Hello everyone, and thank you all for joining us during the Lytham Partners Spring 2025 Investor Conference. My name is Ben Shamsian, Vice President at Lytham Partners. Our next presentation comes from Reviva Pharmaceuticals. Today, Dr. Lax Bhat, CEO of Reviva, will be taking us through their slide presentation, followed by a Q&A discussion. Reviva trades under RVPH on the NASDAQ. Let's get started. Lax, welcome. And now we'll turn over the floor to you for your presentation.
Thanks, Ben. Thanks for having me here, and I really appreciate this opportunity. Before I start my presentation, I would like to, you know, display the forward-looking statements here. I would like all the viewers to look at these forward-looking statements. Now, we are a company focused on developing the next generation therapies for diseases of neurodysfunction, shown here with our pipeline. We have two molecules in development. Brilaroxazine is the most advanced molecule currently in phase III development for schizophrenia, and based on the available data and pharmacology of the drug, we believe we can readily develop this one beyond schizophrenia to additional closely related major psychiatric indications: bipolar disorder, major depressive disorder, and ADHD.
The drug has shown in various translational models, including in the large pivotal trial, anti-inflammatory effect as measured by decrease in pro-inflammatory cytokines, multiple cytokines, as well as an increase in anti-inflammatory markers. Based on that, we believe we can develop this drug to inflammatory conditions such as pulmonary arterial hypertension, pulmonary fibrosis, as well as major skin disease, psoriasis. Some of these inflammatory conditions are very much prevalent in psychiatric patients, and psychiatric patients are predisposed to get these inflammatory conditions compared to non-psychiatric patients. With this background, as you can see on the right-hand side, all the indications highlighted here are large indications with the multi-billion dollar, you know, market share. Now, quickly coming into the lead program, Brilaroxazine, I would like to highlight a few points before I walk through the data.
See, schizophrenia is not a single disease; rather, it is a mix of multiple symptom domains. Major symptom domains are highlighted here: positive symptom, negative symptom mode, and then cognitive deficits. Next generation, currently available drugs are suboptimal to treat all the symptom domains equal potency. In other words, they have suboptimal efficacy to treat some of the chronic conditions highlighted here: negative symptom mode and cognitive dysfunction. By and large, every single antipsychotic currently in the market addresses positive symptoms. If you look at the left-hand side here, a few points are highlighted here. It's a very large indication. Globally, over 24 million people suffer from schizophrenia. In the U.S. alone, around 4 million people suffer from schizophrenia. This is, you can imagine, how serious this condition is.
Now, despite having multiple antipsychotics approved currently in the market, around 30% of patients do not respond to currently available treatment, or they partially respond. If you would like to know what are the top two unmet needs, so, you know, top two unmet needs possibly, you know, based on the profile of currently available standard of care, ability to address negative symptoms, these are chronic conditions, as well as treatment adherence, these two can be considered as top two unmet needs. Now, neuroinflammation is another factor that significantly contributes to, you know, disease progress, and as well as, you know, some of the comorbidities we see in this patient population. The ability to address neuroinflammation can significantly impact the outcome, our treatment outcome. With this background, if you would like to look at the summarize what I said in a, you know, pictorial way.
If you would like to compare currently available treatment with a single yardstick, how do you compare, you know, one drug to another? Possibly, you can consider discontinuation or treatment adherence as a yardstick to measure. Now, having said that, if you look at the profile of currently available treatment, all the antipsychotics currently available in the acute schizophrenia trial, anywhere four- to six-week trial showed anywhere around 32%-45% discontinuation. In the long run, one-year treatment, around 70% discontinuation. This is attributed to both suboptimal efficacy to treat major symptom domains and then side effects, some of the side effects, as well as efficacy requirement or suboptimal efficacy, what we have seen highlighted here.
