I'm Andy Berens. Good morning, everyone. I'm Andy Berens, senior biotech analyst at Leerink Partners. It's day two of our healthcare conference in beautiful Miami with fantastic weather. Thanks everyone for joining us. Very happy today to have Relmada Therapeutics. We have Raj, Maged, and Sergio. Thank you, gentlemen.
Thank you, Andy.
Thank you.
We are very happy to.
Yeah. Well, you guys had some big news recently, and I'm sure we'll talk about that. But before we go into the recent update, why don't you give us an update or give us an overview of the company for investors that may not know the story?
Sure. I'm happy to do that. First of all, good morning, everyone, and welcome, and thanks, Leerink, for inviting us to the conference. Brief overview. Relmada's been around since private since 2012. Was born as a spinoff from Cornell University, and it's been private for a couple of years, then went public in 2014, listed in Nasdaq in 2019. Originally was focused entirely on CNS, and we had very good success, but also we had some setback. Last year, we thought about it and said CNS for a company of our size may be a little bit too risky and just to focus on that. We expanded the strategy.
We are still focusing on CNS with sepranolone, but we extended the strategy to really lower the risk profile, right? Without compromising the upside. We expanded, and we were looking for programs with proven mechanism and eventually, hopefully, that have been in patients already with a good safety profile and relatively late stage. NDV-01 fit absolutely perfectly for bladder cancer, perfectly what we are looking at. We like a lot hard endpoints, right? That you can actually measure. U ro-Oncology in this case is absolutely perfect. NDV-01 is really the focus for the next 1 to 2 years of the company.
Great. Well, just Leerink covered you guys with Marc Goodman when you were a neuro company, and then I knew Maged way back when he was on the sell side. We have a history there. When he approached me and said, "What do you think?" I looked at it and I said, "Wow, this is interesting." You know, it's minimal translational risk, obviously established market. There's some competition, but you know, it's very interesting story. I assumed coverage not that long ago. Great. Why don't we start with REL-1017. Can you walk us through you know, what the drug is and how you guys acquired it?
Sure. I'll give you the top-down, and then we have Dr. Raj Pruthi, who's our chief medical officer, can go a lot more in detail. He's a lot more qualified to talk about the topic. NDV-01 is very simple. Bladder cancer, right? Bladder cancer is a particular kind of cancer that differs from most of the other. First of all, it's rather frequent. It's 4% of all cancer in the United States at least, and has a feature that is not a lethal cancer, but it lasts for a long time. The average age of the patient affected by bladder cancer is around 70, 72, 73 years old, and if it's treated, it can last up to 10 years and maybe even more than that. At that age is a big deal.
The goal is, of course, saving life because if you don't treat it, becomes lethal too. With a good treatment, the goal is really to spare the bladder. Because living without the bladder is absolutely a no-no. The quality of life is very miserable. I've no other way to define it. There are different kind of treatment, mainly immuno and chemotherapy. Over the last 10 years, there is one treatment that became really the one that urology would like to use and they would like to use a lot more. This is a combination gemcitabine and docetaxel. They are two very well-known product. They are synergistic when administered together. I said that they would like use more for a couple of reasons.
One is chemo, and 80% of the patients are treated in doctor office, in urology office, not in academia. It is a different, like where time is a lot more important than in academia. The issue with administering Gem/Doce is that you need a specialized pharmacy that prepares it because it's chemotherapy. You cannot do it in the office. Also it's the administration, right? Then Raj could give you more details. The administration lasts four or five hours, and you cannot give them together. You have to give them in sequence and in a solution. It's very impractical. NDV-01 is a formulation that forms a gel inside the bladder.
You give two components, and the gel is formed inside the bladder and is a sustained-release delivery, and it lasts for a few days, and it can be administered in less than five minutes. It's as simple as I described, and I steal the definition from Raj. It will democratize the use of Gem/Doce from academia, where they can do things without like with they have more time, they have the infrastructure to the 80% of the patients treated in the doctor's office.
Okay. Do you wanna add Raj to what he said?
No, I think, Sergio, you're exactly right. I spent my career in academic medicine as the chair at UCSF and at UNC. In academic centers, you have specialized pharmacy, and you can send them to the infusion center, and they tolerate a level of inefficiency. What really NDV-01 does, it delivers Gem/Doce. This drug that Mike O'Donnell 13 years ago showed its efficacy in the clinic. Now we can deliver it in 5 minutes in sustained release. It allows. You don't have to be at the University of Miami, you can be in Coral Springs or wherever you are, and you can deliver this drug. That the provider gets to keep that patient in their practice. Urologists are entrepreneurial, they want to do that.
