Greetings, everyone, and welcome to our first-ever Investor Day for Quince Therapeutics. My name is Dirk Thye, and I'll be walking you through the beginning elements of our presentation. We've got a full agenda for you today. I'm going to start by giving you an overview of Quince Therapeutics, our technology, our development plans, and our key investment highlights.
And then I'm going to hand it over to a series of departmental and technical experts that are going to walk you through the elements of the technology itself. I'll come back and talk about previous clinical studies and the development plan. We'll hand it over to Caralee Schaefer to explain to you some very interesting and compelling new data on the mechanism of action of encapsulated dexamethasone.
And then we'll talk about some elements of the regulatory plan and go into some details on our commercial planning for post-approval activities. These are some of the people you'll be hearing from today. There are some additional team members on this slide. And the point here is to demonstrate that we've got a very good team of people with a lot of expertise and experience in their particular functional area.
And as I said, some of the key speakers are listed on this slide as well. But let me start by going over the overview of the company and some of the key highlights. This slide outlines my disclosures. And our fundamental technology here is a machine that performs a process that we call AIDE, Autologous Intracellular Drug Encapsulation.
It's a method by which you can take a patient's own red blood cells, so autologous blood, and you can treat them so that they can encapsulate a molecule, a small molecule, a large molecule, even a protein, into their own red blood cells and then reinfuse those drug-loaded red cells back into the patient. Some of the highlights of our current status are that we are in phase III.
We have completed enrollment in our pivotal phase III trial. That trial is in the lead indication of ataxia-telangiectasia. You'll hear a lot more about that disease and that study in the following slides. There are no currently approved therapies for this terrible pediatric disease, and it's a large and important commercial opportunity. The current phase III trial is called NEAT, N-E-A-T. As I mentioned, we've completed enrollment.
We enrolled 105 patients, 83 in the primary analysis population. And I'll give you details about the study and its operations later in the presentation. The key here, though, is that if we are successful with encapsulated dexamethasone and ataxia-telangiectasia, we have a large list of other rare diseases we can pursue with this same drug. And next on the list would be Duchenne Muscular Dystrophy, which would be a really terrific disease target for this particular therapy.
And then we have a prioritized list of rare diseases we could pursue thereafter. For the commercial phase, we're already planning ahead, even though we don't have our phase III results yet. But a key element of that will be our recently announced partnership with a company called Option Care Health, which is an outpatient infusion network around the United States with about 170 different locations in the U.S.
You'll hear from Charles Ryan more about that particular partnership. Importantly, we were successful in raising some money earlier this year to extend our runway, and that extends our runway for several months after we get our top-line results from our pivotal trial. That puts us in a good position to get results and thereafter execute additional financing and/or partnerships of some sort following data in the first quarter of 2026.
Let's go back to the technology. I mentioned it's a machine. This is a tabletop machine. It can sit on a cart. It can sit at the patient's bedside. It can be put in the lab. It is a mobile machine. It's about the size of an old-fashioned desktop computer. You see a picture of it here on the top right of this slide.
Over the years, it has been adapted and amended to be a fully automated system now. It's a 17-step process that uses that touch screen you see on the computer, on the screen on the front of the machine. And essentially, what it does is you take a small volume of the patient's blood. You take 50 mL of the patient's blood. That's about a double espresso worth of blood. And it's in a bag.
You hook up the bag to the machine, and then you just press start on the touch screen. Over the next 90 minutes, what that machine does is it uses a series of hypotonic solutions to slowly swell the cells. They thereby become porous, and then you incubate them with the drug cargo. And then a hypertonic solution and excipients will then be used to shrink the cells back down.
The drug target gets trapped inside of the red blood cell. Our lead program is Dexamethasone Sodium Phosphate. Dexamethasone Sodium Phosphate is a previously approved pro-drug of dexamethasone. It has a phosphate group attached to it. It's therefore ionic. When it gets trapped inside of the cell, it cannot escape because it's a charged molecule. It can't diffuse across the lipid bilayer.
Then what happens over time is intracellular phosphatases will cleave that phosphate group. It renders dexamethasone, the parent drug, nonpolar. Then that nonpolar dexamethasone can thereby diffuse through the lipid bilayer out of the red blood cell as the red blood cells are circulating throughout the body. The key to this is to be able to facilitate the safe and chronic use of dexamethasone. Conventional dexamethasone administration looks like this. This is a graph of daily six-milligram dexamethasone doses.
You can see because of the short half-life of dexamethasone, you get peaks and troughs. This is 30 doses over 30 days. Regardless of the approved formulation of dexamethasone, whether it's subcutaneous or pegylated or liposomal, you still have to give it frequently enough that you're going to have these peaks and troughs many times over the course of a month.
When you do that, even at the lowest effective doses, what happens is you exceed these plasma drug concentration thresholds that lead to toxicity. You see three dotted lines here, horizontal dotted lines across the graph representing plasma drug concentrations that, if exceeded over time, will lead to toxicity. You see one for glucose sensitivity. You see one for immunosuppression. The most sensitive one is for adrenal suppression.
Adrenal suppression is, of course, the most important and the most damaging long-term toxic effect of corticosteroids, and it's associated with all kinds of adverse events that you can see listed at the top of the slide. You get growth delay, delay in puberty. You get weight gain and Cushingoid.
It can lead to diabetes and behavioral issues, hypertension, osteoporosis, many, many problems, so you really can't take corticosteroids for more than a couple of weeks before you start running into these problems related to adrenal suppression, and therefore, despite the fact that corticosteroids would be just a wonderful therapeutic for lots of different diseases where chronic inflammation is a major component of the pathophysiology, you can't take them because they're just simply too toxic, and I had mentioned DMD, Duchenne Muscular Dystrophy, previously.
Almost every child with DMD is on chronic corticosteroids, and it's a major, major problem in their life. So our technology is designed to fix that. And we do that by allowing the chronic administration of corticosteroids while avoiding these toxic drug-level thresholds. And let me explain to you how that works. First of all, in order for corticosteroids to be efficacious, you need a couple of key pharmacodynamic elements to be satisfied.
One is that you need an initial Cmax that is high enough to give you receptor saturation or near saturation in important tissue beds. Then what you need is receptor occupation over time, persistent receptor occupation over time. So you need long-term drug exposure. So you get that with conventional steroids, as I just showed you in that last graph, by giving them frequently.
But on the next slide, what you'll see, the way we achieve that is to have monthly dosing of dexamethasone that is slowly released from the red blood cell as the red blood cells are traversing your body. Initially, what happens, because there's a high concentration trapped within the red blood cell, is you get a peak of concentration. And it's important to have a peak concentration of about 100 nanograms per mL or more.
You get that with the encapsulated version. But then instead of it falling off quickly and having to be redosed, you get this long, slow release of corticosteroid from the RBC over time. And it pretty quickly gets below these plasma drug concentration thresholds that you saw on the previous slide and that are redrawn here at the same concentrations. Over the first couple of days, you're below the glucose sensitivity and immunosuppression thresholds.
And then after about 7 to 10 days, you're below the adrenal suppression threshold. And one question you might ask is, well, you're still above that threshold for 10 days a month. Is that enough to generate adrenal suppression? And the answer to that is no. We have a very strong safety database consisting of about 70 patients that had taken the drug monthly for over three years and had no signs of adrenal suppression and no signs of corticosteroid toxicity.
And there are, in fact, three children that have been taking this now monthly for 13 years, back to the original exploratory trial in ataxia-telangiectasia. And those three children have no adrenal suppression and no signs of corticosteroid toxicity after 13 years of administration. So it's pretty phenomenal.
As a drug developer, I would say that's strong evidence that we don't have a safety issue when it comes to chronic dosing of encapsulated dexamethasone given through the red blood cell. So I'm going to tell you more throughout the course of the day about ataxia-telangiectasia, about our phase III study in AT.
But I also want to mention that this really is a platform, a platform that can be used with lots of different diseases where corticosteroids could be really beneficial if they could be given chronically. And again, I think DMD is a good example of the problems that come with the chronic administration of corticosteroids. But this technology has been in development for well over a decade now. The first machine was developed in about 2008.
And there were a variety of investigator-initiated trials starting around 2010 in ulcerative colitis, Crohn's disease, cystic fibrosis, and COPD. And all of those small studies showed very interesting results with signals of efficacy and no safety issues. So we are using Dexamethasone Sodium Phosphate encapsulated into the RBC for rare diseases.
But we will pursue betamethasone encapsulated into the RBC for non-rare diseases, including some of these you see on this slide. So with respect to AT, we'll get those results in the first quarter of 2026. And if that's positive, it really opens the door for us to pursue a variety of other rare disease indications. We'll show you a list of those later in the presentation today. As I mentioned, DMD is the first on that list. And then we will also develop betamethasone for a variety of non-rare diseases. We'll be announcing that program in the near future. I'm going to hand it over to Giovanni to take you through some of the technical aspects of the machine.
My name is Giovanni Mambrini, and I'm Chief Technology Officer at Quince. I'm co-founder of our predecessor company, EryDel, in 2008. I'm pleased to be here today to provide you with insight into our journey to advance our AIDE technology and lead asset eDSP. Over the past two decades, we have made significant strides in advancing this innovative technology.