However, if you look at the currently available data in close to closely around treating around 800 plus patients with our drug, Brilaroxazine, our drug has shown only around 12%-16% discontinuation for the efficacious dose. In the acute trial, in the long term, around 35% discontinuation. Whether you compare acute treatment in four to six weeks trial as well as in the one-year trial, our drug has shown 50% less discontinuation or 50% better treatment adherence compared to other treatment options currently available. We believe that is derived from superior efficacy and then safety profile associated with our drug. Mechanism-wise, schizophrenia is primarily caused by dysfunctional dopamine -serotonin signaling cascade. That further dysfunctional dopamine -serotonin cascade causes imbalance in other neurochemicals such as choline, acetylcholinesterase , or in other words, nicotinic and muscarinic signaling cascade, NMDA, as well as GABA.
Up recently, what we are understanding is inflammatory cytokines. So our drug has shown efficacy for these downstream markers as well, especially neuroinflammation is of great interest. Now quickly coming to the phase III data. We have already successfully completed pivotal phase III study. It is a four-week trial in 411 patients. It was a global trial with two doses. There was a good dose response from low dose 15 milligram to 50 milligram. We have seen good dose response. And 50 milligram showed statistically significant outcome with the early onset of action to continue to improve at week four. We have seen net of placebo 10-point separation from placebo in four weeks with a significant separation from placebo within a week. To my knowledge, this is a clearly, you know, differentiated profile compared to other antipsychotics currently in the market or widely used.
To my knowledge, again, you know, the net of placebo differentiation, the highest reported for olanzapine, widely used drug in similar trial, and the lowest for Caplyta, around a 3.5-4-point separation. A 10-point separation makes this drug very robust with a 0.6 effect size. Now, this is about the primary endpoint. Even though it is a primary endpoint, it is an approval criteria. In the long run, outcome, because schizophrenia is a lifelong treatment in most patients, if not lifelong in some patients, at least it is a couple of months to years of treatment. In an acute trial of four to six weeks, beyond primary endpoint, the best way to assess the long-term outcome is to look at the secondary endpoints. Every single secondary endpoint is important, but the most important endpoint is negative symptom. Negative symptom is a chronic condition.
They are the predictor for long-term success. If you look at here on negative symptom data, our drug has shown two-point separation, statistically significant outcome. It is very hard to find efficacy for negative symptom. Out of 14 drugs approved currently in the market over the last 40 years, around six to seven drugs showed significant outcome in two randomized trials. The other eight drugs currently in the market showed only in one trial or did not show improvement at all. Having said that, our data shown here on the left-hand side in the graph here, it is for the negative symptom in the phase III study. Similar data we generated in the phase II as well. Two randomized trials showing consistent data. We believe this is very robust data.
Now, how can we assure or make sure that the data is generated is very robust with the biomarker? There are multiple biomarkers, blood-based biomarkers. They are not specific to negative symptom. However, digital biomarker can be more specific to negative symptom. Speech pattern can be considered as a digital biomarker. Schizophrenia patients have a unique speech pattern. In the study, we recorded full from screening to end of study, audio-visual record of these patients. When we analyzed, we found around 229 patients out of 411 shared a high degree of negative symptom. You can consider on a 1 to 10 scale severity of negative symptom close to 8. If our drug has to work for negative symptom, we should see more robust efficacy in those patients compared to total patient population. The right-hand side shown data reflects that.
229 patients with a high degree of negative symptom showed almost double the efficacy compared to total patient population. This further, to our knowledge, confirms the robust efficacy of our drug, Brilaroxazine, for negative symptom. Now to another point I made at the beginning, neuroinflammation. In the last 10 to 15 years, the drug got approved as antipsychotics. You know, the neuroinflammation information reported, but no drug to date showed statistically significant outcome on neuroinflammation biomarkers or cytokines. Shown here is IL-8, which is one of the cytokines widely expressed in or overexpressed in schizophrenia patients. In other words, highly dysfunctional pro-inflammatory marker. The second one is chemokine shown here. MIP-1 is a dysfunctional chemokine or a highly expressed chemokine receptor. Our drug has shown statistically significant reduction in both IL-8 and MIP-1.
