Hello, my name is Dirk Thye, and for those of you who aren't familiar, I'm the CEO and Chief Medical Officer of Quince Therapeutics. If you had the opportunity to watch our previous video, then you heard about our recent acquisition of EryDel and how that's transformed Quince into a biotechnology company with a rare disease therapy called EryDex. EryDex is initiating Phase III in ataxia-telangiectasia in the second quarter of this year. Today I'd like to spend some time describing the technology platform behind EryDex. It's this technology platform that makes Quince unique and provides tremendous potential not just for EryDex in A-T, but also for additional indications with EryDex and future discovery programs using this platform that incorporate different drugs or biologics into autologous red blood cells. So our technology platform is called Autologous Intracellular Drug Encapsulation, or AIDE, and it's extremely powerful and versatile. AIDE was pioneered over two decades of scientific and clinical work by EryDel and made them our clear favorite when seeking a valuable acquisition for Quince. The AIDE platform is a potentially revolutionary drug-device combination that encapsulates small or large molecule drugs, or even peptides, into a patient's own red blood cells. This encapsulation fundamentally alters the drug's biodistribution and pharmacokinetic profile, and that can dramatically improve the efficacy or safety of either older proven drugs with liabilities or new drugs requiring optimization. By using a patient's own red blood cells, we avoid common and complex problems related to biocompatibility of foreign cells or immunogenicity associated with synthetic or engineered cells. Using the patient's own biology eliminates many of these challenging technical hurdles, and this allows us to deliver innovative therapies to patients with devastating rare diseases that are in desperate need of therapeutic solutions. I really am fascinated and excited by the potential of this technology, and my enthusiasm is founded upon closely scrutinizing a large amount of preclinical and clinical data that was developed over the last 20 years with about $100 million of investment by EryDel to date. This prior work and investment had led to AIDE being validated for quality and reproducibility as the device has a CE mark in Europe. Our lead clinical program is a Phase III asset called EryDex. EryDex is dexamethasone sodium phosphate, which is a corticosteroid, encapsulated into the patient's own red blood cells, and it's being developed for potential treatment of a rare neurodegenerative disease called ataxia-telangiectasia, or A-T. Notably, there are no currently approved treatments for A-T, and EryDex has already produced late-stage clinical data in patients with A-T, which demonstrated compelling signs of efficacy while also highlighting an impressive safety and tolerability profile. So to understand why EryDex could be highly efficacious but with a much better safety profile than systemic corticosteroids, let's start with what we know about steroid therapy. First, with respect to efficacy, successful corticosteroid treatment has two important requirements. Number one, an initial dose that achieves a high Cmax resulting in high levels of corticosteroid corticosteroid receptor occupation, and number two, sufficient sustained tissue concentrations that allow for continued receptor site occupancy over time. EryDex achieves both of these requirements with once-monthly dosing of relatively small milligram amounts of corticosteroids. This is because of the AIDE process that encapsulates dexamethasone sodium phosphate, or DSP, into the patient's own red blood cells. DSP is a prodrug of dexamethasone, and as a polar molecule, it gets trapped inside the cell. Once it's inside the red blood cell, intracellular phosphatases slowly cleave the polar phosphate group, rendering the active dexamethasone nonpolar and able to diffuse across the cell membrane and into the surrounding tissues where it can exert its effects. The end result is a once-monthly dosing of dexamethasone that satisfies the two criteria for efficacy that I previously described. But in addition to this dramatic change in PK, pharmacokinetics, you also have altered biodistribution because the dexamethasone is being slowly released from the red blood cell as it traverses throughout the body and through the various tissue beds with many capillaries. These are the tissues where you want dexamethasone to be delivered for its most beneficial therapeutic effect. In order for conventional steroids to achieve those two key characteristics required for efficacy, they have to be dosed frequently, and typically that's daily. But daily dosing regimens sufficient to ensure efficacy with conventional steroids lead to significant and debilitating long-term adverse effects. To distinguish EryDex from typical corticosteroid dosing, look at the orange line in this graph that goes up and down from peak concentration to trough concentration. That line depicts the blood concentrations associated with conventional daily corticosteroid therapy. So I just stated that in order for corticosteroids to work, you must have a high initial concentration, and then you have to have consistent receptor occupation. You can achieve both of those requirements by giving daily steroids, but when you do that, it leads to major long-term side effects. These side effects have been well known by clinicians for decades and have tremendously limited the long-term utility of corticosteroid therapy, especially in areas where it could otherwise be very beneficial. This slide demonstrates why daily corticosteroid therapy leads to these safety issues. The dotted horizontal lines represent toxicity thresholds that, when concentrations of dexamethasone in the blood exceed these over time, safety concerns emerge really quickly. The most important and the most damaging is noted by that bottom dotted blue line, which represents the HPA axis suppression, or basically adrenal gland suppression. If you dose dexamethasone for several days or weeks, you immediately encounter adverse events related to adrenal suppression. Over time, this problem causes many complications such as hyperglycemia or diabetes, hypertension, Cushingoid features, behavioral changes, osteoporosis, muscle wasting, and lots of problematic effects. So while you can certainly get efficacy with daily corticosteroid therapy, you're also going to continually stimulate these toxicity thresholds, so chronic treatment isn't safe. But in contrast, the EryDex PK profile shown here is that solid green line delivers 40% of the total dose in the first 24 hours of infusion, so you can achieve that initial Cmax required for efficacy. But then over the next approximately 30 days, dexamethasone is slowly released from the circulating red blood cells and into the tissue beds where it can exert its corticosteroid effects. So it's the slow release that satisfies the second criterion of receptor occupancy over time that's required for efficacy. But this is really important: after about the first week, with EryDex, the concentration of dexamethasone remains below all of those toxicity thresholds for the remainder of the month. So this results in the ability to dose corticosteroids monthly in a manner that ensures efficacy but avoids triggering those toxicity thresholds that lead to long-term side effects. We've demonstrated this now with clinical data as over 50 children have been on EryDex monthly for more than three years without any signs of chronic steroid toxicity. Remarkably, three children have been on EryDex monthly for about 10 years and without any side effects related to chronic steroid therapy. As a physician and a drug developer, I personally find this data incredibly compelling and encouraging for our upcoming study of EryDex in our Phase III trial. So I hope you can see why we're excited about the potential of our AIDE platform and this lead Phase III asset, EryDex, because if EryDex works in A-T, just imagine the potential to treat so many different diseases that could benefit from safe and chronic delivery of corticosteroids. Patient enrollment in this Phase III EryDex study will begin very soon, in the second quarter of 2024. In addition to that, we're doing a lot of work to prioritize follow-on indications for EryDex. In addition to EryDex, we will expand a pipeline of new discovery programs that leverage this AIDE platform. Well, thank you very much for listening in and allowing me to explain some of the science that makes this AIDE platform so compelling. By pioneering the delivery of drugs encapsulated into the patient's own red blood cells, we're really, honestly attempting to redefine the standard of care, first for chronic corticosteroid therapy but later for other drugs. These will meaningfully improve the quality of life for rare disease patients and their families. Thanks again, and we invite you to follow along with our progress.