The journey began in 1998 when an initial patent was filed, and it was the first of numerous patents on AIDE technology. This moment set the foundation for future development. In 2008, the startup EryDel was founded, marking the beginning of a dedicated effort to develop the AIDE technology. Red Cell Loader was CE marked in 2010.
This regulatory approval allowed the technology to be clinically used in Europe for the first time on COPD patients. Since the company obtained IND approval in 2013, we have initiated and completed a lot of studies bringing us closer to our goal: phase I studies on PK and red blood cell survival in circulation on healthy volunteers, phase II study on 80 patients, the ATTeST controlled randomized phase III trial comparing placebo with low-dose and high-dose arms, and the open-label extension study. In 2021, the human factors program was completed.
In the following year, FDA granted special protocol assessment on pivotal phase III NEAT trial. In 2023, Quince Therapeutics acquired EryDel and started the NEAT trial right after. More recently, enrollment completion of our phase III NEAT study was reached in July this year, which set up for top-line results in Q1 2026.
It's a very exciting time for the company as we work to bring this 20-year effort to fruition. Next, we thought it would be helpful to show you how our unique drug-device combination works in the clinical setting. So let me walk you through our eDSP drug encapsulation process so you can see our technology in action and what the patient experiences when they come in once a month for eDSP treatment.
So once you have all supplies you need, just switch on the Red Cell Loader or RCL. The RCL is super smart and fully automated with a user-friendly interface that guides you step by step. You'll see clear text and images on the touchscreen, making it easy to read, visualize, and confirm each action. You'll always know exactly what you're doing and how long the process will take to completion.
Next up, you'll install the EryKit on the RCL. For convenience, the EryKit comes preassembled with all tubing and components. The EryKit is a sterile, all-in-one system designed to handle blood, drugs, and solution in a controlled way, thanks to the red cell loader's automation. The EryKit parts, like lines, bags, and blood separator, are set up for quick and easy installation.
The tubing connects to the reservoir and filter, pneumatic and roller pumps, and a disposable blood separator. The system contains multiple sensors to enable automation and support consistent process outcomes. EryKit is designed as a single-use sterile component that is disposed of after use, thereby avoiding any possibility of cross-contamination as the RCL does not come in contact with blood or solutions. The system runs a self-diagnostic test during setup to test the functionality of all actuators.
Tubing is automatically positioned around the three pumps. The process requires injectable-grade saline to wash red blood cells and resuspend them before infusion. Two specific hypotonic solutions, hypotonic solution one and hypotonic solution two, are connected to the kit. They are intended to temporarily reduce the osmolarity of red cells and cause their permeability, while a hypertonic resuspension solution is used to restore physiological osmolarity after drug encapsulation.
The syringe kit collects 50 mL of blood from the patient. 2 mL of heparin are added through a sterilizing filter. The filter is removed, and the syringe is connected to the IV cannula. 50 mL of patient blood is collected. After attaching the syringe containing 50 mL of blood to the EryKit, you start the procedure via the RCL's user interface. The RCL takes care of the 18 phases of the eDSP process automatically.
The procedure involves preparing Dexamethasone Sodium Phosphate solution, 25 milligrams per milliliter in a syringe. As soon as dexamethasone is injected via the port, it enters by passive diffusion into permeabilized red blood cells. The entire process takes about 90 minutes from start to finish, while the patient waits nearby for the Red Cell Loader to encapsulate dexa into their own red blood cells.
At the end of the encapsulation process, the resulting eDSP is transferred to the collection bag for immediate infusion to the patient. So this is an overview of the process that a patient would experience for the once-a-month administration of eDSP. Finally, a full procedure report is available for download and printing at any time for record-keeping purposes. We have also gathered a remarkable clinical experience behind eDSP.
Over the years, this therapy has been applied across a range of challenging conditions: Crohn's disease, ulcerative colitis, COPD, cystic fibrosis, and mainly ataxia-telangiectasia. To date, that has translated to more than 425 participants who have received at least one dose of eDSP, including more than 248 patients. That truly stands out is the depth of our clinical exposure.
We have administered more than 7,000 infusions to 80 patients alone, and some of them have been treated monthly since 2012. This experience not only demonstrates the reach of eDSP, but also sets the basis for safety and efficacy profile, which we must establish. Finally, it is worth highlighting that our technology is partly supported by rigorous regulatory review to date. In Europe, we have secured the CE mark, ensuring full compliance across new medical device regulation.
Our consumable kit reflects extractables and leachables validation that have been secured in compliance with European and US regulations. We also get asked the question a lot about the stability of the system, which is ensured throughout our proprietary 17-step automated process that you saw in our demonstration video.
The eDSP system was also designed and deeply automated for high-quality processed red blood cells, which resulted in an in vivo lifespan similar to products for transfusion, and for over a decade, we have maintained an active Investigational New Drug, demonstrating our ongoing commitment to the high standards requested by the agency. All this to say that a tremendous amount of effort and oversight has been invested in our technology to date and gives us the confidence in our pathway forward. I hope you find this discussion helpful, and I look forward to answering any questions you might have during the Q&A session.
Hello, everyone. Dirk here again. I'm going to walk you through some of the details of our lead indication, ataxia-telangiectasia. So ataxia-telangiectasia is a tragic and terrible pediatric rare genetic disease. It's an autosomal recessive disease. Typically, one mutated allele is inherited from each parent, and typically, the parents don't know that they carry this allele.
And it's a rare disease that has about 5,000 patients in the United States. It's primarily at a very young age, neurodegenerative, so the children start to lose neurological function around the age of diagnosis, which is typically in the ages of two to four years. And they typically end up in a wheelchair by about the age of 10 to 12.
And then, during the course of their disease and into their teenage years, they develop multiple infections and frequent infections, and then cancer, and a lifespan is typically into the mid-20s. And now we'd like to show you a short video of a patient named Shane and his family, which is a really illuminating and powerful story about the journey of an AT patient and their family and what they go through.
Hey, little buddy.
Look at you.
Shane, I want to tell you that I love you very much and everything I do, I do for you and your sister and your mom. And I'd give anything in the world to take this away, this disease away from you. If I could take it on myself, I would, but I can't. But everything we do is to make things easier for you and, again, hopefully to find a cure or a treatment, something that'll make this burden easier for you to bear.
So Shane's eight years old right now. Most of his life, he's had the issue with muscle control, falling a lot. In the future, though, with the progression of the disease, he will start to lose more control and most likely will be in a wheelchair between ages of nine and twelve. But right now, our focus is on quality of life and him enjoying it as much as he can. We want to do whatever we can to make him have the best life possible.
When Shane was first diagnosed, we found out when our daughter, Omri, was 11 days old, and we got a call from the geneticist. We'd been through months and months and months of different tasks trying to figure out what was going on with Shane.
My husband came in, and he woke me up, and he was like, "They said the geneticist is on the phone." He told us what it was, and we weren't quite sure what ataxia-telangiectasia was at the time. And he told us not to Google it. And after that phone call, we Googled and saw all the different things, and it was awful.
Ataxia-telangiectasia is a terrible neurodegenerative disease that affects movement, eyesight, communication, that you're checking these kids when they get to their early 20s for things that you would look at a normal adult in their 60s for, just because of what it does to their body.
It was a full week of just shock and just not knowing how this was going to.
It was terrible, and you slowly kind of come to grips with it and just sort of changes your perspective on instead of looking five, 10, 20 years down the road. It forces you to live in the now.
When Shane wakes up in the morning, he first will get hooked up for the breathing treatment. We'll start that. I t's a 20-minute session, and then after that, he does take the medication for his balance. After breakfast, he gets finished getting ready for school. Most of the time, his dad will take him and his sister, and they'll walk to school, and a lot of times, Shane will go up on his dad's shoulders, and they'll go together, and then he gets to spend a fun day at school with his friends. He has a lot of fun just learning and being himself.
He needs a lot of help, a lot more help than any other eight-year-old kid needs. Despite needing the help, he's a regular eight-year-old boy. And we want him to have his childhood and be able to have those childhood experiences that any other kid would have. We don't want to let any moments slip by and look back with regret that we didn't take advantage of all the time that we had.
Just trying to make the best out of every moment for the kids. We want to make sure that they're enjoying life. That's the whole point.
Always looking for ways to make things easier for him, try and keep him as independent as he can be for as long as he can.
I love him to death. He's so cute and fun and funky and clever, and he loves mechanics and he loves just life, I think. He's a fun kid.
So for other families facing similar situations, whether it be AT or another challenge that your child might face, I would say that it's not over. You can fight. You can live as fulfilling and rich a life as you can . That's going to mean everything to your kid.
Originally, I felt like I never was going to be able to have a child. And so to be able to have Shane is amazing. And no matter what condition he's in, I'm so grateful that I have him and I have his sister, Omri. My kids mean the world to me. They're everything.
So the typical pathophysiology is that when the child is born, there's nothing evidently wrong. The child seems normal. And typically, parents don't notice anything abnormal until later in development, maybe around the age of two to three years of age.
