September 28 @ 3:00 pm – 4:00 pm EDT

Additional Resource: CAMP4 Corporate Overview (September 2026)

CAMP4_Corporate_Presentation_20260928 Download

Below is a transcription from the video:

Virginie McNamar
[00:00:10] Hi everyone. Thank you so much for being here today. I am Virginie McNamar. I am the president and COO of CURE SYNGAP1, and I am joined by two special guests today, Caleb Moore, Chief Business Operating Officer, CAMP4, and Yuri Maricich, Chief Medical Officer, CAMP4.

They just held their Analyst Day presentation to share some exciting updates on their SYNGAP1 program with all their stakeholders, and we invited them here so they could share those updates directly with our community. CAMP4 has been a great partner to our organization and our community. They have welcomed our feedback from the beginning on their program and spent a lot of time with our community around the world.

Virginie McNamar
[00:00:53] Uh, to get to know the families and really what it’s like to live with SYNGAP1. I think at this point I don’t need to introduce Yuri. He’s been all around the world. Has met probably more Syngapian than anyone. We really appreciate you being here, guys, today. To share those exciting updates with the community.

We’ll have a Q&A session at the end, but right now we can’t wait to hear for the really exciting updates from you.

Yuri Maricich
[00:01:24] Great. Thank you so much, Virginie, for the invitation to be here. And thank you to… all families and members of the community who are part of this. And frankly, for the welcome that you have shared and all the insights and generosity of welcoming into your homes, in sharing your experiences and struggles, we would not be on the cusp of starting a clinical trial if it was not for your partnership and all the work you did before we even started our work in SYNGAP.

What I’m going to do today is give a corporate update. As Virginie shared, this is an update on what we can speak to today.

Yuri Maricich
[00:02:23] And over time, once the trial is fully enrolling, we will have sites will be able to interact directly and share additional details. So I’ll do my best to share as much as I can. At the same time, recognizing as a public company, we may be limited sometimes in some of the things we can say. And so just appreciate your patience with us there.

This is our forward-looking statement, which just highlights as a public company, we’ll be making some statements that are forward-looking. This is just a disclosure that I’m an employed equity holder at CAMP4. I also want to just highlight that this presentation is for educational purposes only. It is not an offer to participate in a clinical trial.

Yuri Maricich
[00:03:18] And also that CMP-002, which is our investigational product candidate, has not been approved for commercial use in any jurisdiction and its safety and efficacy in humans has not been established.

So what are we going to talk about today? As Virginie mentioned up front, we did our Analyst Day today and we want to simultaneously give an update to the community. So we appreciate that request and also we’ll be having an opportunity for some questions that were sent in the beginning at the end.

As most of you may know, but just as a quick refresher, CAMP4 is pioneering a new class of medicines to increase gene expression. We are now a 10-year-old company.

Yuri Maricich
[00:04:11] We aim out of research that was done at the Whitehead Institute, Massachusetts Institute of Technology, and Boston Children’s and Harvard Med School. We’re approximately 60 employees. We’re based in Watertown, Massachusetts, very near Cambridge. And our goal is to pioneer a new approach to upregulate genes. And our vision is to change the lives of patients with diseases caused by inadequate gene expression.

I am not going to spend time on SYNGAP because you all know SYNGAP from your personal experience in your family. But these are some of the slides that were presented at Analyst Day. And one of the things that’s been so important that this community has done is generate awareness and education. And so I wanted to include these slides.

Yuri Maricich
[00:05:05] Here and also here because it is very important as clinical trials are initiated and as regulators are engaged with that we continue to generate data around the natural history and we continue to generate awareness and expand understanding of what is SYNGAP1 and what does it mean to live with it and what is important to you as families.

This was one of the slides that was also included in Analyst Day, just highlighting the importance of natural history. You are all likely familiar with one or more of these natural history database, and this data is very important.

With that, I’m going to just very briefly talk about our approach. And then we will talk about the clinical trial. So this data has been presented before.

Yuri Maricich
[00:06:09] I just want to make sure that everyone is grounded in our therapeutic approach. So CAMP4’s goal is to increase SYNGAP protein levels and restore SYNGAP1 function and improve disease symptoms.

So our goal is… to target the underlying cause of SYNGAP1, which is, as you know, the fact that we all need two healthy copies and individuals who are affected have one copy that is mutated that either makes no or less functional protein. And so in many individuals, this results in 50% lower SYNGAP protein.

