Okay, awesome. Hey, everyone, thanks so much for attending the Liquidia Fireside Chat. Day two of the conference. The weather in London is, you know, it's getting a little chilly, but it's good for staying awake. So my name is Amy Lee. I am a biotech analyst at Jefferies. I have the pleasure of welcoming Roger Jeffs, the Chief Executive Officer, and Mike Kaseta, the Chief Financial Officer. I'll turn it over to Roger for opening remarks.
Great. Thank you, Amy. Really happy to be here at the Jefferies Conference with you. We're also joined by Jason Adair, our Chief Business Officer. So Mike, Jason, and I, for those in attendance here live, will be available to answer any additional questions at the end of the talk today. I'll give a very short preamble because the situation in Liquidia is a really, really brilliant one. As you may know, we had approval in May for our first PRINT-enabled product, YUTREPIA. We just had our quarterly earnings, and in our first full quarter of launch, we were able to post $51.7 million in revenue. We feel we are capturing the lion's share of both the new patient starts as well as beginning to transition the existing incumbent base from Tyvaso and Tyvaso DPI. Really pleased with where the business has landed.
The question is, is that sustainable? The answer is, it's absolutely sustainable. The reason being that the reason we've started so fast and quickly is because of the product profile. There are three critical levers to any product launch other than execution: you need to have benefits in efficacy, safety, and convenience. If you look at safety first, we have a reduced cough because of our PRINT-enabled formulation and its ability to deposit in the lower airway. Because we have lower cough, there's more tolerance to higher doses, which we can get to not only higher doses, but we can get there more quickly so we can benefit the patient to a higher standard.
Finally, we do this with a low-resistance device that does not expose these patients to any exacerbation of cough that they may have because we do not really require a lot of patient energy to drive the dose. That product profile, I think, really predicts that we are going to continue to get the majority of patient share here, particularly new patient starts, and meet our goal in the future of becoming the leading prostacyclin in the entire PAH and PAH ILD space.
Excellent. Let's just start off with your YUTREPIA launch, right? You've reported an excellent third quarter. You've had over 2,000 scripts at the end of October. You're essentially getting to around 1,000 + or - quarter-over-quarter ads, right? Can you kind of give us an overview of, one, how many patients are currently on therapy as of now, how should we think about the absolute patient ads going forward, and then kind of these levers that we should be focusing on?
Yeah, Mike, do you want to take that?
Yeah, thanks, Amy, for the question. You know, so we're very happy with the launch. As you said, we have over 2,000 referrals, over 1,500 new patient starts. We have had tremendous momentum from the beginning of the launch where we've gained significantly over the most recent months and at earnings last month. Roger mentioned that October was our highest referral month of the entire launch. That momentum is continuing. As we look forward and move forward through the launch and we start to see patients, we start stacking patients, patients who are currently on therapy, staying on therapy, and then ultimately new patients come on, we're going to see that significant growth as we move forward to our, you know, and that should reflect significantly in our revenue as we move forward.
Okay, awesome. When we think about kind of levers back half of this year, you're kind of, you're seeing the conversion rates increase this quarter versus the last quarter. You're saying you're moving into community sites where a lot of the PH-ILD patients are located. You do have a good amount, a little over half of patients on free drug right now. When can we start seeing kind of those dynamics feed into your fourth quarter and first quarter next year?
Yeah, so, you know, as you mentioned, you know, our market access team has executed flawlessly in the early part of this launch. As we said in our Q3 earnings, we're pulling through about 85% of referrals into new scripts. We've also said that our usage of the voucher program has crept over 50%. This is a great program for patients and doctors to try YUTREPIA to see if it works for them with the hope that it's something that makes them feel better and ultimately will transition to commercial product at that point. As we move forward, I would expect that that free drug percentage of overall patients will continue to decrease significantly month over month as we continue to add patients. It is an important part of our launch so that doctors and patients are able to expose themselves to our product.
Awesome. Just going into the current patients that you're getting, right, how early are you penetrated into the PAH patient versus the PH-ILD patient? I think one surprise that we saw is, you know, your PAH patient is still kind of making up the majority of these early patients. You know, was that surprising to you? How are you kind of seeing the dynamics shift as you get later into launch?
