Good morning, everyone. Welcome to our second day of our Piper Sandler Healthcare Conference. My name is Yasmeen Rahimi. I'm a senior biotech analyst at Piper Sandler. Thrilled to have the Quince Therapeutics with us here at our conference, and we have lots of great content to cover in the next 25 minutes. 2026 is gonna be a very big year for the company, as you will have your pivotal studies to, reading out in February, which is right around the corner. I think maybe the first place to start off is to provide a sort of an, for investors who are new to the story, to talk about the therapy that is being developed in the AT population, and maybe let's start there. I have.
Okay.
Lots of questions.
Sounds good. Well, first of all, thanks for inviting me. It's nice to see you. And if you're not familiar with Quince Therapeutics, we're a company that acquired technology about three years ago now. We acquired a company called EryDel that had worked on this drug-device combination technology for about 20 years, with about $100 million of venture investment. So a lot of research has already gone into it. And what it is, is a machine. It's a tabletop machine that sits at the patient's bedside or in the lab. You take a small volume of patient's blood, 50 mL. You hook it up to the machine. And what the machine does is, in over a 90-minute period, encapsulates the drug of interest inside of the patient's own blood. Now, it's only 1% of their blood. They're not connected up to the machine.
You take their blood, you process it, and then you re-infuse it an hour and a half later with the drug encapsulated inside their own red blood cells. So why would you do this? In the case, there are a lot of reasons. You can do this with a variety of drugs or proteins, enzyme replacement therapies, chemotherapeutic drugs. Our lead compound is dexamethasone. The reason you would put dexamethasone into a red blood cell is to be able to give it chronically at an efficacious dose without any toxicity. So that's a huge deal, obviously. You know, steroids have been around for decades, and they're incredibly efficacious and beneficial for lots of different things. But the big problem with them is their toxicity. You can't give them for more than a week or two without hitting adrenal suppression.
And there are many, many very devastating long-term toxicities associated with their chronic use. So this technology allows us, by encapsulating it inside the red blood cell, to give it once monthly to patients, over time, have maintain the efficacious benefits, which is what we hope to prove in our phase III study, which we'll talk about, while not having any of those associated toxicities.
Okay. And I think also the company ran a previous phase 3 called the ATTEST study, which, you know, missed that sig in the ICARS primary endpoint, but it hit that sig in patients aged between six and nine across all endpoints, ICARS, mICARS, RmICARS, and which then led to the selection of this population in your NEAT study, right? I guess the question that maybe for investors come up is what's the biological reason that age group of six to nine, a benefit was observed.
Yeah.
and therefore became the target population in your current study?
Right. So I'd mentioned that we acquired a company called EryDel three years ago. Just prior to us acquiring that company, they had completed a phase III trial in a disease called Ataxia-telangiectasia . Is the trial you're referring to? Ataxia.
Yeah.
Let me start by, if you're not familiar with the company, I should just describe first the disease entity. Ataxia-telangiectasia is an autosomal recessive pediatric genetic disease, terrible disease. Children get neurological degeneration at a young age, and then they get infections and cancers and typically live into their 20s, and the natural history of the disease is really critical to understanding your question about the ages and why a younger age is relevant, so children typically get diagnosed with this. It's a tough diagnosis to make. They typically get diagnosed between the ages of about two and five. From the age of diagnosis until the age of about 10-12, they have rapid and linear neurologic degeneration. They usually end up in a wheelchair by about the age of 10-12. Thereafter, that neurological degeneration sort of plateaus out.
And they continue to have deterioration over time, but it's much slower than in their younger years. They lose a tremendous amount of mobility and kinetic function over that first about decade. So therefore, if you're performing a clinical trial over a short period of time, and in our case, it's six months, what you wanna do in designing a clinical trial is to choose a population and a time course that will highlight the benefits of your drug and improve your chances of success. So if you're deteriorating really rapidly over a decade, it's within that decade that you would want to study patients, not after they've plateaued. In that previous trial, the company we acquired wanted to proceed really quickly, so they included patients of all ages. About half of the patients included in that trial were over the age of 10.
And that's during the period where they're plateauing. So if you wanna see a neurologic benefit in over time, you don't wanna include that population 'cause you're unlikely to see a benefit. And in fact, that's what they saw was not much benefit there. But one half of the patients were in that group. So if you look at the younger patients, the six to nine-year-olds, and they did pre-specify that age population because they knew what I just described was true, but they thought they would succeed anyway. They pre-specified that younger six to nine-year-old age group. The effects of the drug in that population were dramatic and highly statistically significant. So we're redoing a phase three trial just in that younger population, which will be a more sensitive indicator of change over a six-month period.
