Good afternoon, and welcome to the Camp4 Therapeutics Analyst event. At this time, all attendees are in a listen-only mode, and a question and answer session will follow the formal presentations and fireside chat. To our analysts joining us live, please use the raise hand feature to indicate you have a question. As a reminder, this call is being recorded and a replay will be made available on the Camp4 website following the conclusion of the event. I would now like to turn the call over to Josh Mandel-Brehm, Chief Executive Officer at Camp4 Therapeutics. Please go ahead, Josh.
Thank you very much. Good afternoon, everybody, and thank you for joining us for our first-ever analyst event to discuss CMP-002 for the treatment of SYNGAP1. We are going to be making some forward-looking statements today as part of the discussion, and I encourage everybody to visit our public filings for more information. We have a wonderful agenda for you all today. I am going to take some time to make some briefly prepared remarks, but then you will have the opportunity to hear from Beata, a parent and caregiver to their daughter, Kasia, about their family's experience living with SYNGAP1. This will be followed by our Chief Scientific Officer, Dan Tardiff, and our Chief Medical Officer, Yuri Maricich. We are going to review our preclinical data and provide an overview of our ASCEND phase I/II clinical study.
Next, you are going to hear from the Chief Executive Officer of CURE SYNGAP1, Mike Graglia, who will share his thoughts on the importance of our phase I/II study and how we collaborated with Mike and the SYNGAP1 community. Finally, we are quite pleased to welcome Dr. Stéphane Auvin, a leading child neurologist and epileptologist, who will provide a clinical perspective on SYNGAP1 and his views on the potential for a disease-modifying therapy.
I am then going to close with an update on our preclinical pipeline. Many of you on this call today are familiar with Camp4, but before I provide a brief update of where we are today with regards to our ASCEND study, I want to talk about the ambitions we have as a company. We built Camp4 to be a product company with a platform behind it, one that is able to continuously generate life-altering drugs for patients in need.
What we have learned over the past five years is that we believe we can continuously design ASO therapeutics that upregulate genes underlying diseases to promote healthy protein expression. Our platform is broadly applicable. However, for our purposes, we are building a pipeline of upregulation therapeutics to solve genetic diseases of the brain. I am quite excited to have the opportunity to speak later about our newest pipeline programs after the main focus of today, that being SYNGAP1. As many of you know, we now have the approval to begin our clinical study in Australia, Argentina, as well as the U.K. We have an additional regulatory filing underway in review in the E.U. Site activities are ongoing, and we have begun pre-screening patients in a few regions with the expected goal of dosing the first SYNGAP1 patient during the fourth quarter of this year.
Yuri's going to spend a lot more time reviewing the clinical trial design data with you, but I did want to talk about our timeline for the data readout, as well as our overarching goal with this trial to get an answer to: Does CMP-002 represent a disease-modifying therapy for this terrible disease? This is a first-of-its-kind therapy for this type of disease, as well as a first-of-its-kind clinical study. We're going to learn a lot along the way in terms of how and when these patients may respond to our therapy aimed to increase the expression of SYNGAP1 protein. We expect these top-line results to be available in the first half of 2028. The design of our clinical study may also allow us an opportunity to provide safety and pharmacodynamic updates prior to the full data readout.
Where we stand today, just starting this journey, we do not know what kinds of specific, meaningful updates we might be able to provide or when, other than the top-line readout in 2028. However, we will look to provide meaningful updates on our progress when we can for the benefit of all of our stakeholders, including the investment community, and importantly, our patient, caregiver, and clinician community. We are excited to embark on this new clinical development phase at Camp4, and we appreciate your willingness to spend time with us today to learn more. Before I transition, I want to again thank the CURE SYNGAP1 community and all the entire patients for their courage, bravery, and collaboration to help get us to this point. We are inspired by you, and we hope we can make a big impact on you and your lives.
As Chief Executive Officer, I have the privilege of being able to talk about SYNGAP1 to investors and companies alike. However, there are, of course, times when words and pictures on a slide do not do the disease justice. Therefore, we felt it was important for everyone listening in to have the opportunity to meet one of these brave SYNGAP patients. To kick us off today, I'm pleased to introduce Beata, a loving mother of Kasia, to talk about her family's story living with the disease.
My name is Beata Tarasiuk, and I'm most known as Kasia's mom. Kasia is a nine-year-old Syngapian, a nine-year-old little girl living with SYNGAP1-related disorders. I want everybody to understand that SYNGAP1 is a devastating disease. She's nine years old, and compared to a typical nine-year-old, she's very far behind. Her abilities are about 12-month-old, sometimes 18-month-old child, but she's in the body of nine-year-old little girl. She is not able to do anything for herself, and she needs assistance with all daily living activities.
She is fully non-verbal. She has no words. She has a way to communicate with us, and we can understand some of her communication, but it is a very simple communication. "I want this, I want that." It feels like those kids with SYNGAP1, they do have depth to them, the depth of thought, but they cannot truly communicate. It is because she has daily seizures, because her seizures are-- Before she was medicated, they were every 10 minutes on the EEG we observed, so it is 150 seizures a day that you cannot really see. We couldn't see them back then when she was diagnosed at three years old.
She has daily seizures. They are changing now. She is changing. She is not able to feed herself. She is not able to go to the toilet by herself. She is fully diapered. She needs help 24/7 with all her daily living activities.
She has also GI issues. She suffers from gas pain and acid reflux, because of all the medications she is on. She is suffering, and there is nothing. I feel sometimes there is just nothing else we can do. There is no way with the medicine that we have available today, there is really nothing else we can do. The biggest, we had to change our whole life to be with my children and take care of my children, but I never imagined that I would have to completely give up my professional career. Now any other choice, her needs are so great, and my husband will continue his career. He is a physician. It made sense for our family that he will be the one to continue and support family financially, so we just do not collapse under the weight of this disease.
Kasia has trouble sleeping, so we do and I have to sleep. I cannot be on 24/7, so he does give me the certain time during the night that he stays up with Kasia, and he watches her, and she has trouble sleeping. He takes care of her, and I can sleep during that time. He had to adjust his schedule at work. He had to give up some of the work opportunities and some of the career opportunities that otherwise he would probably be able to take on. We do not have a regular home. Our home is open to caregivers and therapists, and we have people in our home seven days a week. We never have any privacy in our home.
Again, it is a choice we made so we can have some resemblance of some normalcy in our life and our younger daughter can have some normal childhood.
All right. With that, we're going to hand it over to our Chief Scientific Officer, Dan Tardiff.
All right. Thank you for the introduction, Josh. I think it's pretty clear in watching this video of Kasia that we have very much focused on being able to help this patient population. Today, before we get into the ASCEND trial, and before Yuri describes what we're going to be doing, I'd like to walk you through the underlying biology and the target that we're going after, as well as the preclinical data that is supporting our efforts moving forward to get CMP-002 to the patient community. Here at Camp4, we are targeting non-coding regulatory RNAs to increase gene expression. What are these RNAs? These are non-coding RNAs that are transcribed from both promoters and enhancers of all genes.