Yeah, so you're correct that the majority of our patient base to date is from PAH. 75% of those are naive or first-time users of prostacyclin, and 25% are switches. In PAH, of those switches, 40% came from oral prostacyclin. I think one of the things that pulled forward a bit more quickly than we even anticipated was the fact that patients who are having extreme difficulty with the oral therapies, particularly from off-target GI side effects, are now looking towards YUTREPIA as an alternative. That's a big market. That's about $1.5 billion in the U.S. V if you look at the oral prostacyclin revenue run rate. Very attractive. In PH-ILD, similar metrics in the sense that 75% new and 25% transitioning from the existing Tyvaso-Tyvaso DPI products as well.
I think if you look at how we've done with prescribers, we think the target prescriber base across both of those indications is about 6,000. We've had about 650 prescribers script YUTREPIA. So we have more work to do. Where we focused our initial phase of launch was in the centers of excellence, the major centers, because we wanted to take the pole position in the new patient starts. That was our day-one motto for launch. We've done that, and we've done it in one quarter. I think it's clear that we're now in the lead position for new patient starts on an inhaled treprostinil. We also do want to transition patients that are not well served by Tyvaso-Tyvaso DPI, either from intolerability or inadequate dose.
The Tyvaso nebulized patients, which is about 35% of their market share still, is low-hanging fruit that we are going to aggressively seek to go after. Other things that we are going to do to be proactive is we are going to do a directed oral transition study. Take patients directly from Uptravi, for example, and move them over to YUTREPIA to show that those patients that are not well served because of toxicities can be tuned up once they are switched to YUTREPIA. The other study that we are very keen to start also is a directed transition from Tyvaso DPI.
Patients that are on a lower dose, 48-microgram cartridges or below, so they're not able to get to higher doses because of intolerance, we're going to move those patients to YUTREPIA and share what we can do with those patients, which we're confident we can tune them up because they'll have a better tolerability profile. Lots to do, but I think in terms of how we're aggregating patients, we're doing it across the board, both indications in multiple ways.
Awesome. Have you quantified, you know, in terms of the distribution of patients that are on lower doses of Tyvaso that, you know, can't titrate up because of some tolerability issue? How much of that market does it make up in PAH and PH-ILD?
Yeah, we don't have a number because they don't really give any statistics on their product profile. What we know, if you look at the National Jewish data in PH-ILD specifically, and those patients are particularly sensitive to cough, in 42 days, 70% of the patients who had started Tyvaso DPI had come off of it and gone back to nebulized. It's a large share of patients that are intolerant and can't be dosed. You can debate if it's 70% like that study, which was a large study, or less, but it's still a higher number than they would like. It's a number that we think we can resolve all of those effects with.
Yeah, and then one thing to add to that, we did our ASCEND study in PH-ILD, which was to address that exact concern. What we saw, the results are very telling. It follows to what Roger said earlier about our benefits and our product profile. What we saw, we studied 54 patients of naive PH-ILD patients, and we tracked them at open-label phase four study. We tracked them at eight weeks, 16 weeks, and 24 weeks. At eight weeks, we were at an average dose of 132.5 micrograms, which is the equivalent of 15 breaths of nebulized Tyvaso and an average walk distance improvement of 21.5 meters. When we went to 16 weeks, we increased the dose to 159, which is 18 breaths, and saw an improvement of walk up to 31 meters.
At 24 weeks, we increased the dose again to 185.5, which is the equivalent of 21 breaths, and had an increase in walk of 41 meters. When you look at it in real data, we did all of that at 24 weeks with a discontinuation rate of just over 20%. You compare a 70% discontinuation rate at six weeks to a 20% discontinuation rate at six months. We are very confident in our product and our product profile, which is why we are continuing to look for additional data in the studies that Roger talked about as we move forward.
Yeah, and in addition, we measured coughs longitudinally. So we did a modified cough score, and you could see no change. So even though we're really pacing the dose upwards, you're not exacerbating the cough in patients who have a high predilection for cough.
