Good morning, everyone, and welcome to Oppenheimer's 35th Annual Healthcare Life Science Conference. My name is Andreas Argyrides. I'm one of the Senior Biotech Analysts at Oppenheimer, and today I have the pleasure to be joined by the managing team of CAMP4. We're here with CEO Josh Mandel-Brehm. CAMP4's RAP Platform uses antisense oligonucleotides to target regRNA to upregulate gene expression in diseases. Lead asset CMP-CPS-001, probably we'll refer to it as 001, is currently in phase one studies targeting CPS1 for urea cycle disorders, with phase one MAD safety and biomarker data expected in the second half of 2025. The company has also initiated a new discovery program for the CAMP4 SYNGAP1 program for the treatment of Parkinson's disease. Josh, thank you for joining us today. Maybe let's first start with an overview of the company and the most recent progress, and then we can dive into some questions. Yeah, that sounds good. Thanks, Andreas, and thanks to Oppenheimer for hosting us today. First, let me start by saying there are many prevalent diseases with no approved medicines where you're missing just a little bit of healthy protein. This is the entire sort of goal of CAMP4, which is to have an approach that allows us to effectively address these types of diseases by changing gene expression by modest amounts to essentially restore healthy protein in these types of diseases. Now, the way that we're able to do that, CAMP4, is a really innovative and new modality that is, we've identified with our platform RNAs called regulatory RNAs that are transcribed out of enhancer and promoter regions across our genome. We know today, thanks to the work of our founder, Rick Young, as well as the work at CAMP4, that these RNAs play a very specific role in controlling the expression of local protein-coding genes. Effectively, we've figured out how the body uses RNA to control its genes. What we then discovered at CAMP4 and built into our platform is the ability to very specifically drug a desired regulatory RNA using antisense oligonucleotides. The combination of the ASO targeting a particular regulatory RNA allows us to have a deliberate increase in a protein-coding gene that's underlying a disease of interest. This biology, let's say, exists in every cell type and every tissue in our body. It's a modality that we can take towards any type of disease in any tissue where you're missing just a little bit of healthy protein. Our starting point, as you put it, is actually a few rare genetic diseases. There's a few reasons for that, but a couple of those are there's a really high unmet need, many times life-threatening. Many of the ones we're working on have no approved treatments. The types of programs that we can advance on our own and create a real valuable enterprise at CAMP4 while also looking to partner on some of these bigger diseases as well, where we think having bigger pharma or bigger biotech involved for the clinical studies makes a lot of sense. Our first program that's in the clinic is, as you mentioned, Andres, for a disease called urea cycle disorder. This is a life-threatening disease caused by a mutation in an enzyme that effectively renders you unable to prevent the buildup of ammonia. You get very toxic levels of ammonia. As you pointed out, we're in a clinical study right now. We finished the SAD portion with no safety concerns. We're more than halfway through the MAD portion, which is in healthy volunteers, however, does have a biomarker that we're really excited about because it'll allow us to prove the principle of how the drug works. The last thing I'll say and I'll pause is another program that we have, which I think is particularly exciting because it's a very big area as far as where our platform can be used, is in the CNS in a disease called SYNGAP1, which people are really starting to learn about now. This is a genetic epilepsy. It turns out that there's really no disease-modifying treatments available for these patients. There are thousands of these patients that have this disease and that affects you with epilepsy and learning disabilities and other types of problems. We're very excited about that program. That program is we have a formal development candidate, and we are looking to initiate IND-enabling studies later this year. We're looking to get that into the clinic. We very recently announced a new CNS program for another haploinsufficient disease called GBA1, which is a mutation that's specific for, let's say, a portion of the population for Parkinson's patients. That allows us to take a genetic approach to it, but it may also very well allow us to get into the idiopathic Parkinson's space. It goes from developing in a very concentrated way where we think there's a high probability of being successful, shifting to a much larger Parkinson's population. A nice example of how we can start to get to prevalent diseases as well using our platform. Okay, very interesting. Thanks for that overview. Maybe before we get into some of the specific programs, you can walk us through what differentiates CAMP4's approach to RNA. You guys have a proprietary RAP platform. I see on your slide here on your corporate slide eight, it's a really interesting, it says here catalogs thousands of regRNAs. Maybe you can walk us through. You have the use of machine learning algorithms to help in assisting that process. Maybe you can just give us a sense of how regRNA approach is differentiated from the other RNA approaches. Yeah, no, it's a great question. I mean, I'll start by sharing that the field of upregulation is a massive opportunity set. It's good to have competition there because, quite frankly, there are so many