They actually help regulate transcription, and they do so by binding to both positive and negative-acting transcription factors and helping maintain high local concentration of these factors so that they can interact with the DNA, with the promoter to help regulate transcription. Again, all genes are generating these regulatory RNAs, and we have uncovered over the last number of years that we can target these non-coding RNAs with antisense oligonucleotides to increase gene expression. What we have found is that by targeting these regRNAs, we influence their structure and change the proteins that they're interacting with. Ultimately, what this means is that there is an increase in gene expression. Again, importantly, there's a couple features here that are highly relevant. One, all genes make these RNAs. They also act very specifically.
When we are targeting a regulatory RNA with an oligonucleotide, we're only having an effect on the gene of interest. Also, the effect size that we get is really well-suited to haploinsufficiencies or diseases where there's about a 50% reduction in expression, and we want to bring that back towards wild-type levels. SYNGAP1-related disorder is caused by haploinsufficiency or mutations in the SYNGAP1 gene that result in about a 50% reduction in activity. SYNGAP1 is a postsynaptic protein. It is involved in regulating the insertion of receptors in the postsynaptic membrane. What happens when there is a reduction in SynGAP levels, there's a stabilization of the AMPA receptor at the postsynaptic membrane. This results in increased signaling, glutamate signaling, and neuronal hyperexcitability.
These synapses are too strong, they've matured too quickly, and this results in hyperexcitability and leads to all the different neuronal phenotypes that you have seen exhibited in the video of Kasia. What we are doing is we're targeting the SYNGAP1 non-coding regulatory RNA with CMP-002. The idea here is that we will restore SYNGAP1 in the postsynapse. This will normalize receptors at the postsynaptic membrane and restore proper neuronal activity. The data that we have generated to date establishes that targeting the SYNGAP1 regulatory RNA is able to increase expression, and that this has a physiological benefit. The data that I'm showing on this slide on the left is looking at an in vitro system. This is patient iPS-derived neurons. We're looking at control neurons with a wild-type SynGAP gene in black, and then in purple is the patient iPS-derived neuron.
These cells have a mutation in the SYNGAP1 gene that results in a 50% reduction of expression, and you can see this. When we add in our CMP-002 development candidate oligonucleotide, you can see that SYNGAP1 levels are restored towards wild type. We've also been able to demonstrate a similar relationship in vivo. How are we going to look at the activity of a human-specific oligonucleotide in mice? To do this, we turn to a humanized SYNGAP1 mouse. This is a model in which the human SynGAP gene, that includes the promoter and the regulatory elements that are transcribing the non-coding regulatory RNA, have fully replaced the mouse gene. There's no more mouse SynGAP remaining. There's only either two copies of human SynGAP or a single copy of human SynGAP.
You can see that comparing the black bar to the purple, that there's a 50% or more reduction in SynGAP protein when there's only a single copy of the human SYNGAP1 gene. Single-dose administration of CMP-002 by intracerebroventricular injection, or ICV injection, results in an approximately twofold increase in protein levels, restoring it back to wild type levels. This nicely shows that both in vitro as well as in an animal system, we can administer an oligonucleotide, engage the regulatory RNA target, and increase SynGAP protein back towards wild type levels. What's critical as we develop CMP-002 is also to show that the increase in expression that we're achieving is having a physiological benefit. To do that, we again use this humanized mouse model and looked at a wide range of phenotypes that are both neurobehavioral as well as seizures.
As we heard during the video, there's a wide range of phenotypes and symptoms that these patients have and exhibit, and by restoring SynGAP, we would hope that we can have some impact in a broad way across the different domains of disease. We looked at learning and memory, and motor function, and hyperactivity as some neurobehavioral assessments and phenotypes. You can see in each case that there is a significant difference or deficit comparing the haploinsufficient SynGAP mice compared to their wild type two copy SynGAP controls. In each case, when we administer CMP-002, we're bringing these phenotypes back towards the wild type level. We're able to have broad-reaching improvements in these neurobehavioral phenotypes in this humanized mouse model. We also wanted to explore seizures. Seizures is a significant component of the SYNGAP1 patient experience.
These mice, on their own, do not exhibit overt countable motor seizures. To assess seizure, SYNGAP1 haploinsufficiency results in neuronal hyperexcitability. By adding PTZ, or by injecting these animals with PTZ, which is a GABA antagonist or an inhibitor of inhibitory neurons, this further exacerbates or makes these animals even more susceptible to seizures. The way we run this study is we give repeated administrations of PTZ every five minutes and then count score whether those animals have a seizure or not. You can see that the wild type animals in the black line with the repeated administration do not exhibit any seizures. However, the haploinsufficient mice that only have a single copy of SYNGAP1 are susceptible to experiencing seizures in this induced model paradigm.
You can see in the teal color that administration of CMP-002 results in a statistically significant improvement and reduction in the seizure threshold in these animals. The data shown in this slide nicely shows across multiple different phenotypes, all caused by SYNGAP1 haploinsufficiency, that by administering CMP-002 targeting the regulatory RNA, increasing SynGAP, that we are able to have a significant improvement in a number of phenotypes. This helps inform our future study in the clinic, where we will like to look at multiple different symptoms. Now I am going to turn to a non-human primate study. All of these studies in mice nicely show that we can increase SynGAP protein when targeting the human regulatory RNA, that the effect on protein has a benefit. This is all with ICV dosing, or again, directly into the brain.
When we are in the clinic with CMP-002, the clinical route of administration will be by intrathecal or IT dosing. It is important to us to demonstrate that we get good distribution of CMP-002 to the relevant brain regions, and that we can achieve concentrations that are having some effect on SYNGAP1 protein that would be expected to be meaningful. In addition, there has been very strong translation of showing target engagement in non-human primate studies with clinical studies and biomarkers as well. On the left, what we are showing are the dose-dependent and dose linear increases in CMP-002 concentration across a number of different brain regions, various different portions of the cortex, as well as hippocampus. These are all regions where SYNGAP1 haploinsufficiency can manifest in some clinical phenotypes. We are getting high levels of oligonucleotide to relevant brain regions.
Importantly, when we look at SYNGAP1 protein levels in these regions, we see a dose-dependent and statistically significant increase in SYNGAP1 protein. Shown on the right panel is frontal cortex, as well as hippocampus. These are two regions highly linked to a number of different phenotypes that patients exhibit. We see a nice dose-dependent increase in these regions. We also see increases in other regions as well. This data nicely shows that with intrathecal administration, we are getting enough drug to the right places that can engage the target, increase SYNGAP1, and this supports advancement to our clinical study. Just to recap what I have said, we have identified a new regulatory RNA that targets SYNGAP1. We have identified the candidate oligo CMP-002. This can engage the target and increase expression in patient iPS-derived neurons, as well as a humanized mouse.