Very helpful. What were some other key learnings of the ATTEST study that was incorporated in the NEAT study?
There was a lot of dialogue with the FDA over the primary outcome measure. And like a lot of these neurological outcome measures, you know, you use a physical exam scoring tool. Like in Alzheimer's disease, you would have ADAS-Cog. And in different types of Ataxias, you'll see different tests like, like the FARS or the SARA, or in our case, it's called the ICARS. And the ICARS is like these other neurological tests where you put the patient through a battery of physical exam maneuvers that are in different domains like gait and posture, kinetic function, oculomotor speech. You put them through a battery of physical exam tests, and then you have a scoring system that adds it all up. And the ICARS adds up to 100. And that's the test that we perform on patients.
It's a physical exam tool, assessment tool that was developed in the mid-90s, validated in a variety of Ataxias in the early 2000s, was used historically in the program, so it was carried all the way through. Over the months and years of dialogue with the FDA from the previous company, the FDA modified their thinking on which elements of the ICARS they think are most important. And so you'll see in some of our publications reference to an RmICARS, a rescored modified ICARS. That's 29 out of the 100 points and primarily focused on gait and posture elements. That's what the FDA believes is most important for this patient population. Europe will be focused on the full ICARS, which is we have as well. But you collect the full ICARS, and then you programmatically determine the 29-point RmICARS.
So that's one of the learnings from the previous trial is that that's what the FDA wants. And we now have an agreement under what's called a Special Protocol Assessment where you submit your protocol to the FDA, and you reach agreement that, if it's successful, it should be sufficient as a single pivotal trial for approval. So that was one of them. You know, the six-month time period is a relatively short time period in a neurological study, but ATTEST showed us that that was going to be okay. Data collection methods, where you can run the trial most effectively, you know, which sites are the best, those sorts of things were learned as well.
Okay. And team, you recently had your safety data monitoring committee, which concluded continued study as is. Maybe help us understand what type of data are they provided to? Is it blinded, unblinded, to give you the green light? And then the second question is, what do you see on a blinded basis across the study?
So I only see blinded information. The DSMB sees both blinded and unblinded and, of course, pays more attention to the unblinded. But the way DSMBs work is that you specify a set of safety tables, listings, and figures that typically include things like demographic data, patient disposition, how many doses they received, whether they received it in the appropriate window, summaries of adverse events, adverse events by severity, adverse events by relationship to drug. There'll be listing data. There'll be ECG data, lab data, CBCs and chemistries, and biomarkers. So the typical, you know, full battery of safety. So the way at the beginning, there is a larger team that reviews all the blinded data together and looks for outlier signals in the population as a whole, which, you know, you're not seeing the imbalances between active and control groups.
So you're just looking for big moves in AEs, are there, you know, too many adverse events or are there too many severe adverse events for a certain SOC's preferred term, those sorts of things. And we've had three such meetings so far, and no issues came from the blinded section. And then, you know, the company staff and all the people that have to remain blinded go away, and the DSMB meets and reviews the unblinded data. And so then they can see the treatment allocation, see if there's any delta between placebo and active for any of those same elements I just mentioned. And in all three meetings, they concluded that there were no safety signals and that we were fine to go.
I should say that just based on, like, you know, there's probably more rare disease historical data for our safety database than any program I've ever seen 'cause EryDel had put it initially did a phase two study where three patients have now been taking the technology monthly, taking the drug monthly for 13 years, and there are 70 patients in open label extension that are now have been taking it for about three years. So the safety database is already huge, and, you know, I see that data, it's open label extension, so I know that they're on active drug, you know, and it looks good. The safety is remarkable.
What's the efficacy?
So if it works, well, we'll find out. You know, we'll find out in Q1, but.
Yeah.
If it works, what that means is it's definitive evidence that what we're giving is an efficacious dose. And that's a big deal because we've already proven, to my satisfaction as a drug developer, that I think it's a safe dose.
Mm-hmm.
So the combination of being able to demonstrate that it's efficacious will be huge. You know, you could use this for, like, you know, 100 different diseases potentially.
For the study reading out in February, you guys have said it's powered to just show a statistical separation. You've also said it's just that any stat sig is enough. Two questions. Is there a magnitude in the RmICARS considered clinically meaningful? Question number two is, do you need to show a separation in any of the secondaries to be able to file, or is a statistical win on the primary sufficient given the high unmet need?