You can see the illustration on the left where it shows the pre-synapse releases neurotransmitters glutamate to the post-synapse, which is where SYNGAP protein is supposed to be expressed, but in individuals who have insufficient amount of SYNGAP—

Yuri Maricich
[00:07:13] protein, those individuals have increased neuronal excitability and makes these synapses very tight and results in all the consequences that we see in affected individuals.

On the right, our approach is to use a type of potential medicine called an antisense oligonucleotide, or ASO. We have named our ASO that we’re taking into clinical trials CMP-002, and the goal of this ASO is to actually bind to a regulatory RNA element that helps control the amount of expression of the protein from the gene and to instruct it to make more protein.

And the way we do this is there are activators and repressors associated with any of these genes. We have identified a repressor. This is like the brakes for the gene.

Yuri Maricich
[00:08:20] And when our ASO binds to the brake, it actually has the brake come off or disengage, and we get increased SYNGAP protein. And so essentially, what we are aiming to do is have the healthy copy of SYNGAP1 make more protein. So it is essentially doing the extra work for the mutated copy.

And this is just another schematic that shows how this works and our ASO. ASO stands for antisense oligonucleotide. ASOs are very small genetic sequences that can be engineered to target the specific sequence. So it is specific, the sequence of our ASO is specific for this particularly regRNA element associated with SYNGAP, and the approach of using ASOs is actually an area that there has been experience. We’ll talk more about those briefly.

Yuri Maricich
[00:09:27] The other thing I’ll just point out is that the chemistry of our ASO is similar to chemistry of other approved ASOs.

For sake of time, and because this data has presented before, I’m not going to review it all in detail, but I am going to summarize it because it is important, I think, as a background as to why now is an appropriate time to start a clinical trial.

So what at CAMP4 has been done is we have found the ability by using CMP-002, this ASO, to actually increase SYNGAP1 mRNA levels that were derived from an affected individual of SYNGAP1 patient. And with—

Yuri Maricich
[00:10:24] treatment of the ASO, CMP-002, to actually increase SYNGAP1 mRNA levels back up to and actually a little bit above a healthy family control.

We then went into a humanized SYNGAP1 mouse model. This was actually supported by, this mouse model development was supported by the SYNGAP1 community. And what we found is that when you have a control, we were actually able to approach back up to that level of SYNGAP protein when we’re treated with a single dose of our ASO.

And then those mice were asked to do a number of assessments that would analyze or evaluate, I should say, learning and memory, motor function, hyperactivity, as well as seizures. And what we found was improvement across all those areas. So this was…

Yuri Maricich
[00:11:29] strongly supportive and frankly exciting. And so based on this, we also did a non-human primate or monkey study.

The advantage of this study is we were delivering the ASO exactly as we would be in a clinical trial and eventually in potential treatment the way it’s delivered in as a medicine in the clinic. And so that’s intrathecally. And we’ll talk more about that in a moment.

This experiment had two purposes. The first was to look at the concentration of the ASO in the important regions of the brain. So you can see this slide here to the left shows the different regions of these monkeys, the frontal cortex, temporal cortex, bridal, and so on.

Yuri Maricich
[00:12:22] And we saw that with increasing dose levels, we saw increased ASO concentration. So that told us we could get the ASO to the important regions of the brain and that there was a dose-relevant tissue concentration.

And then here to the right is looking at SYNGAP protein levels in similar areas. And so here is the frontal cortex where increasing dose levels resulted in increased protein levels. And similarly for the hippocampus.

Importantly, we monitor for safety throughout these and many other animal studies that were performed and were found to be well tolerated. We saw that there was good distribution in the relevant brain regions and SYNGAP protein increased throughout.

Yuri Maricich
[00:13:16] So how are ASOs delivered in order to get to the relevant regions of the brain? This is done through intrathecal or lumbar puncture. This is, in fact, a very common and routine medical procedure that’s done for many different reasons around the world. Leading medical centers do this commonly.

And in fact, ASOs such as nusinersen for spinal muscular atrophy have now been administered to over 15,000 individuals. The way this works is that the individual is sedated, they are laying on their side, and then the team accesses via lumbar puncture the space, the intrathecal space where the cerebrospinal fluid is. This is the fluid that bathes the brain. And by administering the ASO there, it reaches the target cells.

Yuri Maricich
[00:14:19] And also because of that, we don’t have to give doses in the blood that then automatically reaches all the other organs. And because of this, this is a way to get around the blood-brain barrier, which some of you may be familiar with, is a protective mechanism that limits the ability for medicines that are given in IV or given by mouth to get to the brain easily.