The increase in SynGAP that we achieve has a meaningful benefit in a wide range of both neurobehavioral as well as seizure endpoints. We can also administer CMP-002 by intrathecal injection, which is the clinical route of administration, to get good distribution of the oligo throughout the brain. The concentrations that we achieve are able to increase protein levels. This is the data that has really made us excited about moving CMP-002 towards the clinic. We have been working very closely with Yuri Maricich, our Chief Medical Officer who is now going to discuss the ASCEND trial in more detail. Thank you.
Great. Thank you, Dan. Thank you for everyone for being here today. I am Yuri Maricich, Camp4's Chief Medical Officer. To frame our sharing about the SYNGAP1 ASCEND phase I/II clinical trial, I will start with some background on SYNGAP1 as a disease and review some natural history. SYNGAP1 impacts a full spectrum of neurological function, with key phenotypic elements being intellectual disability in all patients, generalized epilepsy, and autism-like manifestations, which include severe behavioral problems. No therapies exist for SYNGAP1 patients, with current care limited to symptom control in the form of anti-seizure and behavioral medication. Importantly, we have heard very clearly from patients' families, as well as their clinicians, that any benefit across the multiple domains of disease highlighted here would be significantly meaningful.
There is a growing natural history data set across multiple studies that informs our knowledge of the disease and is a valuable guide for endpoint selection, as well as comparison for patients who receive treatment with a potentially disease-modifying therapy. As this slide outlines, there are four sources of this natural history, including, first, a SYNGAP1 global census that is run by CURE SYNGAP1, where they have been adding now approximately 200 new patients per year since 2020. Second is the ProMMiS study, which is a prospective natural history study conducted out of Penn CHOP, Children's Hospital Colorado, and Stanford. Camp4 is also a sponsor of this study. The third source is a retrospective EMR cohort that is conducted and held through Citizen Health. Then fourth is the European registry, so-called PATRE, which also has been seeing significant growth and participation.
Collectively, across these, we see over 2,500 patients characterized from the census perspective, as well as real-world and registry cohorts, which provide insight for guiding subsequent development as well as potential comparators. The majority of Syngapians have severe protein-truncating variants in exons 5 through 19, which result in haploinsufficiency, with approximately 50% functional protein, which is the most homogeneous and also the largest population, representing roughly 80% of all Syngapians. This is the ASCEND phase I/II trial initial target population. There are patients with PTVs in exons 1 through 4 who have greater than 50% protein level. They represent only around 1%-2% of the population. Importantly, they provide a natural biologic proof of principle, where even a modest degree of increased protein expression results in a milder phenotype. Here, the patients are more verbal, they have fewer seizures, and many can in fact go to special schools.
The remaining patients are missense, intronic, and/or VUS. SYNGAP1 impacts the majority of neurologic function. The natural history data and publications have in fact replicated the phenotype described earlier and here across multiple independent natural history studies and publication. This gives us confidence in the clinical manifestations, which we are also enriching for in our trial for homogeneity. We see amongst different data sets from different studies a recurring prevalence of symptoms, which include intellectual disability in everyone. Most individuals have epilepsy and a very high rate of autism-like symptoms, particularly behavior also in sleep. When we have some context, SYNGAP1 severity is also similar or higher than analog diseases. In this important analysis, which compared SYNGAP1 natural history to Rett, Angelman, and a collection of 40 other epilepsies, as you can see in the graphs across a number of domains, SYNGAP1 is comparable to even higher.
Importantly, SYNGAP1 has some of the highest frequency of seizures, which you can see in the top left, difficult to manage autism-like behavior in the top right, and then intellectual disability, where you also see, particularly in SYNGAP1, neuroarrest or this developmental plateau. The average cognitive age of two, but you do not see neurodegeneration. Then communication impairment, where many patients are non-verbal or speak few words. The majority of SYNGAP1 patients have epilepsy with a high frequency of seizures. SYNGAP1 has one of the highest seizure burdens among genetic epilepsies, consisting of multiple seizure types. These are patients on background anti-seizure medicine treatment. The alluvial graph that is shown here is published data, and it uses a color coding of the severity score, demonstrating the frequency with patients who are actively having seizures. I want to highlight a couple important points.
In addition to the 85% of patients receiving an epilepsy diagnosis, compared to other DEEs, SYNGAP1 has some of the highest frequency of seizures. The genotype of focus of PTVs 5 through 19 have the highest rates of daily seizures among SYNGAP1 patients. Then there are multiple seizure types, with non-motor seizures being the most common, such as absence seizures. Seizure type can vary by age. Finally, SYNGAP1-specific EEG signatures include changes in the alpha-theta wave. Now for a description of our ASCEND phase I/II clinical trial. Before I get into the trial, I think it is important in framing and to underscore that we have designed this following clinical trial and our entire development plans with the world's leading experts in CNS neurodevelopmental diseases, including DEEs, who have experience studying as well as treating patients with targeted therapy such as ASOs and gene therapies.
They are on the front lines in conducting clinical trials in other related diseases as well. The ASCEND trial protocol was developed in close collaboration with them, as well as the SYNGAP1 patient community, and early input through scientific advice from regulators. Furthermore, we have built relationships with expert drug developers experienced in ASO drug development and other diseases. Thus, this trial design, including our dosing approach, has been cleared to proceed by three regulatory regions, which we will discuss further. I think also it is important to keep in mind throughout that we are the pioneer in SYNGAP1 therapeutic development, and so thus our trial is signal-seeking across multiple domains of disease. We are not pre-selecting nor committing prematurely to particular endpoints, as we have the opportunity to learn and take a data-driven approach.
The study goals are to demonstrate safety and tolerability, to characterize pharmacokinetics and select an optimal biological dose, and identify relevant endpoints that are applicable to SYNGAP1 patients to chart the path for regulatory approval. Categories assessed will include seizure, sleep, motor and gait, communication, behavior, and development and cognition. The trial will be a randomized, double-blind, controlled, multiple ascending dose study with a three to one randomization. Those receiving CMP-002 will be via IT administration or a sham pinprick as a control. At the end of the study, open label extension will be offered to all eligible participants. As for the study population, will include a minimum of eight participants per cohort, and participants will need to be two or older, up to being under 18 years of age at the time of randomization with a genetically confirmed SYNGAP1-related disorder.
All individuals will be required to have daily seizures, impaired sleep, and the inability to speak in phrases. The study periods will have three different stages. The first is screening and baseline period. There will then be a study treatment period with three doses, and then a post-treatment follow-up. The study length per participant is 10 months. As far as the key eligibility criteria, key inclusions are the age, as we discussed, age two to under 18, genetically confirmed SYNGAP1-related disorder with protein-truncating mutations in SYNGAP exons 5 through 19. The haploinsufficiency phenotype, which includes intellectual disability as well as inability to speak in phrases, sleep disturbance that are consistent with haploinsufficiency. All individuals must have refractory epilepsy, which includes daily seizures despite at least one ongoing anti-seizure medication and a prior trial of at least two ASMs, and they must be stable on their ASM regimen.
