Michael Kaseta and CMO Rajeev Saggar. Welcome, gentlemen. Hey, thanks for having us, Kambiz. Thanks for this. Liquidia has a dry powder inhaled formulation of treprostinil. Brand name will be YUTREPIA. Mike, if you don't mind giving us an update of where does YUTREPIA stand today? Yeah, Kambiz, first of all, really a pleasure to be here today to give an update on where we stand with Liquidia. We're really excited. We are really at the goal line here, ready to launch YUTREPIA. We received tentative approval in PAH back in November of 2021. We filed an amendment to add PH-ILD to our NDA back in July of 2023. As of April 1 of this year, there are no legal impediments to prevent YUTREPIA from launching, and we are eagerly awaiting the FDA to approve our product. We are in dialogue with the FDA. We are committed to this patient population and doing everything we can to gain that approval and are really excited to hopefully market and distribute YUTREPIA here in the very near future. Excellent. So there's, you know, you have tentative approval in PAH. Obviously, the FDA accepted your amendment for PH-ILD. What are kind of some of the legal and regulatory considerations we have moving forward to get YUTREPIA across the finish line? Yeah, so from a legal point of view, there are no impediments at this point. Last Friday, our competitor had filed a lawsuit against us for violating a patent in PH-ILD. They had requested a preliminary injunction, and on Friday, the judge in Delaware ruled against that preliminary injunction. It kind of in parallel with that, our competitor has sued the FDA to ask them to request that the amendment be denied, that it was inappropriate. We feel very confident that the amendment was appropriate, it was legal, and it is approvable. And again, the only impediment at this point is getting final approval from the agency in both PAH and PH-ILD. Maybe just quickly touching base on the preliminary injunction motion, which was denied. Correct ... related to the 327 patent. Was there anything in that kind of document that the judge provided that provides you encouragement for perhaps the other case as well? That just because the motion was denied doesn't mean that the case won't move on as well, correct? No, that is correct. And, just to be clear, that trial date has already been set for June 23, 2025. Now, in order to get a preliminary injunction, someone must prove a few things. One, they must, they must, There are multiple criteria to get a preliminary injunction. Those include that, that there is not a substantial doubt of the validity of the patent, also that it's in the public's best interest that a preliminary injunction is granted, and then also that, irreparable harm will be caused or inflicted upon the plaintiff. In Judge Andrews, who was the judge in Delaware, in his ruling last week, he ruled that, Liquidia did raise a substantial doubt on the validity of the patent. He did say that United Therapeutics would not be irreparably harmed, and he did say that it is in the public's best interest to allow YUTREPIA to be launched. So, we're very encouraged by that. We feel that this patent is not valid. We look forward to the trial in June of 2025, and, and ahead of that, we look forward to launching YUTREPIA. And now that you have that ruling from Judge Andrews, you know, that's gonna be sitting also... The other Judge Bates in the case of United Therapeutics against the FDA will have that documentation as well. So, do you think that's positive in terms of the other case? Well, I think, listen, the facts and circumstances are different. The merits of that case are around the validity of the amendment that we filed. But in order to also get a preliminary injunction, they will also have to prove irreparable harm, and it's in the public's best interest to give the injunction. So we feel confident that based on the findings of Judge Andrews, that Judge Bates would get to a similar conclusion, and that would pave the way and allow us to get full approval for YUTREPIA here in the near future. Awesome. Well, thank you for updating that. I know it's always a lot of legalese that we have to get through, but what's exciting is actually YUTREPIA and the option it provides patients. So maybe kicking off, you know, your company's been very confident about how you can position YUTREPIA. What makes you think that YUTREPIA could be treprostinil of first choice and not only compete with the DPI formulations and nebulized formulations of treprostinil, but also the oral formulations? Yeah, absolutely. You know, as you can hear my voice, we're really excited about the opportunity here for YUTREPIA. It is both the PAH market, which is large, and the PH-ILD market, which is, you know, mostly white space. The first product was approved in June of 2021, which was Tyvaso. We feel that opportunity is really a massive opportunity and also an area of unmet need for patients that we feel that we can fill that gap. Now, as it relates to being the prostacyclin of first choice, that is a goal of ours. You know, I think one thing that you need to understand is, you know, our product, YUTREPIA, is positioned very well based on the tolerability, the titratability, the portability, and the usability of the product. We feel really confident that it can, you know, can really be that prostacyclin of first choice. We also have a situation where, you know, our competitors have multiple products that they are detailing against and trying