There is no standard prenatal testing for this, so it's a hard diagnosis to make because it's so rare, and parents start seeking help with the diagnosis around the time they see some abnormal development, and then as the child gets into the ages of four, five, and six, it's clear that they're having problems walking, learning to walk, or persisting with their previously effective walking, and then, as I mentioned previously, their neurological deterioration leads them to end up in a wheelchair around the age of 10 to 12, and then they get infections and cancers throughout their later years in their lifespan in their mid-20s, as I mentioned previously, so there's nothing approved for this disease.
These children get physical and occupational therapy and supportive care consisting of treatment for their infections and their cancers, but there is no disease-modifying therapy ever approved. We are in the process of trying to change that with our NEAT study in AT. But the NEAT study was preceded by a study called the ATTeST study, which has been previously published.
And you may have seen that publication if you're an investor in the company. It was the largest trial of AT ever performed with 175 patients around the world. And it looked at a neurological outcome measure called ICARS, which I'll describe to you in more detail. And that actually is a modification of that ICARS score as mandated by the FDA. And the results were good. I'll walk you through those results. But with respect to the primary endpoint, it's called ICARS.
It's one of these neurological scoring tools that is used by neurologists where you run the patient through a battery of tests, and there's a scoring system associated with each of the tests. It's a little bit like SARA or MFARS or even ADAS-COG for Alzheimer's disease.
You can see here in the left-hand column, the full ICARS score adds up to 100 points. But over the years in the company's communication with the FDA, the FDA changed their focus on which of the elements of the ICARS they wanted most emphasized to reflect the patient, how the patient feels or functions. And so over time, they revised what they wanted to see to a subset of the ICARS of 54 points, which is called the modified ICARS. And that's the primary endpoint that was used in that ATTeST study.
I'll show you some of the results on that study in a moment. And the current primary endpoint for the NEAT study is the endpoint that the FDA has mandated under a special protocol assessment. We have a special protocol assessment in place for the NEAT study. So if that study is positive, it can act as a single pivotal trial for approval.
And the FDA has now dictated that they want us focused primarily on posture and gait to measure how a patient feels or functions. And so that subset of the ICARS scores is 29 points out of the original 100. The good news is when you look back at the ATTeST results and you look at the RMICARS versus the MICARS versus the full ICARS, the RMICARS actually was the most sensitive indicator of change from baseline to month six.
It's not a bad thing that we're using the RMICARS. I think of these three, it is the most sensitive endpoint. Now, the ATTeST study was technically a negative study with a p-value at the end of the study of 0.07. They didn't miss by much, but there's a good reason for that.
That's because they studied children six years of age and above. Here, what you're looking at is a graph of the natural history of neurological function over time in patients with AT. You can see that from the time of diagnosis, about the age of two to four, until they get to be 10 or 12, they have rapid neurological deterioration. I mentioned a couple of times they end up in a wheelchair by the age of 10 or 12. You can see thereafter the neurological deterioration starts to plateau out.
And in the previous ATTeST trial, the enrollment ages were six and above in order to be inclusive and have the broadest label. But the problem in that study was that half of the patients enrolled were above the age of 10, 10 or above. And you can see from this graph that if you're studying neurological deterioration over a relatively short period of time, like six months, you want to study the population that's deteriorating the most rapidly.
So you want to look at those years in the green shaded bar. If you're looking to the right of the green shaded bar, your probability of seeing a change in a six-month period is much, much less. That's obvious from this graph. And that's what they saw in that study. I told you the overall p-value was 0.07. So in the overall population, they're narrowly missed.
In that green shaded bar, it was highly statistically significant at 0.009 for RMICARS, the FDA-mandated endpoint in the NEAT trial. Just to put that into context, that's about a 24% difference versus placebo over a six-month time point. That's a pretty big change over a short period of time. We looked very carefully at these results before we bought the company that performed the study.
We looked at secondary outcome measures and additional outcome measures. We looked at trends. We looked at a variety of different analyses in different subpopulations. They all pointed in the same direction, the direction that suggests success in that younger age group. In addition to the suggestions of efficacy, we carefully looked at safety. There were no major safety concerns from that trial.
There was no adrenal suppression, no steroid toxicity in either the low-dose or the high-dose group from the ATTeST trial. There was a little bit of a dose response in adverse events. The low dose was pretty similar to placebo, actually, with the high dose being slightly higher. The major difference in adverse events between the low dose and high dose were primarily a higher number of infections that were not serious or significant and a higher rate of pruritus.
But to me, that's a positive sign because it demonstrates that there's assay sensitivity with respect to adverse event reporting, so there were no safety concerns from the ATTeST trial with respect to the high dose, and that's the dose we took forward into the NEAT trial, so the NEAT trial is just high dose versus placebo.
And you can get all of the details of that previous ATTeST trial by reading the previously published article in Lancet. We also have another article published in Frontiers in Neurology, which describes the long-term open-label extension safety data that emanated from that trial. So a lot was learned from that trial, and we acquired the company that performed it, and we used their work to build upon.
Instead of enrolling the entire population of six and above, we're focusing it just to that population between six years of age and nine years of age where they're deteriorating rapidly. And I think that gives us the best probability of success because, as described, that's the population that is most sensitive to change over six months. And some bad luck that the previous company had was that they ran that study during COVID.
They ran it in places including places like India and Tunisia that had a lot of logistical and infrastructure problems related to COVID. When that occurred, they had a lot of missing data and a lot of dropouts, which was adverse to their overall outcome. We've been able to avoid that bad luck. That makes our statistical powering and our study operations stronger than in that previous trial.
This is just an outline of the study designed for the NEAT trial. As I mentioned, it's under a Special Protocol Assessment with the FDA. It's being run primarily in the United States and Western Europe, Scandinavia, and one Eastern European country, Poland, with two sites in Poland. We've completed enrollment now with 105 patients and 83 in the primary analysis population of six to nine years of age.
And that gets us at least power of 90% to determine statistical significance. And on the next slide, I'll describe why it might even be higher than 90% power. But it's just high dose versus placebo. It's six months, one dose per month, with then a 30-day safety follow-up thereafter. And after the NEAT trial, primary assessment visit is done, the patients have the opportunity to roll into an open-label extension trial. And so far, every patient in NEAT has elected to do so.
With respect to the strength of the operations and statistics on the NEAT trial compared to ATTeST, this is why I think we have at least 90% power to determine statistical significance. The assumptions that went into the sample size for NEAT came from ATTeST. So the point estimates of response and the confidence intervals around those point estimates came from ATTeST.
Those, of course, those confidence intervals are, of course, affected by the amount of missing data or dropouts because with larger amounts of missing data, you have to use imputation methods that lead to broader confidence intervals. Therefore, if we have fewer discontinuations and less missing data, we will have more narrow confidence intervals. With more narrow confidence intervals, you have increased power to determine statistical significance.
So we use the factors in the right-hand column to determine sample size, but we're ending up with variables that are shown in the left-hand column. We have 6% missing data versus 26% in ATTeST. So that gives us a tremendous advantage and strengthens our statistical power to determine significance in this trial. So I'm feeling very good about how that's rolling out. In addition to the NEAT trial, we have initiated our PED study. It's called the PED study, PED.
It's a study required by the EMA for a Pediatric Investigational Plan. And this study is going to take place in younger children. So instead of taking 50 mL of blood, you take 30 mL of blood. That results in a dose of about 12 milligrams instead of about 17.5 milligrams. And this study is going to
be run in children between the weights of nine kilograms and 15 kilograms. That will equate to an age range of about two years of age to six years of age. So this is a mandatory study required by the EMA. It's primarily a PK and safety study, but we're also using wearable devices. You can't use ICARS or any other neurological assessment physical exam tool in this population because the kids are just too young to follow the instructions. So you can't use what's typically used.
What we are doing is we're using wearable monitors on the wrists and ankles so that we can explore. There are a lot of things you can do with this wearable device data, but we're going to explore what type of endpoint would be best, sensitive, and best to reflect function in this population, so that's exciting data to me. That'll be really informative, and I think if we can help develop such an endpoint, it would be much superior to these typical neurological assessment tools that we currently use. We've initiated our operational planning on the study, and we will be enrolling this study at the beginning, toward the beginning of 2026. We'll see how enrollment goes.
If we finish enrollment quickly, we'll include the data in the NDA, but more likely, it won't be ready in time for the NDA submission so we can supplement our U.S. data thereafter and satisfy our requirements for the EMA by finishing this trial. We sometimes get asked about whether there are advocacy groups in this indication because with other rare disease, advocacy groups play a really important role, certainly with diseases like DMD and cystic fibrosis.
They're incredibly important to the community. AT is much less well-known to the average investor, but there are advocacy groups, and we have a very strong relationship with them. The two largest and strongest advocacy groups are the one in the United States called the A-T Children's Project and the one in the U.K. called the A-T Society.
There are a variety of smaller country-based advocacy groups throughout Europe, but they work in conjunction with the U.K. A-T Society. They do a lot of things together. And so we know people at all of them, but primarily maintain our relationships with everyone through ATCP and the U.K. A-T Society. And they're instrumental in helping us find patients and communicate with the families of patients about the opportunities for being included in our clinical trials.