So what type of experience has been had with ASOs? There are now three approved intrathecal ASOs. And these medicines have now been utilized by many individuals around the globe. And as I mentioned, one of the first, nusinersen, has now been given to over 15,000 individuals. There are also multiple other intrathecal ASOs in development.

Yuri Maricich
[00:15:20] And some of you may be familiar with these for diseases similar to SYNGAP, such as Dravet syndrome, Angelman, and many others. And so these programs continue to add to the safety experience of ASOs.

No medicine is perfectly safe. There’s always a risk-benefit for every type of medicine. ASOs now have a long history of safety data. There are events that are seen with ASOs, and those include headache, vomiting, fatigue, pain, and fever. Many of these can also be just related to the lumbar puncture.

And while less common, occasionally you can have infection and an increase in the CSF protein, and very rarely there have been described what’s called radiculopathy, where you essentially get swelling.

Yuri Maricich
[00:16:25] Inflammation at the site, and that can occasionally have consequences where someone may, for example, not be able to walk for a period of time. Again, that’s rare, but has been observed. And the most common lumbar puncture-related events can include headache, nausea, and lower back soreness.

All right, with that, we’re going to switch to now talking about the plan to send Phase 1-2 clinical trial. Before I talk about the study, I think it’s important to say a couple of framing components about this.

Yuri Maricich
[00:17:06] Clinical trial participation is a really important decision, and I think it’s very important as we prepare to initiate this first study that individuals who might be interested do not feel required or compelled or pressured, and it is a whole family decision.

This is where individuals who might be thinking about participating are having to weigh the potential for risk and with an unknown benefit, because this is the first time that we have a clinical trial of this potential treatment that is being delivered to humans.

Yuri Maricich
[00:17:49] The other thing I think important to keep in mind is that different trials that occur at different stages, so some of you may be familiar with Phase 1, which is the first in human, Phase 2, which is typically later stage where more individuals have been treated, and then Phase 3, which are typically the last stage before taking that data to regulators.

All of these trials are different. They have different purposes. They have different levels of requirements or burden to participate. And they also have different levels of risk. And different people think about that differently. So while if someone is potentially interested, they may or may not be interested in one stage of trial, but they may be more interested in another.

Yuri Maricich
[00:18:37] And then there’s the right to withdraw at any time. And this is important. This is built into protections for all human subjects, is that any individual who decides to participate in a clinical trial—

Yuri Maricich
[00:18:53] has the right to withdraw at any time, but it is important that that decision not be made lightly because when someone participates and then decides to withdraw, that impacts the whole community because they’re using spot and then they decide not to and now that data is missing if they don’t complete the trial, and oftentimes that can impact timelines as well as impact finding another person to take that spot.

So it is just important to highlight that both individuals have the right to withdraw, but they also, their participation is a community-impacting event. And then for disease-modifying trials in genetic diseases like SYNGAP1, there are some special circumstances that are relevant here.

Yuri Maricich
[00:19:43] That are different from, say, other types of clinical trials where it might be a symptom-targeted medicine. So genetic diseases and targeted therapies like ASOs or gene therapies are different than, say, anti-seizure or behavior-only treatments and trials.

Studies that have specific goals within a trial are focused on achieving in the population who participates sameness across the population, or we use sometimes the term homogeneity. The purpose of that is to make sure that everyone is as similar as possible because that enables measurement and comparison of changes over time.

And so what that means sometimes is you may have a clinical trial that is focused on one group of individuals that may not represent everyone with a disease, but you are—

Yuri Maricich
[00:20:45] putting people in that group to maximize the sameness or homogeneity. And so this is common, in fact, in the development of most medicines and in most clinical trial programs, and particularly in disease-modifying trials in genetic diseases.

And so I think it’s important to keep in mind that just because one’s family member might not qualify for one trial does not mean that they wouldn’t qualify for future trials. And if you look at both the approved ASOs that I referenced earlier, as well as ASO clinical trials that are currently occurring, you’ll see that many of these programs have multiple trials focused on different groups to maximize sameness. So, for example, age.

Yuri Maricich
[00:21:36] Age is very important because we know that children with SYNGAP might act differently in some ways or have different attributes than adults with SYNGAP1, and so we would want to have those individuals be similar.

Another factor is, for example, the presence or absence of seizures. We know that some individuals with SYNGAP1 have many seizures and others may not have any seizures or those seizures are now controlled with medication. And so that’s a difference.

We also know that there are different genotypes. Those genotypes can depending on what the location of the mutation is or the type of the mutation. And so because of that, those individuals may differ in their attributes and manifestations of the disease.