to fit into different criteria, and we do not have that issue. You know, Rajeev here, who was previously a KOL in both PAH and PH-ILD, can really give us some specific examples of where we are and why we're targeting not only the existing inhaled market, but also that oral market as well. Yeah, thanks, Mike, and it's a pleasure to be here, Kambiz. So just to take a step back, I think the key standout profile that's gonna allow YUTREPIA, I think, to become the prostacyclin of first choice is built upon the foundation that we use a PRINT formulation, and we combine that with a low-resistance inhaler. We believe that combination of that effect is going to be well suited to maximize the profile of the drug, which Mike alluded to, is you now can advance the drug into patients, you can titrate it efficiently and effectively. It's very tolerable. The key here is that prostacyclins, as of today, are the gold standard for treatment of PAH patients. The problem with all prostacyclins, especially the ones in the oral form in particular, is that they have significant systemic side effects that limit their ability to use long term in terms of compliance and to effectively titrate them to a dose that is clinically effective enough for the patient. The problem with parenteral prostanoids, of course, is that they require indwelling pumps that are used continuously 24 hours, 7 days a week, which is very cumbersome for the patient. YUTREPIA provides a singular choice for patients and providers. It's simple to use, it's portable, it takes a few seconds to use 4 times a day. You can put it in your pocket. Most importantly, because it is inhaled, it avoids these systemic complications. In particular, it substantially reduces the GI irritability that is seen with the oral prostanoids currently. As you know, we have YUTREPIA now has been dosed in our long-term extension phases for more than six years, giving us that confidence that when we launch our product, people will reach to it as a prostacyclin first choice because of these product advantages that I just highlighted. Excellent. And, and now maybe taking even one step further back just in the general inhaled treprostinil space, what are the key trends of inhaled treprostinil use? How is this used between PAH and PH-ILD patients, and kind of what's the split currently for each indication between nebulized and DPI formulation? Yeah. So I think if you look back or you look at, you know, most recent trends, Tyvaso is on about a $1.4 billion run rate, as of the end of Q1 of 2024. Now, if you go back to prior to the addition of the PH-ILD indication, it was about a $400 million a year product. So I think what we would say is we would attribute most of, you know, the vast majority of that increase to PH-ILD. Now, what we've also seen, which has been somewhat surprising to us, is that the split, as you asked, between nebulized and DPI, appears to be about 60/40 right now, and we look at this as a real opportunity for YUTREPIA. For all the reasons that Rajeev spoke earlier, there is obviously a subset of the population that is preferring nebulized versus the DPI. Now, what we know is it's not the drug. It's absolutely not the drug. It's not treprostinil. We believe it's the delivery mechanism, as Rajeev said, and we feel that we have a great opportunity here to come in, provide YUTREPIA to patients. They will not have to start on nebulized and then transition to a DPI. If you look at our INSPIRE study that we did, you know, the patient satisfaction on both naive and transition patients was almost unanimous. So we are really excited about getting this product to market and, in the very near future, and feel that we can take meaningful share and really grow the opportunity and the market opportunity for, you know, inhaled treprostinil. Amazing. Maybe a nice segue into... You are conducting a trial for YUTREPIA in PH-ILD. It's not required for approval, but what have the key learnings been so far from the open-label ASCEND study, and what are, what are kind of the goals there? Yeah, thanks. So, and just to reemphasize, YUTREPIA was first studied in PAH patients. That's our INSPIRE study, now gating with six years patient, that have been on the drug for over six years. But of course, the next step is to showcase our product profile, in particular, its tolerability profile, its titratability profile, and ease of use in patients with PH-ILD. We believe there's over 60,000 patients in the United States with PH-ILD. Currently, we have a study that's open label called the ASCEND study. It's a small sample size currently, but we actually believe that we'll complete enrolling that study, which is up to 60 patients, by year's end. In the first seven patients that have been enrolled in the study, what we have shown is that in patients with PH-ILD that take YUTREPIA, within 4 weeks, the median dose is 106 micrograms, which is on the higher end of the therapeutic range typically seen with nebulized Tyvaso. But at eight weeks, the average dose is 132.5 micrograms, which now exceeds the typical therapeutic zone, which is used with Tyvaso. And that's only at eight weeks. We look forward to seeing how these patients continue to progress. Interestingly, there's a single patient that now is at 318 micrograms, which is threefold the typical therapeutic range of Tyvaso, which is typically used around nine-12 breaths per session. I think, you know, although it's a small sample size, it's extremely encouraging. We