Good afternoon, everyone. My name is Farzin Hak, one of the biotech analysts at Jefferies. It's my pleasure to introduce Sergio Traversa, CEO, Maged Shenouda, CFO, and Leo Watson from Corporate Development. This is the fireside chat format. Thank you for joining us today. Maybe to start off, Sergio, can you provide a quick overview of the company for those that may be new to the story? Well, thank you, Farzin, and thank you to the whole Jefferies team for inviting us. Good afternoon to everyone. I'm Sergio Traversa, I'm the co-founder and the CEO of Relmada. A brief overview. Originally, Relmada is a spinoff from Cornell University back in the days, and it was born as a pure central nervous system, CNS, company. After several years of efforts in CNS, we realized that it's a wonderful space to be, but for a company of our size to focus entirely on CNS is a little bit too risky. A couple of years ago, we made a strategic decision to expand to other therapeutic areas to diversify and pretty much balance and manage the risk. We in-licensed two programs. One is still in CNS, is a bit earlier stage, and we start phase II in proof of concept shortly The other one is in oncology, in uro-oncology to be specific, and is NDV-01. It has attracted a lot of attention for a lot of parties and for investors in particular. I believe that's the NDV-01 is where we'll spend most of the time today. We have been on public since 2014 and trading on Nasdaq since 2019. Great intro. You're coming back to the NDV-01, the main asset. The phase II data was outstanding with any time CR rate of 95% and 12 months CR rate of 76%. You recently presented the data at AUA. Can you go over some of the key feedbacks on the data? Sure. Well, yes, we present more details at AUA, and what attracted a lot of attention is, and not surprisingly, is the 12 months response rate of our phase II basket trial. With numbers with the response rate of 76% overall and 80% of patients with bladder cancer unresponsive to BCG, they are clearly very, very attractive in a space that has been dormant for many years and now is becoming more competitive. This data, if confirmed in the phase III, as we hope and believe, then will make a big advance in the treatment of bladder cancer. One of the pushbacks was that the phase II data was from a single ex-U.S. site, but included a nice mix of CIS with papillary, high-grade Ta, and then high-grade T1 as well. You saw consistent responses across all disease subtypes. The big question is how representative was the patient population versus the real-world setting that you're going to pursue in the global phase III? Well, thank you, Farzin. As you may imagine, this is a question that we get relatively frequently, well, a couple of points here. The main point is this. This is an extended release formulation of intravesical gemcitabine plus docetaxel, Gem/Doce. Gemcitabine, Gem/Doce, has been used in the last 10, 15 years and is getting more and more use. There is a lot of publication around about the combination of the two drugs, and clearly there is an efficacy. What we do like, among other things of NDV-01, is that we don't need to prove the mechanism of action or that the drug works. That has been published. That is a signal and a support for reproducing similar data, same data in the larger U.S. study. Another point is that the study, yes, it's a single center, it's a large university center in Israel. In Israel, the therapeutic approach is pretty much the same. They follow the U.S. guidelines. Also, this is oncology, it's bladder cancer. The endpoint is a cystoscopy and cytology, so it's hard endpoints. We assume they should be reproducible in any place where the trial is run. Makes sense. Hopefully I answer your question. Based on the data, have you had any conversations with the FDA for Fast Track or Breakthrough Therapy designation? Not yet. Breakthrough, you need some data, and to get the Breakthrough. Fast Track, we will apply, and Fast Track also helps when you are doing the clinical study, the clinical trial, and when you start to generate data. The answer is yes. We look into that, but we haven't done that yet. Got it. When is the next data update from this phase II expected with a longer-term follow-up? Yeah. The 12 months data is kind of the landmark that the FDA looks at, and then the investment community, and we look at too, because whatever results you get at 12 months, then it's a confirmation that you have a response and you have a durability of response. We will have the 18 months data and with a larger number of patients, also at three, six, and 12 months, in, we'll say, mid to early Q4 this year. We haven't decided yet how to present and when to present, but we will present something, a summary of this data. Got it. Probably, we believe, before year-end. Got it. BCG unresponsive pivotal, FDA has accepted a single-arm registrational path. That is in the more refractory setting. How narrowly will you define this refractory population? Is it like CIS after induction maintenance, or would it include any early recurrences, like six months or so? Well, we have a protocol that defines somewhat the patient population. The FDA was in agreement with the single-arm open-label study with the 87 patients for this indication for a few reasons. The main reason is that the alternative for these poor patients is a radical cystectomy. We get some suggestion that this was a space where there was a need for a product, Gem/Doce