Conference Transcript - RLMD 2026-06-04

Farzin Hak, Analyst — Jefferies

Good afternoon, everyone. My name is Farzin Haak, one of the biotech counselors at Jeffries. It's my pleasure to introduce Sergio Traversa, CEO, Maggit 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?

Sergio Traversa, CEO

Well, thank you, Farzin, and thank you, the old Jeffries team, for inviting us. Good afternoon to everyone. and I'm Sergio Travers, I'm the co-founder and the CEO of RealMada. A brief overview, right? Originally, RealMada is a spin-off 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. So 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. And so we in-licensed two programs. One is still in CNS. It's a bit of an earlier stage, and we start phase two in Prader-Willi, through a concept shortly. And the other one is in oncology, in neuro-oncology to be specific, and it's NDVO1. And it has attracted a lot of attention for a lot of parties and for investors in particular. And I believe that the NVIDIA-01 is where we spend most of the time today. And we have been on public since 2014 and trading on NASDAQ since 2019.

Farzin Hak, Analyst — Jefferies

Great intro. So you're coming back to the NVIDIA-01, the main asset. So the phase two data was outstanding, with anytime CR rate of 95% and 12-month CR rate of 76%. You recently presented the data at AUA. Can you go over some of the KOL feedbacks on the data?

Sergio Traversa, CEO

Sure. Well, yes, we present more details at AUA, and what attracted a lot of attention is, and not surprisingly, is the 12-month response rate of our phase two basket trial. and with numbers with a 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. So this data, if confirmed in the Phase 3, as we hope and believe, then will make a big advance in the treatment of bladder cancer.

Farzin Hak, Analyst — Jefferies

And one of the pushbacks was that the Phase II data was from a single ex-US site, but included a nice mix of CIS, CIS-fospapillary, high-grade TA, and then high-grade T1 as well. But you saw consistent responses across all disease subtypes. But 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?

Sergio Traversa, CEO

Well, thank you, Faradzim. As you may imagine, this is a question that we get relatively frequently. And, well, a couple of points here. The main point is this. This is an extended-release formulation of intravesical gencitabine plus docetaxel, gen-dozy. Gen-dozy has been used in the last 10, 15 years and is getting more and more used. And there is a lot of publication around about the combination of the two drugs, and clearly there is an efficacy. So what we do like, among other things, of NDVO-1 is that we don't need to prove the mechanism of action or that the drug works. It has been published. So that is a signal and a support for reproducing similar data, same data, in the larger U.S. study. And another point is that the study, yes, is a single center, is a large university center in Israel. And in Israel, the approach, the therapeutic approach, is pretty much the same. They follow the U.S. guidelines. And also, this is oncology, is bladder cancer. The endpoint is a cystoscopy and cytology. So it's hard endpoints. So they assume they should be reproducible in any place where the trial is run. So I hope I answer your question.

Farzin Hak, Analyst — Jefferies

And then based on the data, have you had any conversations with the FDA for FastTrack or breakthrough therapy designations?

Sergio Traversa, CEO

Not yet. Breakthrough, you need some data to get the breakthrough. FastTrack, we will apply. And it will, you know, fast track also become, it helps when you are doing the clinical study, the clinical trial, and when you start to generate data. So the answer is yes. We look into that, but we haven't done that yet.

Farzin Hak, Analyst — Jefferies

Got it. And then when is the next data update from this phase two expected with a longer term follow-up?

Sergio Traversa, CEO

Yeah, the 12-month data is kind of the landmark that the FDA looks at in the investment community, And we look at two because whatever results you get at 12 months, then, like, it's a confirmation that you have a response and you have a durability of response. We will have the 18-month data and with a larger number of patients also at 3, 6, and 12 months in, say, mid to early Q4 this year. we haven't decided yet how to to present and when to present but maybe we will we will present something a summary of these data probably we believe before

Farzin Hak, Analyst — Jefferies

year-end. For the BCG unresponsive pivotal FDA has accepted a single arm registration path and that is in the more refractory setting but how 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?

Sergio Traversa, CEO

Well, we have a protocol that defines somewhat the patient population. The FDA was in agreement with a 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. So we get some suggestion that this was a space where there was a need for a product. And GEMDOSY is already somewhat used as a salivist therapy. And so the inclusion criteria is patients that fail BCG, and then they fail one of the products is approved or is in development for BCG and responsive. And after a failure of this product, the only alternative would be taking the bladder out. So that's where we come in. So 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.