once again believe that it's the combination of our PRINT formulation and our low resistance device together that allows the patients to titrate the drug. We believe it's more tolerable, especially in patients that have impaired lung disease, which all patients with PH-ILD do, and we think that's going to be the tremendous advantage over the current inhaled treprostinil market currently. ... Excellent. And then you said enrollment for that should be completed by? By the end of the year. Do you expect to share any substantial data on that study beyond what you've already shared on the seven patients? Correct. Yeah. So there's a few congresses coming up in the near future, and we'll be highlighting a larger sample size and showcasing some of our more elaborate versions of our safety and even some early efficacy profiles of the drug. Excellent. Well, that's all really exciting. Any other things you want to touch base on with regards to YUTREPIA? I know we're all just waiting for the FDA to kind of make their decision, but we're really excited for the potential approval there. Yeah, Kambiz, we are equally excited. We've been waiting a long time for this, and I think, you know, the last message we want to send about YUTREPIA is that we're ready. We are ready to commercialize this product. We have manufactured product. We have product ready to be distributed to distributors and subsequently to patients. We have a sales force that we onboarded back in Q4 of 2023. They've been in the field since the, you know, since the latter part of Q4 of 2023. They've been messaging around our PRINT technology. They've been messaging around Liquidia. I think that there is a, you know, a real excitement in both the patient and doctor community for YUTREPIA to come to market. So as soon as we get the green light from the FDA, we will be ready to go. We will be shipping product out to have product available almost immediately, and really can't wait. Like I said, we've been waiting a long time for this. We're really excited. We are laser focused on execution here to launch and feel really excited about the launch trajectory that we're going to have here. In terms of your sales force, obviously, you kind of expanded after you had the RareGen sales force, but this is a very experienced group of people, and they are already, you know, have generic treprostinil formulations in the market. What's kind of some of the metrics you have on your sales force? Yeah. So our sales force is about 50 professionals. It's a national-based sales force that'll focus both on large PAH centers, but also the local community doctors, which we feel where a lot of PH-ILD patients are. When you look at the demographics and statistics on our sales force, they all have a tremendous amount of rare disease experience of over 10 years. The vast majority of them have PAH experience specifically. So again, the team is very focused, the team is ready, and really just waiting for that green light. Awesome. Well, YUTREPIA, we're all excited for it, but you also are doing some very significant, maybe beyond just life cycle management. You have another formulation of treprostinil in the works or device in the works, L606. Maybe you could just broadly start off, what is L606, and why is it exciting, and how can it complement, YUTREPIA in your portfolio? Yeah. So, you know, despite the many attributes of YUTREPIA, it's still dosed four times a day, and that. So we have not solved the dosing issues, which also can, you know, impact, you know, patient compliance. So the next step is, well, how do we do that? And that's where L606 comes in. L606 is a liposomal sustained-release formulation of treprostinil. We have shown, using healthy volunteers, that the pharmacokinetics of L606 are such that it can actually be dosed twice a day. It has the same systemic exposure profile or the AUC, similar to four times a day of inhaled treprostinil, but given twice a day. But most importantly, it has a sevenfold decrease in its Cmax. The reason why this is important, because even though we believe that YUTREPIA can substantially limit the systemic side effect profile of inhaled treprostinil in general, the sevenfold decrease in Cmax can further enhance that tolerability profile. And of course, the twice-a-day profile, we believe is actually going to be met with high degree of enthusiasm for these patients. We currently have the L606 drug right now that's being studied in a U.S. open label safety study. We just highlighted some of the safety profile of our drug recently at the ATS Congress that was just presented last month. Can you provide some of the key highlights on that ATS presentation? Yeah, sure. So these were the first 24 patients that were in the open label safety study of L606. A few things emerged, which we were really excited about. First, one of the things everyone's concerned about is when you inhale treprostinil, one of the concerns is that you develop cough. We did see cough. We saw it in four patients. Three of the coughs were mild, one was moderate. Most importantly, none of the side effect profile of the drug led to any drug discontinuations, and it did not limit the drug titration. To that end, what we showed was that the median dose of the drug was 207 micrograms of L606, given twice a day. The reason why this is important is because that's equivalent to two times the therapeutic, typical therapeutic zone of Tyvaso. So this is equivalent to 24-26 breaths of Tyvaso, fou