is already somewhat used as a salvage therapy. The inclusion criteria is patient that fail BCG, and then they fail one of the product is approved or is in development for BCG unresponsive. After a failure of this product, the only alternative would be taking the bladder out. That's where we come in. The inclusion criteria will be somewhat flexible, but pretty much they have to fail BCG, and they have to fail at least one and no more than two of these therapies. Got it. If there's acceptance of CR rate at any time, that's the primary endpoint. Does it explicitly define a time period for durability? Do you have to wait for 12 months data to match the ADSTILADRIN precedent then, or just six months? How much follow-up do you really need? Yeah, that's a great question, that was a very interesting conversation and discussion with the FDA. There is no alternative with these patients. The endpoint is CR at any time. The comment that the FDA made was very interesting. They said, "We want to see the totality of the data." In FDA language, it reads like they want to see a certain response, they didn't give us any number. A certain response, also they want to see a response for some duration of time. We look at the 12 months as a landmark, the endpoint is the complete response at any time. We do believe the FDA wants to keep some flexibility and look at all the data together. Makes sense. You have noted there's like 50 high-volume centers in the U.S. They account for majority of the BCG unresponsive cases. How many sites are you targeting for phase III, and what is your enrollment assumptions? Right. We are targeting, as you may imagine, we already spoken with pretty much all of these sites. We are targeting 60 sites in the U.S., they will run both trial. It actually is one protocol to make life easier, you go only with one IRB approval with two cohort. That is, one is the high-risk BCG unresponsive second line, the other one is adjuvant therapy for intermediate risk. Right. We contacted all these sites. What I can share, there has been a lot of enthusiasm in participating in this trial. Gem/Doce Chemotherapy is one of the preferred treatment for urologists, among chemotherapy, Gem/Doce is the one that is attracting a lot of attention in term of efficacy and tolerability. Yeah. Any comment on the enrollment assumptions given that there's a lot of trials ongoing? Yes. We look at historically, guessing enrollment, we have a lot of experience in this field. Guessing enrollment is always a little challenging, but we look at historically. We assume for the high-risk second-line therapy, 87 patients, we assume 12 months enrollment. For the intermediate, that is a large number of patients we are targeting, 276 patients, we assume 18 months is enrollment timeline. If I may, one big difference between the two studies is that for the high-risk second line, it's open label, it's one arm. We believe we'll be able to present data every three months while the intermediate is a randomized two arms, treatment arm versus observation, but is randomized. We won't be able to show data. The FDA will not allow us to show data during the trial, so we'll have to wait the end of the trial. Got it. In phase II, five patients relapsed, and they were successfully re-induced with a second course. Yeah. Four out of five attained CR, and one discontinued. What are the provisions for re-induction in phase III? Right. In phase III, there is only allowed one re-induction. One re-induction. Okay. Got it. That is in line with the practice. Got it. Common practice of urologist. Okay. Switching gears to the intermediate risk setting. That one is notoriously heterogeneous. It ranges from multifocal low grade to recurrent low grade. There's a whole wide range of them. You're starting a phase III without having proof of concept data comparing NDV-01 plus TURBT versus TURBT plus observation. Correct. Will you enroll all intermediate subtypes or focus on the higher risk that will most likely benefit from the adjuvant therapy? There are enrollment criteria. We'll try to enroll a good representation of patients, and we will stratify versus higher risk and lower risk patients. It's going to be more widely open in term of patient population. Have you disclosed the event rate in the observation arm? How are you powering the study? Well, that's a great question. We had to make some assumption to calculate the number of patient that we want to enroll to reach statistically significant. These are all assumption, right? If you look at the literature and the publication, the data are all over the place. Exactly. It goes from 45% to 60% or 70%. The assumption we made, we assume for the observation arm, 60% response of disease-free survival. We assume 15% better for the arm, so 75%. These are statistical assumption, and they're only useful to establish a number of patients. The study is 90% power to detect 15% different in disease-free survival. We will have an interim. It's an event-driven study, so we'll have an interim review at 64 patients. Not to stop the trial for efficacy or purely to look at the statistical assumption and to see if the 276 patients is the adequate number. Typically, interims are done with 50% or 70% of the events. Correct. You're doing this earlier with 64 patients just to have a look at. Is the futility analysis, or I didn't get that point. Yeah, it is 50%. The total number of event is 128. 