CAMP4 THERAPEUTICS CORPORATION (CAMP) - GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - CAMP4 THERAPEUTICS CORP

Innovation Conference here in Boston. I'm Delma Cagliatti and I'm a research analyst here at Guggenheim. And it's my pleasure to welcome Josh Mandel-Brem, the Chief Executive Officer from Camp 4 Therapeutics. It's a pleasure to have you here, Josh. So maybe it's an exciting moment for the company because you are moving into the clinic and you expect the first patients to be dose by the end of the year. But before jumping into the Q&A session, why don't you give us an overview of the different programs you're running, where you stand, and the key milestones that we should expect over the next 12 months or so? Yeah, absolutely. And thank you for inviting us. I appreciate it. And good pronunciation of the name. Most people get it right. I was really afraid. No, you did good. That was good. So maybe just to take a step back. So Camp four is using antisense oligonucleotides to increase gene expression. So you can think of us as the inverse of the ionuses and the anilomes of the world, which is really a greenfield and massive opportunity. The way our technology works is by increasing genes twofold. That's where we live. And that positions us in a really good sweet spot for diseases that have a haploinsufficient nature, meaning one of the two alleles is no longer functional. And so essentially, you have one functioning gene that gives you 50 percent of what you otherwise need to be healthy. So that's how we think about the types of diseases that we go after. For our own purposes, we are building a pipeline of CNS haploid-sufficient diseases, and that starts with SYNGAP1. But the platform itself is broadly applicable to any tissue or any disease where you want to increase a gene. So, for example, we've put in place a relationship with GSK to go after larger indications. This next year is a year of building, I think, execution. So we are the first company to bring a disease-modifying approach into SYNGAP1, which I know we'll talk about more. So, we're going to be making a lot of progress over the next year as we start dosing patients, as you correctly pointed out, and we've got into data in the first half of 28. We've also just recently announced some new programs with SHANK3 as well, Phelan-McDermid syndrome behind that. So that'll be another thing that we're working on. Thank you for that great overview. So maybe stepping back to the platform, can you walk us through how does it work? So how is it different from other genetic approaches? How do you identify target regulatory RNAs and do you ensure selectivity for them, which is a critical part of especially for genetic programs? Yeah, absolutely. So to start with, every protein-coding gene in our body has its own unique RNAs that control the expression. These are called regulatory RNAs. Now, what makes them very unique and special is that regulatory RNAS are specific to the protein-coating gene that they're acting on. So every protein coding gene has its on RNA. That RNA is not acting on many different genes. So you have built-in specificity at the genetic transcriptional level. We've chosen to use antisense oligonucleotides to drug those regulatory RNAs to maintain that specificity because ASOs are specific as well due to the nature of their chemistry, which is RNA binding. So we preserve that specific city for the reason you're acting because we agree specificity is important. What makes us really unique is that we are acting at the transcriptional level, meaning we're essentially turning the faucet on more right at the source of the problem. Other approaches are either packaging some type of RNA or protein and delivering it like an AAV approach, or they're acting further downstream. So they're trying to essentially change things at the RNA level, if you will. And we can talk more about the advantages and disadvantages of that. Yeah, maybe following up on that point. So as you were mentioning at the beginning, A key feature of your program is the ability to regulate, to increase expression up to two-fold. So how do you answer, is that enough, first of all, and considering the type of disorders you are targeting? And also, how do You ensure that You don't overshoot expression, which is always a risk when You modulate gene expression? Yep. So we have learned, because we've been doing this for so long now, that we actually never get above a two-fold increase. And there's some biological reason for that, but we think that's a feature of the system, right? Because you're certainly correct that there's many diseases where overexpression would be a problem. So, we don't believe we have that problem just based on the biology and what we've seen so far. To turn that around, then you would ask, well, where is that most relevant? And as I mentioned earlier, any disease that has a loss of protein in it, if you will, is a really good place for us to start. Now, we like single gene diseases because those are easy to understand, if we will. It's very clear what the culprit is that's causing the disease. And interestingly, in