 and then Phase 3. That's the closest example you can compare. Yes, that's a good example.
All right. So let's discuss the scenario, possible scenarios.
And then just one more thing to point. Even if you look at Cobenfy, this is a five-week trial. In that first one week is a titration. Technically, that's a four-week trial as well.
Yeah. All right. So let's discuss the NDA filing scenario, right? So in one scenario, let's say you have your meeting with the FDA, and then the FDA may say, "All right, fine. The data that you have is sufficient, so you can go for early filing," which means it's possible that you can file NDA in second quarter of 2026. So let's call that scenario one. And then the second scenario could be that the agency will say, "No, you have to do the second Phase 3 study," which means you have to think about your preparations for RECOVER-2 study. And this could basically push the timeline of filing to, I don't know, maybe to fourth quarter 2027 or even to sometime in 2028.
So assuming these are the only two possible scenarios, can you discuss the chances of seeing scenario one versus scenario two and then the cash requirements for both scenarios?
Sure. You very well outlined two scenarios. So it is very clear from the two scenarios that risk is very well mitigated here with the data. If you look at the first scenario where FDA feedback is the best case where FDA says feedback, it's a viable NDA, then we will go ahead and then file NDA in early Q2. And then on the standard timeline, we expect to have in early 2027 the drug to get approval. And then the second case scenario, base case scenario where FDA feedback is if we had to do the second trial, then in that case, we would comply with the FDA feedback and then do the second study. Then typically this type of study is four-week trial. Historical data, if you look at, we can complete in one year.
We expect to file NDA in Q3 2027 since we have completed all other requirements for NDA. There is also an option called in the past, there are regulatory precedents of rolling NDA submission that would significantly expedite the review process, so we will explore all the options to even in the base case scenario, how best we can expedite and then in 2027 to get drug approval, so in either case, we believe with the generated data here in over 900 patients, close to 900 patients, this binary risk is not there to our knowledge, and then this is a good situation to be.
All right. Maybe one last question from me. I know we are out of time, but this is a very important question, so still wanted to ask, so let's look at the developments in the schizophrenia clinical development landscape. So we have at least three late-stage assets, probably more, but the three important ones, one from LB Pharmaceuticals and one from Newron and one from Neurocrine. So can you maybe without attacking very so can you discuss the merits and advantages of your approaches or what gives you more confidence that your approach takes precedence or it's much better than other approaches? Thank you.
See, again, these are in development stage drug like ours. My comments based purely on scientific knowledge and then publicly available information, in no way it is a comment or a feedback on others' drug. To my knowledge, often we assess based on the mechanism and other things. To a great extent, we should see the clinical data as well. Now, with respect to LB Pharma, this is a repurposed drug from amisulpride using a longer PK profile. If you look at the Phase 2 data, it still has a significant prolactin increase as well as a motor side effect. Prolactin increase is a host to patients to depression and the lack of difficulty in recovering a negative symptom or a various other problem. So that is a I consider based on the historical data, it may have some limitation. And coming to Newron drug, this is an add-on therapy.
Again, an add-on therapy has its own limitation and an advantage as well. Limitation with respect to one of the things what we see with the add-on therapy, this is very critical. So often we talk about negative symptom. Negative symptom add-on therapy, we call a secondary negative symptom. They are caused by some of the side effects caused by drug-induced side effects, existing antipsychotics. So that causes negative symptom, secondary negative symptom like motor side effect and then other endocrine side effects. And then how do we address that one? That has a lot of impact on patients recovering. That one has to be very careful. I'm not sure how with this drug add-on therapy, how they are going to address this. Of course, primary endpoint, it may be possible to achieve, but in the long-term sustainability, it would be difficult. Lastly, muscarinic with the Neurocrine.
We have seen with the data the Phase 2. We don't see dose dependence and then with the other class of drug as well. So why do we don't see dose dependence? There is a mechanistic relevance in that. If you look at mechanism-wise, muscarinics are not a primary target for dopamine or serotonin. The ultimate goal of muscarinic is to indirectly modulate dopamine and then see the efficacy. But unless a drug addresses the serotonin modulation, it is very hard to achieve efficacy for schizophrenia in the long run, negative symptom depression. They are hardcore component of schizophrenia. I'm not sure a muscarinic agent addressing a negative symptom. Of course, in the acute patients, even Cobenfy showed efficacy. But one has to be very careful in analyzing negative symptom efficacy in acute symptom in the primary negative symptom and secondary negative symptom.
Mechanistically, to my knowledge, and I haven't seen anywhere in the literature strongly supporting muscarinic indirectly modulates serotonin dysfunction. To my knowledge, if a drug can't address serotonin dysfunction, it can't have a complete efficacy. This is my take on mechanistically. But again, at the end of the day, proof will be in the pudding. The clinical data should support that.
All right. We are out of time, so thank you so much, Lax. It's always a pleasure to engage in a scientific discussion with you, and congratulations on all your progress.
Thank you.
All right. Well, move along, Lax. Thank you for your time today. Certainly found the conversation helpful. Before we wrap up, again, just a quick reminder, anyone out there who would like to schedule a meeting with Reviva, please send me an email at shamsian@lithiumpartners.com, shamsian@lithiumpartners.com. Once again, thanks to all the participants, and we hope you enjoyed the rest of the conference.
Thank you.