Yeah, that's an important question because, you know, we talked a little bit already about these, these neurological assessment tools, and they're based on numerical scoring systems, and it's not always clear whether a difference of one point or two points or 10 points is important. In this case, for Ataxia-telangiectasia, I described the disease horrible pediatric disease. There's nothing approved.
Mm-hmm.
Any clinically meaningful change is important for these patients. If you look at the RmICARS, it's a 29-point scale. A statistically significant change would be 1.5 points. Minimally statistically significant for our trial would be 1.5 points out of the 29.
Mm-hmm.
It's powered to show a difference of about 2.5 points out of 29.
Mm-hmm.
In a six-month period, that's about, you know, a 10% difference from baseline. So that's a pretty significant change over six months. And if you look at what the numbers actually mean, what is a two-and-a-half-point change, and you look at the scoring tool, it could mean the difference between walking autonomously and walking with support over a six-month period. So that's a big deal. I mean, longer term, you'd look for other things like, you know, how long can you maintain independent walking? Is your rate of cancer decreasing over time? Lifespan? That's in the long term, those are the sorts of things you would look at. But in the short term for the trial, that's, that's what we're hoping for.
Okay.
Anything in the range of two would be terrific.
Okay, and team, another question is that the data, I assume, is coming in February, so an opportunity probably after Q1.
I think we should make Q1, but, you know.
Yeah.
Yeah. But.
Okay.
Yes.
I just fine-tune it. Yeah.
Gonna get in trouble with IR if I get too specific.
Yes. No, not a problem. And then, team, maybe help us understand how soon post the data could you be in a position to file?
To file the NDA?
The NDA, and how much work has been done behind the scenes to prep a lot of the modules that are maybe you can already pre-write?
Oh, yeah. That's a good question. A lot, and you know, I'm historically a drug developer, so this is the strength of what I do. I'm the Chief Medical Officer as well as the CEO. So, this is the part I'm pretty decent at, and we are well ahead of the game in a couple of areas. The first thing to mention is that this is a 505(b)(2) pathway. So with respect to the nonclinical development plan, it's minimalistic, and we use a reference drug for safety pharmacology and toxicology. So that writing that part of the NDA is a lot easier and is already underway. And then from a CMC perspective, it's you have the machine component, which is more complicated, but from an API and drug product perspective, it's dexamethasone in solution in an ampule, and that's commercially available.
So that part is already being written, and we have our three stability batches, three validation batches on stability. So we're, you know, generally, in my experience, CMC is usually the rate-limiting step or close to it. And in our case, we're well ahead of the game there, and so we're writing that module as well. And so, when it and the other thing that'll make it more efficient is that it's rare disease. So the number of studies that are involved in. I don't think we're gonna have an ISE. We will have an ISS that's already been designed, and we're working on the statistical analysis plan for that. We have a final statistical analysis plan for the primary protocol. So to answer your original question, when can we file this? I mean, it'll be in the second half.
It'll probably be, you know, in the transition between Q3 and Q4, too, and that's because drugs take about six months to file, but drug-device combinations historically take about 10 months because they're more complicated. You have the device component that adds a lot of additional elements that take time to write up.
Okay, and that's very helpful. Which division at the FDA will be reviewing?
This is the division of neurology, and it's regulated as a drug-device combination, and the DN1 division, the DN1 office in neurology gets consultations from the device and biologics divisions.
Okay. It would be good to also talk about the A-T space. Publicly, you guys have noted that there are about 5,000 patients in the U.S. Maybe help us understand what type of claims database or bioinformatic work you've done to understand that this is the size of the opportunity?
A couple of things. We have ICD-10 codes from IQVIA that give us 4,600 diagnoses that are confirmed with SNOMED codes.
Mm-hmm.
So that number's pretty solid. And then we've also embarked on sort of reverse engineering a number by using we're working with a professor at Baylor, Dr. Bonin, to sort of reverse engineer epidemiology and statistics using a genetic database. So looking at the types of mutations and their frequency in a large cohort of public data, and then you use those genetic mutation frequencies to and census data to sort of calculate what it should be. And that number comes out to more like 5,500-6,000.
Mm-hmm.
So it's in that range. So the data's pretty consistent that there are probably about 5,000 kids in the United States and likely underdiagnosed because there's nothing approved for it. So that'll improve over time as well.
How much does the device cost, that technical device to make each machine?
The machine?
Yeah.
It's pretty cheap. It costs about $25,000 to make each machine.
Okay.
The cost of goods for the therapy's gonna be very, very low, less like about 2% or less.
There is definitely sufficient time to make the machine with the.