So just with respect to our chances of success for phase III, I'm extremely confident. I've done a lot of phase IIIs in my time. I think I feel the best. I have the highest probability of success with this particular trial. And I base that on the fact that we saw those ATTeST trial results previously, and we dug into them very carefully. And I'm convinced that they look good.
We took the best elements of that ATTeST study, and they're reproducing it in the right population, and as I mentioned, we have a very high statistical power to determine significance, so I'm feeling very good about the results. I'm eager to see them, and we'll get them in the first quarter of 2026, but I'd like to hand it over to Caralee because we sometimes get questions about, other than evidence from the ATTeST trial and just evidence about the dexamethasone mechanism of action in general, it's not obvious why dexamethasone as an anti-inflammatory would benefit a neurodegenerative disease, so we do have fascinating and compelling data from that previous clinical trial with respect to quantitative RNA sequencing and what that means for the mechanism of action, and Caralee Schaefer, our head of nonclinical development, is going to walk you through those results now.
I'm Caralee Schaefer, and I'm the Vice President of nonclinical development at Quince. I'm excited to share an overview on the mechanism of action of eDSP and the results of RNA sequencing work that we recently completed. But first, before we get into that, I'd like to show you a short video describing the eDSP mechanism of action.
Corticosteroids are relied upon across many medical specialties given their anti-inflammatory, antiproliferative, and immunosuppressive effects. However, chronic use is limited by serious toxicities. Corticosteroids have a short half-life in circulation, necessitating frequent high-dose administration, potentially exacerbating toxicities. Leveraging the benefits of corticosteroids while minimizing toxicities has been a long-standing treatment goal. Human red blood cells, RBCs, are the most abundant cells in the body. Their flexibility and elasticity allow these long-lived cells to navigate narrow capillaries.
RBCs are designed to carry cargo, and membranes can be permeabilized to receive drug payloads and then resealed, making them ideal drug delivery vehicles. Using our autologous intracellular drug encapsulation, or AIDE technology platform, Quince Therapeutics is developing Encapsulated Dexamethasone S odium Phosphate, or eDSP, that consists of a corticosteroid encapsulated within a patient's own RBCs.
The process involves drawing blood from a patient. RBCs are then loaded into a device where they are treated to open pores within the membrane. DSP, which is unable to pass through the intact RBC membrane, is then added and enters the cells through the open pores. The RBC membrane is then closed, capturing the DSP within, forming eDSP. These modified RBCs are transfused back into the patient. Once circulating, intracellular enzymes remove the phosphate group from DSP.
Once the phosphate is removed, dexamethasone is gradually released into the bloodstream with the goal of providing a sustained therapeutic effect. eDSP has the potential to offer advantages over traditional corticosteroid administration. Data has shown that monthly eDSP administration results in sustained release, and plasma dexamethasone concentrations fall below those that trigger toxicities. For indications that require chronic administration of dexamethasone, eDSP has the potential to help make this life-changing therapy a standard of care for rare disease indications.
Before we get into the RNA-seq data, I want to delve a little deeper into the pathogenesis of AT. AT is caused by mutations in the ATM gene. These mutations lead to a deficiency in the ATM protein, which plays a central role in DNA repair, cellular stress response, and immune regulation.
The clinical burden of AT is significant, with these young patients experiencing ataxia, immune deficiency, recurrent infections, and a heightened risk of cancer. Progressive loss of neurons is a hallmark of AT, in particular cerebellar Purkinje neuron. At the cellular level, the absence of functional ATM disrupts the response to DNA double-strand breaks and oxidative stress. This leads to elevated reactive oxygen species and altered redox status, contributing to genomic instability.
Importantly, ATM dysfunction also triggers chronic activation of NF-kappa B and then an increase in pro-inflammatory cytokines and chemokines, leading to a persistent neuroinflammation and immune dysregulation. Overall, ATM deficiency results in DNA damage and genomic instability, oxidative stress, mitochondrial dysfunction, chronic inflammation, and neuroinflammation, all leading to progressive neurodegeneration. Next, I want to walk you through the design of our recent RNA sequencing project.
Utilizing whole blood samples that were available but had never been analyzed before, these are from the prior ATTeST phase III trial, RNA sequencing was performed to investigate the mechanism of action of eDSP and to identify biomarkers that may predict treatment response. ATTeST was the largest clinical trial ever conducted in AT, featuring a three-arm design where patients received monthly doses of either high-dose eDSP, low-dose eDSP, or placebo.
Whole blood samples were collected for RNA sequencing at three key time points in the ATTeST study: at baseline, immediately before eDSP infusion at m onth two, and immediately before eDSP infusion at month six. It's important to point out that the two and six-month time points were collected around 30 days after the last eDSP dose, so these are considered trough samples.
In total, we successfully sequenced RNA from approximately 300 ATTeST blood samples spanning placebo, high-dose, and low-dose eDSP groups. There were 29 placebo-treated, 33 high-dose eDSP-treated, and 35 low-dose eDSP-treated patients, all with baseline, two-month, and six-month whole blood samples that we sequenced. This gives us a robust data set to investigate the mechanism of action of eDSP and identify potential treatment-responsive biomarkers through gene expression changes.
Additionally, we also collected whole blood samples from 10 healthy adult volunteers to use as negative controls. We then compared the transcriptome of all AT baseline samples from ATTeST to those healthy adult controls. This allowed us to investigate the biology of AT and potential disease-specific biomarkers. The next slide describes the RNA sequencing workflow implemented for the ATTeST samples. We completed RNA sequencing on whole blood collected at baseline, month two, and month six, again at trough.
This allowed us to capture stable treatment effects over time. The whole blood was collected in the PAXgene RNA tubes, which are designed to stabilize RNA for sequencing. From there, we performed RNA extraction, achieving high-quality RNA in over 96% of our samples. cDNA libraries were prepared, and the sequencing was performed using the Illumina platform.
The final step was bioinformatics and data analysis, focusing on differential gene expression and pathway-level changes. The result is the most comprehensive RNA-seq data set ever generated from the largest AT clinical trial to date, giving us a very unique window into both the underlying biology of AT and how eDSP impacts disease biology at the molecular level. With high-quality RNA sequencing data in hand, we next asked, what does the transcriptomic landscape of AT actually look like?
This slide presents a comparison between all AT baseline samples in ATTeST and the healthy adult controls, revealing widespread gene dysregulation and offering critical insights into AT disease biology. Comparing the AT patients to healthy adults revealed striking shifts in gene expression, with more than 6,000 genes differentially expressed. This gives us one of the clearest molecular signatures of AT ever defined. The volcano plot on the right shows gene expression in AT samples compared to healthy adult controls.
On the right-hand side of the plot, past the hatch line, are the genes that were significantly upregulated in the AT samples. On the left side of the plot, past the hatch line, are genes that were significantly downregulated. Many of these differentially expressed genes are directly tied to disease biology. Key pathways affected in the AT samples included DNA repair and redox response, which are central to ATM function.
We also saw significant reductions in immune-related genes, including those involved in B cell and T cell development, highlighting the immunodeficiency seen in AT. There were also significant increases in pro-inflammatory cytokines and chemokines. Importantly, we also observed a marked upregulation of interferon-stimulated genes in the AT samples, which are known to contribute to chronic inflammation and may serve as potential biomarkers of disease activity.
Additionally, we found significant dysregulation in ion channels, neurotransmitters, and mitochondrial genes. Together, this provides a landmark RNA-seq data set with the most comprehensive molecular characterization of AT generated to date. With a clear view of the transcriptomic disruption in AT that I just shared with you, the next slide focuses on how eDSP treatment modulated these pathways, highlighting gene expression changes that provide insights into the eDSP mechanism of action, as well as potential treatment-responsive biomarkers.
RNA-seq data from eDSP-treated patients revealed modulation of pathways directly implicated in AT disease biology, along with evidence of a gene expression signature that's consistent with methylprednisolone exposure. First, Interferon-stimulated genes, which are typically elevated in AT and contribute to the chronic inflammation seen, were significantly downregulated after treatment with high-dose eDSP. Downregulation of Interferon-stimulated genes is the hallmark glucocorticoid gene signature.
The significant downregulation of Interferon-stimulated genes by eDSP reflects a marked impact on decreasing the inflammatory state of AT. These genes may also serve as potential treatment-responsive biomarkers. We also saw meaningful changes in immune and inflammatory pathways. There was an enrichment in humoral immune response genes and a significant reduction in pro-inflammatory gene expression, indicating a shift toward a more regulated immune profile after eDSP treatment. Third, we found modulation of neuroprotective genes.
For example, Wnt signaling genes, which have been shown to be neuroprotective in other neurodegenerative diseases like ALS, Parkinson's, and Alzheimer's, were upregulated after eDSP treatment. Wnt activation has been shown to promote neuron survival, reduce oxidative stress, and enhance DNA repair, mechanisms that are all highly relevant in AT. Finally, ion channel genes, which are critical for neuron excitability and function, were also modulated by eDSP.
Since Purkinje neurons are highly vulnerable due to disrupted calcium homeostasis, this finding is very important as it ties directly to mechanisms driving neurodegeneration in AT. The graphs at the bottom of the slide show the striking downregulation of interferon-stimulated genes after high-dose DSP treatment. Interferon alpha genes shown in the graph on the left and on the right were showing interferon gamma genes, all downregulated after eDSP treatment.