Farzin Hak, Analyst — Jefferies

And then FDA's acceptance of CR rate at any time, that's the primary endpoint, but does it explicitly define a time period for durability? Like, do you have to wait for 12 months data to match the elder strains, Estillardins precedent then, or just six months, how much follow-up do you really need?

Sergio Traversa, CEO

Yeah, that's a great question, and there was a very interesting discussion, conversation and discussion with the FDA. there is no no alternative with these patients so the the end point is CR at any time but the comment that the FDA made was very interesting they said we want to see the totality of the data and in FDA language it reads like they want to see a certain response and they didn't give us any number a certain response but also they want to see a response for some duration of time. We look at the 12 months as a landmark, but the end point is the complete response at any time. But we do believe the FDA wants to keep some flexibility and look at all

Farzin Hak, Analyst — Jefferies

the data together. Makes sense. And then you have noted there's like 50 high-volume centers in the U.S. They account for a majority of the BCG unresponsive cases. How many sites are you targeting for phase three and what is your enrollment assumptions right we

Sergio Traversa, CEO

are targeting and as you may imagine we already spoken with yeah pretty much all of these sites we are targeting 60 sites in the United States and they will run both trial is actually is one protocol and to make you know life easier to go you go only with one IRB approval with two cohort it is one is the high-risk BCGN responsive second line and the other one is adjuvant therapy for intermediate risk and you know this we have we contacted all the sites what I can share there has been a lot of enthusiasm in participating in this trial Gendosi is kind of chemotherapy is one of the preferred treatment for urologists and among chemotherapy region dose is the one that is attracting a lot of attention and in terms of efficacy and and and tolerability so the any comment on the

Farzin Hak, Analyst — Jefferies

enrollment assumptions given that there's a lot of trials ongoing yes so we like

Sergio Traversa, CEO

we look at this historically guessing enrollment we have a lot of experience in this field and guessing enrollment is always is always a little challenging but we look at historically so we assume for the the high risk second line therapy 87 patients we assume 12 months enrollment and for the intermediate that is a large number of patients we are targeting 276 patients we assume in 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 is one arm So 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 it's randomized. And so 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.

Farzin Hak, Analyst — Jefferies

Got it. And then in phase two, five patients relapsed and they were successfully re-induced with a second course. And then four out of five attained CR, and one discontinued. But what are the provisions for re-induction in Phase III?

Sergio Traversa, CEO

In Phase III, it is only allowed one re-induction. One re-induction, okay. Got it. That is in line with the practice. Got it. Common prostate of urologist.

Farzin Hak, Analyst — Jefferies

Okay. And then switching gears to the intermediate risk setting. So that one is notoriously heterogeneous. It ranges from multifocal low-grade to recurrent low-grade. Like, there's a whole range of them. And you're starting your phase three without having proof-of-concept data comparing NVIDIA-01 plus starbit versus starbit plus observation. So will you enroll all intermediate subtypes or focus on the higher risks that will most likely benefit from that given therapy?

Sergio Traversa, CEO

Well, there are enrollment criteria. we'll try to enroll a good representation of patients and we will stratify versus a higher risk and lower risk patient. So it's going to be more widely open in terms of patient population.

Farzin Hak, Analyst — Jefferies

And have you disclosed the event rate in the observation realm? Like how are you powering the study?

Sergio Traversa, CEO

Well, that's a great question. We made some assumptions. We had to make some assumptions to calculate the number of patients that we want to enroll to reach statistically significant. But these are all assumptions, right? Because there is really, if you look at the literature and the publication, the data are all over the place. It goes from like 45% to like 60% or 70%. And the assumption we made, we assumed for the observation arm, 60% response or disease-free survival. And we assume 15% better for the arm, so 75%. But these are statistical assumptions, and they're only useful to establish a number of patients. So the study is 90% power to detect, 15% different in survival, disease-free survival. and we will have an interim, it's an event-driven study, so we'll have an interim review at 64 patients and not to stop the trial for efficacy or purely to look at the statistical assumption and to see if the 270 patients is the adequate number.

