Wainwright 27th Annual Global Investment Conference. My name is Maya, and I'm a Research Associate here at Wainwright. We're excited to introduce you to about 600 companies presenting at our conference this year across our key sectors of life sciences, cryptocurrency and fintech, clean tech, metals and mining, and TMT. I'd like to welcome Dirk Thye, MD, CEO, Chief Medical Officer, and board member of Quince Therapeutics. Quince is developing eDSP, formerly ERIDEX, which leverages the company's Autologous Intracellular Drug Encapsulation or AIDE technology platform to encapsulate the corticosteroid dexamethasone sodium phosphate into the patient's own red blood cells. I'll yield to you the floor, Dirk, to introduce yourself and the company. Thank you, Maya, and hello everyone. Dirk Thye here. The name of the company, as you just heard, is Quince Therapeutics. Our logo is unlocking the power of a patient's own biology for the treatment of rare disease. It's nice to be here at the 27th Annual Wainwright Conference, and here are my disclosures. The technology we have is called AIDE, Autologous Intracellular Drug Encapsulation. It's a machine, which I'll show you in a moment, which is capable of encapsulating large or small molecules or proteins within a patient's own red blood cells. These are autologous red blood cells. The entire purpose and the key to this technology is it allows the delivery of chronic corticosteroid therapy without any of the corticosteroid toxicities, which are, of course, limiting to long-term therapy with corticosteroid treatment. Some of the highlights of our company: we are currently in phase III for our first indication. The indication is ataxia telangiectasia. It's a rare, terrible rare pediatric disease that I'll tell you more about. There's nothing approved for this disease, and it's a good commercial opportunity of $1+ billion in the rare disease space. We have completed enrollment in that trial as of several weeks ago. We have 83 patients in our primary analysis population and 105 patients in total overall. It includes some patients that are not included in the primary analysis population, which I'll describe here in a few subsequent slides. That's our first indication. As I mentioned, this is a method of giving steroids chronically without toxicity. As you can imagine, there are scores of potential indications we could pursue here, and there are a lot of them we would like to pursue. First on the list is Duchenne muscular dystrophy. You may be familiar with that. It's a more mature commercial market than ataxia telangiectasia. Steroids have already been approved for use in that population, and the vast majority of patients with DMD are on steroids, and essentially all of them have chronic toxicity problems. This would be an opportunity for patients to transition onto a steroid therapy that does not have those chronic toxicities, which are a huge impediment to their life. Probably, undoubtedly, I would say the biggest problem in their lives, although they do help with their underlying disease, at least with respect to the therapy for their disease. It's their biggest problem. With respect to the commercialization of the program, we've recently entered into an agreement with a company called Option Care. They have about 170 outpatient infusion sites around the country, and this will really facilitate the distribution and launch of our product as we'll be able to get about 80% of the eligible patients within about a 90-minute distance from an Option Care site. From a cash position, we're in good shape to get through our next major value inflection point, which is the data readout in the middle of the first quarter of next year. Q1 2026 is when we'll get our phase III data readout, and our current cash will carry us through the middle of next year. This is a picture of the machine that I mentioned. It's a fully automated system. You can see the touch screen there. I'll describe in a second how it works, but it's a 90-minute process, and as I mentioned, it uses the patient's own red blood cells. There's no blood matching. There are no synthetic cells. There are no manufacturing issues. You take a little bit of the patient's own blood, and you process it to, in the case of our lead product, encapsulate a steroid, dexamethasone sodium phosphate. Specifically, the way it works is you take a small volume of blood from the patient first, 50 ml. That represents only about 1% of the circulating blood volume of a child. You hook up the syringe with 50 ml to the machine I just showed you, and you push start on the touch screen. Over the next 90 minutes, the machine, the patient's not hooked up to the machine, okay? They go off and do something else for the next 90 minutes while the machine processes the cells with a series of hypotonic solutions to slowly swell them and make them porous. It incubates them with the drug cargo, and then it uses hypertonic solutions and some other excipients to shrink them back down. During that process, many molecules of the dexamethasone sodium phosphate get trapped inside the red blood cell because the phosphate group is ionic, and therefore it can't diffuse across the lipid bilayer of the erythrocyte. Intracellular phosphatases within the erythrocyte will cleave the phosphate group, rendering it nonpolar over time. The nonpolar dexamethasone can leak out through the lipid bilayer as the red blood cells are circulating throughout the body. How does that take toxic corticosteroids and change