Amazing. I guess just quickly, what's been the physician feedback? Because I remember last time we talked, you said they were kind of waiting for durability data, and that was very important for real-world use, right? Have you seen kind of shifts in prescribing a PH-ILD specifically after this data?
I think the data is obviously very convincing. We've now had it presented and published, so we can go out and promote on the data. I think once physicians see the data that Mike just talked about in terms of the doses that we can achieve, the benefits that we can provide, and the lack of cough, they're very intrigued. Really, that's just to encourage them to get over the threshold and do the first prescription. Once they've done that, all of the realities of the benefits and the levers that we can pull on safety, efficacy, and convenience manifest themselves to the point where major practices are now saying they're going to do wholesale transitions of their whole practice to YUTREPIA, and they're only going to start new patients on YUTREPIA. Again, we need to keep building.
We're not going to relax until we capture the share that this product and these patients deserve.
Awesome. Moving on to legal. I know this is the biggest overhead.
It's our favorite topic.
Clearly. How are you prepared to kind of respond to the different scenarios? I think some of the feedback that we've heard is recently. I just want to clarify, has there been any fundamental changes to how you're viewing the lawsuit recently? I think there's been some concerns that maybe, you know, there's been a tone shift. I just wanted to kind of hand it to you to, one, go over your thoughts on the scenarios, and then, yeah.
Yeah, I think as we get closer and closer to a decision, people get a little more anxiety. So maybe, Mike, if you want to talk about kind of how we view this.
Yeah, so I'll say tone shift. There's no tone shift. We believe the facts are on our side. We believe we should win. Now, with that being said, like any good company and any good management team, you're always going to be prepared for whatever scenario is put in front of you. We're waiting for the judge to rule. It could come any day. It literally could come today, tomorrow. We expect a decision imminently. Now, in terms of the outcomes, like I said, we believe we should win the case. Our tone has not changed on that. What I will say is that there are, in the event that the judgment is against us, there are a multitude of scenarios. And those scenarios could range depending on how the judge rules, on what claims he rules on. It could range anywhere from a reasonable royalty rate.
It could move to a skinny label of removing PH-ILD. The last piece, which I think is important for us to point out, only because United Therapeutics, as part of post-trial briefing, requested that the entire NDA be removed, we do not believe that will happen. We do not believe that should happen. At the same time, we need to lay that out. Now, with all that being said, we're prepared for any scenario. As of right now, we are 100% focused on this commercial launch. We're focused on the execution of that launch. We're very happy with where we are. In the background, we're preparing. If a ruling were to go against us in any of those scenarios, we're working through what we would need to do in order to react to that.
For us, at least for us, what's most important is patience and not to have any disruption. We are doing everything we need to do through conversations with the FDA, through our internal readiness procedures to be able to react immediately. We are steadfast in our belief that we should win the case. At the same time, we are going to be very prepared in any scenario.
Excellent. How do you think the judge will consider that YUTREPIA is already approved and there's a substantial amount of patients on treatment already? You know, like you said, there's 25% that are switches from Tyvaso. I would assume a proportion of them are either refractory. In PH-ILD, like we've seen with real-world studies, you know, patients can aggressively decline, right? Keeping them on efficacious treatment is critical. Yeah.
Yeah, I think he'll render his opinion based on the rule of law, based on what was presented to him. Remember, Judge Andrews has been the judge in our prior patent litigation. There were three other patents asserted against us previously. All of those claims were either found to be invalid or not infringed. One of those, the 793 patent, which is a precedent patent to the 327 patent, actually claimed all forms of PH, including Group 3 or PH-ILD, which 327 is specific to. He found it invalid or not infringed. I think he's very learned. He'll base his opinion on how the case was litigated. Now, the question that you're asking is, will he then consider the consequence to patients, which is real?
You've got a potentially life-saving therapy that's meeting an unmet need and serving a different subset or even the full set of patients in a different and better way. I think he'll consider that. Certainly, in his remedy, as Mike said, we're prepared for all different kinds of scenarios from a skinny label to maybe we have to negotiate a royalty rate or whatever that may be. We'll deal with that when it comes. I think the case will be decided on the facts, and the remedy will be decided based a bit more compassionately.