Yuri Maricich
[00:22:24] And so I think it’s just an important reminder that just because individuals may not match the eligibility criteria of one clinical trial or the first clinical trial does not mean that there might not be future opportunity to participate in other clinical trials that are attempted to match that sameness or homogeneity.

Let’s talk about the goals of the ASCEND clinical trial. So ASCEND is the name of the clinical trial that we’ll be launching, and we have three primary goals. The first is to evaluate safety and tolerability. The second is to select an optimal biological dose for future studies. And the third is to collect early signal data to support subsequent development.

So the ASCEND is a Phase 1-2.

Yuri Maricich
[00:23:27] That means while there’s some clinical trials that are just one and other clinical trials that are Phase 2, we’re combining these, which is not uncommon in rare diseases.

It’s going to be a randomized, double-blind, controlled, in what is called multiple ascending dose study. And multiple ascending dose means that we’ll increase dose levels in a new group as the study goes on. We do think it’s important to have a control, and I’ll say more about that as we go on.

Yuri Maricich
[00:23:59] Part of the reason we think this is important is we all need to have confidence in the results, and we know that some of the assessments, for example, in this trial are rated scales by parents as well as the investigators and clinical team, and it’s important that we minimize bias.

And so if everyone knows that someone’s on the potential treatment versus the control, then that may influence how people respond. So the way we try and minimize or reduce that bias to some degree is through randomization and control.

So three to one means that for every three individuals who get randomized to receive the ASO CMP-002 via intrathecal administration, the one individual would be randomized to the control condition, which is the sham pinprick.

Yuri Maricich
[00:24:53] And the sham pinprick is where they go through all the same aspects of, they would come into the procedure room. They would be sedated. But then rather than actually having a lumbar puncture that would be completed accessing the cerebrospinal fluid space, they would instead have a scratch and then a bandage put over it. And they would then recover from the anesthesia.

So that team that would do that would be different from the investigator team. So the investigator team would be blinded similar to the family.

And then at the end of that would be an open-label extension. This is where—

Yuri Maricich
[00:25:40] upon completion of the trial, if it is deemed to continue to be safe to study, and if we see some signs that there might be a response, then we would move into an open-label extension and all individuals who are eligible from this Phase 1-2 trial would then be able to receive the ASO CMP-002, regardless of which group they were put into in this trial.

So if they got sham pinprick, they would still get the ASO CMP-002, or the study drug, as we call it, in the open-label extension. And also important to highlight everyone in the open-label extension would get the dose we selected as the appropriate dose to carry forward.

Yuri Maricich
[00:26:31] And that’s really important because that is a key goal of this trial that I mentioned earlier, is to select the dose that we think is going to be the most appropriate dose.

In terms of the size of the study, each cohort, and this will be shown on a schematic shortly, will have a minimum of eight participants. It can include more, but there has to at least be eight participants to help with evaluating for safety, and participants must be two years of age or older. And they must be under 18 at the time of randomization. And they must have a genetically confirmed diagnosis of SYNGAP1-related disorder.

Yuri Maricich
[00:27:14] Because we talked earlier about homogeneity or maximizing sameness, at this stage, individuals for the ASCEND Phase 1-2 must also have daily seizures, impaired sleep, and an inability to speak in phrases.

There may be time in the future where there are different eligibility criteria that expand from that or different trials that would expand from that. But for now, for maximizing homogeneity and sameness, these are requirements to participate in the trial.

For study periods, there’s going to be three main study periods, and I’ll show this in a moment in a graphical. There’s a screening and baseline period, a study treatment period with three doses, and a post-treatment follow-up period.

Yuri Maricich
[00:28:04] For an individual and their family, the approximate time of participation in just the Phase 1-2, not the open label, is 10 months per participant.

So what are some of the key eligibility criteria? This is a summary. There are additional ones, but these are the key ones. So in order to be eligible to participate, as I mentioned, ages 2 to under age 18, male or female. Individuals must have genetically confirmed SRD or SYNGAP1-related disorder.

We are starting, as shared earlier, to maximize homogeneity for the first genotype would be in individuals with protein-truncating mutations in SYNGAP1 exons 5 through 19. Again, over time, there may be trials or different pathways for individuals with different types of genotype.

Yuri Maricich
[00:29:06] In terms of haploinsufficiency phenotype, everyone who would be eligible to participate must have an intellectual disability, inability to speak in full phrases, and a sleep disturbance.

