Everybody, and thanks for joining day one of the Citizens JMP Life Sciences Conference. My name is John Walden, Senior Analyst here. We're pleased to have Quince Therapeutics and CEO Dirk Thye to give a presentation, about everything they're working on with some recent updates this morning. And we'll save, some time for Q&A in the room. So with that, Dirk, please take it away. Thank you very much, and good afternoon, everybody. My name is Dirk Thye. I'm the CEO and the Chief Medical Officer of Quince Therapeutics, and what we do is we use a patient's own biology to deliver rare disease therapeutics. These are my disclosures. The company is fairly new. Last October we completed the acquisition of a company called EryDel, which is located in Italy, and we acquired their lead phase III asset called EryDex that I'll tell you quite a bit about today, and that's for the treatment of ataxia telangiectasia. This phase III program that we're just embarking upon right now is under a special protocol assessment with the FDA, already been agreed to, so we have agreement that if the study is positive it can form the basis of approval for the indication of ataxia telangiectasia. One of the key elements that we highlighted with respect to our searching of an acquisition was that we had enough remaining cash to get to an important inflection point, and in this particular case we have sufficient cash to get to phase III data, which will be coming in the fourth quarter of 2025. So this is the technology. It's a device that is about the size of an old-fashioned desktop computer. It can sit on a cart. It can sit on a table. The purpose of the device is to take a patient's blood, a small volume of blood, about 50 mL, represents about 1% of your circulating blood volume, and it uses a series of solutions to swell the cells, make them porous, incubate them with a molecule of interest, then uses hypertonic solutions to shrink them back down, and then they get washed and isolated. All that happens in about 90 minutes, in an automated process using this machine. So you take 50 mL of autologous blood from the patient, you run it through the machine, it encapsulates the drug of interest, and then you reinfuse the blood a couple hours later back into the patient, but now it has a drug inside, which has, confers a variety of properties. I'll explain, the advantages that we have with respect to our lead product, which is dexamethasone sodium phosphate. So with dexamethasone sodium phosphate, that's a prodrug of dexamethasone. It's polar. So once it's locked inside the cells it cannot diffuse across the lipid bilayer, so it stays within the cells and it circulates throughout the body. Intracellular phosphatases cleave that phosphate group, rendering it nonpolar, and then it leaks out of the cell. Ultimately what that results in is a PK curve that looks like this. It gives you it results in the key characteristics that are required for corticosteroid efficacy. Specifically, you need a high Cmax, and then you need continuous receptor occupation in the tissues of interest. So you're looking at a one-month time period here. So what you get is you get a Cmax on day one, so higher concentrations over the first 24 hours or so, and then in a concentration-dependent manner you get that dephosphorylation of the prodrug intracellularly, and over the next month you get this slow release of dexamethasone from the cells. So that in itself confers some really important advantages, which I'll elaborate on in a second, but you also have the advantage of having the dexamethasone biodistributed in a very different manner because it's in the red blood cells, which are circulating rapidly throughout the body, and they spend more time in tissue beds with large capillary beds like the lungs or the brain or the liver. With respect to safety, this is really key. This is sort of the key value proposition for this particular program, dexamethasone sodium phosphate. We call it EryDex. So if you want to get corticosteroid efficacy, I said you need a high Cmax and you need continuous receptor occupation. You can get that with daily corticosteroids, or more than daily, more frequently than daily, but you have to dose them more or less daily. When you do that you get a Cmax and you get receptor occupation, but you also get safety problems because you're continuously stimulating toxicity thresholds, which are described on this slide here. Everybody's heard about the many adverse effects that come with chronic steroid dosing. The most sensitive toxicity threshold is related to adrenal suppression, and that's the lowest threshold here on this slide. With daily dosing you're constantly triggering these, so after a matter of days and certainly weeks, and you can't take steroids for months. You can't take it for days without running into problems. The problems change the longer you take it, but it's highly toxic when taken chronically, and that's why. With our approach, you're below these toxicity thresholds after about a week. To support this theoretical construct, you know, we have data. There have been three patients taking this for about 10 years now, monthly, and they don't have any signs of chronic steroid toxicity. We have about 100 patients on compassionate use that have been taking it for about three years now, and they also don't have any signs of chronic steroid toxicity. So the key here is that this appears to be a method by which you can treat chronically with corticosteroids without any safety liabilities. So as you can imagine, that would be huge for lots of different diseases. Our initial focus, and we're interested in many of those, but our initial focus is on ataxia telangiectasia. Ataxia telangiectasia, there's