128. Yeah. Well, we can call it futility, but in reality, since the comparison is observation- Right. It would be surprising if the drug does absolutely nothing. We assume there is an effect, and the goal is to recalculate the statistic and to see if the number of patients is adequate. Got it. Let's switch to the market opportunity. How big is the patient pool in the U.S. for the BCG unresponsive setting? Can you give us a sense of how much off-label Gem/Doce is used in the real world by urologists? Well, the number of patient, we did some math looking at the publication. For second line unresponsive, the number of patient estimated in the U.S. is about 5,000. Okay. Right. The second question was. The sequential Gem/Doce, how much is it really used in practice? Look, that's very difficult to establish, right? Because it's almost exclusively used in academia, where the five hours administration time is less of a problem. That's off-label. It's going to be very difficult. We will let the doctor to decide. We won't promote the drug off-label, that's for sure. Maybe talk about the differences, like the Gem/Doce sequential one, they need compounding pharmacy specialized, and then you have a ready-to-use pre-filled syringe. Correct. Do you think this will truly eliminate the barrier for uptake? Will the time difference, the ease of administration really make a difference? We do believe we'll make a big difference. The proof is that, as of now, the vast majority of Gem/Doce is used in academia, in universities. While roughly 80% of the patient is treated in the community, that they use very little, or if not, they use it at all, the combination as a conventional Gem/Doce. You need a pharmacy, specialty pharmacies that prepare the solution, and you have to use it in a very short amount of time. For a doctor and for a patient, pretty much they have to spend the entire day in the clinic because four or five hours you have to wait between the two administration. It gets a wait for the patient and the doctor and the clinic to use it. We do believe that the pre-filled syringe administration less than five minutes, it would make a big difference. The doctor does not need to do the administration. A nurse can do it. It's a game changer. Okay. We do believe we will expand the use of Gem/Doce from limited to academia and universities to the medical community that is 80% of the patients treated. Makes sense. Once you disclose the data earlier this year, the number one question I got was basically where does this really fit into the treatment paradigm? With all these drugs in development, clinical trials, and multiple agents approved. What is the takeaway here? Well, clearly the data from the two studies will dictate the positioning. I go back a little bit to the chemotherapy concept. Chemotherapy has been the basic treatment for oncology, especially for bladder cancer for a long time. BCG is the mainstay, but doctors like chemotherapy. Gem/Doce is very popular. We just came from the AUA in Washington a few weeks ago. Gem/Doce, there was a lot of presentation on the use of Gem/Doce. The position with clearly the first indication that will come faster, if approved, of course, is the high risk for second line because there is nothing there, and the alternative is radical cystectomy. Life after radical cystectomy is very bad. That would be the first potential approval. The largest indication intermediate will come after, and then we probably won't look for any other registrational trial because this one is the market for high risk, second line, and the large market for intermediate, it capture large number of patients. We let the doctor and the urology guidelines to indicate if there is any other use. We do believe these two indication there already capture a large% of the patients. How would the doctors really sequence the treatment, with all these other available agents? Oral agents are also coming on board. Right. Yeah, that's a great question. Speaking with the urologist, the sense is that in a few years, not many, but when the other immunotherapy eventually will get approved, the way to treat patient would be a combination of immunotherapy and chemotherapy. Chemotherapy clearly give you the efficacy. Right. It's clearly efficacious. The immunotherapy helps to give you the durability. Right. The combination makes a lot of sense. If you look at, there is another couple of companies, they're already running trial with their immunotherapy in combination with gemcitabine and in combination with docetaxel. These approaches starting to become more known, and so that would be probably the way to go. Makes sense. There's this Bridge trial that's 870 patients that's evaluating Gem/Doce versus BCG. Correct. If the trial shows non-inferiority, do you think NDV-01 basically will be used instead of BCG, or can replace it completely? Well, the BCG has been used for many, many years, right? We are very familiar with the. They've shortage, right? With the BRIDGE trial. Right. There is a shortage to say replace it completely is a little bit, maybe it's too much. Clearly, if it shows non-inferiority, and there are publication of BCG versus Gem/Doce already, and the data looks pretty good in favor of Gem/Doce. Clearly, we'll have the use of frontline. What we can say is that we most likely will not try to repeat the BRIDGE study to look for any indications of frontline because I believe they over-enrolled. There are 900 patient. It's taking many years. These kind of studies can only be done by- Right