Variants such as on exons 1 through 4 or uncertain significance. Other CNS diseases that are unrelated to SYNGAP. Unsafe for intrathecal dosing, and any other clinically significant lab abnormality. This is a schematic that will help visualize the three periods of the trial. You can see starting on the left, the baseline period where there's screening followed by a minimum of four-week assessment to really help us set a firm baseline on which to make comparisons. Then those who are confirmed in their eligibility will go into the treatment period, where you can see three to one randomization with three doses given over a three-month treatment period. Then individuals who participate will move into a follow-up period where there'll be multiple time points of assessments over six months.
In terms of transitioning from the first cohort to subsequent cohorts, after two doses in eight participants, all safety data will be reviewed, and upon review by the safety review committee, then the dosing can begin in the next cohort. Throughout the trial, there will be a daily seizure diary, side effect and medication review. There'll also be numerous safety and functional assessments across multiple domains, disease that we'll talk about momentarily, and there'll be actigraphy prior to each study visit to help assess sleep. Now we'll double-click on some of the key assessments. There are multiple validated instruments that are going to be important for assessing categories of SYNGAP1, including behavior, development, communication, and motor function. These are measures that have been used in other neurodevelopmental disease therapeutic trials and also utilized for regulatory decision-making.
These assessments map to the domains of disease that have been found to be important in the natural history of SYNGAP1, and are themselves being utilized in one or more of the natural history studies, thus providing a potential comparator. You can see, for example, that across scales such as the Bayley, the Vineland, we actually are able to assess multiple domains. Through this series of validated assessments, we are able to collectively assess across those domains that are important in SYNGAP1. We are utilizing the gold standard methods for assessing seizure and sleep, which include multiple methodologies. First will be video EEG, which is common across both domains. For seizure, there we are also utilizing seizure diaries and the Seizure-Related Impact Assessment Scale, so-called SERIAS.
For sleep, there we are using the Children's Sleep Habits Questionnaire as well as actigraphy on top of the video EEG. This will allow dual methods for measuring key sleep metrics. You can see in the inset on the right that four EEG measures will be assessing multiple parameters that will continue to provide deeper insights into the patient population as well as the impact of CMP-002. This is a global trial with the goal to enable collaboration with the leading experts across the world, as well as to support recruitment and agility in executing as well as moving beyond our phase I/II. We will have 11 + sites across nine countries and five regulatory regions. We have four sites in regulatory regions that are already approved to initiate the trial and seven EU sites that are part of the review by the EU.
We already have a strong execution track record with those three regulatory regions cleared to initiate the trial in the U.K., Argentina, and Australia. Before I conclude, I would like to take a moment to share on a personal note how excited and motivated we are at Camp4. Personally, I have had the true privilege to meet with the leading experts around the world and the SYNGAP1 community. I have met SYNGAP1 patients now across multiple continents with a multitude of different genotypes, where their families have invited me into their homes, shared their experiences and struggles, and just generously invited me to spend time with them and their Syngapian. You have heard earlier from Beata and Kasia's story, and you will hear shortly from Mike Graglia. I am so grateful for the trust that the community around the globe has shared with myself and my Camp4 teammates.
We have become deeply knowledgeable because of this sharing, and we have requested and received feedback on our developmental plans, our protocol, and how to set up and conduct a patient-friendly trial from the patient community. At Camp4, we are on a mission to develop a medicine for individuals with SYNGAP1 and their families. As you have seen, this is a multifaceted disease, and we have heard from the patient community and their physicians that they have nothing. Even impacting one domain of disease could be transformative. In conclusion, as we have shared, Camp4 is pioneering SYNGAP1 development.
We have clearly defined phase I/II study goals, and as the pioneer, we are signal seeking with multiple domains of disease and multiple potential comparisons from baseline, between groups, and natural history to demonstrate signal and measure success. SYNGAP is a severe lifelong disease with consistent natural history data across multiple studies to guide our development.
We've partnered with the leading experts, the patient community. We're signal seeking across all the domains of disease where there are validated measures or assessments. We expect to have first patient dosed by year-end, and top-line readout is targeted for first half of 2028. With that, I would like to introduce Mike Graglia, who's the Chief Executive Officer of CURE SYNGAP1. The CURE SYNGAP1 community has really played a pivotal role, and I think it's important to hear from him.
My name is Mike Graglia. My wife, Ashley Evans, and I founded CURE SYNGAP1 eight years ago when our son Tony was diagnosed with SYNGAP1 at the age of four. Today, he's 12. When he was diagnosed, we called around. We went to all the usual places. There were a handful of great scientists working on SYNGAP1, but there weren't enough great scientists working on SYNGAP1, and there were no companies. There were zero companies with SYNGAP1 in the pipeline. We created the organization, and we tried to basically make SYNGAP1 tractable, investable, and then trial-ready. But at the minimum, where we were starting was de-risking the disease so that companies like yours could come along and bring your expertise and develop therapies for SYNGAP.
Having a child whose brain never gets out of two years old while having seizures and not sleeping, et cetera, et cetera, et cetera, the whole family gets diagnosed, and the burden is. I'm not even going to touch the way the education system fails and the group housing fail. The failures just keep coming, and people just do not appreciate the burden on families day one when they're little and cute and you're trying to help them. But these things mount and grow as their bodies mount and grow. It's a huge. The unmet need is endless, and I could talk about this for hours. But it really is important that we get a disease-modifying therapy, the kind that you are developing, because sleep, seizures, behavior, intellectual disability.
For eight years to put the natural history in place, to put the EEG knowledge in place, to identify scales that made sense, and we've brought all that to help inform your clinical trial design, as well as actively giving you feedback on everything from how the day should look to the level of support our patients require, and we've been grateful both that you asked in the first place and that you've taken on board what we've said. People are jumping out of their seats. I get a call every week. "Should I move to Australia?" And I say, "No, stay there. Wherever you are, stay there." The trial's probably coming to you. There's patients in Australia who are probably going to get into that trial first because they know the PI. Like calm down is what I've been telling people, but there's tremendous excitement, right?
And it is our responsibility to our children and to all the kids who have yet to be diagnosed, because we know there are thousands out there who have not been diagnosed yet, to contribute to these trials, to take part if we are able, and to make sure that we figure out if CMP-002 can work and can help our kids. We are committed to doing whatever work is required to giving this drug a fair shake in a rigorous trial. I think that starts with education, making sure people understand what is involved in a trial, what placebo is, why we need placebo. Awareness, telling everybody. We are already kind of all over that, but we will keep doing it.
Support to families who are in process, giving them whatever they need through our own patient support people, as well as making sure you guys have things in place, and also expectation management. We are excited for this partnership, both because we have a great working relationship with Camp4, and we want the drug to be successful, we want you to be successful. There is a much bigger opportunity here for SYNGAP1 globally to show that humans are rescuable.