times a day, but given twice a day with L606. So we believe that data set is extremely encouraging. We also have patients that have reached our highest achieved dose in that study, which is 378 micrograms, four times a day. So we remain very excited about the safety profile of L606. We believe it's extremely tolerable, and most importantly, that data that we gathered gives us enough confidence to move forward with a Phase III global placebo-controlled efficacy study. Excellent. So I believe L606 is going to be utilizing the 505(b)(2) pathway. Can you take us through kind of the, the phase III trial, but not only that, the kind of all the registrational trials required and, and kind of what indications you're going to be pursuing for that? Sure. So L606 is going to be moved forward, as Kambiz's noted, through the 505(b)(2) pathway. This references the label drug, which is Tyvaso. Because of that, we had a Type C meeting in December of last year, in which we have agreement with the FDA agency that a single phase III placebo-controlled efficacy study with L606 will lead to approval for both indications for PAH and PH-ILD. In that regard, we feel the best process to move forward would be specifically to study patients in PH-ILD, in which true placebos will be compared to L606. So we have the opportunity to maximize our product profile, showcase its tolerability and titratability, with using a primary endpoint of six-minute walk distance. So that study, we plan to initiate by late at the end of this year of 2024. Any idea around kind of study the size you're going to be looking at there, key primary endpoint, time point, any details? Yeah. So as I stated, the primary endpoint of the study will be six-minute walk. It's similar to how Tyvaso was approved for the indication for PH-ILD. We believe that the sample size should be very similar to the design of the INCREASE study, so roughly around 300 patients. But these patients will be obtained globally, so you know, both in United States, for example, as well as in Europe, and potentially other parts of the world as we move forward for that. Would you say kind of what you're looking to, I wouldn't say replicate the INCREASE study, but have very similar kind of baseline characteristics for your patients? Yeah. So I think there's a lot of lessons learned from the INCREASE study. And, you know, a few things is how best to enroll the right patient into the study. These patients tend to be very sick. They have high rates of hospitalizations, and unfortunately, you know, their three-year survival is impaired with a survival rate of around 30%-40%. So I think ensuring that we enrich the profile to have significant pulmonary hypertension, irrespective of the interstitial lung disease, is going to be a critical profile. Number two, we need to ensure that we can titrate L606 to a level that we can maximize our ability to improve that walk distance. Of course, we'll be looking for key secondary endpoints, such as clinical worsening, to help modify over the course of that time as well. You're going to be, just to reiterate, you're going to be enrolling that study starting the end of the year? Correct. Yeah, we plan to initiate the study late 2024. Excellent. Very exciting. There's been a number of competitive developments, both in the PAH space and PH-ILD space. We recently had sotatercept approval and then, TPIP data in, in PH-ILD. It would be great to get your perspective on kind of what are... What, how are the competitive developments going to affect PAH? And then separately, kind of what are your thoughts on, of, the developments in PH-ILD? Yeah, sure. I mean, of course, you know, sotatercept was recently approved for the indication of PAH only. Of course, it's not indicated for PH-ILD. I think it's early in its launch phase, and so, you know, we look forward to hearing more about their impact on patients in the United States. That being said, you know, where sotatercept fits in in the guidelines, we will know that, you know, sometime late at the end of June, when the guideline committee, the international guideline committee, meets at that time. So we'll see where it actually sits. Again, just to reemphasize, as of today, prostacyclins are still the gold standard. I think, you know, in regards to TPIP, you know, this was a small sample size. I think, you know, it highlighted a safety profile of the drug. I can't really speak to its efficacy because of the limited data set, but I think it showcases that... It shows that our confidence in advancing L606 as a twice-a-day formulation is actually what is needed in this field. Again, the differences between L606 and TPIP, we're moving forward with a single phase III study for both indications. I'm unsure of how their regulatory path works. They may have to do individual studies for both indications. Excellent. And so, well, thank you so much for your time, gentlemen. We're really excited for potential YUTREPIA approval imminently. Maybe, Mike, I'll leave you for the last words. Yeah, I mean, it's been a really long road. The team has done a tremendous job. I think our focus has always been on execution. I think we've knocked down every legal hurdle that's been placed in front of us. We've successfully developed this product, and we look forward to launch, and we look forward to execute on a launch that, you know, provides a much-needed treatment for patients and also, you know, provide a real opportunity for Liquidia. Thank you.