The patient wants to stay there, it's the right thing for the patient who's 75 years old. I think this is a drug we know works. It's sustained release, and I think TAR-200 has shown us the benefits of a sustained release chemotherapy. Then on top of that, the ease of use, five minutes, an MA, an LPN, an RN, no BSL-2s, no hoods, no viral containment.
You know, as a naked chemotherapy regimen, what percentage of patients got Gem/Doce?
Yeah. If you look at kind of some real-world evidence posters, it's probably 15%-20%. It's a low number. That's almost uniquely at academic centers. I think that number, the growth in that is tremendous. I think from going from a baseline where we're so difficult to deliver a 15%-20%, you know, it's wide open.
Okay. Why don't we talk about the data that you've demonstrated to date?
Go ahead, Raj.
Yeah. Our study was in high-risk NMIBC and we showed numbers. Now we showed 12-month numbers, so 12-month landmark CRs and we showed some Kaplan-Meier, but landmark CR in that group of 76% at 12 months and in a particularly tougher-to-treat group to treat the BCG-unresponsive. They've had BCG, they failed, and we think that's biologically now a little more resistant. 80% 12-month CR. I would say that is the highest number, 12-month CR in that group of patients bar none.
What have others shown?
Yeah, it's the apples to apples, right? Others have shown BCG unresponsive with papillary disease or with CIS. It's interesting 'cause it's a little bit of an artificial construct. When I practice, if you were BCG unresponsive, that's what you were. We didn't tease out whether you're CIS and Gem/Doce doesn't tend to have that differential effect anyway. I think it's a by-product of the FDA's guidance in 2017 teasing out CIS as an important kind. Now everyone talks about does it have CIS in it or not. Our 80% still is, it's not a large number, but had four out of four CIS complete response any time and two out of two at 12 months. Granted small numbers, but still we're seeing a significant efficacy there.
Okay. What would Gem/Doce have in that group?
Yeah.
It doesn't sound like they distinguish that much, but there must be some data.
Yeah. In the others that are approved, that nu mber is for the CIS about 46% is the best in class.
Okay.
If you look at just papillary only and ours is a mix, that the best in class is 74% CR KM 12 months, ours is 84%. Even if you just take papillary but CIS 12 months, best in class CIS is 70, 46%. Your question, what's Gem/Doce?
Yeah.
It's about 60%.
Okay.
I knew when I joined this company if we could hit Gem/Doce numbers, which I know, we know works and we know is the de facto standard per Mike O'Donnell's statement, get to 60% it's a win. Our 60%-80% I think is that sustained release.
Yeah. Yeah, I mean it seems very low translational risk to me. That was what stood out because you're taking known APIs that are active and not only are you making them more convenient, but like you said, you're improving the delivery, your extended release and I mean that shouldn't make the efficacy worse. It shouldn't. Any?
No, Andy, you bring up, if I may say, like a point, you know, my prior company. You're looking at immunotherapies and I know they're important, but it's a little bit of a tough thing for urologists and patients. Like it's a whiteboard, right? I'm suppressing IL-12 and I'm gonna increase your NK cell and they're, you know, it's a little bit theoretical until you do the experiment, you do not know. A cytotoxic chemotherapy that's been around for 30 years in gem and then 13 years in Gem/Doce, it's an easy leap, like you said.
Okay. How did the data evolve from what you got? I think you showed the 9-month. I'm new to the story, so please forgive me, but just then what was the 9-month data that we saw before the 12-month? Had that made, obviously the stock reacted very favorably to the update.
Yeah. It was basically a continuation of this story. I think you always have by quarter often a 15% haircut, so you might go from 60% to 45% or whatever it might be. I think we went from close to 90% to 80% at 12 months. I think we kept it. We're seeing durability which was very important and 12 months seems to be a bit of a, like a landmark time to get to for durability.
Okay. Now obviously, when you increase the exposure of a drug, efficacy should go up, but there's also then, safety tolerability issues. Have you seen any compromise in the safety tolerability with this drug versus what you would expect to see with the chemo, the naked chemo regimen?
We have not. In fact, the safety we tend to see up front, like the discomfort with urination, and it tends to be 24 hours. We don't end up seeing the maintenance phase. I dunno if it's, you know, you become accustomed to it or tolerability to it.
Right. Okay. Can you just walk us through the way the drug is you said five minutes. How is it administered? I know when we first connected, you showed us a video. I should have asked you to bring the video, but maybe you can walk us through and describe it.
