QNCX KOL event

Good afternoon, everyone, and thank you for joining Quince's KOL event. For those of you who are not yet familiar with this story, we turn to slide 3 please. Our company is focused on LAM-001 that we're studying across three pulmonary conditions. The first is PH in the setting of interstitial lung disease, estimated to affect about 200,000 patients between the U.S. and Europe. Based on promising phase IIa data that Dr. Paul Yu presented at ATS this year, we have moved forward into a phase IIb study, in PH-ILD with expected data in the first quarter of 2028. The second indication is Bronchiolitis Obliterans Syndrome post-lung transplant, estimated to affect about 30,000 patients between the U.S. and Europe by the early 2030s. This is a very severe complication, post-lung transplant. Unfortunately, the leading cause of death in the majority of patients.

We are currently in an investigator-sponsored study being run at UCSF by Dr. Steve Hays, and that data is expected in the first quarter of 2027. Finally, we're also studying the drug in a third indication, sarcoidosis-associated pulmonary hypertension, estimated to affect about 60,000 patients between the U.S. and Europe. Another very severe disease, complicating about 15% of patients with underlying pulmonary sarcoidosis, and we'll be starting a phase II study toward the end of this year with a readout expected approximately two years thereafter. Next slide. The entire premise behind this drug was the goal was to try to find a safe and well-tolerated means of delivering rapamycin to patients' lungs in disease settings where the mTOR pathway was known to be truly implicated.

What we created here is a product where we are delivering one-twentieth of that standard oral dose, 100 micrograms is being delivered daily via this DPI, delivered directly to the pulmonary tissues. That is one-twentieth of the typical oral dose. Because of that, what we are seeing in humans is a less than one nanogram per mL systemic level, which is less than one-fifth to one-fifteenth the systemic level seen with oral delivery. Thus far, that has translated into a very benign profile in patients, and importantly, at least so far in our initial studies, efficacy as well. Next slide, please. Next slide. Oh, sorry. On that prior slide, it just highlighted our upcoming timelines for datasets. We, as mentioned, will have that PH-ILD data in Q1 2028.

We'll be delivering this BOS data in the first quarter of 2027 and that SAPH data toward the end of 2028. It's now my pleasure to introduce our three KOLs who are going to be presenting today. For the PH-ILD discussion, we're joined by Dr. Aaron Waxman and Dr. Paul Yu. Dr. Waxman is the Director of Pulmonary Vascular Disease Program at the Brigham and Women's Hospital, and he's Professor of Medicine at Harvard Medical School. Notably, he's been the lead PI on numerous PH clinical studies, including the phase II SPECTRA study for sotatercept and the phase III INCREASE study for TYVASO, which led to the first approved agent to treat patients with PH-ILD. He holds an M.D. from Yale University, a Ph.D. in anatomy and neuroscience from Albany Medical College.

He completed his residency in internal medicine at Yale and his fellowship in pulmonary and critical care medicine at Yale. He's board certified in pulmonary disease, critical care medicine, and internal medicine. Dr. Waxman was the lead PI for our phase IIa study of LAM that was just presented at ATS, and he's the lead investigator for our ongoing phase IIb study in PH-ILD. Turning to Dr. Paul Yu, he is the Director of Cardiovascular Research Center at the Massachusetts General Hospital and an Associate Professor of Medicine at Harvard Medical School. He holds an M.D. from Duke University and a Ph.D. in immunology from Duke. He completed his residency in internal medicine at UCSF, a clinical and research fellowship in cardiovascular disease at MGH, and a postdoctoral fellowship in cardiovascular biology with Dr. Kenneth Bloch at MGH. He's board certified in cardiovascular medicine.

Dr. Yu has made a significant impact in pulmonary hypertension through his translational work, including the study of BMP and TGF-beta signaling and cardiovascular homeostasis, repair, and disease. Among his many contributions to the field, his work helped to elucidate the vascular remodeling activity of sotatercept, the first agent approved for PAH with a disease-modifying mechanism of action. Turning third to Dr. Steve Hays, who will be leading our BOS discussion. Dr. Hays is the Medical Director of the UCSF Advanced Lung Disease and Lung Transplant Program and a Professor of Medicine at UCSF. He holds an M.D. from the University of Kansas and completed his residency there in internal medicine. He completed his fellowship in pulmonary and critical care medicine at UCSF and in lung transplant at Stanford University. Dr. Hays is board certified in critical care medicine and pulmonary disease.