diseases across different tissues where there's really nothing there for these patients. We haven't really cracked the code to be able to address those types of diseases. There are companies. For example, RNA editing could go into that category. Other types of, let's say, transplicing companies, I think a nice example is Stoke Therapeutics and Dravet Syndrome. Dravet happens to be very similar to SYNGAP1, by the way, and they showed, I believe, some really nice data. We expect to want to do that for SYNGAP1 as well. We are the only ones who are working on this new area of biology. Partly that's because we had the advantage of having Rick Young as a founder, and he held off on publishing for a while while we really pioneered this area. At the same time, we've built a proprietary database because you need our platform to be able to identify these RNAs. You can't just use standard sequencing technology. We have tens of thousands of RNAs coded in different tissues for different genes that allows us to effectively rapidly generate an emerging pipeline, but also feeds into business development. That's really the core of CAMP4 is that this intersection of the RNAs that are all cataloged and the ability to move quickly, where I don't think other people have really built this, and it's not an easy thing to build, coupled with the fact that we've actually figured out how you can use oligos to drug these, which also has its own unique capabilities built into it in terms of where you direct them and what you're looking for in terms of the data to know that you have something that starts to look like a drug with the features that you want for upregulation. The slide you're referring to really lays out how we go about doing this. It's about the wrap platform. The first step is we always work with human cells when we can get them, and many times we can. We apply our platform, which is a combination of next-gen sequencing technologies as well as machine learning capabilities. The output of that is we take billions of different data points and we turn gene expression into an in silico exercise. Once we've applied our platform to a cell type, that database is created. Now, if we have a gene that we want to go after to upregulate, we go into our database, we query it, and we identify the RNAs very quickly that we think can control that particular gene. That allows us to do a certain type of screen with antisense oligonucleotides to increase that desired gene. I should mention, what we're not doing as a company, we're not trying to reinvent new chemistry. Actually, we think the chemistry that's out there is already pretty good. For example, it's the same chemistry that's in approved products like Spinraza for spinal muscular atrophy. The purpose of our platform is to really open the aperture for a technology that we think is already, I mean, it's already in many approved drugs and in hundreds of clinical studies. We're taking advantage of all the decades of work that's been done there, safety data, tox data, all kinds of the properties to really design the types of oligos that can allow us to upregulate, but in a, I'd say, less risky way because we're not also taking on the challenge of inventing new chemistry, which there's always a risk with that as well. There is an opportunity in that that allows us to move more quickly. Regulatory agencies are familiar with what we're doing. I think that speaks to the fact we're able to get this new modality into the clinic as well for urea cycle disorders. Do you, when you think about the potential for the platform, you mentioned it's almost optimizing binding for upregulation of a target gene. Is there the potential to discover novel targets for known diseases other than in relation to also just kind of optimizing the approach to those known target genes? Is that the kind of broad applicability? It's a nuanced question. It's a really good question. Part of our thesis for CAMP4 and for platform companies, when you look at it, is one of the most important things you can do, and you're kind of hitting at it, Andres, is pick the right diseases to work on. One of the things we've learned at CAMP4 is a sweet spot for our technology is diseases where the gene has high, let's say, genetic validation that if you can shift it up by modest amounts, we believe it's anticipated to have a disease-modifying effect. That's not to say we can't identify sort of novel targets for diseases, but we're starting with things that we think reduce the risk, meaning here's a haploinsufficient disease. One allele works. One is dysfunctional. It's not deleterious. It just doesn't make healthy protein product. We know that if we can shift it up through the genetics of the disease, it's going to have a disease-modifying effects. There's, in the CNS alone, over 30-40 of these diseases with no approved treatment. That's a pretty big set to work from that are sizable commercial opportunities, we think. Now, to answer your question that you're asking, the RNAs themselves that control genes are novel targets. We're identifying sort of a novel RNA that allows you to move the gene. The gene itself, to your point, is not novel, which is a good thing because that's sort of the point, that it's not novel, that you don't have to worry about the risk in that biology. That should work if we get into the clinic. The risk is, can we find a way to upregulate the gene in the human setting? That's the novelty of the RNAs as the targets. Hopefully that addresses your concern. For question, excuse me. Not concerned. Yeah, I know what you're asking. Right question. Great. Thanks for that. Maybe we can get into, and you kind of alluded to this earlier, but