Awesome. Finally, in terms of kind of timelines around decision, I know you've said time and time again, you know, you don't have visibility on that. If we were to think, will the judge decide on remediation and infringement in the same ruling, or do you think that could be spaced out? As we think about remediation potential, is there a potential you can discuss royalties right then, or is it through appeals? Yeah.
Yeah, I think the broad answer is yes to all of that. You know, again, we'll deal with the reality as it's presented. As Mike said, we've prepared ourselves exhaustively for any reality that is presented to us. Do not leave here today without our belief is that we should win the trial based on the facts as presented.
Excellent.
Because you could talk about the nuances for hours, but it doesn't serve us well because the decision is imminent. He asked for accelerated briefing. The case was in June. It was heard. Post-trial briefing was completed in August. We are well within, if not beyond, the window of expectation of when we should receive that.
Awesome. Moving on.
Let's stay here.
IPF, PPF. I think you went from saying, hey, this is something that we'll look at for L606 to, hey, this is something that we can look at for YUTREPIA. What led to that decision? I think more provocatively, if you look at the TETON 2 data, right, you're still seeing signs of a dose response. I believe in their forest plot, you're seeing patients on 9-12 months. They're showing higher efficacy, even and also from a weight-based exposure. Do you have confidence that YUTREPIA could show clinical superiority? How are you thinking about designing that trial for YUTREPIA?
I think with YUTREPIA, again, we'll do an open-label study just to understand how YUTREPIA behaves in those types of patients, both IPF and PPF. You know, if you look at what their data was, it was more placebo was going down further than maybe active was going up. We actually think because of the point you made about dose porting benefit, if we can have a better tolerated drug and can give more drug, then we can actually improve the FVC parameter, not just retain it. Those are proof of concepts. It is really just to see, does this product, YUTREPIA, behave in those populations the way it is behaving in PH-ILD and PAH, where the three levers we talked about, safety, efficacy, and convenience, are clear measures of differentiation. For registrational studies, we would use L606 to do formal trials in IPF and PPF.
The other one we're considering doing is PHCOPD. They did run a study in PHCOPD, but to their unfortunate circumstance, it was during the pandemic. That whole study was compromised because there was loss to follow-up because patients couldn't come back to the center. I think there were issues with compliance, and there was obviously COVID in these patients. They shut that study down for safety. It's our view that PHCOPD is actually ripe because we will improve the pulmonary hypertension component in a COPD patient, and that has to benefit them. I think you need to carefully select the sample of patients that you would study and then execute that study flawlessly. We have all of that teed up. The good thing is L606 is a nebulizer.
If you took your worst case and for some reason we lost claim 14 on the DPI, that claim restriction would not really intervene in terms of what we would do with these next-gen programs.
Awesome. Perfect. Pivot to L606. I mean, the open-label data took a little bit to digest because, one, like you've said before, the trial design is completely different than the one your daily competitor ran. This was something you've kind of inherited from Formosa. There wasn't standard titration. The patient baseline is very unique because you have a bunch of Tyvaso switches. I guess based on your and physician feedback from the data, how are you thinking about how L606 will be positioned long-term relative to the once daily and also Tyvaso and YUTREPIA?
Yeah. Maybe just kind of a background. What are you trying to achieve with a sustained-release formulation? The critical point here is you want your peak effect to be on top, to match your trough effect to best effect because you're trying to replicate parenteral therapy where you're at steady state. What L606 showed very, very nicely was that after a year of therapy, the peak and trough benefit sat on top of each other at around 23, 24 meters each. Perfect outcome for what we wanted to achieve because that defines what a sustained-release molecule does or should do. Our half-life is approaching five hours. The TPIP half-life is just over six hours. You can see that from their recent publications in patients.
