Welcome back, everyone. Next, we have Gossamer Bio, Inc. It trades on the NASDAQ under the symbol GOSS, and is a clinical-stage biopharmaceutical company focused on the development and commercialization of seralutinib for the treatment of pulmonary hypertension. Please welcome its CFO and COO, Brian Giraudo. Nice to see you, Bryan. How are you today? Doing well. Thanks, Ana. Great to be here as always. Wonderful to pursue you. Thank you so much. Thanks, everyone, for patching in. I'll quickly spend about 15 minutes going through Gossamer Bio. As Ana said, our therapeutic Seralutinib for the treatment of pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease. We think these two markets collectively represent a $6-$10 billion opportunity for Seralutinib. I'll walk you through where we're doing clinical work today and where we're about to start, and talk a little bit about our partnership with the European pharmaceutical company Chiesi, as well as some developments in the marketplace. Some quick facts about Gossamer. We were founded in 2018. We're headquartered in San Diego, California, with our European headquarters in Dublin, Ireland. We are focused on treating rare, fatal lung and cardiovascular diseases, the intersection of where your heart pulls oxygenated blood from the lungs and distributes to your body. There are a number of orphan diseases that, quite frankly, are absolutely terrible and very lethal. We are initially starting in pulmonary hypertension. As I said, we're going into pulmonary hypertension with interstitial lung disease. I'll go through some of those etiologies, but in PH, just as a background, the median mortality rate is roughly five years, about half that in PH- ILD, and just terrible afflictions we do not want any of our family members to ever get. We ended the third quarter of last year with $327 million in cash, so all of our clinical work is fully funded. Quickly on seralutinib. seralutinib is a very novel therapy for the treatment of pulmonary hypertension. As I said, we're first going into pulmonary arterial hypertension. What is very interesting about seralutinib is it was designed to be an inhaled drug. And I'm showing if you can see it on the camera, the inhaler that we use. The drug is delivered via this dry powder inhaler, which we think is critically important because, as opposed to every other medicine in the field, which is dosed or administered systemically, either through a pill or through an injection, our drug goes straight to the site of disease. We think that is very important because it allows us to dial up potency as well as selectivity, but it allows us to avoid a lot of the deleterious side effects we've seen with other therapies. I think the important piece we'll talk about is that we've had positive phase II data in pulmonary hypertension in the TORREY study. Importantly, as we'll talk about, our safety has been really best in class in any therapy that's ever been brought forth over the last 35 years. We also have patent protection until 2039, orphan disease designation from the Europeans, from the FDA in the U.S., and just recently have an updated slide from Japan. Real quick, let's talk a little bit about pulmonary arterial hypertension and this disease and what happens. This disease affects about 50,000 people in the United States, similar numbers in the European Union, same percentage of populations in places like Japan and Australia. This disease is foundationally an inherited disease and affects women of childbearing age. What ends up happening is that the smooth muscle cells, as you can see in the cartoon here on the right, within your lungs, the pulmonary vascular system within your lungs, those smooth muscle cells that make up those arteries basically turn themselves into tumors, and those cells don't stop growing. As a result, the vessels occlude and get smaller, as you can see on the right side of the cartoon. Those of us who don't have PH, our vascular lumen remains open, and so what ends up happening in pulmonary arterial hypertension is that with the occlusion of the pulmonary arteries and really the entire vascular system in the lungs, your right heart has to work harder to pull oxygenated blood from your lungs to the heart to then distribute to the rest of the body. That ends up becoming or putting your right heart into failure, and that's what these patients die for. Again, as I said, median mortality rate is about five years. What ends up happening with this challenge to being able to pull oxygenated blood and ultimately, if you think about the vascular system within your lungs, almost like branches of a tree, as they occlude and die, that leads to both inflammation and fibrosis and ultimately also destruction of the lung tissue. We think Seralutinib is possibly the most novel approach to treat pulmonary arterial hypertension because we affect not only that cellular overgrowth or that proliferation of cells by targeting what's known, as you can see in the cartoon on the right, the PDGFR, or platelet-derived growth factor pathway. This is a known pathway, for example, in oncology, where we're able to stop or turn off that switch for that cellular overgrowth, but importantly, we're also able to treat the underlying inflammation and fibrosis by targeting two other key kinases, CSF1R and c-KIT. Certainly, we have seen in preclinical models that we are able to really turn off this three-armed cascade that causes damage to not only the heart but also the lung. But importantly, we believe that what we've shown in phase two, both at week 24 and at week 72, are suggestive of a treatment paradigm that has never been seen in the pulmonary arterial hypertension space. Real quickly on what the space does look like, because I think it's important to level set the investment community, what's been going on in PH over the last 35 years. The first therapies, endothelin receptor antagonists, as you can see, ERAs were approved roughly about the turn of the century in around 2000, followed by PDE5s. Some of you will know PDE5s from the erectile dysfunction world, where effectively these are very potent vasodilators. What does it mean by a vasodilator? It means that you take this and it does not stop that cellular overgrowth. It does not stop that fibrosis. It doesn't stop the inflammation, but it has a temporary opening of the arterioles. So for a brief period of time, depending on how