maybe you can explain the decision to go into urea cycle disorders, maybe paint a picture for us of the market opportunity, and then how you guys are tackling this disorder. Yeah. This is a really interesting disease in the sense that it's been known about for some time. In particular, people have heard about OTC deficiency. That's the largest subtype. Just to zoom out for a moment, this is a disease that is caused by a mutation in the active urea cycle, which is six enzymes and two transporters that work in combination to take ammonia and convert it to urea. Although it's a liver-based disease, because ammonia is a very toxic molecule, if it builds up, it doesn't just stay in the liver. It can go throughout your body. That's called a hyperammonemic crisis. It can lead to all types of severe neurological problems that are permanent in nature. More so, it becomes a life-threatening situation. Very, very severe disease. It obviously affects children, but you can live life with these attacks happening and get into adulthood and still be very sick. The point is that you can live longer, but it is a very debilitating disease. As far as the unmet need, there are only two real ways to address this disease. One is an extremely strict diet. Essentially, you cannot give these patients protein because it will trigger a hyperammonemic crisis. They are effectively on malnutrition diets. It is pretty serious. There are nitrogen scavengers. There is a drug called Ravicti, which was part of Horizon. It is a nitrogen scavenger. These are not disease-modifying. They essentially are like sponges, and they can absorb some of the ammonia. They help, for sure, but they do not prevent the hyperammonemic spikes from happening. They certainly do not relieve these patients on this very strict diet that they are on. You can see why this is a huge burden to live with. In the U.S. alone, we think there's probably around 4,000 severe patients. More recently, we started talking about a really interesting aspect of this disease, which is there are female carriers that were previously thought to be asymptomatic. These are heterozygote patients. For all intents and purposes, they're functionally haplo-insufficient. It turns out they too are sick. They aren't sick enough that they would take something like Ravicti. They've sort of been sidelined, if you will. Given the TPP or the target profile of our drug, which would be a subcutaneous once-month delivered drug, we've been learning a lot about these types of patients as well. There's probably around 1,000-1,500 in the U.S. That goes on top of the other 4,000 in the U.S. As far as rare diseases go, we think there's a market there, and there's certainly an unmet need. This is a life-threatening disease. One where it's been very clear to us as we've gone out and established relationships with the KOLs and with the patient organizations that they're waiting for innovation in their particular disease because it's been a long time since that's happened. Great. Thanks for that additional color. Just maybe adding to the profile of the opportunity here, could you maybe even speak to pricing a little bit? I know it's very early on, but when you have RNA-based therapy in an ultra-rare disease, you kind of command some very strong pricing power. Just what are some initial thoughts on that? I'll answer it in maybe a way that I think will get you to what you're wondering, which is if you were to go look at the price of Ravicti, for adults, it can be up to $750,000-$850,000 a year for urea cycle disorders. That's not to say that's where we intend to price our drug, right? We're in very early days. It's just to say the magnitude of the unmet need supports a price for a drug at that level, right? I think it just speaks to the opportunity there. I wouldn't expect us to be any different than any other disease-modifying RNA therapeutic for these types of diseases, for what that's worth in ways. I wouldn't expect us to act egregiously, but I would also expect us to, we choose these diseases because of the high unmet need, which allows us to have a flexible approach, assuming the potential of our drug does what it's supposed to do as far as being disease-modifying. By the way, SYNGAP1's no different. There are no disease-modifying treatments for these patients. These patients can suffer from multiple, tens and 20 seizures a month, all types of other learning disabilities. I mean, these are significant challenges for these families and these patients. Again, there's nothing there for them. That creates a real opportunity, both for the patients, for us to create something that can help them, but also for CAMP4. Great. Thanks for getting to the crux of my question. I should have been more pointed about that. As I mentioned earlier in my opening remarks, 001 recently demonstrated favorable safety results in the SAD portion of the phase one for urea cycle disorders. How did those data shape your confidence for the upcoming MAD portion? Yeah. Two comments I'll say about that. Well, three. One, it's not surprising to us. Based on our preclinical data, we would have anticipated this to be a very safe drug. Nonetheless, anytime you go into the human setting, that's something that you pay close attention to. What I can say is the SAD data, which went from 0.2 mg per kg all the way up to 4 mg per kg, covering what we believe is the therapeutic range that we saw in our preclinical studies, showed very unremarkable safety, let's say. That's what we want to see to be able to give multiple doses of our drug. It sets us up for a very clean, I'd say, approach using the MAD portion of the study. Likewise, and this is a little detailed, but the