You come in, I'd put a catheter in you. Well, actually I would like see how you're doing and then my nurse or my MA would take care of you and allows me to go into another room and just from a community urologist from an opportunity cost to do something else that it's not me delivering it. Put a catheter in which all of these are intravesically delivered. The first thing I put in is a, we call Part A, is a hydrophilic gel. It's about 50 cc. We empty the bladder and 50 cc's. The bladder can hold about 400 or 500. So 50 cc's, it's kind of like a KY gel. Then the catheter stays in, I remove the syringe, and I put in the active drug substance and instill about 15 cc's.
That's hydrophobic, and that sits in that hydrophilic gel. Then it starts to dissolve, urine, then the catheter is removed. It starts to fill. It's a little bit like soap and water, right? You have the soap in there and the water, and the gel comes out, urine fills, and the soap just sits there and over the next 10 days dissolves.
Uh, and-
You go home after that catheter is removed.
The urologist is there for what parts of the procedure?
Yeah, press the flesh. How are you doing?
Okay. Interesting. How often would you administer it after that?
Yeah. With a sustained release of 10 days, every other week times 6. That's the induction course. Once a month, maintenance, 1 installation.
Okay.
They probably wouldn't be there for that just because you come in on a schedule.
Okay. Urologists are procedure-oriented. They're surgeons at heart. You know, what kind of billing will they be able to do for this, administering the drug?
Yeah, I could comment and then.
Yeah, sure. Go ahead.
Increasingly, I saw a specialty network survey which, you know, kind of does the community urologist. Increasingly, since 2008, professional fees have gone down significantly. Used to be 60% of urologist income. Now it's in the 30s. Buy and bill and in-office dispensing has exceeded that. I think there is financial incentive to say, you know, whatever the ASP plus 5-6%. Then I can go in another room and do a procedure.
Okay.
I think just the economics of it are favorable for us and for everybody.
Okay. All right. What about, why don't we talk about the other options for these patients and some of the experimental drugs that are coming?
Yeah. Right now you have. I'll lean into then discuss a little bit of like where we're going based on that.
Yeah.
The FDA has approved four drugs for BCG- unresponsive NMIBC with CIS. Keytruda, which has a 19% 1-year CR. Adstiladrin, 24% 12-month CR. INLEXZO and Anktiva, 45% 12-month CR. When we went to the FDA to discuss what they want to see, I'll be honest with you, they do not want to see yet another drug because the reason they created this construct is to avoid cystectomy. Now they're saying 55%-80% are going to recur within a year. We're back at square one. Give us something in a second line, because otherwise. Even the ones coming down the pipe, the CG Oncology and I think Protara, enGene, we don't know, but are in that same ballpark. We did. They're looking for a second line. We know we're gonna sequence these agents.
What we're looking to do is come after one of these in development or approved agents as a second-line therapy and be the first there and be the only one that has a label in second-line therapy. The urologist can just say, "Okay, I'm gonna sequence. What do I have evidence and a label for? Okay, I have NDV-01 here." I think they'll probably, once again, enthusiastically move it earlier, too. That's one place I think where we will effectively compete. The other is in intermediate risk disease, and I'm happy to talk about that at some point.
Okay. What type of development path, you know, because I've definitely have gotten some questions about how your path, you know, the guidance for what you're going to need to do differs from some of the other companies.
Yeah. As that as a second line, I think that's unique. That's gotten a lot of attention to it, even from other sponsors and investigators, because that has been left untapped. We filled a short-term gap only to leave a later one. Gemcitabine tends to be a rescue study. That is for there. That's the development path. We'll start that in an 87-patient study in the middle of this year. I think we're optimistic with, again, the FDA's kind of enthusiasm for that we'll be able to move along with a CR and duration of response as the endpoints for that study.
Okay.
Intermediate risk is BCG-naïve, right? It's not a huge population, right? It's not a huge incidence and prevalent population. Intermediate risk bladder cancer is a much larger population. That's more like 75,000-80,000 incidence and prevalent patients. Because the other ones are maybe about 5,000, and you're trying to save them from cystectomy. But 75,000, 80,000, these are tumors that recur, and they recur, and they recur. They're not going to die from this disease, but it's the burden of care of a 75-year-old coming in twice a year to have a surgical procedure and a TURBT. So they want to know, like, "How do I not have this happen again?" That's adjuvant therapy. Ours is a study, a randomized versus drug versus observation.
It's very similar to PIVOT-006, which is drug versus observation. They've completed their enrollment. I think they're nine months ahead of schedule, which I think shows you the enthusiasm for patients and for investigators to have something in intermediate risk disease, where currently there's no label.