them into nontoxic corticosteroids? Let me explain that for a second. What you're looking at here is a PK curve of a typical dexamethasone daily dose of 6 mg a day. When you give corticosteroids, due to the limitations on half-life, and this is true of all various formulations of corticosteroids, even if they're long-acting formulations and regardless of the route of administration, subcu, IM, oral, whatever, they all have relatively short half-lives, and you have to give them typically at least once a day. When you do that at the lowest effective dose, you consistently exceed plasma concentration thresholds that are associated with toxicity, and that's what these parallel dotted lines are for: hyperglycemia, immunosuppression, and the most sensitive parameter in light blue is adrenal suppression. You cannot give corticosteroids for more than a couple of weeks without starting to run into problems with adrenal suppression, and that's the biggest chronic toxicity associated with corticosteroid use, long-term corticosteroid use. You can see there are a variety of things related to adrenal suppression at the top of the slide that cause big problems. It can lead to diabetes, osteoporosis, growth delay, delay in puberty, behavioral issues, hypertension, etc. That's what's limiting for the efficacious dosing of these types of drugs over time. By putting it in a red blood cell, you fundamentally change both the pharmacodynamics and the pharmacokinetics of how corticosteroids work. It's important to understand a couple of things about efficacy in corticosteroids. You need a couple of key PD parameters to be met in order for them to be efficacious. One is that you need a Cmax of at least about 100 ng/ml. On the previous slide, those Cmax peaks associated with typical corticosteroid therapy were exceeding that, so they're very likely to work. That's a requirement. You need to get glucocorticoid receptor saturation in the tissues in order to achieve the non-genomic effects associated with the mechanism of action. The second thing you need is you need prolonged glucocorticoid receptor occupation over time. Due to the short half-life of corticosteroids, that's why you have to give them consistently, so that you maintain some proportion of glucocorticoid receptors that are occupied. You need the Cmax and you need the long exposure. That gives you both the non-genomic effects that are beneficial and the longer-term genomic effects related to persistent receptor occupation. How do we change that? Now you're looking at the same period of time. Previously, I showed you 30 doses over 30 days. When you encapsulate the corticosteroid into the red blood cells, you give it once per month. The patient comes in, you take their blood, you process it, as I described, you give it back to them. You do that once monthly, and you get this PK curve you're looking at here. You can see that you exceed 100 ng/ml. You get the Cmax required for the non-genomic effects of the corticosteroids, but then you get this long, slow tail of plasma concentrations of corticosteroids, and that gives you the longer-term receptor occupation required for the genomic effects. In addition to that, the point there is that it satisfies the major requirements associated with efficacy. The results of our phase III trial will prove whether this is an efficacious dose, but theoretically, that's how it should be efficacious. In addition to meeting those efficacy requirements, you can see that with this PK curve, you pretty quickly get below the toxicity thresholds that are the plasma concentrations that are associated with toxicity. You get below hyperglycemia, immunosuppression, and then after about seven to ten days, you get below the cortisol sensitivity parameter. We have a very strong long-term safety database consisting of about 70 patients that have been taking this monthly for over three years, and they have no adrenal suppression at the same dose. There are three patients that have been taking it monthly for 13 years now from an early exploratory study, and they have no adrenal suppression. We have a very strong safety database to demonstrate that this is a safe dose. The question is, is it efficacious? Right now, we're studying this indication, ataxia telangiectasia, to find that out. It's a terrible pediatric genetic disease. It's an autosomal recessive disease. It affects about 5,000 children in the United States. It's primarily manifested by neurological deterioration at a young age, starting around the age of 2 years-4 years. Children usually end up in a wheelchair by about the age of 10 years -1 2 years. They also get frequent infections and develop cancers in later years, and their typical lifespan is in the mid-20s. There are no drugs approved for this indication. This is a graph showing the neurological degeneration over time in a natural history setting. You can see that they typically get diagnosed around the age of 2 years-4 years, and they have rapid neurological deterioration until approximately the age of 10 years or 12 years, where they're often in a wheelchair. Thereafter, the neurological deterioration plateaus, but they continue to have problems with infections and cancer. There was a previous study done by the company that we acquired that developed this technology over a period of 20 years. That company was called Aeradel, and they performed a large study called the ATEST study in 175 patients with ataxia telangiectasia. The design issue with that study was that they