For those with refractory epilepsy, they must have daily seizures despite already being on an ongoing anti-seizure medication and have previously tried at least two anti-seizure medicines in the past. Individuals stay on their stable anti-seizure medication, so they do not discontinue it, but it needs to be stable, which means no changes before they were to start in the trial.

Those that would be excluded for this current trial would be those SYNGAP1 variants that are not truncating. So missense or microdeletions or individuals with mutations in exons one through four or of uncertain significance.

Yuri Maricich
[00:30:09] If individuals have another CNS disease unrelated to SYNGAP1, that would disqualify them, as well as if they were not saved for intrathecal dosing or had other significant lab abnormalities.

One of the things I do want to just highlight or double-click on here is that non-motor seizures are common in SYNGAP1. We know that roughly 85% of individuals with SYNGAP1 have seizures, potentially some individuals experiencing upwards of 10 per day.

And the most common SYNGAP1 seizures are non-motor. So these can include seizure types such as absence, which are brief staring spells. It can include eyelid myoclonia, which is the eyelid fluttering with a brief loss of awareness. Those are called eyelid myoclonia with absences.

Yuri Maricich
[00:31:01] You can have myoclonic jerks, which is the sudden muscle jerk. You can have atonic, which is a loss of tone, such as dropping a head or completely falling to the floor. And you can have a myoclonic jerk followed by a drop.

All of these are different types of seizures, and we are not pre-specifying a particular type. It is just across these types. So it is important that that kept in mind.

Yuri Maricich
[00:31:30] All seizure types can be captured and collected via, we’ll be having a seizure diary throughout the clinical trial where families and caregivers track both the seizures that an individual has if they’re in the trial, the number of them, as well as if they do not have any seizures on a given day, that is also very important to record.

There will be a new scale called SERIUS, which is being developed, and this is to evaluate the impact of seizures on someone’s daily life. And then we will be evaluating, uh, EEG. Um, we’ll speak about non-seizure endpoints momentarily.

But this is a schema which shows basically my description of the trial earlier, but shows it in a graphical form.

Yuri Maricich
[00:32:28] So you can see if an individual were to participate, they would potentially start in the baseline period. They go with screening. Screening is done with the site. So the site and the family are the ones that communicate, and ultimately it is up to the investigator to determine whether someone is eligible or not, and do they meet that criteria from screening.

Then if it is determined that they are eligible, then they start this assessment period of the baseline. This is very important because it sets the stage for what is the starting point for these individuals.

Yuri Maricich
[00:33:09] This is four weeks and would include a visit, followed by continuing to track things remotely at home, such as the seizure diary and other assessments, looking at sleep and other endpoints that we’ll talk about shortly.

And then at the end of this period, there is what’s called a confirmation of eligibility. That is where it is all the data from the baseline period is reviewed and confirmed. Does the individual continue to meet all the eligibility criteria in the trial?

If they do, then the individual is then randomized. And so there’s the first cohort. This is the first dose level. And there’s randomization. And then individuals would receive three doses over three months.

And then at the end of the treatment period—

Yuri Maricich
[00:34:02] there would be a follow-up period, and that would be multiple time points of assessments over six months.

Upon individuals in a minimum of eight participants in the treatment period receiving two doses, the safety review committee meets. They review all the available safety data, and if they deem it is safe to proceed, then the second cohort at a higher dose initiates and these are all new participants who then come in to this additional second cohort.

These are individuals who would go through the similar process of screening assessment. So if an individual is in the MAD Cohort 1, they stay in the MAD Cohort 1, and it is only new individuals who would start a MAD Cohort 2. And then it’s the same process.

Yuri Maricich
[00:34:56] If after two doses and eight participants, it is deemed safe to proceed, then a new cohort is open.

Throughout the study, there’ll be a daily seizure diary, review for side effects, medications, and then many other safety and functional assessments. There will also be actigraphy, which is a band to measure sleep at home, in addition to the assessments we’ll do in the hospital.

I want to say a little bit about the importance of a control arm in the clinical trial. So one of the important goals from data from this trial is to gather longitudinal data on individuals who are not treated. And this becomes a benchmark against natural history, as well as for comparison of those who do receive the study drug.

Yuri Maricich
[00:35:48] And so this gives all of us confidence in the data. The other thing is it helps from a safety perspective because we know that there can be safety events that might in fact be due to the disease of SYNGAP itself and not to the study drug.

Well, how do we know or separate out what is due to the study drug versus what is due to having SYNGAP1 unless we have a group of individuals who are during the time of the trial not receiving the ASO. And so that’s another reason is from safety.