many of these cases, human genetics can give us a clue as to how much upregulation you actually need. So in the case of SYNGAP1, probably 95 to 98 percent of the population is haploinsufficient, meaning they only have 50 percent protein expression. However, there are a very small subsegment of patients that are, say, 1 to 2 percent. They have a milder mutation that gives them about 75 percent instead of 50 percent, So you're halfway to being fully normal. We know that these patients are milder. They can respond to some medications. They can go to certain types of schools. So Mother Nature has essentially told us that if you start to put more SYNGAP back into the system, it's essentially a gradient, and you're going to create a healthier way to live for patients. Makes sense. And maybe digging more into that indication. So SYNCAP1, your first clinical program, that's a very severe disorder. characterized by both seizures, neurobehavioral delay, problems with cognition. So maybe what's, first of all, from an epidemiological point of view, what's the target population there? And how should we think about the difficulties in diagnosing? And how is the diagnostic rate changing over time? Yep. So this is one of those rare diseases that I believe will become very important moving forward. Every three to five years, a new rare disease shows up, and people start with, I haven't heard of that, and then it becomes a household name, if you will, which is a good thing for the patient organizations. So Syngap, I believe, will be like that. This is a disease that was discovered about 15 years ago. It's a single-gene disease, meaning one of your two alleles is no longer functional. It has an ICD-10 code. It has a natural history study. And this is all thanks to a very well-organized and powerful patient advocacy group. And really, that is, I think, the most important thing about these rare diseases. It used to be in this type of disease that you went on an odyssey. You would have a kid, a child that had it. They didn't quite know what was going on. And now, thanks to, one, just awareness, but two, whole genome screening, as well as genetic panels, typically what happens is these children miss their milestones or they have seizures by the age of two or three, and they're immediately referred to what I just said, and they get diagnosed. So diagnostics went from a 10-year odyssey down to one year, right? So I think that's really great. It's still massively underdiagnosed. And why is that? Well, it's just a case of rare diseases. Before you really have an approved treatment, there's sort of a lag in diagnosis. But we are very confident that there are at least 10,000, if not more, patients in the U.S. I think That's been well-validated by KOLs, by secondary research. research. And so we, you know, the more we learn about this disease, the more we talk about it, the most we start talking about treatments, the more patients are coming out of the woodwork as well. Makes sense. And we spoke before about the rational, the scientific rational for this indication. But what about the preclinical data that you have generated? What did you learn from the different approaches you have tried? And how did that inform the phase one trial? Yep. So we are fortunate, and to give credit again to the patient organization. They really did a nice job here. They had the foresight of creating a humanized mouse model. And, you know, models are models, but as far as preclinical models go, this is a pretty good one. So the way we think about things at Camp 4 is we start in vitro, like many companies. We like to work with patient-derived cells to start with, and we did that, and we saw a two-fold increase. Then we went into this humanized mouse model, right, where we showed we could have a dose-dependent increase in the Syngap1 protein. But then we also showed that we could completely reverse the symptoms of the disease. So learning and memory, cognition, anxiety, which were replicated in the mice, were completely restored when we gave them our treatment. And then also, we were able to create an induced seizure state, if you will, by using a chemical, and we showed we could reverse that as well. So that was, I think, a very important proof of concept that you can, in fact, at least from a model perspective, have a reversal of this disease. The next thing we wanted to do was to go into primates. Now, primates are really interesting when you're talking about antisense oligonucleotides because they have great homogeneity with the human sequence. And so it turns out that our human clinical drug is perfectly cross-reactive with primates. So when we deliver the drug intrathecally, right, which is exactly how we're going to do it in the clinic for patients, we show that we can upregulate the gene in a statistically significant way at doses that would be projected to be relevant in the human setting. So that was very powerful for us, because if you look at the history of antisysalgalonucleotides, things that tend to work in primates tend to translate to the clinic as well, if not even better. And so I think that was Very