Overall, these results reveal novel insights into the mechanism of action of eDSP, as well as potential treatment-responsive biomarkers. The next slide offers an overview of how high-dose eDSP impacted gene expression in ATTeST, highlighting the key pathways and their therapeutic relevance. On the left, the bar chart highlights the direction of change across these key pathways, with significant suppression of interferon-stimulated genes and inflammation, and upregulation of adaptive immunity, mitochondrial function, and neuroprotective genes.
The robust suppression of interferon-stimulated genes is a hallmark of glucocorticoid activity, while the downregulation of NF-kappa B-dependent pro-inflammatory cytokines and chemokines points directly to reduced inflammation after eDSP treatment. Mitochondrial dysfunction drives neurodegeneration in AT, and we saw upregulation in mitochondrial genes that play roles in both restoring energy, metabolism, and function, which is consistent with neuroprotective effects.
We also saw upregulation of neuroprotective genes and neurotransmitters that promote synaptic resilience and neuron survival. Excessive calcium influx leads to mitochondrial stress, oxidative damage, and excitotoxic neuron death. Ion channels are known to regulate neuron excitability and calcium homeostasis, and modulation of these genes stabilizes neuron firing and protects against Purkinje neuron dysfunction and death.
Overall, the key takeaway here is that high-dose eDSP not only reproduced the expected glucocorticoid gene signature but also drove modulation of key disease-relevant pathways, including inflammation, oxidative stress, neuroprotection, and ion channel biology. The next slide summarizes the key goals and results of our RNA-seq project and some next steps that we're taking to build on these results.
Our ATTeST RNA-seq project was designed to expand our understanding of AT biology, demonstrate that eDSP has a measurable biological effect, and show that the magnitude of those changes is meaningful compared to other traditionally administered steroids. First, we obviously succeeded in expanding our knowledge of AT biology. By comparing AT samples to healthy adult controls, we identified over 6,000 differentially expressed genes, providing a comprehensive data set for discovering potential biomarkers of disease activity.
Next, the data revealed novel insights into the eDSP mechanism of action, with a significant number of genes differentially expressed after treatment. These gene expression patterns were similar across both the two- and six-month time points. Notably, this activity was measured at trough, approximately 30 days after the last eDSP dose, confirming that eDSP has sustained and durable biological effects throughout the 30-day treatment period.
Lastly, pathway analyses uncovered evidence of a classic methylprednisolone gene signature, reinforcing that eDSP engages steroid-responsive pathways while also revealing unique treatment-responsive biomarkers. Looking ahead, we're working to correlate gene expression changes with clinical outcomes and genetic mutations in the ATTeST trial, and we're continuing to investigate potential disease-specific and treatment-responsive biomarkers. Importantly, the RNA-seq results that I've shared today have been confirmed using an orthogonal method, which is long-read DNA sequencing, which underscores the robustness of this data set.
We're very excited to continue to pursue this work and expand upon this landmark data set from the largest clinical trial ever conducted in AT, which we believe will be foundational for the discovery of biomarkers of both disease activity and eDSP treatment response.
The final slide summarizes the synergistic mechanisms of action of eDSP, including a unique and optimized PK profile that enables sustained dexamethasone exposure while avoiding severe toxicity, improving both safety and efficacy, optimized glucocorticoid receptor occupation, maximizing exposures and improving efficacy, systemic and targeted biodistribution to the CNS, and importantly, eDSP engages both genomic and non-genomic glucocorticoid pathways, providing immediate as well as long-term anti-inflammatory, immunomodulatory, and neuroprotective effects, and given the compelling transcriptomic data from ATTeST, we are really optimistic about the potential of eDSP to deliver the first disease-modifying treatment for AT, which would be an incredible step forward for patients and their families. In closing, I thank you for your time, and I look forward to answering any questions you might have during our Q&A session.
Hi, my name is Pamela Williamson, and I'm serving as Head of Regulatory Affairs for Quince Therapeutics. It's my pleasure to be able to take you through a high-level overview of our current regulatory planning. By way of background, orphan drug designation has already been granted by the U.S. FDA and the E.U. EMA for the treatment of AT. As you may know, orphan drug designation provides certain benefits in each of these jurisdictions, including, but not limited to, waiver of certain fees, such as the application fee, which in the United States can be $several million, and also affords marketing exclusivities following approval for those first to market.
In the United States, we've also been granted fast-track designation by the U.S. FDA for treatment of AT. This affords the company additional opportunities for interactions with the FDA to move the program through more expeditiously and hopefully to approval.
While not guaranteed, fast-track designation often connotes the opportunity for priority review once the application is submitted, which allows for a shortened review clock. The eDSP system is regulated in the United States as a drug-device combination product. This means that the primary center for review at the FDA will be the Center for Drug Evaluation and Research. However, they will also consult with the Center for Devices and the Center for Biologics.
The eDSP system devices and the single-use treatment kit are already E.U. CE marked, further de-risking the evaluation of the device components in the United States. Next slide, please. In the United States, the phase III NEAT trial, which is the pivotal phase III trial, is being conducted under a U.S. FDA special protocol agreement. The SPA includes the primary endpoint of the rescored modified ICARS tool with a primary efficacy population of the six to nine-year-olds.
The FDA has reviewed and agreed with the design of the protocol and also the statistical analysis plan. In Europe, there's also a pediatric investigational plan, referred to as the PIP. In the United States, a pediatric investigational plan is not required. It's waived when you have an orphan drug designation. In the E.U., we will be conducting an additional study, which is about to commence, for those patients that weigh between nine and 15 kilos, so smaller patients than are currently in the current NEAT trial.
The design of this protocol has also been agreed to by the PDCO in the E.U. In the United States, the regulatory pathway that we will be following for the NDA is referred to as a U.S. 505(b)(2) pathway. This allows sponsors to rely on data and findings from outside of their program in order to support FDA's review of safety and efficacy.
In this particular context, because dexamethasone has been approved for many, many years and is very well characterized, we will be able to rely upon non-clinical data not generated by the company. Therefore, additional non-clinical studies are not expected to be required. Ultimately, the U.S. NDA submission is currently planned for the second half of 2026, given that the recruitment has been completed, and we anticipate data readout in Q1 of 2026. I'd be happy to answer any questions that you have during the upcoming Q&A session. Thank you.
Hello. My name is Charles Ryan, and I serve as President of Quince Therapeutics. In my role, I oversee a number of functions and activities, including legal, finance, quality, day-to-day management of our Italian operations, as well as working closely with the team to support our effort to prepare eDSP for commercial launch.
So let me begin by talking a little bit about the commercial opportunity that we see ahead for us for our lead indication of AT. At a high level, AT represents a rare opportunity to provide a real benefit to patients and create a billion-dollar-plus market. To ensure we fully capture the scope of this unmet need, we have completed extensive work to understand the true size of this market, both from a prevalence, physician, and payer perspective. We estimate that the prevalence of AT patients is approximately 5,000 patients in the U.S .
I'll get into the details in just a moment. Assuming we have success with our final clinical study, we're also in an advantageous position as eDSP holds the potential to be first to market to meet the high unmet need of AT, as there are currently no approved therapeutics on the market.
Our prospects are further supported by attractive comparables in rare disease, with a number of recent launch analogs that we can look to that provide us with a good line of sight and understanding of pricing dynamics in this area. We're also in a strong position from a financial perspective, and we stand to benefit from both a highly scalable manufacturing infrastructure and a very low cost of goods.
And finally, relative to exclusivity, we have an Orphan Drug Designation, a very strong patent position, and additional technology barriers that should serve us well and provide for long-term market exclusivity. And all of these factors translate into the billion-dollar-plus opportunity in AT alone, with more opportunities ahead for Quince. So let me talk about each of these things in a little bit more detail, beginning with existing epidemiology.
Unfortunately, epidemiology in the literature is not great, and what is there is from the 1970s and 1980s, before genetic testing was even available. Instead, we turned to third-party resources, and we partnered with IQVIA, which is one of the leading providers of work in this area. You'll see our findings here. We worked very closely with IQVIA to go through their medical claims database, and we found approximately 4,600 diagnosed patients with AT in the U.S. by utilizing ICD-10 codes to validate the number of diagnosed patients.
We were able to corroborate this patient finding size with a genetic prevalence study conducted at Baylor University that found approximately 6,000 patients in the U.S. using a genetic database. Comparatively, it helps to look to Friedreich's ataxia, which has a very similar epidemiology and market size with 5,000 diagnosed patients in the U.S.
So all of these factors give us confidence in this starting place for accurately sizing the U.S. market at approximately 5,000 AT patients today, creating a very strong commercial opportunity for us. But we are also aware that because there's no currently approved treatment, there's a number of patients out there who could have AT who don't currently present in the marketplace.
To that end, we think we can increase the number of treatable patients with additional market awareness, increased testing, working with our partners at key advocacy groups, and launching an approved product for AT patients. So we believe that once we get the drug approved and it's launched, we're actually going to see some greater awareness in the marketplace, both with caregivers and patients. And this should actually help improve the commercial size of the opportunity ahead for us.