And so this data helps us to do what’s called a risk-benefit analysis over time. And then lastly is the isolating the effects and trying to reduce bias.

Yuri Maricich
[00:36:36] It is very natural, it is a natural human inclination for all of us that we hope that individuals who participate in the trial and potentially receive the study drug have benefit.

The challenge is that because of this hope, this anticipation, we oftentimes see what’s called often a placebo response, where we see the individuals, once they start the trial, on the assessments of measuring potential benefit, we see sometimes that there may be a response that is not due to the study drug, that is just due to anticipation of benefit.

And so this is an effort by having a control to reduce that bias. We still see it if you look across other disease-modifying as well as non-disease-modifying clinical—

Yuri Maricich
[00:37:31] trials, it is very common to see so-called placebo effects. And so it’s very important that individuals who do decide to participate in trials try and remove that potential placebo spec because it does make it harder to show a difference between the control and the potential benefit.

At the same time, we want to make sure that anyone who were to decide to and be eligible and participate in the clinical trial, that they would, even if they were assigned to the control at the beginning, they would have an opportunity to receive study drug later.

And so that is the purpose of this open-label extension. And so all patients who would complete—

Yuri Maricich
[00:38:13] the ASCEND trial would be eligible for treatment then in the open-label extension.

So very quickly, as we start to wrap up, what are some of the other ways that we’re going to be measuring potential impact or response to the medicine? Or potential medicine, I should say.

So the first is we’re using a number of validated scales that look across behavior, development, communication, and motor function. The scales listed here to the left have been used in other trials of potential disease-modifying treatments, and also are being used in natural history studies of individuals with SYNGAP1.

And so that’s very important because we know that these scales can potentially help detect a difference and furthermore are validated.

Yuri Maricich
[00:39:09] And so those include the Bayley-4, which looks across communication, motor, behavior, development, Vineland, the ABC2, which is looking at communication and behavior, the ORCA, which is looking at communication, and the gross motor function measure, which is looking at motor.

And then we will be looking at seizure and sleep. This will be utilizing gold standard methods because this is the first time we are ever doing a potential disease-modifying therapy in SYNGAP1, and as I shared, the types of seizures are in some cases subtle and not easy to count.

And so one of the ways we help make sure that we are catching any potential seizures as well as looking at the waveform that individuals have in SYNGAP1 is through video EEG.

Yuri Maricich
[00:40:06] One of the benefits is we can look at both seizure and sleep with EEG. So video EEG will help us look at both of those. And then we’ll also have the seizure diary and the SERIUS scale for sleep.

We’ll be looking at sleep in three ways. There’ll be the video EEG in the clinic. There’ll be the children helps sleep habits questionnaire and actigraphy.

And then over here in the right, this box highlights a number of different parameters that we’ll also be looking at in the EEG.

So it would be very natural to be asking, well, what is this participation like in terms of the number of visits? And I think it’s important to highlight that. The clinical trials are a lot of work.

Yuri Maricich
[00:40:54] They’re a lot of work for everyone. They’re a lot of work for the family and the infected individual and their whole community supporting them. It’s a lot of work for the investigators, and there’s a lot of work for those of us designing the trial and helping support its operation.

And so you can see here each of these chevrons or triangles are in fact visits or assessments throughout the visit. And so you can see here that there would be the screening visit and then you would have the baseline visit. And then you would have a visit one under which dose one would occur. So this would be a single visit with a bunch of assessments.

Yuri Maricich
[00:41:40] There would then be a safety assessment at the end. This would be repeated with each dose. And then at follow-up periods over six months, there would be multiple assessments.

So participating in this trial is a lot of work. And so I think it’s important to keep in mind for individuals who may be interested and want to talk to sites when they’re open to be aware of the involvement.

It is important to note that sponsors like CAMP4 do support through funding the costs of participation. And so it is important, I think, in all clinical trials to not let financial resources prevent individuals who may want to participate.

Yuri Maricich
[00:42:29] And so that is something that is offered as part of this trial when it gets going. Throughout the study, you can also see there’ll be the daily seizure and sleep assessments that are done at home and other assessments.

So the ASCEND Phase 1-2 clinical trial will be conducted around the globe. Initially, we are anticipating 11 or more sites. This will be across nine countries. We have five regulatory regions planned. Those are the regions that are represented by a regulatory jurisdiction.

We currently have four sites that are in regions that we’ve received regulatory approval or clearance to proceed. That is in Argentina, that’s in Australia, and that is in the United Kingdom.

Yuri Maricich
[00:43:23] And then we currently have our clinical trial application that is under review with the EU, and there are anticipated seven sites that would be part of that. And then future potential expansion as once we talk with FDA.