Compelling from an efficacy perspective and from a safety perspective, and essentially showing that we could actually model this out and have a shot of going into the clinic with it. And do you get broad tissue distribution? Yeah. How important is that? It's very important in the sense that there are certain regions of the brain you want to make sure you get to. So we are using Gen 2 chemistry, which is called state-of-the-art. It's the same chemistry and approved products like Spinraza for spinal muscle atrophy. We're not reinventing the wheel there. We are doing intrathecal delivery, which perfectly fine for this disease and gets you right into the brain. And you asked a question about distribution. We get very good distribution into the hypothalamic regions as well as the cortical regions. And these are the key areas where you want to get drive expression for Syngap1. Got it. Okay. So now you're moving into phase one. Where do you stand with the site activation and with the regulatory clearances both in the U.S. and outside of the U。S.? And maybe walk us through the key features of the trial design itself. Yep. So we took a very ambitious initiative here. And what I mean by that is we wanted to take a global effort for our Phase I-II study. So maybe I'll just start with the study itself. We're going directly into patients. It's a Phase I, II. We are going directly to a multiple ascending dose study. Every patient will have the opportunity to get three doses over the course of three months, and then there will be a six-month follow-up. We've also put a control arm into this study. We felt that was important, so it's three-to-one randomization. In addition, we do have natural history data that we can leverage. There's over 1,400 years of natural history data. And lastly, all patients will have a one-month baseline run-in, so every patient will be their own control as well. So that's three different control systems we have in place. And the reason for that is if we see a signal we like, we want to have full optionality to talk to regulatory agencies. And for that reason, we believe a control is important. From a sort of approval perspective, we went and got regulatory clearance in Australia, in Argentina, in the UK, and now the EMA. So that's four distinct regulatory regions, which I think just speaks to the unmet need and speaks to the fact that the study we've designed has been consistently approved across the world. We are approaching the FDA now for the same discussions, and it's just more just following people's processes. There's no rhyme or reason for that as well. And you asked about site activation. Yes, every jurisdiction, every hospital has their own sort of process. And we are in that process. We are looking forward to dosing the first patients. Got it. So this is a signal-seeking study, right? Is it powered or not? I guess not. It's not because we don't know the optimal biological dose yet. Makes sense. So we are, as you pointed out, we have three cohorts to start with, I should have said, at least eight patients per cohort as well. And we're safety, finding the optimal biological dose. But in order to do that, you need to see efficacy as well, makes sense. And from an efficacy perspective, you are measuring several clinical measurements there, ranging from seizures to, I guess, behavior. So when we look at the data, I think the first staff of 2028. Where should investors focus on in particular? So what matters there? What's the part for defining clinical success and for moving forward to, I guess, a pivotal program? Yeah. So maybe just to start with, these patients that have this disease can have hundreds of seizures a day. They can't speak many times, so they're cognitively impaired. They have motor problems they can't sleep you name it they have it if you were to meet the parents of these children they have bite marks up and down their arms because the kids are so frustrated they can communicate so it's a devastating disease and it's caused by one gene that is mutated that doesn't make enough protein we're assessing all of these things in the clinic and for example seizures which of course is an approvable employment we're using EEGs as well so there'll be an overnight stay where you can look at the EEG signals because we know from the natural history data that the EEG signals are different in healthies than they are in patients. We also know that we can look at things like GMFM, Bailey, and Vineland to look at cognition and other types of metrics where we see separation from natural history. We're doing actigraphy, which means you wear a band to measure sleep. So all these different things we're looking at, and why are we doing that? Because we believe if we see an effect in any one of these dimensions of the disease, that is a win for the patient community and something that we can move forward. And so we believe the drug acting at the transcriptional level will be disease-modifying. We believe it should have an impact across all these. Nobody's ever done this before, so you used the right term. We're signal-seeking, but we get to define success. And