long patients can stay on these therapies, you are able to have some movement of the blood from the lung to the heart. But again, you are not actually treating the underlying disease. You're not stopping that cellular overgrowth. You're not stopping the fibrosis. You're not stopping the inflammation. Think of this as just treating the symptoms. We have for sicker patients also in this approved pathway, prostacyclins, also another vasodilator. They have a serious side effect profile and very potent drug, so they're used later line. Why does this matter? Because for the past 35 years in this disease, we've been treating the symptoms. Now, in a very fatal disease like PH, treating the symptoms has actually been quite lucrative. When the PDE5s, ERAs, and all the prostacyclins were on brand, it was roughly a $7 billion marketplace in the United States. So we're talking about pricing of about $300,000-$400,000 a year for some of these medicines that insurance happily paid for because of the mortality rate. There have been some new additions to the PH market, specifically a drug called sotatercept, now known as Winrevair, was approved in March 2024. It is an activin ligand trap, a very different mechanism of action from the vasodilators you can see above on the chart, and very different mechanism of action and delivery. It's delivered via an injection every three weeks versus, again, Seralutinib being an inhaled therapy. Sotatercept launched in April of 2024. Merck reported their numbers last week, which came in under consensus. Sotatercept's a very good drug. Sotatercept has one issue. Sotatercept carries a very, very significant safety and side effect liability, specifically significant rates of bleeding that manifests itself. We've seen this now on what's called the FAERS website or the FDA Adverse Event Reporting System. Things like gastrointestinal hemorrhage, severe nosebleeds resulting in hospitalization. In the first nine months, for example, they recorded 17 deaths, as well as over 10 intracranial bleeds, 27 gastrointestinal hemorrhages, and over hundreds of hospitalizations. Now, one would say, why would a drug like this be approved and why would people use it? I think it speaks to the unmet medical need, the fact that patients are so desperate for a new therapy that they're willing to try just about anything. That being said, we think that while sotatercept is a good drug, the liabilities and the challenges it has create a significant opening for Seralutinib. Let me talk a little bit about the clinical data that Seralutinib presented in our TORREY phase II data, which was presented in December of 2022. Our phase II study, the primary endpoint was called a reduction in pulmonary vascular resistance, or PVR. That's a fancy way to take your blood pressure via right heart catheterization, where we're trying to measure the pressure of where the blood is coming from the lung into the right heart. For 24 weeks, Seralutinib was able to reduce PVR by 14%. This data was somewhat controversial. The investment community wanted Gossamer to do something similar to what the Merck drug I previously referenced had done, where in their phase II study, they had shown a reduction of PVR from 18% to 32%. As we have gone through that data, there was no way we were ever going to be able to match Merck for one reason and one reason only. We were doing our study of this phase II study during the height of COVID. So we were enrolling a meaningfully less sick patient population than what Merck did in their phase II study. They had completed their phase II study in, I believe, December of 2019. We all know what March 2020 meant when the pandemic started. That was just when we were kicking this study off. But importantly, when you look at sicker patients, patients that looked more like what were studied in the Merck trials, which are known as functional class three patients, or those who have a risk score, a composite that was developed by Dr. Raymond Benza, who's now at Mount Sinai in New York, those sicker patients, our treatment effect was consistent with what Merck showed in their phase II study. And this is the type of data that got the clinical community quite excited because, first, to see statistical significance in such a less sick patient population suggested the drug had meaningful impact, and that was validated by what we could do in sicker patients. I'll come back to why this is important because in our phase III study, we are enriching for those that are in the functional class three as well as the REVEAL 2.0 risk score. Quickly on what we achieved in this phase two study. Again, we were statistically significant in PVR, albeit at a level that the street found underwhelming. I'll come back to that. As you see in the bottom, we'll talk about our 24-week and beyond data. Many of our secondary endpoints, including biomarkers as well as echo, other hemodynamics, were very, very statistically significant, and so when the clinical community saw what we were doing at week 24, they hypothesized that as we looked out longer, that the drug would continue to have benefit, and in fact, that's what happened. As you can see in the bottom part of this page, every study has what's called an open label extension, where those who have been on drug or allowed to stay on drug really it's a perpetuity until they want to come off. When we think about those that were randomized to drug at month one and stayed on drug through week 72, we took another one of these PVR measurements. Again, a pretty objective way to measure one's blood pressure. In fact, we showed at week 72 or 18 months afterwards, for those that have been randomized to drug, a continued progression of efficacy where we've had no safety issues. Again, I juxtapose that to the Merck drug that had two serious bleeding events. We have a little bit of cough. But importantly, our efficacy at week 72 is unprecedented, where we showed an additional 10%-15% reduction in PVR. We were actually able to achieve what Merck did at week 24. Importantly, the Merck drug in their own open label extension data showed no improvement at week 72. This is why the clinical community is quite excited about seralutinib when they juxtapose it to other therapies on the market. Quickly, where are we today with seralutinib? We are in a multinational phase III study known as the PROSERA study, roughly 350 patients. You'll see on the right