The patients would get the TURBT, and then, after the treatment, they would get your drug.
Yeah. Randomized versus observation. In observation arm, if they recur, they can cross over, which is just a patient-friendly.
Okay. What would be the course, the n atural course of patients that get observation?
Yeah. They likely will recur. The matter of time is when do they recur?
Right.
Not all of them will, but significant.
What percentage would recur, and how l ong would that usually take?
50% within a year.
Okay.
30%-50% in a year. By 5 years, 50%-60%.
What do you hope to achieve?
Well, an increase in recurrence-free survival at 2 years. It's an event-driven study, but we're using 2 years. Increase in recurrence-free survival, meaning a reduction in number of recurrence events, which then translates into TURBT and surgical events, which are secondary endpoints.
Okay.
If I may add, the de-risking part of the program is that the first indications that most likely will end up filing the NDA is the BCG-unresponsive high-risk, and that's an open-label trial. 87-patient, open-label. There is no comparison, and that makes it clearly lower risk compared to any other kind of control trial. Gem/Doce is already used in that indication. And so, it's that the results are good. We see that really the de-risking part of the program to get the product approved.
Okay.
Well, we hope, if I may say that both studies will start in the middle of this year, and with the BCG-unresponsive single-arm open-label, that we'll be able to share data by the end of this calendar year, some three-month data, 'cause it's open-label to say right.
Yes
By the end of this calendar year, here's a handful of patients. Are they responding or not?
Okay.
At a cadence of every three months.
Okay. You said the FDA wants something more like 50%?
Not for that study. No. There's no benchmark.
Okay.
When in first line, the first drug that was approved was actually valrubicin in 1998 at 8%.
Okay.
I don't know what that bar is. They said CR and duration response, and they intentionally, I think, used these words. "We wanna see the totality of the data.
Yeah.
'Cause right now, what is that number? We don't know what that is. Any effect to avoid cystectomy.
Okay. What about combining with chemotherapy? Or chemo with immunotherapy?
You know, Andy, that's a great question, and that's the question three years from today or two years in this room, we will be talking all about combination therapy. What is the best combinations? Because I think it makes sense, you lead with a chemotherapy, right? The chemotherapy is cytotoxic, lyses the cells, kills the cancer acutely, releases neoantigens, and then an immunotherapy can lock into these new antigens and maybe have a tail of a response. There's actually been interest from others to work with us on some sort of combination. Right now it's about like, you know, can you get a single API, what is the effect, and understand that.
Okay. Can we talk a little bit about the competition in intermediate-risk bladder cancer, a larger opportunity?
Right now there's no approved study. CG's doing their pivot study. Tyra and J&J are doing a study with FGFR inhibitors, and that's a little bit different because you have to be tested for FGFR. You have to be FGFR positive in intermediate risk. I think it's only 70%. I think their biggest challenge is urologists do not test for FGFR. Where in the workflow does that happen? Who pays for it? Who pays for FGFR testing? I mean, that's a real issue. If I'm gonna send off for a next-generation sequencing, it costs thousands of dollars. I gotta know why I'm using it. I think that'll just have to be a paradigm shift.
I think CG and I think then it'll come to probably ease of use, and that's where I think we have. It'll probably be both, right? It's a huge enough market. I think it can be both.
Okay. What have they shown so far, those companies in terms of-
You know, I hate to misspeak, but they don't have, I think, data this year has come out. They've shown that they can accrue fast, and their number of events are good. That's great for us in that there's an FDA path. They've never shown data in low-grade intermediate-risk disease. I think that'll be a question mark for them.
Okay. What about gene therapies?
Never been shown in except the FGFR inhibitors.
Okay
in intermediate-risk disease.
Okay. Do we have any questions from the audience?
Can you just talk about the structure of the financing this week?
Sure. Maged, do we have the-
Sure. Thanks for the question. We raised $160 million at $4.75 a share. That was a premium to the closing price on Friday. We did, you know, offer pre-funded warrants, so to those who didn't wanna get above a certain percentage of ownership, but there was no, you know, typical warrants given. We're very pleased. I can tell you that the deal was oversubscribed. We had $540 million of demand, and we raised $160 million.
Thank you.
Sure.
Tom, I think you have the mic. Please.
For both the intermediate and the high risk.
Mm-hmm
It sounds like rather than getting 1 or 2, we could be in a new paradigm for bladder cancer where you see many. Can you talk about, like, conceptually, could you get 3, 4, 5, 6 treatments, or after a couple, is the patient, is the doctor gonna send them to radical cystectomy?