I think we'll work closely with the regulatory agencies to pull that forward as we see from the data. And maybe pushing further on that point. So as you said, there is no disease- modifying therapy approved for this indication. So there no regulatory precedent on what should we expect from a potential pivotal program. What's the FDA's standing so far in terms of what could be the potential path that you're going to follow? Are you thinking about accelerated approval, for instance, or for the classical double blind trial? Which kind of endpoint would you be focusing on, or would you expect to be accepted in you know, people that try it. Yeah, I mean, look, I'm really encouraged by what we're seeing at the FDA with regards to the discussions they're having around just rare diseases writ large. I think that's a really positive thing. We're doing a lot of work. We, I say we, I include the patient organization with the FDA already, for example, in educating them about SYNGAP, right, making sure they know what it is. I Think that's really important. So you don't just come in with, here's my disease, here's my data. It's a little too early, I think, to weigh in on what the path forward would be, beyond saying that of course we're going to pull the thread on accelerated approval and ask questions and try and understand, given this unmet need of this disease and that there's absolutely nothing for these patients. So that goes back to our trial design. One of the reasons we have taken a global approach, one of the reason we are putting a control arm in, is that depending on the types of results we see, we do want to be able to have those discussions. And we know just from looking at precedents that if you don't have a control, I think it's very difficult to even open the door with the FDA for accelerated approval, for example. So I think we've built in really nice flexibility to create that optionality based on the data that we get. Makes sense. Okay. And your initial data will be in the first half of 2028, right? Should we expect any interim readout on safety or pharmacokinetics between in now and then? No. I mean, we are in, well, we like to under-promise and over-deliver. And so we've told people, you know, the cake will be baked and ready to be eaten in the first half of 28. And if it comes out sooner, we'll let you know. We'll give some updates along the way in terms of just the progress we're making. We think credibility is important in doing what we said we're going to do. But we're really heads down here. And we want to maintain that blind as long as possible, unless there's a reason to not have it. Got it. And when we think about the commercial opportunity here, which, of course, includes also the potential for premium pricing, I guess. So if you can give any idea of potential peak sales in this indication, or at least target population, how are you thinking about that? Yeah, I would use the word massive. I think this is a big opportunity. I don't say that lightly. I won't weigh in on the revenue other than to say if you look at this unmet need, right, and you compare it to diseases like spinal muscle atrophy, cystic fibrosis, I would argue it's as bad if not worse, okay? In terms of the amount of patients, you know, I think that there's at least 10,000 in the U.S., many of which, you knows, some portion of that's already diagnosed. So if you just comp it out to other rare diseases that look and feel like it, to your point, you put a reasonable price on it, you start to get to something very provocative very quickly, right? And I think that's what's really important here. And so I think there's a massive opportunity there. But it starts with the patience and the unmet need and having that impact there. Makes sense. And maybe can you give us an overview of the competitive landscape? Yeah. It's pretty sparse. We are by far furthest along. More competition is coming, and that's a good thing. You know, what gives us an advantage is this gene itself has six different isoforms, and because we act at the transcriptional level, it's a benefit of our mechanism of action, all six isoформs get produced. And nobody knows which isoformed is most important, but we don't have to solve for that because we're just keeping the natural proportion of those isoiforms. Gene therapy can't do that, and there's no real commercial efforts there yet. There's some academic efforts. Now, there's some splice switching approaches that act downstream, but those haven't seemed to move the needle yet. They've been in discovery for quite some time, so we can't weigh in there. But I expect there'll be competition at some point, and I think that's a good thing. But I still believe our approach is the most rational for the reason I said, which is biologically, we're just asking the gene to do a little more of what it's already supposed to be doing. Got it. Okay, and moving now to the pipeline, you recently announced a shank tree as a second indication. So why that one in particular, and where do you stand with that program? Yeah, so Phelan-McDermott syndrome, haploinsufficient CNS disease caused by a single gene mutation, SHANK3, very similar in regards to sort of the setup for Syngap. 