As of today, there have been no sites that have been activated and are not yet recruiting.

So in summary, as I’ve shared, we’re really pioneering the SYNGAP1 development with the first potential disease-modifying treatment. One of the things that we have as a huge benefit is that there’s… of significant natural history data that’s helped guide the development of this.

I’ve been so grateful for all the engagement with you all as part of the patient community and the leading experts.

Yuri Maricich
[00:44:24] And many of these are individuals that you’ve heard speak before are part of our trials. So we’ve really designed this trial based on your feedback and the feedback from the experts as well as the regulators to help us conduct the best trial that gives us all confidence in the future potential outcomes while also maximizing safety.

I think it’s really important to consider that early clinical trials, particularly the first type in a disease like this, are so-called signal-seeking. And that means that we are not focused on any single endpoint, that we’re measuring all domains of disease using validated measures.

And based on the data, that will help guide how to think about subsequent development and what are areas where we see impact.

Yuri Maricich
[00:45:14] Our goal is to have the first participant dose by the year end. And also our goal is to have the top-line readout. So that’s the initial top-line results in the first half of 2028.

So again, really just want to thank you all for all your generosity in sharing information with us, providing feedback on this study and the protocol, and for really helping support all the research that’s allowed all of us to get to this point in time.

So with that, I’ll pause. We’ll have some time for some earlier sent questions.

Virginie McNamar
[00:46:04] Thank you so much, Yuri. This was a great presentation. I really appreciate you spending the time to explain everything to the community.

I’m sure we’ll be flooded with a lot more questions. We received a lot of questions with the registration for this webinar, which shows how excited and engaged our community is. But we selected a few questions that were the most commonly asked.

And as you know, and Yuri mentioned it at the top of the webinar, CAMP4 is a publicly traded company, so they can’t just answer all of the questions right this minute. But they will answer questions as they are able to do. And this is not the only webinar we will host. There will be many more to come.

Virginie McNamar
[00:46:45] But for today, we have several questions that were commonly asked by the community.

The first one, Yuri, is has enrollment started for this ASCEND trial?

Yuri Maricich
[00:46:57] Yes. So the answer is not yet. Um, and I think what’s important to keep in mind is that as enrollment does start that, one, there will be communication from sites.

So I think one of the first thing is no one should worry is somehow this, the study going to start enrolling and I’m not going to hear about it. But it’s important to know that the study may start enrolling in different regions at different times.

And so that’s the key thing, which is you may not hear, if you haven’t heard about the region that you are in enrolling, then that means it’s probably not started.

Yuri Maricich
[00:47:35] And that once that region has been not just had the regulatory body approved to initiate, but the site has to be fully active and ready to field those questions.

So at the appropriate time for each region, there’ll be local communication that’ll be shared.

Virginie McNamar
[00:47:56] All right. Well, thank you for that.

So in the same kind of theme, so if families are interested in participating and enrollment has started, who do they reach out to and how do they contact, who do they reach out to to get enrolled?

Yuri Maricich
[00:48:17] Exactly. So the main interaction is with the site. And so it is the local investigators at those sites.

There will, over time, as those sites get active, there’ll be areas where those lists will be shared. There will also be information at government-hosted sites like ClinicalTrials.gov and also in the EU.

But then also… CAMP4 will plan at the appropriate time to put up a website that would provide additional details, and it would also provide an outlet where people are still unsure about what sites might be open. They can actually send in their interest and ask for information about what might be the best site for them to reach out to.

Virginie McNamar
[00:49:12] Okay, great. All right, talking about sites, you said right now, uh, three regions are, have regulatory approval, uh, the UK, Argentina, and Australia, which is really exciting, and you’re working on the EU. Um, do you have any timeline for approval in the EU right now? Or?

Yuri Maricich
[00:49:33] I wish I could provide a timeline. I wish it already had passed and that they would have cleared. But the review is ongoing. And as soon as we have news from that, that’ll definitely be shared.

I think it’s important to highlight that, and hopefully this was clear from the presentation, that different regions may have different number of sites. And so the name of those sites, the investigators, and that information will be shared as those sites come online.

But there is the intent for multiple sites. Right now we have seven that would be part of EU.

Virginie McNamar
[00:50:18] All right, now the U.S. What is the status in the U.S.? Have you interacted with the FDA? And when do you expect to have an IND filed?

Yuri Maricich
[00:50:30] Yes. So we’re not able to provide guidance as to when an IND would be filed, but we very much are intending to engage with FDA.