Well, we have a supply chain, you know, and we plan way ahead. And, you know, we have enough machines to do our clinical trials now. And then we're constantly buying parts and assembling machines, which is about a nine-month process so that, you know, we have it all mapped out through our additional indications.
Okay.
And our launch strategy.
Obviously orphan pricing varies, right? For Luxturna, it's $430,000, and KYMRIAH was approved early in the year. That was a one-time, but it starts off with $450,000. So how do you think about what work have you done with payers given this high unmet need? How much flexibility do you have in terms of pricing?
You know, this changes over time, and prices seem to be going up. There is some flexibility, and it seems like for a disease this rare with, that the price point will probably be somewhere in the $500,000-$700,000 per year range.
The company would also be transitioning to being a commercial company. Help us understand what work you guys have done to understand mapping out. Where are these patients located? How large of a sales force? Shout out to Stacy. You guys are doing a commercial day webinar. She may need to help me from what's what is that date, Stacy? The commercial day, the marketing day in December that you guys are doing. So what? Yeah. Oh, there is okay. There is maybe a.
I don't remember the date.
Yeah. We don't remember, but it.
I don't remember the date, but.
But we will give a shout out to Stacy because you did.
Sure.
Make a very good R&D day that.
She did.
In the fall and I think.
And I would encourage people.
Yeah.
It's on our website, and you can.
Okay.
If you're limited on time, you can listen to it at.
Too far.
Faster speed, you know.
Yeah. But it's, it's very well done. You can actually see how the machine works, and you can actually also hear the testimonials of the families.
Yeah. There's a patient video on it.
Which is absolutely devastating. After seeing this, you really wanna vote for the positivity of the therapy.
That's definitely worth watching. It gives you a real sense of what the kids and the families go through.
Go through. Yeah.
Comfort to watch people.
Yeah. How are they?
Cry when they watch it.
Yeah. No. I was in tears when I was listening to it live. So, how are the patients concentrated in specialty centers or where are they?
No, not really. They're sort of, you know, we based on what we know,
Yeah.
About existing patients and our assumptions about, you know, where new cases pop up, it probably just follows the population centers.
Mm-hmm.
There's no, when patients get diagnosed, they usually do end up getting to a center of excellence, but there's nothing approved for the drug, so they usually get worked up, and, you know, the standard of care is physical therapy and occupational therapy and supportive care for infections.
Mm-hmm.
And then ultimately, they get cancers. They'll get treated for that. But usually, what happens is they get fully worked up, and they might have some plans put together, but then they get, you know, sent home and managed by their local physician. They might check into a center of excellence every year or two.
Mm-hmm.
But it's they don't get normally managed there on a day-to-day basis. So our commercial plan is linked to population centers. We signed a contract with an outpatient infusion network called Option Care , and they have about, I think, 170-180 sites around the United States, and we'll launch initially with about 50 of those in the major population centers, and we estimate that that should get about 85% of the patients within a 90-minute drive of an infusion center.
That's just a horrific disease, not only in pediatrics but also as a parent finds out that they have a child with A-T, they Google it, and they realize that they also reduce the risk of the parent to significant cancers.
That's right. I think it's underappreciated. But this gene that is mutated, I think that came up in the video too.
Yeah.
That you referenced is the doctor said, "Don't Google it.
Yeah.
So of course, they Googled the first thing they Googled, and they found out how terrible it was. But, this protein that's mutated is called the ATM protein.
Mm-hmm.
One of its primary roles is the sensing and triggering responses to double-stranded DNA damage. Triggers DNA repair pathways. And if it gets mutated, you have more double-stranded breaks and more oxidative damage. So the risk of cancer in an adult just carrying one of the alleles is about a 25% increased risk of cancer. And two people who are heterozygous for the mutation have a 25% chance of having a child with AT. It's possible it could have variable penetrance but or severity. But sometimes they don't find out. You know, it takes a while to make the diagnosis, tough diagnosis to make, usually between the ages of two and five. And sometimes they already have a second child, and then they have to get that child tested.
Mm-hmm.
To see 'cause there's a 25% chance that child could have it as well.
Can you imagine?
I know people who've had, you know, they thought it was a normal, healthy second child, and they found out that child will subsequently show symptoms because they're genetically AT.
Imagine having to find that out, and you find that you, as a parent, also have a 25% increased risk of cancer. So we are so excited for the work that you guys are doing for this patient population, and really are excited for this readout in NEAT. So thank you so much for being part of our team. I encourage many of you to listen to the story and to the webinar and talk to the team. So let's give them a big applause.
Thanks, Yash.