45,000 patients in the U.S. with this disease, no approved treatments. These patients have massive learning disabilities, cognition problems, all types of other issues. Sounds familiar to Syngap1. And, you know, what I think makes it really interesting as far as the setup is if our Syngat program shows that it works, this should show that it's going to work because you're doing an intrathecal delivery with an antisense oligonucleotide to increase a gene that's in the cortical regions where you just want to shift it up modestly. And so it should be a rinse, wash, repeat. So, you Know, our own preclinical data. It starts to look and feel like Syngap. But the reason we chose that disease is the biology, the unmet need, and the overlap with Syngab. Many of the same patient provider treaters and whatnot. And there's a few other ideas that look and field just like that that we haven't disclosed yet, but we said we're working on as well. Makes sense. There is actually a lot of excitement also from pharma on the DEs, the developmental and development. And have you consider the possibility, I know it's early, but of a basket trial for like a pivotal program? Or are you planning to go indication by indication? Because these are genetically distinct diseases, I think we go indication-by-indication because we're acting at the genetic level, which means each oligo is designed for that specific disease. I'm not sure, were you asking about different diseases or different patient populations? Well, yeah, different diseases like Dravet or GSK? No, we're not acting at the symptomatic level, and our mechanism is really at the genetic level, so I think we have to stick to this thing. You have to speak to each of them. Makes sense. Okay, so from a BD perspective, you have a partnership with GSK. How is that going, and are you considering other possible partnerships, especially for programs outside of CNS? Yep, it's going very well. So those are the types of deals we like to do. It was announced at the end of 2025. GSK came to us with two diseases they were interested in upregulating the gene underlying that disease. One is a large CNS disease. One is large kidney disease. So that speaks to, I think, going beyond the CNS. The deal is that we identify the regulatory RNAs and create antisense algonucleotides to increase the gene that they're interested in. And then at some point, we hand it over and they take over from there. We get milestones and royalties. You know what we like about that is what I tell investors is I don't want you to pay for my platform I want you pay for assets. You know that's what you're buying for right now We're going to keep the engine running through business development, which makes a lot of sense because we unlock more volume value there So we like to do those types of deals We're very selfish about our own assets right now, but discovery deals You know we are we are working towards doing a few more of those as well Thank you for that. And maybe in these last few minutes, what's the cash-run way? How should we think about the spending rate moving forward? Yeah, we like to keep it tight. We have $124 million at the end of Q3. For us, that's a lot of money. It takes us to the endof 2028. We've got to do the first half of 2028 for our Syngap milestones. So with that money, we can do a few different things. One is we can flip the card over for CMP-002 for Syngap, which is, I think, a massive value driver. We can also advance our Schenck 3 program as well as the other undisclosed programs as well. So we're really heads down and focused on that for the moment. Perfect. And maybe there is a question I like to ask all the time. And what do you think is most underappreciated about your platform, about the company? Yeah, I mean, I'd give a two-part answer to that. I mean, I think if you look at our stock and our market cap relative to what I just told you, I think we are deeply undervalued if we're right, right? I think there's comparable companies. I think it's very clear where the value goes if we'RE correct for Syngap based on Syngaps alone. But as I just tell you as well, the probability of success should go massively up if we ARE correct about Syngapt because the next things we'RE doing are exactly like this, right. And the thing about oligonucleotides is it's mechanical, right, Once you get to DC, you know exactly what to do to get to the clinic, and you can move pretty efficiently. And so I think it's sort of once we show that this works in the clinic. I think a lot of value gets unlocked pretty quickly. Thank you so much for that. And maybe just to sum up, what should investors focus on over the next 12, 18 months? Yeah. Well, I mean, starting with the data readout in the 12, 18 months, of course, that's a main focal point. That's a value creation one. But we're moving very quickly. And as a result of that, you know, we'll be updating as much as we can. And a lot can happen. And sometimes things can happen faster than you think. Thank you. That was great. Great. Thank You. I appreciate it.