A consortium of clinician. Right. If the data show good equivalency, there is a chance there will some use there. The urologists, they tend to adhere and use the guidelines as the way to treat patients, and so would be important to fit in the guidance in some way. The readout of BRIDGE is not imminent. It's another couple of years. We have time to move forward our program and to show data. How are you thinking about the pricing? It's two generic chemotherapies, but it's a novel formulation. Well, we do think about pricing, right? We look very closely to the competition of the other companies doing terminal pricing. We do not believe that NDV-01 should be priced at a discount just because the clinical data they show good efficacy and very good safety profile. It's at our rate. The discount is, at least at the beginning, is not likely to be the strategy, right? We look at the bigger company, Johnson & Johnson, just to make the name. The price is around $700,000 a year. It's chemotherapy. They use gemcitabine alone. We use a combination, and NDV-01 is easy to administer. If you look at the model, at least for the high risk, that could be the model we look at. For the intermediate, that's a little bit more challenging because there is really no comparison for now. There is no drug approved for the use in adjuvant and intermediate. There is one company that will have the nice problem to have both indication in high risk and in intermediate. We'll look closely how they will price. We will look how Johnson & Johnson will do in the marketplace with their pricing, and we have the luxury to have maybe one or two years of advantage in watching what other people do, and we'll do it appropriately. The key message that we don't believe that discount or pricing will be a competitive tool that we'll use for NDV-01. Just to clarify, for both pivotals, you're using the same dose and frequency, right? The same product, same dose, same frequency. There's no scope by weight-based pricing adjustments or anything- No. The formulation. No. Well, look, you know us. We don't like these kind of things. You use the same product, you change the name, you slightly tweak the formulation, and you charge 10 times the price. These days, it's not going to work, and we won't do it anyway. We don't feel that is the right way to approach patients. Makes sense. Then, are there any unique CMC challenges, like stability of the gemcitabine formulation or anything specific to the IP or technical know-how that basically compounding pharmacists cannot try to replicate your product? Yes and yes. IP, clearly, we just filed a provisional patent on the formulation, and that extend the IP up to 2047. That's happened very recently, so we are very happy about that. It's a good patent, too. That's a barrier for compounding pharmacy. We do believe that the biggest barrier is to make the product, because it's clearly not an easy product to make. It's not as a viral vector, but still has its own challenging. We just cannot see a pharmacy to try to do it. We know how complicated and how the process of manufacturing, we are in the middle of it right now in the U.S., and it's challenging for us. I can imagine for a compounding pharmacy, it would be even more challenging. It's chemotherapy, right? Right. These are not easy compounds to handle. In the last few minutes, I want to briefly touch on the sepranolone program. You have the PWS phase II study about to start. Can you elaborate on what endpoints you aim to assess and what do you want to see to advance to a next stage? Sure. This is a phase II study, right? It's a proof of concept and/or signal finding. The primary endpoint is clearly safety. Now, the sepranolone has been in over 200 patients, so we know the drug is safe, but we have to prove that it's safe also in Prader-Willi patients. The secondary endpoints is a combination of weight, hyperphagia, and quality of life. There is a few exploratory secondary endpoints, but hyperphagia then weight and BMI are the principal. Do you want to pursue the Tourette syndrome in parallel if the data is positive for PWS? We thought about it. The data looked good in Tourette and would be good enough to go after that indication. It's a subcu, and Tourette is a competitive space with the antipsychotic. For now, we stay with Prader-Willi. Eventually, maybe with a different formulation, if there is a signal, we may think about it. For now, Prader-Willi is the way. What's your appetite for BD? Do you want to bring in more assets or develop sepranolone on your own? We look at everything we can. To be direct, NDV-01 is a big commitment. It's worth to focus on that for now. Right, we keep on looking at everything. If we find something like next NDV-01 or the next sepranolone, but I think for now, our hands are full. Got it. To close off is, what is your cash runway and catalyst that investors should focus in the next six months? No. Well, I'll let my CFO answer that. Sure. On the last earnings and the last 10-Q, we reported $234 million of cash and marketable securities. That gives us enough runway to take us through 2029 and to complete the clinical program for both indications, BCG unresponsive indication and the adjuvant indication as well. It also takes us to approval for the BCG unresponsive indication. We're fully financed. It's a good place to be in. Yes. Well, thank you so much for your time, sir. Thank you. Thank you. Thank you, Farzin Hak, and thank you, Jefferies, again.