Different regulatory regions require an additional amount of information or different amounts of information that are required as part of that regulatory filing, and the U.S. FDA requests some additional type data that the other regions that we talked about don’t. And so that results in them being a little bit later.

So once we have that data, we’ll be engaging with them and then at the appropriate point filing our IND.

And maybe I’ll just say, well, I can’t give you specific timelines. We want to do, we want to submit the IND and also get sites in the U.S. as soon as possible. So that’s important.

And I might just add as a point, we continue to also meet with investigators and talk to sites outside of the regulatory regions that I’ve talked about. And while I can’t say specifically when those regions that we would talk about. We are constantly thinking about what are going to be the next steps, either as part of this trial or potential future trials.

And so that’s something that’s very important for us as well, because we recognize there are people with SYNGAP all over the globe.

Virginie McNamar
[00:52:06] Another question I was asked quite a bit that came through was, what is the earliest you expect to know if CMP-002 is working?

Yuri Maricich
[00:52:14] So we are aiming, if all goes to plan in terms of the timeline, and we… meet our goals of what we call recruitment. So getting enough people to fill in all the spots in the trial.

Our goal is to have what we’re calling top-line data in the first half of 2028. So this would be, first, I think importantly, do we continue to see that this is something that’s safe. Two, we need to determine what is the right dose. And this is a really important question, actually. So sometimes it kind of gets second-tier attention, but it’s a critical decision and question.

And then third is, is there some signs that this is working or is there a signal?

Yuri Maricich
[00:53:11] And so we do not want to prematurely determine what those types of signals are. So that’s why, as I shared, we’re measuring everything that we think is relevant.

Also, what is being those measures being used in the natural history so that then we can determine which are areas that we think are the best to chart a path for the future.

Virginie McNamar
[00:53:40] Final question. And I knew you addressed it as you were going over the eligibility criteria, but I was getting text and I’m still getting text about it. So I think it might be good to address that again.

What is your plan to address population that don’t fit the current eligibility criteria? So different genotype, phenotype, age group, etc.

Yuri Maricich
[00:53:59] Yeah. So I’m glad that you re-asked this question, Virginie, and I think I’ve shared with, like, the whole community. It is, I would say personally for me, very hard to have to say today that there’s some people who may qualify for the trial and there’s some people who are not.

I wish I could say that everyone could qualify for the trial all at once, but that would not be a wise decision because what that could result in is a lot of different people starting in different places.

So we need to very deliberately and carefully put people into groups for trials or studies by their sameness, or the term we use is homogeneity.

Yuri Maricich
[00:54:41] And so while I can’t give specific timelines yet, we are actively working on thinking about once we know the right dose, and once we have sufficient data from this trial to be able to determine it’s safe and the things that we would need to, to start other trials or to have other options, like another thing that some of you may be familiar with is N-of-1 for really small groups of people with a different type of genotype, would be that we would think about those, instituting those.

And so again, we’ll share information as that goes on. And one of the things that’s key to help guide actually how we do that is the natural history.

Yuri Maricich
[00:55:25] So, for example, adults, you know, right now there’s data that could suggest that individuals above 18 and potentially throughout life might benefit based on some of the animal data.

And so we are actively thinking about what would that look like at the right time. And so this is where the natural history is really important. And the same is true of every other genotype, etc.

Virginie McNamar
[00:55:51] I think that’s a, that’s a, we covered all the question, and that’s a really good closing point when you mentioning natural histories and then the way you’ve used our natural history study data.

I think we have a lot of families in here that are part of the ProMMiS Natural History Study or are participating in their local similar natural histories. I think if you are not participating right now, and I’m just going to do the CURE SYNGAP1 plug here, but if you’re not participating in the ProMMiS Natural History Study, please consider doing so.

It’s really important. You’ve seen today how the data is being used. And so reach out to us. It’s promiss@curesyngap1 to sign up.

Virginie McNamar
[00:56:39] We have travel stipend to help you get to the different sites. We have a site at Colorado, at Children’s Hospital of Philadelphia, and at Stanford. So that is really important to get information and the data to support the clinical trials.

Yuri Maricich
[00:56:57] Thank you so much, Virginie, for having me. And thank you to everyone who shared so much and also for participating in natural history and supported the work that’s allowed us as a community collectively to get to where we are today.

Virginie McNamar
[00:57:13] We appreciate you sharing all that with our community. Thank you so much.

Yuri Maricich
[00:57:17] All right. Take care.

Virginie McNamar
[00:57:19] Bye.