nice thing about the SAD study is it allowed us to optimize enrollment and other features and work out the kinks. There's always things that you do your best to get the trial design right. Then sometimes you put it in place and you realize, oh, this might be a little too burdensome for the trial participants. Let's shift it a little bit. We were able to make some tweaks that I think, and our CMO would say also, really optimized for success in the MAD portion of the study. We were very thoughtful about that. Great. Continuing on this topic. What safety and biomarker signals in the MAD portion will be most critical for the upcoming readout and expected in the second half? Yeah. From a safety perspective, look, we're observing and paying close attention to all the known risks around oligos, which goes back to the comment about using established chemistry. We know the knowns there. That can include rising platelets and complement and liver transaminases, etc. We have not seen any signs of that, which is very, very encouraging. This is newer state-of-the-art chemistry. We wouldn't expect to see sort of classic issues that had kind of plagued that technology in the earlier generations. We'll continue to look for that data, which is what people would expect, making sure, I think, part of the value proposition for this drug. These patients are very fragile. They have very fragile livers. Safety is really important. Not to mention, if those who are familiar with OTC, that was Jesse Gelsinger, who died of the gene therapy approach back in the day. That is only to say that this is a very watchful and guarded community, right? They are very protective of themselves, and it is understandable. Safety matters. From a biomarker perspective, interestingly, one of the things that you can do is take something called sodium acetate. This is a completely harmless labeled version of sodium. Essentially, what you do is you ingest it. It gets taken up by your urea cycle, and you can measure the rate at which it gets cleared out, just like ammonia to urea. That allows us to effectively give that to both healthy volunteers or patients, have them then take our drug, and we can compare the rate at which they are able to convert the sodium acetate versus patients or participants that did not, for example, get the drug. That allows us to say, we're looking for an increase in the ability to clear that out because fundamentally in this disease, it's the ability to convert ammonia to urea that is correlated with severity. If you can shift that, if you could shift the rate at which you can do it, you could shift patients from being very sick to much healthier. We are using that biomarker to ask the question, can we actually change the dynamics of the urea cycle using this drug, starting in healthy volunteers? One other thing I'll mention is the reason we've decided to do that is in primates, we did see, which are totally normal and healthy, when we gave them our drug and the same assay, we could shift their ureogenesis and measure it in healthy primates, those that got the drug and those that got placebo. That told us, one, it gave us more confidence that the drug should work. It also allowed us to say we could at least start testing it in healthy volunteers, one, because safety will allow us to move faster in the later stages, again, going back to this patient community. Also, if we see any signal, even a little signal, that's a home run, I think, in terms of being able to translate to what we think will be success in patients. Okay, great. It's encouraging. How are you thinking about these results enabling a registration of phase two, three trial in 2026? What are the considerations for your trial design and regulatory interactions? Yeah. We haven't talked too much other than just to say, given the unmet need and given that this is a rare genetic disease, we're being very thoughtful about having an efficient path forward. I should mention we do have orphan drug designation and rare pediatric designation. I think that, again, that speaks to, one, the unmet need and two, I think the willingness that we'll have an ability to work with the agencies in a very positive way. I think if you're following what's happening at the FDA, they're doing a lot of talking about biomarkers and these rare diseases. I think it's all very encouraging, let's say. We will certainly let the data help inform what the future path looks like. We're actively engaged in thinking about that and those types of discussions. It won't be a U.S.-centric thing. We'll take a global approach to this. Our goal, what I can tell you, is going to be getting into patients as efficiently as possible, getting to them when they're younger because we know that if you can prevent damage, it's not just about being life-threatening. It's about preventing cumulative damage. Getting to them earlier is better and being very thoughtful about how we go after the subtypes of the patients. One thing I should mention is the target that we're going after with our drug is called CPS1. It's the first enzyme in the cycle. What's unique about this is we believe it can allow us to go after all the subtypes. We call it the pan-UCD approach. Although OTC is the most prevalent subtype, there are other subtypes, for example, mutations in ASS, ASL. We'd like to be able to address those patients too. I mean, if you go talk to KOLs and the patient community, they say, "Don't forget about us." We'd like not to forget about them. That also factors into how we're thinking about trial designs and whether it's a basket study or you do separate studies. More to come there, but it's all to say that we know the unmet needs there. We