That, you know, further supports strong efficacy or enhanced efficacy besides, you know, besides say demonstrating that this could address the, it could have an anti-inflammatory effect in these patients. Now, quickly to summarize, the, you know, the middle column shown here are the primary and then secondary endpoints. Lastly, 16% discontinuation compared to 22% placebo. It not only less than the placebo discontinuation here, but also it is around a 50% less discontinuation compared to any other antipsychotics currently in the market. These efficacy endpoints are further supported by biomarkers shown in the left-hand side of the panel. BDNF hormones, prolactin and thyroid changes as in the right direction. With the inflammatory markers reduction or changes in the right direction. Lastly, on the right-hand side shown here is the biomarker, digital biomarker for negative symptom.
As you can see here, negative symptom in total patient population is 2.1 reduction over four weeks of treatment. In the high degree of negative symptom patient, it is close to 3.7, almost double. You might ask a question here, why is in the total patient population, it is less. Schizophrenia is not a single disease, first of all. Also, we see quite heterogeneity in severity of negative symptom in this patient population. That is why in a total patient population, you see slightly less treatment effect because some of the patients may have kind of a secondary negative symptoms, we call it. That is the reason why you see less reduction or treatment effect in total patient population. That does not mean that drug is not working for negative symptom.
Only way to confirm that when I say use biomarker and then find out more dysfunctional negative symptom patients and then see what's the outcome. That's what we did in the right-hand side. You see more dysfunctional patients with negative symptom showed higher efficacy for negative symptom. That confirms, further confirms or supports the strong efficacy for negative symptom. This is the safety table. You know, the safety profile is very much comparable to placebo. We haven't seen, often we see motor side effects is a major concern. In the four weeks of treatment, motor side effect as well as an overall side effect is very much comparable to placebo. Over 5%, you know, side effects seen in the somnolence and then headache around 7.5%-7.5%. Weight seen in a few patients around 5.9% for the high dose.
Again, all patients, eight patients showed slightly higher weight compared to four in placebo. All weight gain are not necessarily something of concern because most patients in the acute trial, they have malnutrition and then once they feel better, they come into normal diet. Adding a small weight shown here around 1 kg to 1.5 kg compared to 1 kg in the placebo. We believe this is related to some patients, it's a healthy weight gain because a BMI in the majority of the weight gain patients still below 25. If the weight gain is related to mechanism one, they are irreversible or could be a problem. In our case, we haven't seen that one. In fact, lipid profile is one of the markers very closely related to weight gain. We haven't seen increase in lipid, rather lipid profile reduced in these patients.
That's a good sign. Now quickly move on to top line data and open label study. We are, you know, on track to announce full data set for the study soon in Q2 as announced yesterday in the earning release. In Q2, in the next, you know, two to four weeks, we will be announcing the full data sets. Highlight here some of the key points. Even after treating for one year in a top line data that we announced, we hardly seen motor side effect that is consistent with the double blind data. Weight gain in the long run, as you can see here, versus in the acute. Acute was 5.9. In one year treatment, we have seen hardly 3%. This is really a good outcome.
Dropout rate is 35% versus other antipsychotics in similar trial, almost double. It is very consistent data, double blind to long-term treatment, predictable data. This is just to highlight a few points here. As you can see, all three doses very well tolerated, showed efficacy, sustained efficacy over a period, dose-dependent efficacy outcome. Now, to summarize here, we have completed two large randomized trials. First one is phase II in 234 patients. Second one is 411. Both studies met primary endpoint and then key secondary endpoints. Top dose showed efficacy in both the trial and long-term safety. We have announced the top line data in the next two to four weeks in the Q2 this quarter. We will announce the full data readout in this quarter in the next two to four weeks.