The key takeaway is that we believe that this is a strong starting place as eDSP is well positioned to meet the high unmet need in AT, quickly becoming the standard of care. Now, you've heard from Dirk and others speak about the patient journey, from diagnosis to rapid neurodegeneration that's further complicated by frequent infections, respiratory issues, as well as heightened risk of cancers.
Unfortunately, patients really have a very challenging time in the earliest of days with this devastating disease. Our goal at Quince is to offer eDSP treatments as soon as possible, targeted at the neurological symptoms that prevail throughout the entire AT patient journey. What that means from a commercial perspective, we will seek every opportunity to expand access to this therapy.
While the NEAT study is focused on treatment effect in patients six years and older, you've also heard that we're beginning a pediatric study to reach smaller, younger children with the hopes of providing our treatments to kids early in their life and having them on eDSP as soon as they're diagnosed for the rest of their life.
As we introduce the drug to the marketplace, we also recognize that we're going to gain a deeper understanding of the impact of our therapy for these patients. And as we collect more data with eDSP over time, we hope to see a reduction of infections and cancers and hopefully extending life, all of which will certainly help advance and support our commercial efforts.
Another important factor that will underpin prospects for commercial development is to capitalize on our first-to-market potential and establish eDSP as a standard of care in AT by matching the benefits of our innovative therapy to the clear unmet need in the space. First and foremost, AT is underdiagnosed, and the time for diagnosis is quite extensive.
With increased awareness, the company is a first-to-market therapeutic, along with support from KOLs and advocacy groups, we expect to bring increased awareness and diagnosis to support early treatment, and since there's no existing therapy today, our focus will be on communicating the value of eDSP to hopefully help modify or even slow the progression of the disease, which will be the key value proposition.
Another standout is our ability, with a successful NEAT readout, to validate not only the efficacy of steroids for the treatment of AT, but also to dose steroids chronically and safely without toxicities, opening up another therapeutic avenue that is simply not currently available. And finally, current treatment options are really just limited to things like physical therapy and other types of supportive care, with the goal of retaining ambulation as long as possible.
Our hope is that our therapy will play a role in keeping kids out of wheelchairs and dramatically altering the life of patients day to day. Put it all together, an eDSP really checks all the boxes, a first treatment that directly addresses the key challenges patients with AT and their families and caregivers face.
Since this is a drug-device combination, one thing I wanted to highlight here is the work we're doing around a number of supporting materials that are required to run the Red Cell Loader. We've worked with a leading provider in understanding the best way to organize the materials for each monthly infusion, and that's reflected here in the EryKit.
Our goal is to launch a product that is as easy as possible for physicians and infusion centers to use with no issues, while establishing clear processes that promote consistency and quality from one site to another. It's also going to improve our packaging footprint, and we'll be able to just drop ship materials as needed and help streamline supply chain overall. I'm pleased to say that we've completed this work. The final prototype is ready.
We filed the patent application, and now we're working to select the commercial CDMO, so we'll be launch ready. So now let me talk to you a little bit about other companies across the AT landscape. Given the size of the potential commercial opportunity, the development pipeline for AT is quite minimal. In addition to Quince, there are a few other players that are looking to provide a treatment for ataxia-telangiectasia, which are summarized here.
I won't go through each of these assets, but I do want to note that we are uniquely positioned in many ways. We have the benefit of positive phase III efficacy signals from our previous testing, which is very encouraging to us. We also have treated hundreds of patients already, and we know that our therapeutic is both well tolerated and has a very good safety profile.
For the patient, our treatment is a once-a-month therapy that delivers benefit throughout the entire course of treatment. I would point out here that IntraBio's N-acetyl-L-leucine is the only other therapy in late-stage development. Our current phase III trial includes patients over the age of four and only provides treatments for three months, which increases the difficulty for their trial, but we'll be watching this one closely.
However, as is the case with many severe diseases, our therapy currently has the ability to be dosed concomitantly should one of these assets advance to approval and be available for physicians and patients. But we have a lot of confidence in the prospects of our success for all the reasons I shared. Now let me talk to you a little bit about pricing. We continue to do the work to understand our market and all of our stakeholders.
Certainly, in drug development, one of the key stakeholders is the payers. To that end, we recently conducted a qualitative payer research study. This study involved qualitative research with payers that covered more than 200 million lives in the U.S., quite extensive in terms of the coverage of patients. Our initial research was both insightful and encouraging. What we learned is that many of the payers were not immediately familiar with AT.
This wasn't surprising to us, as the lack of knowledge of AT reflects the absence of sponsor engagement due to the modest product development pipeline I just discussed. However, what was encouraging is that within just a limited amount of education, payers quickly understood the graveness and burden of the disease and the significant unmet need, and that our asset really holds the potential to dramatically alter the life of patients with AT for the better.
So we really found a very supportive voice within the payer community. In terms of pricing, we have a number of comparables with other rare disease therapies that have recently come onto the market, which you see highlighted here on the right. But we certainly have more work to do in this area. After the completion of the NEAT phase III study, we will have comprehensive data on efficacy and safety, and now we can establish the value of eDSP and our pricing.
Then we will continue with a more thorough quantitative payer research study to gain a deeper understanding of what price points would be appropriate for this therapy, and we'll keep you updated on that progress. In terms of effectively delivering this therapy, in early August, we announced an exciting partnership with Option Care Health. Option Care Health is the nation's leading outpatient infusion provider.
They have more than 180 sites around the country, which will allow us to have the ease of a single contract provider while benefiting from greater geographic flexibility to match patients' locations with sites strategically located throughout the U.S. So as we gain a deeper understanding of our patient community, where they're located, we want to do everything we can to make sure that we can provide our therapy in the easiest way possible for these patients, and certainly, going to an Option Care center where you pull up and walk through the front door is much easier than navigating a large major medical center, especially when these kids are not highly mobile.
This strategic relationship will also play a role in improving and standardizing the patient journey with higher control and consistency across Option Care sites, while offering a comprehensive suite of enhanced capabilities to handle commercial services for us as well. Finally, and importantly, Option Care will also allow us to have the ability to roll out other therapies like treatments for DMD and to leverage this partnership to execute these programs seamlessly to support our pipeline expansion.
So it's a really exciting program for Quince, and we're delighted to have Option Care as a partner in providing eDSP to patients. Lastly, let me tell you about our substantial market exclusivity position and how we believe we're well protected from generic competition. Because eDSP has orphan drug designation, we automatically get seven years of market exclusivity here in the U.S. and 10 years in Europe. This is a really significant amount of exclusivity.
But in addition to that, we have an extensive patent portfolio, and our patents run until 2036 with some additional extensions available. And we also have other patents that we are currently pursuing. In terms of technology barriers, as you know, this is a drug-device combination, and our Red Cell Loader has a lot of proprietary components and processes that would make it very difficult for a generic competitor to copy.
For example, they would need to have extensive clinical studies and process validation to even consider copying our technology. So we really look at our technology as having a unique position in the market in terms of our ability to have competition kept at bay. In closing, we are very excited about the market opportunity of eDSP, with the potential to be the first approved therapy for AT, an area with no existing treatments.
And we believe eDSP has true blockbuster potential. We have engaged leading consultants with proven success in commercializing rare disease therapies, and we are working closely with physicians, patients, caregivers, and payers to ensure a successful and timely launch. We are confident that eDSP can deliver a meaningful impact for patients and significant value for all of our stakeholders. Thank you so much for your time, and I look forward to answering your questions during our Q&A session.
Hi everyone. I'm Brendan Hanna, the COO and CBO of Quince. You've heard a lot of great information from our team so far today, but now I'd like to spend some time detailing how we believe our efforts will translate into driving value creation for our shareholders. Quince is very well positioned with a highly innovative asset that has potential to be the first steroid that can safely be delivered chronically.
We're lining up for a very large value inflection point with phase III data coming in Q1 of next year, with a differentiated rare disease asset in an indication with no currently approved therapies, and given the profile of eDSP being a very potent, but safe steroid, there's a large number of different indications we can go into to significantly increase the value of the product and then the company as a whole.
We're in a great capital position. We finished Q2 with about $35 million in cash, which provides runway through phase III data and into the second quarter of 2026. We're also setting up for both strategic and financing activities following data like right-by-capital all the way through launch.
Now, taking a look at the orphan disease landscape, over the past couple of years, there have been several rare disease drugs launched as the first product for a disease, which we believe serves as a strong comparable for eDSP's commercial potential. These drugs are Daybue for Rett syndrome, Skyclarys for Friedreich's ataxia, and Vyjuvek for DEB. These were all launched with premiu
m pricing into small populations and are forecast to attain at least $1 billion in peak sales, and what's interesting here is that within 18 months of launch, they were all on annualized run rates of about $400 million, either primarily or exclusively from U.S. sales, so it shows the pent-up demand for new products and indications, particularly in rare disease where nothing currently exists, like that in AT. A great case study is Reata's Skyclarys for Friedreich's ataxia.