nothing approved for this disease. It's a horrible genetic pediatric disease. It's due to mutations in the ATM gene, which produces the ATM protein, which is involved with lots of different important cellular processes, proliferation, maturation, but it has a really critical role in double-stranded DNA repair. So what happens to these children with mutations in this protein is initially they have neurological deterioration, and that starts, it really starts around the ages of four or five, and then typically by the age of 10 they're in a wheelchair. And then in their later years they start to get infections, repeated infections. Their T-cell counts drop, and then because of the DNA damage they start to get cancers. So they typically live between 15 and 25 years of age. There's nothing approved for it, so it's typically there hasn't been a big push to get it diagnosed. It's really difficult to diagnose it. There is no prenatal screening for this. They get the only care that they get is supportive care with respect to, you know, treatment of infections, treatment of cancers, and physical and occupational therapy. So EryDel, prior to us acquiring them, had performed a phase III study in ataxia telangiectasia, and they narrowly missed statistical significance, but this is another really important point for reasons that we believe we understand very well and are logical. So essentially I told you that the natural history of the disease is that neurological deterioration is quite rapid between the ages of about five and 10, and then it starts to plateau. You get continual neurological degeneration until the end of life, but between five and 10 it's really rapid, and then it starts to slow down. When EryDel did their phase III trial, they used, at the request of the FDA, they used an outcome measure called the revised modified ICARS score. So the ICARS score is a neurological scoring tool. It's similar to, like in Alzheimer's disease, for example, you have ADAS-Cog. In AT or some neurological diseases you use this ICARS tool. It's a 100-point scale in various domains, and you run the patient through a series of neurological tests. You put the heel to shin, and you look at their speech and their oculomotor movements and things like that, ability to walk, to stand, things like that, balance. The FDA requested a subset of the scale that they thought best reflected how a patient feels or functions. So out of the 100 points they specified that the primary endpoint would be in a 29-point scale called the revised modified ICARS score. That's the one on your right with the box around it. Okay, so back to EryDel's study. EryDel did a study using that score, which is heavily focused on lower limb function. So logically, based on what I just told you, you should see a big effect, a bigger effect, in patients between the ages of five and 10 when they're rapidly progressing. And by the way, their study was a treatment period of six months, so it wasn't that long. So kids between the ages of five and 10 you're going to see a bigger difference versus placebo than kids over 10 because that's when the deterioration slows. Well, in their trial they enrolled about half of the children from ages six to nine and half of the children over 10, 10 and over. In the children six to nine, the difference to placebo was highly statistically significant. In the children over 10, there wasn't too much of a benefit using the Rm ICARS. We're going back and looking at the full ICARS to see if there were other measurements, subdomains, that did show benefit, but when they looked at the overall, the primary endpoint, which included, you know, everybody, the p-value was 0.077, so they just missed statistical significance. So when we, you know, dove in and did our diligence on this, we were highly encouraged that another trial only in the population of most interest, not most interest, but the population that's deteriorating most rapidly, if we repeated a phase III trial in that population using the same endpoint, that we would have a high probability of success. So that's exactly what we're doing. We're just starting it right now. We have our regulatory approvals in the U.S. and Europe to start the trial, and we are actively screening. It's pretty similar to the previous trial, with the exception that the age is only 6-9. It's in 86 patients. It's randomized 1:1 to EryDex versus placebo, monthly treatment for six months, and then it's the difference from baseline, active versus placebo, and it's 90% powered based on what was seen in that previous trial, which was called the ATEST trial. It's also using the endpoint that I described, that RmICARS that you saw the box around in the last slide. This study is under a SPA with the FDA, so if it's positive it will form the basis of approval. Okay, now this is a rare disease. With respect to epidemiology, it's very similar to Friedreich's ataxia. So there are about 10,000 children in the U.S. and Europe, an estimated 10,000 children in the U.S. and Europe. I told you diagnosis is complicated here. That 5,000 in the U.S. number was discovered through epidemiology and bioinformatics to come up with an estimate, but recently what we did was purchase IQVIA data to look at actual, A-T diagnoses that are used for hospital claims, and that was surprisingly high, we thought. It was at 3,400, so 3,400 would probably support a number higher than 5,000, so we think that 5,000 in the U.S. is a pretty conservative estimate. And then, if you look at just the standard pricing comps in this with epidemiology in that range, like an annual price on the order of $300,000-$400,000 a year that gets you to a billion-dollar market opportunity for this indication. But we, you know, like