For approving this drug based on the standard criteria, we would need another trial, phase III study highlighted here, RECOVER-2. FDA has already reviewed the protocol and then, you know, we hope to initiate this trial soon. With the trial design, it's very identical to what we successfully completed, RECOVER-1. Only difference we would like to make, low dose replaced with mid dose 30 milligram. That showed good efficacy in the long-term study as well. Otherwise, you know, some of the secondary and exploratory endpoints in the RECOVER-1, we would be graduating that one to secondary endpoints with an intention to get label claims. Otherwise, the RECOVER-2 is identical to RECOVER-1. That's where we stand with respect to, you know, development and then timeline to initiate the next study. If everything goes well, we expect to submit NDA sometime end of next year.
This is the comparison of our drug, Brilaroxazine, compared to widely used standard of care antipsychotics highlighted here. Every single drug shown here are for $500 million to a couple of billion sales. Right-hand side shown here are drug versus Abilify because the reason for comparing Abilify is Abilify is one of the widely used antipsychotics in the long-term treatment as well. If you would like to compare the primary endpoint total paths as well as the key secondary endpoints, they are critical for long-term outcome. Our drug certainly, you know, we believe it's differentiated compared to not only primary endpoints, secondary endpoints, and as well as a sustained efficacy in the data presented here. With this, you know, I would like to thank you all. I would be happy to answer any questions.
Thank you, Lax. Just wanted to touch on some topics.
Just going back to the other drugs that are trying to solve the same problem here. You mentioned Abilify among some other blockbuster names. Can you talk about why your mechanism is superior and sort of what are you hearing from doctors when they see the differentiation?
You know, again, this is the fundamental, you know, the differentiation we can talk. You know, first of all, the schizophrenia is primarily caused by dysfunctional dopamine–serotonin signaling. Now, there are only two approaches one can think of developing new drug. One, you develop a drug that directly modulates dopamine and serotonin targets and then translates into expected efficacy. Or you target downstream target, indirectly target another receptor that in turn, you know, modulates the dopamine–serotonin receptors and causes efficacy. These are the only two approaches to develop drugs.
Now, having said that, what we are doing here, our drug directly modulates dopamine–serotonin receptors highlighted in the receptor efficacy profile. All the blockbuster drugs currently in the market are a dopamine–serotonin receptor target. The differentiation what our drug brings into, you know, the treatment here is the currently available treatments by and large address only dopamine D2 receptor 5-HT2. Our drug, beyond that, has potent efficacy for 5HT2B7 and D4. These are implicated in chronic conditions. They are very hard to address, like negative symptom, cognitive, and more. We have shown the data for including neuroinflammation data that other antipsychotics, you know, did not demonstrate. Efficacy-wise, the mechanism we believe key is the 5HT2B activity that makes a significant difference in the behavioral symptom, addressing not only behavioral symptoms, but also the inflammatory casket that makes the difference.
Okay, great. Finally, can you just talk about the timeline going forward here in terms of getting to the NDA process?
We have completed, you know, for approving an antipsychotic to market, the requirement is two randomized trials. That is the absolute criteria based on all the approved antipsychotics currently in the market. Then long-term safety study. We have completed two randomized trials and then long-term safety study. You know, we think, you know, we require another study, randomized trial that the FDA RECOVER-2. We are in the process of, you know, initiating the second study. The second study would take around 12-14 months to complete.
Having completed all other most requirements for NDA, including the CMC development, we believe once we, you know, if you start the second study in mid of 2025, as highlighted here, we hope we'll be able to submit NDA by end of next year. That is our plan. I think based on the historical data, the development that is, we believe that is doable.
Okay. Great. Thank you for your time. Dr. Bhat, thank you everyone for watching. If you have any questions or would like to schedule a meeting with Reviva, please send me an email at shamsian@Lythampartners.com. That is shamsian@Lythampartners.com. If you'd like to learn more about Lytham Partners, you can visit our website at Lythampartners.com or follow us on LinkedIn to stay connected about our future events. We hope you all enjoy the rest of the conference and have a great day. Thanks everyone.