His clinical focus is the treatment of advanced lung diseases, and his research focus includes lung transplant immunology and airway remodeling, chronic lung allograft dysfunction, infectious disease, and transplant digital health. Dr. Hays is the principal investigator for the ongoing investigator-sponsored phase II study of LAM-001 in BOS patients. Before starting, just to note, we are going to be breaking today's presentation into two sessions. The first will be on PH-ILD, the second one will cover BOS, and at the end of each session, we'll be opening it up for a 10- to 15-minute Q&A, and questions will be taken in the order in which they're received. With that, I'll turn it over to Dr. Waxman and Dr. Yu to discuss pulmonary hypertension.

Okay. Thank you, Brigette, and hello, everyone. We can go to the next slide. I always like to start out with a general statement of the problem and really just pointing out, which probably isn’t that necessary anymore, that Group 3 PH is something we encounter increasingly as people recognize the disease state and now that we actually have a treatment for it. I like to show the histopathologic slides that are on the right of this slide just to illustrate, for so long, we kind of ignored the idea of PH in the setting of Group 3 disease, and especially in Group 3 ILD, but these are all from patients with Group 3 except one.

If I were to challenge doing that, the point is that vascular remodeling is a big deal when it comes to advanced lung disease and something we shouldn’t have ignored for the many years that we did. Next slide, please. This is just a summary of the prevalence and epidemiology of the disease state. I actually think that we underestimate how much is out there. I think part of the problem has been that because we had no treatments until recently, people didn’t get right heart cath, they didn’t get a diagnosis, and were pretty much ignored. But I think there’s no question that when we do have pulmonary hypertension in the setting of interstitial lung disease, we see a significant decline in the pulmonary function itself. We can go to the next slide.

This is, again, restating some of the prevalence of the disease and showing what happens as far as mortality when we add pulmonary hypertension onto interstitial lung disease. Generally, there’s about a threefold increase in mortality once patients develop pulmonary hypertension. It’s always been kind of siloed into ILD clinics, but more and more as people recognize that pulmonary hypertension is a significant component, it’s overlapping with the pulmonary vascular clinic. But in spite of that, I think there’s still very significant delays in diagnosis, and as more treatments are coming to clinical trial, I think we’ll get better at finding the disease earlier in the disease process. You can go to the next slide. This is just the algorithm for diagnosis of PH-ILD because it is now putting two bad diseases into one patient.

I think the things we start looking for and what we’re preaching out to the audience of pulmonologists, cardiologists, rheumatologists is that as patients start to become increasingly short of breath out of proportion to any changes in their pulmonary function or maybe their CT scan, it’s time to start thinking about pulmonary hypertension. There are some subtle findings on other tests like EKG. Echo is still an important screen, but echo becomes much less reliable when patients have advanced lung disease, so we start to look for other clues in the pulmonary function testing realm. If that DLCO, the diffusing capacity, which for those not familiar, is a measure of the surface area of the lung involved in gas exchange, as that starts to fall out of proportion to the forced vital capacity, that’s a time to be thinking about pulmonary hypertension.

Certainly, if the patient’s exercise tolerance is on the decline, but lung function is not, then we start thinking about it. Echo still remains the important screening tool, but a low bar to take a patient to right heart cath is key, and I think that is starting to change as treatments become available. This is the general algorithm. You can go on to that next slide. This is just looking at the track record, and I think this raises a couple of important questions. I think we know endothelin receptor antagonists have now got themselves a black box warning, which I think is unfortunate because it’s probably related to clinical trial design more than any harmful effect of the drug itself. But so far to date, trials have not shown any consistent benefit and do raise the question of harm.

The data right now does not support their use in PH associated with ILD. If we think about the PDE5 inhibitors, sildenafil and tadalafil, some studies have shown improved hemodynamics. Some have shown some improved quality of life or preserved exercise capacity. But the functional benefits to date have been inconsistent. There is always concern that these drugs can worsen gas exchange in patients, especially with COPD, but also ILD. The prostacyclins have been studied to some limited approach. They may improve some pulmonary hemodynamics and right heart function, but have also been found to worsen ventilation perfusion matching and worsen hypoxemia. The inhaled prostacyclins preferentially treat those well-ventilated lung regions. Although iloprost, which is not used in the U.S. much anymore, has shown mixed effects on exercise tolerance and oxygenation, and the recent PERFECT trial, which is PH-COPD, also raised some concerns with the drug.