I said, I think we're pretty confident that it's going to work for this indication for the reasons I outlined, but you can imagine that the ability to give steroids chronically without safety issues would be huge in a lot of different diseases. Now it's not devoid of burden. The patient has to come in once a month, and you take some blood, and you process it, and you give it back to them, so, you know, it's not going to be ideal compared to a pill for certain diseases. But there are many, many diseases in which this would be super beneficial. One of those is Duchenne muscular dystrophy. Despite all the advancements and therapies for that particular disease, pretty much all children are still on steroids, and they all have problems with steroids. So this would be a really good alternative for chronic steroid therapy in that indication, and so that'll be our next indication. Right now we're in the process of working with experts in the field to design exactly what a trial would look like in that indication, and we'll probably do some exploratory work in the clinic first before going into a pivotal trial there, but that'll be next on our list. And then we're also in the process of taking we had about 70 different diseases that were our favorites that we could pursue, and those fall within a variety of different therapeutic areas that you see here, but the strategy will be first to focus on rare disease in pediatrics. That's where we're developing expertise, and that's where we've started, and we can expand in that area. Then we'll move into rare disease in the non-pediatric population, and then from there we can move into non-rare disease. Back to, you know, one of my first slides, I mentioned it's a platform. We can encapsulate other things into the red blood cells. So for example, we could take a different steroid and use the same approach. It'd be very easy to swap it out, and then we could pursue other types of indications like non-rare disease with that other product, and then there are enzyme replacement therapies we can put within the red blood cells. So there are a variety of things we can do with this that are really interesting. And then with respect to, of course, we always like to look at the Reata comp because it was so good for us, but, you know, I mentioned the Reata, the Friedreich's ataxia epidemiology is very similar to us, and their pricing is similar, so it has a lot of good parallels with our situation. And as you know, rare disease has been pretty popular lately, so it's a good area to work in, and it's also a good area to work in with respect to regulatory affairs because the pathway to approval is so rapid and efficient compared to other therapeutic areas. And I've been doing this for a long time now. I've been doing this for 25 or 30 years, and I was a physician. I did my residency at Stanford and went straight into starting companies after that and have a number of drug approvals. And along the way I've been able to collect my favorite people in different functional areas, and with this particular company I've been able to bring a lot of those people together, so I feel like we have an extremely highly experienced team that knows how to do this. And as I mentioned before, I think that this trial has a very high probability of success. One thing that we really wanted to emphasize when we were looking for something to acquire is that we'd have enough money to get to an important inflection point, and with this particular program, when we took it over we had, we still do, we have enough money to get to data, and data will be coming out for this in the fourth quarter of 2025. Of course, along the way if we have the opportunity to raise some money and accelerate our DMD programs and other programs we'll certainly do that, but with respect to A-T we're in good shape. Here are some TV shows. What should we watch? [audio distortion] No problem. So the next big news that'll be coming out is that we'll be initiating enrollment in the phase III trial that I mentioned has started up now. We have regulatory approvals, and we're screening for that. As I mentioned, we have selected DMD as our follow-on indication, so we'll be working on our plans for that. We'll also be working on plans for follow-on indications after DMD. And then in 2025 the big one, of course, is going to be getting data for this. It's called the NEAT trial, N-E-A-T. That's our phase III trial in ataxia telangiectasia. So I think that's it. So I'll open it up to questions. Thank you very much, Dirk. I have a few myself, but I just want to check if there's any in the room to start. Do you want me to sit down? Yeah, you can take a seat. Are you mic'd up? Yeah, yeah, we're good. [audio distortion] get out of this treatment? Yeah. Like before, and does it, at the age of ten, does it [audio distortion] Yeah, let me tell you some subjective things and some objective things. Subjectively, EryDel started developing this, well, they started developing the machine 15 years ago, and they did some exploratory work in A-T about 12 years ago, and 3 of those kids in that exploratory work are still taking it monthly. And then we had, from that prior trial I told you about that narrowly missed, many of those children rolled over into compassionate use studies, so there are about 100 patients that are still on it monthly. And the families and the children believe they're getting something out of it because they're going through the burden of some of these people fly from Brazil monthly and things like that, so they're going through the process of showing up at the clinic every month and going through the procedure. What they say is they feel better, and what the families say is they function better