Great. Before we go to the fireside chat, Dan and Yuri, we just have a question that came in through the webcast for you. Given that your initial ASCEND trial stops at age 18, what does Camp4's preclinical data show about whether this regulatory RNA upregulation can successfully reduce or control intractable seizures in a young adult brain?
I can start here. We have shown in younger animals that we are able to engage the regulatory RNA target, that we can increase SynGAP, and we can reduce seizures, along with all of the additional neurobehavioral phenotypes. In terms of the age of onset, these children are typically diagnosed around the ages of two or three. We are able to intervene at that point. There is also evidence that even later on in older animals in preclinical studies, that intervening at older ages as well is able to reduce a number of different phenotypes. It seems that across a broad range of ages, there is an ability to intervene. I think clearly the data that we have generated, and based on the natural history as well, we are certainly going to prioritize administration of CMP-002 to younger patients.
I'll just maybe add very briefly that I think importantly, as Dan mentioned, there's no evidence at present that there is some kind of limited therapeutic window in SYNGAP1. Furthermore, the natural history does not show neurodegeneration. In fact, it shows more of a neural rest or plateau, with actually very gradual improvements over time. So you do see the ability to continue to potentially have new skills or learning. This, coupled with the preclinical data that Dan referenced, gives us, I think, some insight that there may be the potential to intervene beyond pediatric population. The ASCEND phase I/II clinical trial is starting in individuals under 18. But this is an area where I think as we get more natural history, we'll think about where do we go in the future.
Great. Thank you both. Just one more before we go to the fireside chat. What clinical outcomes do you hope to improve with CMP-002, and which endpoints will be used to assess treatment efficacy? For example, seizure burden, communication, and language, cognitive function, behavior, sleep, or daily functioning.
Yeah. I think importantly, we're the pioneer here. This is the first potential disease-modifying randomized clinical trial, and so we're signal-seeking. We've heard also very clearly that impacting any of those domains would be really transformative for the patients as well as the families. Clinicians have reinforced this view. So I think there's a lot of different places we can go, and we want to be data-driven. We don't want to pre-commit to any particular endpoints, and so that's why wherever there are endpoints we think that are able to be assessed and are meaningful, then we're going to measure those. Lastly, I'll point out the things that we're assessing are also being assessed in the natural history data. So we have data that can support the use of those assessments, and as well, a potential comparator.
Great. Thank you both. Yuri, I think we can go to the fireside chat now.
Great. It is my great honor to introduce Professor Stéphane Auvin, who is a pediatric neurologist and epileptologist. He is recognized for his expertise in developmental and epileptic encephalopathies. His work really bridges translational neuroscience across clinical development, but also regulatory science. He has co-authored more than 350 publications. He has advised over 30 pharmaceutical and biotech companies on developing innovative, both anti-seizure and importantly relevant disease-modifying therapies for rare neurological disorders. Professor Auvin is also the deputy editor of the ILAE journal, Epilepsia, and he served on multiple regulatory committees. It is my great privilege to welcome Stéphane. Stéphane, thanks for taking the time to speak with us today.
Thank you. Very happy to be here.
I have a couple questions for Stéphane that I thought could be helpful for everyone to hear. I think we will first start broad. Stéphane, in your experience, how are new medicines and precision treatments impacting the landscape, both in neuroscience, particularly genetic DEEs? Do you think these treatment modalities seem to be increasing in clinical trials and as part of the resource for clinicians?
For a long time, in the epilepsy field, and in particular in DEE, we were using treatment focusing on one single symptom, that was the seizures, basically. Now that we are accessing treatments that can target the mechanism of the disease, of course, we are hoping to have action not only on the symptoms that are the seizure, but what is the constitution of a DEE, meaning impact on the seizure and the non-seizure outcomes. That could be behavioral, that could be cognition, or sleep that is affecting the quality of life of these patients. A lot of preclinical work has been generated, but now, as clinician and investigator, we are seeing more and more of this trial coming, and it is generated a lot of hope, not only in the family, but also in the investigator and the clinician community.
Great. Thank you for that. It really has been exciting. You can feel the enthusiasm at medical conferences and in talking with you and your peers. What is your experience with ASOs? You mentioned in terms of disease-modifying therapies, how large is the need? Is there anything unique, given the different modalities out there, about Camp4's approach for up-regulation?
What is interesting is if you think about epilepsy and a lot of the monogenic disorder, meaning they are accessible for targeted treatment, targeting the gene or the RNA, then it's probably up to 10% of the epilepsy that we are talking here, and we are talking about the more severe one, that are very important because you're not dealing with seizure only, but also with the non-seizure outcome, cognition, behavior, and so on. There are different tools, and what is kind of interesting in the Camp4 technology is you are not switching on or off a gene. You are targeting the regulator, meaning you can do a very fine-tuning about the change of the expression, and this change of expression is based on the normal gene. That is kind of a cool technology.
Thank you for that, Stéphane. Maybe let's zoom in on SYNGAP1 now. For the audience, investors, observers, what do you think is important for them to know about SYNGAP1? Also, what are key learnings from other DEEs that you think has read through to SYNGAP1?
Something that is interesting for SYNGAP1 and for all of these DEEs, know what is the need of the patient, and the need of the patient is based on the incidence and the prevalence of the different symptoms. What is kind of distinctive in SYNGAP1 compared to other DEEs, the fact that families, academia, have generated a lot of natural history studies. We are aware, with a large number of patients, even it's a rare disorder, what is the phenotype and what kind of symptoms the patients have to deal with, and what are the priority for patient and family. Sometimes you have to run from zero, learn about the disease, and try to understand with natural history study. The amount of data for SYNGAP1 is great, and it's very helping how to look for change in treatment, how to design a trial, that is very helpful now.
I think that's something that I've been so impressed with, and frankly, Stéphane, you and your colleagues are doing an incredible job of encouraging participation in the natural history data, and we're seeing that in terms of the increase of people joining and participating in those types of studies. We just talked through the first clinical trial, the ASCEND clinical trial, a potential disease-modifying therapy for SYNGAP1. What are some of the important attributes about the clinical trial do you think for observers to be aware of?
I think what's important is the foundation is based on the symptoms, and what are the prevalence and the incidence here. With key challenges, because you are not developing a treatment that are just targeting seizures, but you want to deal with the full disease based on the mechanism of the disease. Meaning that the trial has been designed with that idea. Let's focus on the seizure and the non-seizures with different domain that will be assessed with different kind of validated scale, just aiming to understand the heterogeneity, the complexity, and what are the key symptoms that could emerge, and demonstrate that you have a signal for further demonstration of the efficacy of the component later on.