side of the page, right? That which the street criticized us for, which was not having sick enough patients in our phase II study, we have an inclusion criteria that ensures that we are getting patients who are meaningfully sick, whose disease is active and will show an effect at week 24. We have taken a look at the first half of the patients that have enrolled in the study and their baseline characteristics. I'm very happy to report that the baseline characteristics are in total patients that are sicker, as sick or if not sicker than what Merck showed in their phase three study. So we believe we have a very high probability of success based upon getting the right patient population in the study. Talk a little bit about where we're going next. While we're doing this, the PROSERA study in PH, we will also initiate a phase three in PH-ILD, which is actually a tremendous economic opportunity. It is 2x the size from a patient population, but there's only one approved therapy, and it's only in the United States. So that leaves a massive opportunity for seralutinib both in the U.S., but also outside the U.S.. And again, a 40% three-year survival rate shows just how terrible this disease is for patients. Very quickly on the balance sheet, we have $327 million in cash. A number of that came from our partnership with the European pharmaceutical firm Chiesi, who will be responsible for commercializing Seralutinib outside the United States, as well as doing a 50/50 profit share in the United States with Gossamer. We split expenses 50/50 for everything other than the PROSERA study. That's critically important, especially when you think about PH-ILD, where there is no competition outside the United States. Chiesi is an 85-year-old respiratory pharma based in Europe. They know how to sell product and get paid in the European Union, which we think is quite tremendous. $327 million in cash. As I said, we have a convertible note of $200 million that is due in May of 2027. But importantly, we expect to complete enrollment in the phase III study, PROSERA, in the second quarter of this year with top-line data in the fourth quarter. So this is our year, Ana, to deliver data. This is where we think we will be able to make a terrific splash in the PH market and, importantly, be able to bring forth what we think will be the most powerful therapy that this marketplace is seeing. So with that, Ana, I'm happy to take any questions. Great. Thank you, Bryan. We have a question from Dan. Let's talk a little bit more about the PROSERA study. Can you give a little bit more of a timeline? When do you expect to start documenting results? So we expect to complete enrollment late April, early May. It's obviously a 24-week study, so it'll take that last patient 24 weeks to complete. It'll take us a few weeks to clean data, close the database. Our hope is to have the top-line data report in the fourth quarter of 2025, so hopefully sometime around November-ish, and Jim wants to talk a little bit more about side effects. Are there any side benefits related to any other illness or conditions or side effects? I'll say that, so certainly, when it comes to our side effect profile, our side effects are mostly cough and minor headache consistent with what you would see with people who use a dry powder inhaler for asthma or COPD. Now, the mechanism of action targeting proliferation, fibrosis, and inflammation certainly has impact and possibility, not just in PH-ILD, but diseases like idiopathic pulmonary fibrosis and potentially pulmonary hypertension associated with COPD, so we think there's a lot of places that we can go. It's part of the reason why we brought Chiesi on board. Their financial muscle, as well as expertise, should allow us to really take Seralutinib really and maximize it as a portfolio within a product, Ana. And with the PVR, can you go over again how you got similar results with Merck and what did that test and efficacy look like? So PVR, again, pulmonary vascular resistance, it is a blood pressure measurement via right heart catheterization. So they put a catheter either through your neck or through your armpit and measure the blood pressure of the pulmonary artery emptying into the right ventricle. At week 24, we showed a decrease of 14%. Merck showed at their low dose 18%, at the high dose 32%, for a mean of roughly 25%. At week 72, we did another PVR reading. And for those patients who had been initially randomized to drugs, who've been on drug for 72 weeks, the mean decrease in PVR was roughly 25%. Now, what's important for folks to understand is that the baseline PVR for those who received Seralutinib upfront was roughly about 610, 620. That compares to 780, the measurement that Merck had. So our patients were 35%-40% less sick than what Merck had, yet we over time were able to get to the same efficacy place that they were. If you think about what physicians want, they like to see a slow walk of efficacy with no side effects. In the case of the Merck drug, yes, you get a dramatic improvement early in your PVR or in your disease symptoms. But one, it starts to wane after about 12, 13 months, and you're carrying a side effect profile that can be very dangerous to patients. So it's why many of the KOLs have declared, at least to date, seralutinib the winner in PH. And Quinn asks, with regard to pulmonary hypertension, what was the go-to prior to seralutinib? So the go-to was, if I can maybe go back to the slide, hold on a second. So the go-to were, again, these drugs. And today, they still are the go-to: the ERAs, the PDE5s, because they're generic. So when you think of PDE5s, think of sildenafil and tadalafil. We know them branded as Cialis or Viagra because that way it works in erectile dysfunction of opening up the vasculature. Also works in pulmonary arterial hypertension. ERAs and PDE5s will continue to be the first therapies that insurers ask patients to go through before they go on to sotatercept or Seralutinib. Prostacyclines, as you see on the bottom of this page, will still be used, but they have both a side effect profile that is very serious, but also are still on brand, so roughly run about $400,000 a year. You'll see prostacyclines be used for the sickest patients, those that are on transplant lists. Today or in the future, I think you'll see it'll be PDE5s, ERAs because they're generic, then Seralutinib, then sotatercept, then the prostacyclines.