Mm.
Like, what could change here?
Yeah.
Does it look like multiple myeloma?
Yeah. I think that's a great analogy. I think. Let me look back before I look ahead. This space was BCG, BCG, radical cystectomy. I've done a lot of radical cystectomies on non-invasive disease because a window of opportunity was closing. We got to rush in. That's not the way it's practiced anymore. Thank goodness, right? Because it's so morbid. I think you will definitely see sequencing. That's where I think our ability to step in and actually have a label that says, "This works in sequencing here," you can always move forward, but then we can be placed. At what point do you say, you know, enough is enough, the window's closing? I don't know. That's such a great question, because you don't want progression to happen.
I think you start getting 5, you start saying, "Okay, this is just a virulent organism. Let's not play with fire." But I don't know the answer. That's a great answer.
Yeah. Is it like how often like you said the progression. I was wondering, on the one hand, can you keep getting a sequence, but at some point, how often do you get caught by surprise and the tumor just goes metastatic or something?
Yeah. It's more predictable than I think my generation, you know, when I was younger, gave it credit for, but it's still a risk. Again, the risk of progression is about 20% at 10 years. It's. You have time, right? I think once you start getting out, three, four, five years, nothing's working, I think you gotta know when to. That's kind of the art of medicine, I think.
For the cystectomies, you're noting, do urologists like to do them or would they rather avoid it? Is it a good or bad reimbursement? You mentioned morbidity. Maybe talk about.
Yeah
how much they're trying to avoid it or not.
They are absolutely trying to avoid it. I'll give you one reason why. I'll give you a couple of reasons why. Medicare reimbursement for an 8-hour operation radical cystectomy, $1,500.
Oh.
That includes a 90-day global that when they get readmitted and so forth. Readmission rate's 40%. Complication rate's 75%. That $1,500 takes care of all of that. So no. Why do you think I did $1,700? Because they sent them to the professor. Because they don't wanna do that, right? In the community, they don't have the infrastructure, they don't have the residents, they don't have the ICUs. It's absolutely not what. The community urologists wanna keep them in the community, right? They lose them, they'll never see them again. Again, the imaging and the things that, like, they generate income off is then gone. So they want things to keep them in the community, whether it's the intravesical therapy or avoiding cystectomy.
I hated to answer your number with a dollar, but it kinda says it.
You mentioned earlier, 12-month complete response rates for a bunch of drugs that FDA has approved in NMIBC.
19%-45%, which means 55%-80% fail.
In what line was that complete response rate demonstrated?
After BCG, so you can call that first-line therapy.
Thank you.
You bet. Anybody else? All right.
Can I-
Yeah.
Also about, like people are sometimes talking about the 12-month CR, then they're talking about an anytime CR. What matters more, or do they matter equivalently, a 12-month versus an anytime CR? Of course, CG, which has been out a little longer, is talking about their 2-year-
Yeah
even three-year CRs. I'm just like, what's the pinpoint-
Yeah, yeah.
driving decision for the urologist?
Yeah. I think first, I think 12-month is important. Anything you get beyond that, sure. 12-month is important. I think you don't take CR any without duration of response, right? Because if you look good at 3 months, but it doesn't work for, you know, it stops at 4, then that's kind of not a big win. I think the FDA is looking more towards CR any plus duration of response. It's great. Maybe you didn't have a great initial response, but you worked for 2 years. That's a win of sorts. Or you had a great initial response, didn't work that long. I think they wanna see that totality of it, rather than say, "Here's a number at 12 months.
Okay. Earlier, you talked about the convenience of just chemo. Can you talk about within the urologist workflow of the office, like CG has great results, but it is a virus. There has to be more containment. I just don't understand the how significant it is, the extra work they might have to do versus just giving chemo or for enGene, just giving a non-viral delivery vector?
Yeah. I think you're right. Those things, it's viral and maybe need terminal decontamination or cold chain storage. Those are things that practices don't wanna have to change the operations at a practice. That costs money and it costs workflow, to have to set aside a room for the rest of the day because it's had a viral therapy. Real issues, right? I think chemo, you don't need any of that. They're already used to giving intravesical chemo. I think from the enGene side of it, ease of use is wonderful, right? Like, of course it is. You have to have efficacy too. It has to work.
All right. Thank you, gentlemen. Congrats on the progress. We look forward to the updates coming.
Thank you, Andy, for the invitation.
Thank you.
Thank you, everyone.
Thank you everyone.
for the interest. Thank you.
Thanks.