And maybe as a follow-up to that point, Stéphane, as we shared at the beginning of the presentation and time together, SYNGAP1's completely devastating, impacts basically all aspects of neurologic function. How do you think observers should think about the proposed trial endpoints, and what do you think might be successful for patients in the pediatric neurology field?
I think the way to look at the trial is the design and the different endpoint has been done in a way that we are not giving a chance to not capture a signal for treatment that could work just because we are not using the right endpoint. That is, we are covering that in a way with, if there is any chance that we have a signal, we'll capture it. That is probably important. I think at the stage we are, this is the first time that we might have a disease modification treatment for SYNGAP1, meaning that any clinically meaningful change will be a success. We are in a landscape that nobody walked before, then it's probably something that is key here. Any progress, any clinical significant progress will be a win for patient and the community.
Great. Thanks so much, Stéphane. Maybe I will just ask one final quick question, because I know you have had experience from other related trials, and you have also had first-hand interaction with the SYNGAP1 community. What have you seen that might be helpful in understanding interest around participation in a trial and enrollment?
There is a lot of excitement, both from the patient community and the investigator here. At some point, at some time, I say, "Oh, slow down. The expectation should not be that high. We are doing clinical trial. We are not expecting that it is a magic bullet." It could be, hopefully, but also, this enthusiasm is meaning that the community is fully aware, is fully dedicated to the participant, and not taking the example of the SYNGAP trial because it did not start really. But I am part of several phase I, II study. I am receiving email every week for family looking for having a spot in trials. This is a landscape of the modification treatment for targeted treatment. We receive a lot of solicitation because the family want to be part of it, to move the science and have positive outcome later on.
Stéphane, thank you so much for your time. It is really great. Really appreciate you sharing your wisdom and experience with myself and with everyone here today.
Thank you.
All right. With that, we're going to turn it over to Josh.
Great. Thank you very much, Yuri and Stéphane. I don't think I could have said it better myself. Before I move on, I want to once again thank the CURE SYNGAP1 Foundation, as well as all the patients. We hope to make a big difference for you and your families. As I previewed earlier today, we have bigger ambitions at Camp4, and I want to conclude today with a sneak peek of our future pipeline, where we are focused on haploinsufficient neurodevelopmental disorders to expand on the expertise we have gained through our SYNGAP1 program. Phelan-McDermid syndrome, PMS, or SHANK3, is a severe neurodevelopmental disorder caused by mutations or deletions of the SHANK3 gene, resulting in a true haploinsufficiency, making it a sweet spot for our platform technology. Just a bit about SHANK3. It encodes a postsynaptic scaffolding protein, which is critical for synapse development, maturation, and maintenance.
As it is a haploinsufficiency, one of the two copies of SHANK3 gene is either deleted or contains a pathogenic variant. As a result of this mutation, patients suffer from profound developmental delays, intellectual disability, autism, and milestone regression. They have limited to no speech, often non-verbal, and have severe motor impairment and hypotonia. Like SYNGAP1, patients have behavioral challenges and elopement behaviors, leaving them in danger and under constant supervision. There are no approved treatments addressing the underlying cause of PMS, and the standard of care is limited to symptom management. There's a notable caregiver burden, and patients require lifelong constant supervision and care. It sounds quite familiar and is very similar to SYNGAP1's situation. We estimate there are at least 45,000 SHANK3 patients in the U.S. alone, including a multi-site, multi-year ongoing natural history study and global registry with more than 3,500 patients included.
Like SYNGAP1, it has validated disease-specific clinical scales we can leverage once in the clinic and a strong SYNGAP overlap in terms of KOLs and centers of excellence. Based on emerging data, we are pleased to be able to announce SHANK3 as a new pipeline program that we are intending to advance towards DC nomination in 2027. Behind that, we have two other DEE haploinsufficiency programs that we look forward to talking to in the coming year. We will also talk more about the SHANK3 program and share data in the coming months. With that, I'd like to conclude today's prepared remarks and open it up to questions from our analysts. Thank you very much.
Great. Thank you, Josh. Yes, at this time, we will be conducting a question and answer session with our four speakers. To our analysts joining us live, we kindly ask that you limit yourself to one question and then one follow-up. Please hold for a brief moment while we poll for questions.
Our first question comes from Anupam Rama at JP Morgan. Please go ahead, Anupam.
Hey, guys. Thanks so much for taking the question, and thanks for hosting this analyst day, super informative. I have a question for the company as well as Dr. Stéphane, the KOL on the line. I know everyone's going to be looking at the totality of the data as you get data from the ASCEND study. But what level of seizure decline do you think is clinically meaningful? Have you heard anything from regulators on what's a clinically meaningful threshold, or are there comps that we should be thinking about in other developmental spaces? Thanks so much, guys.
Thanks, Anupam, and I'll definitely, after sharing my thoughts on the question, pass it over to Stéphane. I think as we shared earlier, really because this is the first, we don't know what the potential magnitude of impact is. I think also, and Stéphane as well can speak to this, that seizure impact and how it might forecast other changes that are disease-modifying can vary across different genetic epilepsies and particular DEEs. I think where the regulatory discussions have been, just as an aside, have really been more around, do we have all the right ways of assessing any change, and are we going to be looking at multiple ways of also measuring that as well?
I think what I feel really good about, and Stéphane can speak to this now, but he also mentioned as well, is making sure that if there is a change, we are going to be able to assess that adequately in a reliable way that both the clinical community, but also regulators want to see. Stéphane, anything you want to add?
Yeah. This is also a new landscape, even for the regulatory, because when you look for DEE, most of the time, a lot of the DEEs, the change in the seizures was based on motor seizures, while in SYNGAP1, it is a lot of non-motor seizures. If you look at the protocol, there are multiple ways, clinically and also EEG, and also EEG with stimulation to make sure that we are capturing the type of seizures and non-motor seizures, meaning absences or myoclonic seizure, or absence with myoclonic seizures that is very common in these patients. Coming back to my research, in other DEEs, the day without seizures are something that has been associated frequently with increase in quality of life. It is probably something that we have to think about.
It is part of the assessment that has been put in the protocol, but it is not the only way to measure it. Then difficult to give a number, but all the instruments are in place to show the significance. After that, of course, the association with changes in quality of life or daily burden will tell us what is clinically meaningful or not.
Thanks so much for taking the question, guys.
Great. Thanks for the questions, Anupam. Our next question comes from Steve Seedhouse at Cantor Fitzgerald. Please go ahead, Steve.
Oh, great. Thanks so much for hosting the session. I wanted to ask first on SYNGAP1, of course, on ASCEND, if you could just put the initial dose, that you response curve, if it's going to be low or if it could already be highly active at that first dose cohort, and then how fast are you ramping up dose with each cohort?
Sure. No, I appreciate the question, Steve. What I can say is that all our dose levels are within expected therapeutic range. Like other peer companies, we're not disclosing dose levels at this time, but will at the appropriate time in the future.