know that I think the agencies have a willingness to want to work with us, and we're going to be very thoughtful about it. Okay, great. Maybe switching gears to Parkinson's. How does your approach differentiate from the other programs in development for Parkinson's? Maybe you can give us a sense of timelines as well. Yeah. I also want to bring us back to SYNGAP1, though, because I. SYNGAP, yeah, yeah, as well. Sorry. SYNGAP too, yeah. Yeah. Just a comment because I understand what you're asking. Look, there's a lot of Parkinson's, it is a large unmet need. People have been working on it for decades. There's a decent amount known about the biology. In particular, the reason we're excited about it is there is this genetic mutation, GBA1, that is a true haploinsufficiency. If you've got, for example, a million Parkinson's patients in the U.S., 100,000 of them have this mutation. We think that's in the sweet spot of our technology. We also think oligos are one of those modalities that can get to the brain because you can do it through intrathecal delivery. I think given the unmet need of Parkinson's, that's not a barrier to do intrathecal delivery. I think what differentiates us is a very specific way to upregulate GBA1 and ability to get our drug into the brain using intrathecal delivery. That's where we think it's a unique approach for CAMP4. Shifting back to SYNGAP1, what I'd say about this is our estimates are at least 10,000 patients in the U.S. based on the epidemiology. If you took a different view of 1% of intellectual disabilities or SYNGAP1, you'd get up to 30,000-40,000 patients in the U.S. Where's the truth in there? This is an interesting disease because the gene was only identified in 2012. It's a relatively newer disease. In fact, people sometimes get misdiagnosed as having Dravet when they have SYNGAP1 syndrome. It's one of those where it is true there's probably more patients that are going to come out of the woodwork here. The patient organization that runs it is very, very active. They do a really nice job. They just published a paper that talks about characterizing the unmet need, all the features of the disease. They have a registry. They're doing a natural history study. This is really, I think they've set it up to say, "We're ready for companies to bring innovative approaches. We're doing what we can on our end to make it successful." What I can tell you there is that there are people working on it. Nobody's in the clinic yet with a disease-modifying approach. I think we might be one of the sort of more, we might be one of the first to get into the clinic with a disease-modifying approach. Others are taking RNA splicing approaches or sort of gene therapy approaches. There's different ways to try and go at this. Again, our approach, which I think is sort of elegant, is we're using an oligo to increase SYNGAP1 through that RNA target. We're really excited about it because, one, it's a big unmet need. It's a sweet spot for our technology. We think our data, which is emerging, is really exciting. We're very bullish on being able to have an opportunity to help these patients and get in the clinic. Okay, great. We're almost close to time. Maybe we can allow some closing remarks, so to speak. Maybe just give us some key takeaways for the year as we follow the CAMP4 story. Yeah, absolutely. Our starting point is to say that, and I'm going to repeat myself just to remind everybody, there are many prevalent diseases as well as rare genetic diseases where you're missing a little bit of healthy protein. That's due to a genetic mutation. There have not been many technologies that have been able to crack that nut. We believe at CAMP4, we've built a platform that's going to allow us to go after this in a way that I think is analogous to what Alnylam did in the liver. We're thinking about this for the brain too, where there's many of these haploinsufficient diseases, and they tend to follow the same sort of model of identify the RNA, drug with an ASO, increase subtly, modestly, and have an effect. Most of these have no approved treatments. That's going to remain something really interesting behind UCD for CAMP4. Business development is going to be a core part of our platform. Again, taking a page from Ionis, Alnylam, and others, there's too much that we should be able to do with our platform that we can't do on our own. You should see us be pretty active in that regard in different types of deals and different types of tissues. We actually announced last year a deal with BioMarin, which we're very excited about, where we're applying our technology to upregulate a gene, a couple of genes that they're interested in. I can tell you it's outside of our core areas where we're building our own pipeline, but we haven't disclosed too much more. We are very excited about those types of deals. We have some major readouts coming later this year, including our UCD readout as well as looking to advance SYNGAP1 towards the clinic. I would say those are the major themes for CAMP4 that you should pay attention to. We think this is a story that we think because of, if you look at RNA and many of the companies have outperformed the market in the last few years, it's because you can basically, if you choose the right diseases, I think show responses that quickly show you can have a drug and have a major impact here. We think about it that way for what we're doing at CAMP4. Super exciting. All right. Josh, thanks for your time. Thanks for walking us through the story. It's exciting to follow the progress, and we'll do just that. Thanks again for joining today and walking us through, and we'll catch up soon. Great. Thanks, Andreas. Thank you.