in every way. They walk better, they move better, they're more energetic. Objectively, in the six-month period, remember I told you about the 100-point score and the 29-point score? In the 100-point score it was about, over a six-month time period, a 5.6-point difference between active and placebo. So that's a 5% difference in a six-month period. I don't know how that changes over time because it's just a fairly short period in these kids' lives, and in compassionate use studies you can't continue to, you're not allowed to continue to collect this kind of data. So I don't have long-term efficacy data. I only have long-term safety data. You still have to report the safety in the compassionate use studies, but in the Revised Modified ICARS, that 29-point score, it was a 2.4-point difference out of 29, so even a larger percentage difference for that sub functional score over six months. So in the over ten, you were asking about the over ten, do they continue? I'm not sure. If we look at the over ten as a subgroup in that first trial that was done, when you look at just the Revised Modified ICARS there was a slight benefit but not a lot, but of course that's looking primarily at lower limb function. So the hope would be that this delays the progression of neurological disease in a meaningful way by months or even possibly years, and if it works via that mechanism I think there's a strong hypothesis to be made that it would also potentially delay the development of repeated infections and cancers. Hopefully what we're ultimately trying to do is try to improve and increase the length of their lives. [audio distortion] at the end of 2025? Well, that's data. That's data, yeah. Oh, yeah, data, sorry. So is it 86 patients, right? Right. Just going to be enrollments the challenge getting them because it's a six-month treatment period? Yeah. You know, enrollment's always a challenge, but the EryDel, the study they did previously was 175 patients, and that was three arms, two doses, and a placebo, so they were able to enroll. Now, remember that was six and above, and half of them were over 10, so it's a little harder for us because we have to find kids within this narrower range of age, and we don't have as many sites. They went to places like India and Tunisia and Australia, and they had problems because of that. It was also during COVID, so they had a lot of logistical issues and missing data because it happened during COVID. So we have fewer centers, which makes it a little more challenging, but on the flip side we also have a lot of control over the quality of the patients, and we're dialed in with the patient advocacy groups in the U.S. and Europe, and they help us with outreach and patient identification so that we can steer the kids to the closest site. [audio distortion] treatment naive, or can you look at the claims data? Yeah, treatment-naive. [audio distortion] data that you've already seen with these 3,400 patients or whatever because [audio distortion]. Honestly, I'm not sure. I don't think claims data gives you patient identification. I think it's just, yeah, we know they exist, but we don't know who. Six and above? [audio distortion]. No, we just announced it today. [audio distortion] Today, yeah. Our press release came out. [audio distortion] Okay, good. Well, great. You know, so far what we've done is get to know some of the experts in the field that were pivotal in designing other programs, and introduce them to our technology, introduce them to the value proposition, and start to work with them on potential study ideas. And so that's where we're at right now is we have a few different approaches we could take into clinical development and finding the right fit between the medical need and the commercial opportunity and how we're going to design a study. That's what we'll be working on over the next coming months, but we'll be opportunistic. The dynamics of our stock trading is they're weird. We reverse merged into a failed Alzheimer's company, so we have low volume and low stock price. It's hard for new investors to get in, but we will be opportunistic along the way if things change by increasing our awareness of our technology, or we're in a position where we can raise some money with less dilution. We will, and then we can advance DMD a lot quicker. [audio distortion] drug that's already in existence, right? Just taking it off of whatever drug that's been around, putting it in a device. Defensible at price that you want to be saying it's a rare disease type of pricing, and then IP? I don't understand the technology exactly, but it didn't sound that complicated. Oh, no, it's complicated. I mean, people have been working for 50 years to try and encapsulate things into red blood cells. Encapsulating things into red blood cells is not novel. I mean, it's been an idea of scientists for a long time. It took them 20 years and $100 million to build this machine. So there is IP on method of use and the machine itself through 2025, and it'd be so hard to reverse engineer this, and I think, are we almost done? Yeah, we're. Okay, I'll just say with respect to price, it's a complicated commercial endeavor, which I think justifies the approach and the pricing to rare disease because we have to, it's an entirely different model where we have to place these machines in centers of excellence, and we have to get the patients there, and it's a half-a-day procedure to bring them in and get them treated. So there's a lot more to it than you're not just giving a vial or a pill or anything. That's a good problem to have down the road. Well, exciting technology, exciting data, and we're looking forward to updates on DMD and then data next year. Thank you very much. Thanks, Dirk.