Okay. Maybe on SHANK3 then, I was hoping, I think, Josh, you mentioned there could be some preclinical data from that program forthcoming over the next few months. I was just hoping you can talk about maybe how well established the preclinical models are for SHANK3, and if you could just compare and contrast with your SYNGAP1 preclinical experience.
Yeah. I'll kick it off here, and then I'll pass it over to my colleague, Dan Tardiff, who can speak in more detail. But we are very fortunate for SYNGAP1 that there is a humanized mouse model that's quite robust and we're able to leverage. SHANK3 is a bit different, although there are models, but we are going to also rely on primate data, which we think is going to be very important. But I will ask Dan to comment in more detail here.
Yeah. There are related mouse models, murine mouse models, looking at the impact of SHANK3 haploinsufficiency. There's evidence that genetic reintroduction in those mouse models are able to impact a number of different phenotypes. I think to the point of looking at oligo activity or ASOs targeting a regulatory RNA and increasing gene expression, I think that is one thing where, again, both non-human primates as well as a potential humanized mouse would be impactful. But in terms of, again, the mouse models, there's demonstration of reversibility, which I think is very important again, to provide that support, that intervening multiple ages throughout development can have an impact on phenotypes.
I think all these synaptopathies, or where these DEEs or neurodevelopmental disorders where the protein is functional in the synapse, showing reversibility really gives us a lot of confidence that intervening with an RNA targeting oligo will have some impact.
All right, thank you. Look forward to following the progress here on both programs.
I will just build on that, Steve, and say one other thing, which is we're fortunate in that we see a franchise opportunity in that all the diseases we're starting to work on here in our pipeline are in the same areas of the brain, are intrathecal delivery, are haploinsufficiency. So we're really hoping to build off of SYNGAP1 and potential success there, where we think there's a direct read-through if it's a successful clinical study, that this should work in similar indications with a similar mechanism of action and path of delivery. So that's kind of the line that we're thinking through, and I didn't mention the other two indications, but they are DEEs, haploinsufficiencies also in the brain as well. And so those will be coming in the next year or so. But that's how we think about it here at Camp4.
Terrific. Thank you, Josh.
Thanks for the question, Steve. Our next question comes from Myles Minter at William Blair. Please go ahead, Myles.
Thanks, everyone, for putting this on. This is great. There was a pre-print of the ProMMiS natural history study kind of explaining the protocol for it and some initial data, I think it was out earlier this year, and you showed us some data for monthly seizure frequency expected in these patients. My question is, what can you actually compare to in your trial versus the natural history, given that most of those readings are taken every six months, and I think yours is a three-month trial? Just wondering what you can compare to in natural history versus relying on your own internal placebo control. That's the first one.
The second one is just, given it's a three-month study here in ASCEND, do you expect to show your maximal potential seizure frequency reduction in that timeframe, or are you going to look more like ZTALMY and Dravet syndrome, which showed a signal but did take nine months to really show that dramatic seizure reductions for those Dravet syndrome patients? Thanks very much.
Thanks, Myles. Great questions. For the natural history, maybe I'll just say two things there, because you're obviously right that in natural history studies, the visit frequencies tend to be less frequent than in a clinical trial. I think what's good and very useful is that those natural history studies, though, do tend to assess a broader window. Even if they're coming in, it's not just a snapshot on that one, it's a broader window. And one of the things that we are working very much on, and there should be more news at later points, is around continuing to expand the natural history data, I would say both potentially in other geographies, but also in depth. I think that's one. And I think that as we go through that, there's going to be the potential to show trajectories.
That's important, and the good news here is SYNGAP1 has some of the highest frequency of seizures, even if they're a multitude of different types. The other thing for us, and this was very intentional, is in the baseline period, we're going to get a nice, healthy baseline of a minimum of at least four weeks of that baseline data. And that includes seizures, but that includes many other things. And that will enable us also to do that comparison, but also to do that data. And then lastly is we do have a control, and we've been very thoughtful and diligent about including that. And while the size of this study is not intended to have necessarily the ability to make statistically significant comparisons to that control, there is the ability to make comparisons there.
I think for the second question that you had now about time point, I think it's really premature to say. I wish I could give you some direction. Obviously, you referenced Stoke and zorevunersen, and we're very close to them. We've looked at that data. I think the thing is that while there are definitely some parallels, this is also a very different disease. The seizures are different, our mechanism's different. I think I wouldn't want to guide to any particular data time point, given the fact that this is the first and it's a different disease.
Makes sense. Thanks for the questions.
Thanks for the questions, Myles. Our next question comes from Ted Tenthoff at Piper Sandler. Please go ahead, Ted.
Great. Thank you. I am not sure, can you hear me okay?
Yes, we can.
Okay, great. Thank you for this. I found it really, really useful, and it really just underscores the massive medical need for these patients. Appreciating that you're, I'm wondering if the FDA's had any input or other regulatory bodies. Again, I know it's early, but what are they kind of thinking? Do they need to see something functional? What is sort of the feedback you've gotten from global regulators? Thank you.
Yeah, thanks so much for the question, Ted. We've definitely been engaging with regulators around the globe. Also, what I can say is the SYNGAP1 patient community is also engaging. We've been very intentional, though, about actually trying to make sure that regulators are keeping an open mind. I think that's really important here. We're charting that first path. We want to be data-driven. It's important that there's natural history so that we can all learn. I don't think it does, though, anyone a service if we try and pre-define or pre-answer.
I think what we're most focused on, and Stéphane also mentioned this, is making sure that the methodologies and the assessments we're using are ones that are reliable, they're validated, so that where we see movement, that movement is something that we feel like is through a measure and a methodology that everyone agrees we can have confidence in. I think that's really where we're focused. There hasn't been discussion about trying to pre-select any of these areas. While difficult for patients, one of the opportunities we have here is that there are many domains of disease that we can assess, so there's many potential areas to impact.
Yeah, I'll underscore that from what Yuri said, which is, one of the interesting things here is we see it as an opportunity since we're blazing the path here is we get to define success with the patient community. As you heard from Stéphane, there's a lot of opportunities here to have an effect, and anything can be quite meaningful for these patients. As Yuri's saying, we want to let the data guide us, almost in a way like it was done for SMA, where CHOP INTEND was created as an endpoint.
Yeah.
We think we have that opportunity here as well for SYNGAP1.
Excellent. Thank you for the time.
Thanks for the questions, Ted. Our next question comes from Basma Radwan at Leerink. Please go ahead, Basma.
Good afternoon, everyone. Thank you so much for taking our question. We just wanted to ask you about the sleep outcomes and your expectations around it based on your preclinical work. Literally in terms of, do you expect effect on sleep architecture or sleep durations? If you can guide us to what we really should be looking for. Also, in terms of timelines of this outcome, do you think it's going to be very similar to the epilepsy timeline, given that that's basically they both are related to the hyperexcitability of the circuitry, so you'd expect that both of them you should detect an effect along the same time? Do you actually have to show that the effect on the sleep is decoupled from the effect of epilepsy, or it doesn't matter at this point? That's it for us. Thank you.