The epidemiology and market size for Friedreich's are roughly similar to that of AT, with about 5,000 diagnosed patients in the U.S. Skyclarys is the first drug approved for Friedreich's and has forecasted peak sales of over $1 billion. Both Friedreich's and AT have very similar symptoms regarding ataxia and then moving towards non-ambulation, but AT is actually more severe and has a shorter life expectancy, and from clinical trials, Skyclarys has shown modest efficacy in its phase III study at 48 weeks with some significant adverse events, while eDSP has shown a much larger effect at six months in the younger population and was well tolerated.
But shortly after launching Skyclarys, Reata was acquired by Biogen for over $7 billion, which just goes to show the value of a rare disease drug in a population of 5,000 patients in the U.S., especially considering Skyclarys can't be used for other indications. With AT alone, we think there's potential blockbuster sales, but given the profile of eDSP being a potent, but safe steroid, there's a significant number of indications we can go into.
We completed a comprehensive analysis of a wide variety of indications where steroids are standard of care or would be if it wasn't for steroid toxicity. And then we assessed each potential indication with a few key factors in mind. First, we narrowed down the list based on indications allowing for the safe pricing as AT. Then we condensed it to chronic diseases where patients would be treated on an outpatient basis.
With an eye towards commercial synergies, we also focused on pediatric indications that could be sold through a single sales force. We only targeted orphan indications that would not trigger IRA price negotiations. Another one of the key variables was diseases with over 5,000 patients in the U.S., given that it appears to be a standard cutoff for many investors and potential partners.
Then to do the final cut, we interviewed KOLs and treating physicians to understand if eDSP would be viable clinically and commercially given the current treatment landscape and development pipeline. To give you a better idea of the disease funnel, we've reviewed nearly 100 indications at this point and narrowed the list down on epidemiology, competitive landscape, commercial opportunity, steroid usage, and clinical impact.
We narrowed the list down to 20 diseases following interviews with KOLs and treating physicians to better understand the unmet need and commercial opportunity for eDSP, and then we did a final cut down to 12 indications based on clinical trial size, timing, cost, feasibility, and probability of success, so as a result of this robust diligence process, we selected DMD as our second indication to follow AT, and then we prioritized rare neuromuscular, autoimmune, and rheumatological diseases where patients will be willing to go in once a month for an infusion given the severity of their disease.
These indications should allow for similar pricing as AT, and there's a significant commercial opportunity in each of these, potentially allowing for hundreds of millions of dollars of sales per indication, if not more. And then given the wide applicability of eDSP and unmet needs in many of these indications, there is ability for it to become a blockbuster product in multiple indications. But from this assessment, DMD was the clear second indication.
While it's a seemingly crowded competitive landscape and commercial market, there are a significant amount of unmet needs in DMD, especially in the steroid space. Regardless of other drugs that patients are on, steroids are standard of care in DMD, so they usually add two to four years of ambulation. So even if a patient is on a gene therapy or an exon-skipping therapy, they're still on steroids in the vast majority of toxicity, which leads to tapering dosing, intermittent dosing, or fully taking the patient off the steroid.
The physicians we've talked to said that DMD is the obvious second choice for eDSP as patients are currently losing out on efficacy while still having toxicity. If we can provide equivalent efficacy while mitigating the safety issues, treating physicians have said that they want to try it out in the vast majority of their patients. The clinical team has finalized two different clinical study designs, one in treatment naive patients that we use for approval, and the other in patients transitioning from standard steroids, which would be more of a real-world use case. We plan to start dosing patients in these studies next year.
And to provide a quick comparison of eDSP to other steroids commonly used for DMD, on the left side, you can see prednisone and deflazacort, which are standard of care, and they have reasonable efficacy, but a whole host of safety issues. Whereas the Agamree was launched about 18 months ago by Catalyst in the U.S., and it doesn't hit the bone as much as it doesn't have growth suppression and seems to have less osteoporosis, but it still has all the other steroid-related safety issues.
So definitely better than the older steroids, but it's viewed as only an incremental advancement. But given the comprehensive safety data package of eDSP and over 600 years of patient safety data, we believe that eDSP has a fundamentally different safety profile that allows for steroids to be dosed safely chronically.
And moving on to finance, we finished Q2 with about $35 million in cash that provides runway through data into Q2 of next year. We have a very capital-efficient operating model and development plan for AT and plan to use investigator-initiated studies to get data and additional indications. And given that we own worldwide rights to eDSP, we have the ability to partner ex-U.S. rights following phase III data to provide additional runway as we start preparing for our own U.S. launch of eDSP.
We've also had very robust engagement with investors and potential strategic partners, hopefully setting up for a range of different options, both phase III data. I hope you found this helpful, and I'll be happy to answer any questions you may have during the Q&A session.
Well, thank you, everyone, for joining us today. I hope you found the. Okay, I think that was a great overview of all the activities we're working on. I'd like to open the floor to questions now. This is Dirk, by the way. Thank you, Mike. John, you're on mute. I think I see you.
Oh, sorry. Hey, do you guys hear me now? Yes. Hey, sorry about that. John Walton from Citizens. Thanks for hosting the day. Very helpful information. Just wanted to focus in on the upcoming readout, Dirk, and I was hoping you could. Okay, sorry. I got a delay because I got the YouTube going too. For the upcoming readout, what are your powering assumptions?
And then when we look back at RMICARS, you gave us those two charts showing the more sensitivity for RMICARS versus the other endpoints, but wondering if you could, I'm confused by the placebo-adjusted benefit and then the worsening of symptoms. So can you te ll us if the change is driven by stabilization or worsening of placebo or a drug effect? And then when you talk about worsening of symptoms on a scale like this, is this like patients have any worsening, or is there some categorical consideration to say that their symptoms have worsened?
Okay. Let me start with the question of powering, and then I'll move on to RMICARS versus ICARS and the magnitude of change versus placebo over time. So I mentioned this in my part of the presentation, but the statistical assumptions for powering the NEAT study came from ATTeST, and ATTeST had that problem with 26% missing data. So the confidence intervals around the point estimate of response were wider than we will see in ours. Nevertheless, those were the assumptions we used to come up with the sample size originally of 86 patients.
As you'll recall, we ended up enrolling 83 of the planned 86. It was powered at 90%, and I think we're at or above 90% because we only have 6% missing data versus 26% that was used for the data set that generated the statistical assumptions. So does that address the question around the powering?
What's the effect size you're powering for, though?
I think it was a, Brendan, you might have it in front of you, but I think it was a 2.14 points versus placebo.
Correct. 2.4 points against placebo. And then confidence intervals of 3 for active and 3.7 for placebo.
Got it. Okay. All right. That's helpful.
Yeah. Okay. So now with respect to your question about is this disease modifying or delays progression. So the placebo group gets worse over time, and the ICARS score goes up over time, and the treated group stabilizes. So it's really a delay in progression of disease. And 2.4 points of an RMICARS is pretty significant over a six-month period. Relative to placebo, it's about a 24% difference. So the full ICARS itself is divided into different domains. You have gait and posture, kinetics, speech, and oculomotor. And each of those four domains has a number of points.
Over the years, when the FDA started narrowing down what they wanted to look at, they focused more and more on the gait and posture domain. When you get from the ICARS to the RMICARS, you end up going from 100 points to 29 points. Most of those, the vast majority of it, is in the gait and posture domain. Really what we're looking at when we look at a two-point difference versus placebo, it's mostly with respect to the ability to walk. A two-point difference, for example, could mean for RMICARS the difference between walking autonomously and walking with help. It's a very clinically significant difference over that short period of time.
Got it. Okay. All right. That's helpful context. Thanks again, Dirk.
Sure.
Hi, everyone. This is Omer Pirosh from Lucid Capital Markets . Thanks for taking my questions. I would like to go back to the RNA sequencing study for a moment. Is there a difference between low-dose and high-dose eDSP in terms of the magnitude of the changes in gene expression?
Yes, there was. There was a very strong dose response. That was one of the exciting things that we saw in that data set. But I'll let Caralee expand upon that.
Yes, Dirk is absolutely correct. There was a dose response, especially in the genes that we highlighted today to you. We really wanted to focus on the high dose for this presentation since that's where we saw efficacy in ATTeST and where we're focusing NEAT. And have you been able to pick up a signature and the difference between core responders and non-responders? Great question, and we're actively working on that now. So stay tuned.
Okay. And I just have two more. I don't know, Dirk, if you talked about the size of the pediatric trial that the EMA requested? Was there a discussion about the wearable device or what sort of potential efficacy indicators you might be able to pick up? Was it their suggestion, or was their requirement purely foc used on the safety aspects?
Their requirements are purely focused on PK and safety, and I did not mention the number of patients, which is 12 evaluable patients dosed over six months, six doses over approximately six months. It's only safety and PK. The wearable device was my idea, and I had to battle some of my team members to actually implement it because it's expensive and it's not generally considered standard.
But I think these devices, to me, they're really interesting because they have the potential to be far superior to these physical exam tools that we use right now. So we don't know exactly what it's exploratory work. It hasn't been discussed with either agency in Europe or the US, but we'll collect a lot of data, and we're working with academic investigators who have experience in these neurological rare diseases to look at a variety of different endpoints.