Farzin Hak, Analyst — Jefferies

Typically, interims are done with 50 or 70 percent, like of the patients like is that no 50 to 70 percent of the events correct but you're doing this earlier with 64 patients just to have a look at if the is the futility analysis or what was i

Sergio Traversa, CEO

didn't get that yeah it is 50 percent the total number of events is 128 128 yeah and the well we can call it futility but in reality it's more uh since the comparison is observation and it would be surprising if the drug does absolutely nothing so so then the the we assume there is an effect and the goal is to to recalculate the statistic and to see if the number of patients is adequate

Farzin Hak, Analyst — Jefferies

got it so let's switch to the market opportunity so how big is the patient pool in the u.s. for the bcg unresponsive setting and can you give us a sense of how much off-level like gem dose is

Sergio Traversa, CEO

used in the real world by urologists um the well the number of patients we did some some math looking at the publication for a second line unresponsive the number of patients estimated in the united states is about five thousand okay right and um the inter the second question was

Farzin Hak, Analyst — Jefferies

the sequential gym dosi like how much is it really used in practice look that's very very difficult

Sergio Traversa, CEO

to establish, right, because it's mostly, almost exclusively used in academia, where like the five hours administration time is less of a problem, so that's off-label, right, it's going to be very difficult, right, we will let the doctor to decide, we won't promote the drug off-label, that's for sure, so.

Farzin Hak, Analyst — Jefferies

Maybe talk about the differences, like the Jim Doce sequential one, they need compounding pharmacy specialized center, and then you have a ready-to-use pre-fill syringe, and do you think this will truly eliminate the barrier for uptake, like will the time difference make a, like the ease

Sergio Traversa, CEO

of administration really make a difference? We do believe will make a big difference, and the proof is that as of now, the vast majority of the, of gen doses used in academia and universities, and while 80%, roughly 80% of the patient is treated in the community, that they use very, very little, or if not, they use it at all, the combination as a conventional allergen dosage. You need a pharmacy, especially pharmacists, that prepare the solution, and you have to use it in a very short amount of time. And 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 administrations. So it gets like a wait for the patient and the doctor and the clinic to use it. So 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. So it's a game changer. And he will We do believe we will expand the use of germ dosy from limited to academia and universities to the medical community. That is 80% of the patients treated.

Farzin Hak, Analyst — Jefferies

Makes sense. And then once you disclosed 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 developing clinical trials and multiple agents approved, So what is the takeaway here?

Sergio Traversa, CEO

Well, clearly the data from the two studies will, like, dictate the positioning. But, you know, I go back a little bit to the, you know, the chemotherapy concept. Chemotherapy has been the basic treatment for, you know, oncology, especially for bladder cancer, for a long time. And, like, BCG is the mainstay, but doctors like chemotherapy. and gendosi is very popular we just came from the aua in washington a few weeks ago and you know gendosi was there was a lot lot of presentation on on like the use of gendosi and so the position with it clearly the first indication that will come faster is the if approved of course is the high risk for second line because there is nothing there and the alternative is uh radical cystectomy that is really like it's not like life after radical cystectomy it's very is very bad and and so that's that's would be the first potential approval the largest indication in the media will come after and then the we probably won't look for any other registrational trial because this one is like the market for high risk second line and the large market for intermediate capture like large number of patients and then we let the doctor like in the guideline the urology guidelines to like to indicate if there is any other use but we do believe these two indications already right

Farzin Hak, Analyst — Jefferies

capture a large percent of the patients but how the doctors really sequence the treatment like with all these other available agents like oral agents are also coming on board

Sergio Traversa, CEO

right yeah that's a great question the speaking with the urologist the you know the sense is that in a few years not many but when like the 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 because it's clearly efficacious the immunotherapy helps on the to give you the durability so the combination makes a lot of sense and if you look at the division not another couple of companies they already running trial with their immunotherapy in combination with gencitabine and in combination with gemdose. So this approach is starting to become more known, and so that would be probably the way

Farzin Hak, Analyst — Jefferies

Makes sense. And then there's this BRIDGE trial that's like 870 patients that's evaluating gemdose versus BCG. If the trial shows non-inferiority, do you think NVIDIA-01 basically will get a, instead of, will be used instead of BCG or can replace it completely?