Thanks, Basma, for the question. What hopefully we conveyed is that there are going to be multiple methodologies used for assessing multiple of these domains, because this is the first potential disease-modifying therapy in SYNGAP1, and sleep is no different. For sleep, we have gold standard method, which is basically overnight sleep recordings during the overnight video EEG. That will allow us to get all the specific sleep metrics, so sleep onset latency, wakefulness after sleep onset. It will include REM and sleep architecture as you shared. Then we are also getting that at home. That is the actigraphy that I mentioned allows us to measure that at home in their natural environment. Then there is the children habit sleep questionnaire, which actually is really important because sleep in these families, sleep impacts many things. It can impact, obviously, development and cognition.
Insufficient sleep can also be a threshold lower for seizures, but it impacts the family as well in a major way. The multitude of assessments, I think, allow us to look at that in multiple ways. Then we are also going to have things like clinical global impression and caregiver global impression, and that is wrapped up. In terms of timing, again, this is the first disease-modifying therapy. I wish I could give you some more guidance. I think it would just not be a service to anyone to try and put a window on it. We want to make sure, and that is part of the study, is that we are going to be capturing this very rigorously at the baseline, and then we will be capturing this throughout the study at multiple time points.
Thank you.
Thank you for the questions, Basma. Our next question comes from Seema Sheoran at Rodman & Renshaw . Please go ahead, Seema.
Thank you. Thank you for hosting this event. Very helpful. I have a question on the dosing frequency, and also after three months, if you plan to include maintenance dose, and I have a follow-up.
Certainly. Go ahead, Dan.
Well, I think what we have said is we are going to do three doses over these three months. I will just start by saying this has all been informed by our preclinical studies, both in mouse, in the humanized mouse model, as well as the NHP model, and then the follow-up safety studies that are supporting the clinical study. Further nonclinical assessments will need to be completed before going beyond the current three-month study, but those will be completed to enable an open label extension.
I see. In terms of the data that you mentioned that you will be receiving and communicating to the street about the safety and some of the PK parameters. As a company, will you be receiving data like, oh, there has been seizure reductions, and will those be communicated to us before first half of 2028, or you are going to look at the totality of the data and then communicate?
Maybe I'll share a couple comments on that question, Seema, and Josh can add on here. I think we're just, as a framing, trying to be really thoughtful here. Our aim is to conduct a high-quality, double-blind controlled study, and we want all of us here and the street, our investors, the patient community, investigators, to have confidence in the results. We really want to position ourselves for the optionality of development pathways, post the ASCEND phase I/II. Then very specifically to your question, this isn't an open label study. We're not going to be reviewing data on a streaming or routine basis. We really need to maintain the integrity of the double-blind for both parents, caregivers, and investigators, and particularly given the presence of the caregiver and clinician-rated assessments. Right? We want to make sure that there's not any undue bias there.
There will be pre-specified study points whereby maybe a small set of individuals would be viewing data, but that would be limited to trial conductance. It's possible that we may see things we like, but we won't be able to speak to them in order to maintain the quality integrity of the trial. There are a lot of considerations that go into that, and we just can't pre-specify what those may be, and we don't want to break the blind. Josh can speak a little more to this, but if we see something that it makes sense to talk about, we will do so, but we really can't predict when or what that would be.
Yeah. The way I think about it is we're baking a cake here, and the cake's going to be done in the first half of 2028. But it is possible, to your question, that we may see something sooner that we're excited about. The things we have to take into consideration are, as Yuri said, maintaining the blind and whether or not we would break that. Obviously, I think there are scenarios where you may wish to do that. Ultimately, we want to get to the best outcome as quickly as possible, but also the best outcome doesn't just mean safety and showing proof of concept, but also sets us up to potentially move forward and get to market as soon as possible. Those are the considerations that go into it. It's hard to predict if anything and when would come before that 2028.
We're trying to take the most conservative view so that we're fair to ourselves, the patients, and really, that we can underpromise and overdeliver here. We don't want to overpromise. I think Yuri said it well, that there will be predefined study points, which we haven't yet solved for in a small group looking at it. We're going to be patient and thoughtful here as we go forward.
Very helpful. Thank you.
Thank you for the question, Seema. Our final question comes from Yun Zhong at Wedbush. Please go ahead, Yun.
Hi, good afternoon. Thank you very much for taking the question. This might be a little redundant. I understand your emphasis on the signal-seeking, but just wanted to confirm that based on your discussion with regulatory bodies, there is possibility, and I wonder how reasonable it is to expect that you might be able to find some type of biomarker to show correlation with a clinical benefit instead of relying on clinical endpoint for future. I know it might be a little premature to talk about this, but just wanted to confirm this possibility and your intention to do that. If is that the case, is seizure reduction the most reasonable candidate, please? I have a follow-up question on dosing, please.
Maybe I can just quickly add, I think, to those first two points, Yun. The SynGAP protein is not secreted in the CSF, so we don't have the ability to measure that directly. There continues to be work done around potential biomarkers, and I think importantly, there's some published data here, that there may be the potential for different types of electrophysiologic changes. This has been actually shown in some other DEEs as well. There's SYNGAP1-specific power spectral changes. That is a possibility. At the same time, I think we want to make sure that anything that would be used both for determining potential effect from a neurophysiologic perspective as well as from outcomes is something that we all have confidence in. That's, I think, really important. I would caution against putting any one of these endpoints as primary.
All the assessments, we're looking at all of them. We want to be really thoughtful. We obviously hope to have an impact that's meaningful, that's really our goal, and this is an area where there's many different ways that we can be meaningful, just given our discussions with patients and talking with Professor Auvin and others. We don't have a hierarchy of different endpoints over the others. It's really, they're all equal.
Okay, thank you. On the follow-up question on dosing, I probably missed part of the previous question when I was getting into the live room, but did I see it correctly that those patients are only getting three doses but not active treatment anymore in the follow-up period? If that's the case, why don't you treat patient chronically?
Dan or Josh can add on. You did hear correctly, so the treatment period is three months, and there'll be three doses over those three months. The follow-up period is six months, and there'll be assessments throughout, safety, different other endpoints that we talked through that are exploratory. Where we'll get to the chronic long-term maintenance dosing would be in the open label extension.
Yeah. So maybe just to double-click on that. As you already mentioned earlier, we are starting our study in a therapeutic range. We are approaching the low dose more as a safety, as Steve Seedhouse has pointed out, similar to other companies. But we feel really good about all the doses that we are bringing forward, and we will have an open label period where patients will receive continued treatment and TBD on the details there as we are just getting going.
Great. Thank you.
Great. Thank you for the questions, Yun. This concludes today's Camp4 Therapeutics Analyst event. Thank you to all of our speakers, and also thank you to everyone who has joined us today. You may now disconnect.
Thank you.
Thank you.