To me, as a pharmacologist, both of those should be dosed at least twice a day because a six-hour half-life for a once-a-day is suboptimal. I think we can all agree. You actually have proof that it's suboptimal from their own study. If you look at PH-ILD patients, 30 patients, there were 10 active, but let's just, in placebo, but let's ignore those. The 20 active patients, their median change was minus 4 at trough. By the way, that means no effect. They didn't benefit the patients at all because they gave a TPIP as a once-a-day regimen, and it should minimally be more than that, in my view. In PAH, they had a better benefit, but those patients had the most predictive covariate for outcome is six-minute baseline walk distance.
They had a difference in that they had a lower walk distance in their active group versus placebo. All that active group did was correct to the placebo baseline walk. They did not control for, and they did it in third-world countries, so to speak, where there was an availability of background therapy. It certainly was not on top of Wynrivare, which they will need. To me, there are a lot of issues with that data and how it has been sort of summated and viewed in terms of category killer. It is not. If there is a category killer, it is L606 because we are going to give it in a modern-day mesh nebulizer that is portable. This is from Philip Metasize. We had an R&D day, and I encourage you to go to our website. There is a webcast if you missed it, and you can get full description from KOLs around L606.
Because it's liposomal, the cough rate was in the low 30s and drug-related was 14%. It's going to have the safety lever. We achieved doses of 28 breath equivalents or higher in a lot of patients. It's going to have the dose lever. Convenience, it takes about a minute to administer the drug through this, and you just do it twice a day. It's optimally delivered twice a day. We could do it once a day. I'd show you a very nice effective peak, and I'd show you minus 4 meters at trough, which is not good for sustained-release entity. I think the way you need to digest the data, be very careful when it's presented to you in a promotional way.
Awesome. You bring up a really intriguing point about peak to trough, right? I think we've seen peak to trough in other drugs, GLP-1s, for example, TBD if it actually translates to anything. I think the most important thing is for peak to trough, you have potentially easier titratable drug and better safety profile. Also, your second point is you think you will need kind of more exposure on the back half of the day. Can you go over kind of what early data points you're showing? You're seeing that kind of one justifies maybe a better tolerability profile, but also kind of needing that effective twice-a-day coverage.
We haven't done it, but if you look at their cough, it was typical of Tyvaso. I think we've shown now what are historically low levels of cough for an inhaled treprostinil that's encapsulated in the liposome. It doesn't actually release from the liposome until it's in the lower airway. You're avoiding all of the upper airway irritation. Again, this is a different animal. I think because we've seen benefits in peak and trough, you talked about the magnitude of effect. Remember, we did switch them from Tyvaso. Then we tuned them up. The change we saw in 24 meters was above and beyond where they were after they'd already had Tyvaso. This is the next gen. We're very, very excited about it.
I think no matter if both TPIP and L606 are in the space, across all these five markets that are $5 billion-plus, there's room for both of us to do very well together. The future will move to a reduced regimen paradigm for sure.
Awesome. I guess last question. You became operationally profitable two quarters ahead of your expectation, actually a quarter ahead of our bullish expectations. We're seeing YUTREPIA has high margins, I think 96% in third quarter. Like you said, maybe this is a natural run rate because there's some pre-launch inventory. Where do you think kind of the long-term gross margins is for this drug? The ability for opEx and margin expansion over time.
Yeah. So obviously, we're very happy with how the launch has gone. As you said, we've achieved a profitability in our first full quarter of launch. We also generated positive cash flow in September as a company. So we are sitting in a very, very good position just financially. As we move forward, we believe there's no reason for improvement there. Our SG&A costs from Q2 to Q3 remain relatively flat. The expectation is it will continue to remain flat. So as we increase revenue and we have growing profitability, as Roger outlined all of these R&D programs, what we believe is we'll be in a unique position to be able to take some of that profitability and reinvest it into our pipeline.
Being able to do that with the financial capabilities, but also with the discipline to look to continue to grow that profitability, having a small company mentality while having big dreams and big expectations, we think serves us very well. As we move forward, we think from a gross margin perspective, from an SG&A perspective, and generating overall free cash flow, we think we're going to be extremely successful.
Awesome. We will leave it at that. Thank you so much for attending.
Thank you, Amy.
Thanks so much for coming.