Sergio Traversa, CEO

Well, BCG has been used for many, many years, right? We are very familiar with the BICH trial, right? Maybe it's a short, just to say replace it completely is a little bit like, maybe it's too much. But clearly, if it shows non-inferiority, and there are publications of BCG versus Gendosia already, and the data looks pretty good in favor of Gendosia. So 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 like 900 patients. It's taking many years. these kind of studies can only be done by right consortium of clinician and but you know if the data show good like equivalency there was a chance to be some use there you know the urologist they tend to adhere and use the the guidelines as you know the way to treat patients and so it would be important to to fit in the guidance in some way so but the readout of bridge is like not imminent. It's not another couple of years. So we have time to move forward our program and to show

Farzin Hak, Analyst — Jefferies

data. How are you thinking of the pricing? Because it's two generic chemotherapies, but it's a novel

Sergio Traversa, CEO

formulation. Well, we do think about pricing, right? And we look very closely to the competition or the other companies do internal pricing um the we do not believe that ndview one should be priced at the discount just because the clinical data they show good efficacy and very good safety profile so it's the discount is is at least at the beginning is not it's not likely to be the strategy right we look at like the bigger bigger company johnson and johnson just to make the name the price is around $700,000 a year it's chemotherapy they use gen cytobine alone we use a combination and NDVO1 it's easy to administer so if you look at the model at least for the high risk that could be like 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 Zajuan and Intermediate. So there is one company that will have the nice problem to have, to have both indication in high risk and in Intermediate. We look closely what 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 you know we'll do it properly but you know the key message that we don't believe that uh will discount or pricing will be a

Farzin Hak, Analyst — Jefferies

competitive uh tool that we'll use for ndvo one just to clarify for both uh pivot also using the same dose and frequency right the same product same dose so there's no scope by weight based

Sergio Traversa, CEO

pricing adjustments or anything no no look you know as 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 that's not these days it's not going to work everyone do it anyway we don't feel

Farzin Hak, Analyst — Jefferies

that is the right way to approach patients makes sense and then are there any unique cmc challenges like stability of the gym dosi formulation or anything specific to the ip or technical know-how that basically compounding pharmacists cannot try to replicate your product?

Sergio Traversa, CEO

Yes and yes. So IP, clearly, we just filed a provisional patent on the formulation that extends the IP up to 2047. And so that's happened very recently, so we are very happy about that. It's a good patent, too. And so that's a barrier for compounding pharmacy. but we do believe that the real the biggest barrier is to make the product because it's clearly not I mean the an easy product to make it's not like it's not as a viral vector but still has its own challenging we just cannot see a pharmacy like to try to do it and we know how complicated and how the process of manufacturing we are in the middle of it right now in the United States, and it would be, it's challenging for us, I can imagine, like compounding pharmacy would be even more challenging. It's chemotherapy, right, so it's not, these are not easy compounds to handle.

Farzin Hak, Analyst — Jefferies

In the last few minutes, I want to briefly touch on the Sepra Nolan program, like you have the PWS Phase 2 study about to start, like, can you elaborate on what endpoints you aim to assess and what is the, basically, what do you want to see to advance to the next stage? Sure,

Sergio Traversa, CEO

Sure. This is a phase two study, right? So it's a proof of concept or signal finding. So the primary endpoint is clearly safety. Now, the patient is, the soprano 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-William patients. And then the secondary endpoints is a combination of weight, hyperphagia, and quality of life. So there is a few exploratory secondary endpoints. But, you know, hyperphagia and weight and BMI are the principle.

Farzin Hak, Analyst — Jefferies

And do you want to pursue the Tourette syndrome in parallel if the data is positive for PWS?

Sergio Traversa, CEO

We thought about it. The data looked good in Tourette and would be good enough to go after that indication. It's a sub-Q, and Tourette is a competitive space with the antipsychotic. And so for now, we stay with Prader-Willi. Eventually, right, maybe with a different formulation, if there is a signal, we may think about it. But for now, Prader-Willi is the way.

Farzin Hak, Analyst — Jefferies

And what's your appetite for BD? Like, do you want to bring in more assets or develop separate on your own?

Sergio Traversa, CEO

We look at everything we can to be direct. NDBO-1 is a big commitment. is worth to focus on that for now. So, right, we keep on looking at everything and we find something like next NDVO1 or the next soprano, but I think for now, our hands are full.

Farzin Hak, Analyst — Jefferies

And then to close off is, what is a cash runway and catalyst that investors should focus on the next six months?

Sergio Traversa, CEO

No, well, I'll let my CFO answer that.

Maged Shenouda, CFO

So on the last earnings and last 10Q, we reported 234 million dollars of cash and marketable securities and that gives us enough runway to take us through 2029 uh and to complete the clinical program for both indications bcg unresponsive indication and the um adjuvant education as well and it also takes us to approval for the bcg unresponsive indication so we're fully financed it's a good place to be in

Farzin Hak, Analyst — Jefferies

yeah well thank you so much for your time so thank you thank you thank you for seeing thank you