I don't expect that we'll be able to use it for any type of efficacy claims, but I do think it'll be extremely valuable for guiding future work. That's especially important in these young kids, too, because you can't even use these neurological assessment tools. You can't walk them through the physical exam components in order to do the score.
Yeah. Yeah. I just had one more, maybe it's a bit of a short question. When you look at the IQVIA data and look at the geographic distribution of the patients and compare it to the footprint what Horizon has, roughly what percentage of the 5,000 patients would be close enough to these infusion centers to go on a monthly basis?
Yeah. So our analysis is that we could capture at least 80% in a very close geographic range. So you certainly could have some outlier patients that are in a more remote area. But the nice thing about Option Care is that they have a very significant footprint, and they're continuing to expand. So we think that there's a lot of flexibility, even relative if we were to have some pockets of populations that were not geographically connected now that we could actually resolve that.
So thank you very much, Charles.
This is very valuable. Thank you for inviting.
Yeah, my pleasure.
And it looks like we have a couple of questions from Hartaj in the chat box here. One is I'm going to direct to Pam. Will the pediatric trial, I think he's referring to the PIP requirement from the EMA, supplemental NDA, get a pediatric priority review? And I don't think that's, I don't think that's the right way to look at it because it's a requirement at the EMA to study the safety and PK in that population. It's not designed to get an indication. But Pam, do you want to, is that correct? Do you want to expand upon that?
Yes, I can. So of course, you cannot request a priority review until you actually submit the marketing application, or in this particular example, the supplemental marketing application or NDA. However, if the main application receives a priority review, there's no reason to suggest that the smaller weight children supplement would not also receive a priority review. Importantly, for the study that we're referring to in the EU, the data being generated are indeed safety and PK primarily, as Dirk has described, with an exploratory use of the wearables.
But those data are then intended to be included in a currently existing PK and simulation model, which would allow confirmatory dosing in those smaller patients, which we anticipate could, in fact, allow the supplement to be supported in terms of efficacy for the small children.
Okay. Second question is, assuming a positive phase III and approval of the product in AT, how long will it take to screen, treat, and record revenues from an AT patient? This lag can often affect first and second-year revenues.
Yeah, I can handle that one. So it's going to depend on the patient. Some are already known and either in a registry with A-T CP in the U.S. or known through IQVIA, one of the genetic testing databases. So with them, it's going to be much quicker. They'll have to go through the patient hub, usually work through a prior authorization with the physician, and then we'll be able to record revenue shortly thereafter, hopefully within a month or two, as we'll be shipping just in time to each Option Care site.
For those that haven't been confirmed as AT yet, they will need a genetic test, likely for the prior authorization. So that will take additional time to actually get patients diagnosed, work through the patient hub, get them on therapy, and record revenue. So it's going to be dependent on patient.
Hey, everyone. Jason here representing Leland Gershell and Oppenheimer today. Great presentation and progress so far. I have two questions. First is going to be, what disease-specific biomarkers or treatment response of biomarkers are you going to be looking at as you build on the RNA sequencing pathway analysis? And do you have any insight on how that might map to the neat trial outcomes?
The short answer is not exactly not yet, but I'll let Caralee walk through some of the details there.
Yeah. We're taking a broad look at the treatment response of biomarkers on all possibilities from the A test study. We're also going to be doing this in neat, and we'll focus especially on anything that comes out confirmed through the DNA sequencing that we're doing as well on the same samples.
Great. And one more question. So unlike AT, there are a couple of steroids approved for DMD, some of which are generically available. I guess, how do you see eDSP's opportunity given the landscape, and how are you thinking about positioning that product?
Yeah, I'll say a couple of things, and then I'll let Brendan expand on some of the commercial details about it. But yeah, if you go to the last couple of years, I've gone to the DMD academic conference, the big academic conference. It's a really interesting conference because it's very much patient-centered, and there are a lot of patients and their families that attend the conference. And one thing that's very obvious when you go to this conference is that a lot of the discussion is focused on the problems associated with the therapies. And corticosteroids are the primary therapies for almost all of the children.
Despite ASOs and gene therapies, almost everyone is on steroids, and other than the underlying disease, it's the biggest problem in their lives. It causes a lot of adverse events. They get a lot of weight gain. They get Cushingoid, behavioral issues, osteoporosis. They develop diabetes. So it's a major, major problem, and Deflazacort and Vamorolone have slightly different safety profiles and some marginal benefits, but even when you speak to the KOLs in this field, they'll tell you they're still steroids.
They're still very, very toxic, so I think if we can demonstrate that we have comparable efficacy, it doesn't need to be better efficacy, just comparable efficacy, and we can eliminate the adverse effects. This was, by the way, we at EryDel years ago did a study in ulcerative colitis where they took steroid-dependent patients, and they randomized them to converting over to encapsulated versus staying on their current steroid.
Then they weaned both groups. Upon weaning, 80% of the patients that remained on standard of care had a recurrence, and only 20% in the encapsulated group had a recurrence, and all the steroid toxicities resolved. That's what we want to see in DMD. We want to see that the efficacy is the same or even better, maybe, but the steroid toxicities resolve. If that happens, it's less convenient than taking a pill.
You have to go to the clinic every month. If we can demonstrate that, we're likely going to have a different price point. So we anticipate, and this is where I'll hand it over to Brendan, but we'll anticipate you'll have to step through a couple of therapies before you're authorized to take ours. But I'll let you carry on from there, Brendan.
Yeah, Dirk is completely right. So there's likely going to be step edits for branded Deflazacort and even Vamorolone before getting to eDSP, given the premium price point. But as he mentioned, nearly 100% of these patients have toxicities. So we don't expect there to be issues with prior auths, given that the first and second-line steroids are considered toxic. So even with a small percentage of DMD patients, you're still getting the very significant sales with about 15,000 DMD patients in the U.S.
Appreciate the comment from both of you. And thank you to the rest of the team as well.
Thanks. Great presentations. So I just had a couple of questions with regard to the timing of the NDA filing. What needs to be done before you can file the NDA, and how quickly can you supplement the supplemental NDA? When you say supplement, are you talking about the pediatric docu ment?
Yeah. Yeah. Yeah. Okay. Well, the first thing that has to happen is we have to have positive data. So that's the thing we're all eagerly looking forward to in the middle of Q1 next year. And we're already planning and working on elements of the NDA as we speak. But I'll let Pam outline for you kind of the major milestones along the way in the NDA process. And with respect to that, she can add comments about the mechanism by which we would supplement with the younger data, the PIP data.
But we don't yet have an exact idea of how quickly we'll be able to enroll that study. I'm not sure if it'll go quickly or if it'll be a little bit challenging. We do have a bunch of pre-identified patients, and we only need 12. So it's possible it could go pretty quickly. And most of the patients should be eligible because the screening criteria are not extremely strict. But Pam, I'll let you kind of walk through the major milestones along the way with respect to the NDA filing.
Sure. Thanks, Dirk. So as we've mentioned, we are looking forward to seeing top-line data in Q1 2026. And assuming that those data are positive, we have a very good plan in place to efficiently develop and submit our NDA in the last half of the year.
We intend to continue, and frankly, we are already engaged in routine discussions with the FDA as we move forward here to make sure that what we include in our application is going to meet their standards. And as I mentioned during the earlier presentation, in addition to the actual protocol, which has been reviewed and agreed by the FDA, they've also reviewed and agreed to the statistical analysis plan.
So prior to database lock, we intend to provide the final versions of those documents. And then after top-line data are available, we'll move forward earnestly with our NDA submission process. We have work streams in place already for each of the functional areas. We have plans in place for inspection readiness.
We have plans in place for pre-submission meetings with the FDA prior to submission of the NDA to make sure that we're all on the same page with respect to the content and format of what will be included, and then we look forward to submitting toward the end of the year.
While we mentioned, it cannot guarantee a priority review, we have every reason to believe that the application given the unmet medical need, assuming positive data, that we would be eligible for a priority review. When it comes to the second part of your question and the pediatric study that's ongoing in the EU, as Dirk has mentioned, we don't have timing for completion of that study yet. If it's not completed in time to include in the initial NDA, then that would be submitted as a supplement, as you've indicated earlier. That would be submitted as soon after the initial NDA approval as possible.
Okay. Great. And in terms of the label expectation, is it that it will be six years and older initially, and once you have the supplemental, it will be from two years and older?
So while we can't, until the final label negotiations are completed, we can't state that emphatically. But my speculation would be that there would not necessarily need to be a limitation of six to nine-year-olds, especially since while the primary efficacy analysis is on the six to nine-year-olds, the study is actually enrolling patients above 10. And that was actually at the recommendation of the FDA so that we were not excluding the older patients, even though the efficacy signals for the older patients may be more difficult to detect.
Okay. Great. Thanks so much. You're welcome.
And that group of older patients isn't included in the primary analysis population, so it doesn't have an adverse effect on our chances of success for the primary outcome measure. Looks like we're coming up at the end of our time. Thank you very much for joining us today. It was a lot of effort to put this together, so it's great to see people actually show up and listen to it. And thank you for your great questions. And we look forward to updating you as we generate more news throughout the rest of the year and into next year when we'll have data from the phase III NEAT trial. Take care, everybody.