included patients from six years of age and above, and about half of the patients were 10 years of age and above. You can see from that previous natural history study that you wouldn't expect to see a large effect in that population since they already would have plateaued neurologically at that point in time. Indeed, that's what they saw in the overall population that included half patients that are younger, half that were older. They did not, they had a P-value of 0.07, so they did not meet statistical significance. When they looked at the younger group of patients in the 6 years-9 years of age, they had a highly statistically significant result in that previously specified subgroup. Essentially, what we're doing, and the magnitude of the effect was pretty large, it was a 24% advantage over placebo over a six-month period. The magnitude was quite significant. Essentially, what our phase III study does is it repeats just one dose, the higher dose of encapsulated dexamethasone versus placebo, given once a month over six months, just within that higher dose in the younger age group, in the six to nine-year-old population, that showed that very big delta versus placebo in the previous trial. As I mentioned earlier, we've completed enrollment, and in our data monitoring activities, we're seeing very excellent scientific integrity and adherence to study protocol mandates. We have very little missing data compared to the previous trial and very few dropouts. Essentially, the effect of that is that it increases your power to determine a statistically significant result. We're pretty confident that whatever result we get in the first quarter of next year will be a truthful result. We think we'll have a high statistical power to determine a difference there. This protocol that I just described is under a special protocol assessment with the FDA. We have a priori agreement that it can be a single pivotal trial, and if positive, will support an approval. We do have orphan drug designation. It is regulated as a drug-device combination product through the Division of Neurology, CDER, DN1, and they will get consultations from both the biologics division and the device division. After getting data in Q1 of next year, we will then prepare our NDA and file that NDA in the second half of next year. I didn't mention this, but the device itself already has a CE mark in Europe. The device has proven that it does what it's supposed to do, but it is not approved for use with a drug. In the U.S., it's regulated a little bit differently as a drug-device combination. AT is a really attractive commercial opportunity. The best way to think about it is probably similar to Friedreich's ataxia, for which there have been a couple of recent drug approvals. About 5,000 children in the United States and 5,000 in the major European markets, so about 10,000 addressable patients for the initial commercialization. At typical rare disease pricing, you're easily getting over a $1 billion market with that type of epidemiology. I mentioned the Option Care machine deployment strategy, which will really help us in the United States with commercialization, and we will partner commercialization efforts in Europe. We have done some epidemiologic work and record finding through IQV and identified about 4,600 patients with a confirmed diagnosis of ataxia telangiectasia in the United States. That just supports the epidemiologic numbers I gave you on the previous slide. I've talked about Option Care already. I mentioned they have about 170 sites around the United States, maybe closer to 180 now. They have pharmacies at a lot of these. They have the ability to handle the shipping and logistics and third-party vendors and the administration of the product at the site. They're starting to focus more on rare disease because it's an attractive commercial opportunity for them. I think historically, they've focused on oncology infusions and IV therapies. AT is a great opportunity for us because it'll be the first ever drug approved in AT, and it's interesting commercially. As I said, if it works in AT, there are many, many different indications we would like to pursue where steroids are either already beneficial, proven to be beneficial, or could be beneficial. Here's a list of those. I had mentioned that DMD is the first on that list. We now have a development plan designed for DMD, and we'll be rolling that out after we raise additional money following our phase III results in 2026. I don't have time to walk you through all the differentiating features of this versus existing corticosteroids, but you can imagine that a safe corticosteroid for DMD would provide a lot of benefits in that indication. Just looking at the next milestones, we've already completed a lot of milestones for 2025. The remaining ones for 2025 are to start our pediatric investigational plan, which is a study required in younger children for Europe and could have label enhancement benefits here in the United States, and then to advance our DMD program. Next year, the big milestones will be getting data in AT, and subsequently the activities related to filing our NDA and advancing our other programs. Thank you for listening and enjoy the conference. All right. Thank you very much, Dirk, for sharing the Quince Therapeutics story with us. We appreciate the time and effort that went into your presentation, as well as your presence at our conference. We, of course, hope to host you again next year, and thanks, folks, for dialing.