Roger Jeffs: Yes, I’d love to. So, Rajeev’s also overseeing that effort. So, Rajeev, if you wouldn’t mind answering the question.
Rajeev Saggar: Yes, thank you, Matt, and good morning to you as well. So, as you alluded to, L606 is our liposomal formulation of sustained-release for Treprostinil that’s going to be delivered twice a day with really a smart portable nebulizer. So, we’re really excited about this program as it’s sort of the leading effort to a Phase III program. The program is designed using a similar strategy like we have with YUTREPIA. So, this is a 505(b)(2) pathway with the label drug being Tyvaso. In our Type C discussions with FDA that had occurred back in December of 2023, once again, we had confirmation that a single placebo efficacy study with L606, would lead to approval for both indications for group one PIH, as well as group three PH-ILD. In that regard, as you stated, we specifically have chosen the indication for PH-ILD to take into a global large Phase III study. That study is gated to initiate sometime in the – near Q4 of 2024.
Roger Jeffs: Great. Thank you, Rajeev. And I think the one thing to add to that is, I guess the other part of your question is, how long will that take? I think because there’s such a scarcity of treatments for PH-ILD, the clinical trial, particularly when we do it in European centers for instance, has potential to enroll quite rapidly. I think the normal time course for the sample size we’re contemplating would be two years or so, but I think maybe we can shorten that a bit. Then there’s time to get through the six-month endpoint and then time to collect the data, submit, and review. So, I think just in broad brush strokes, we’re looking at, from first patient in to an FDA decision, is probably in the three and a half to four-year arrangement, Matt. Next question, please, operator.
Operator: And one moment for our next question. Our next question is going to come from the line of Kambiz Yazdi with Jefferies. Your line is open. Please go ahead.
Kambiz Yazdi: Morning team. With the filed motion for preliminary injunction with regards to 327, what would be the timelines associated with that? And then can you remind us the FDA’s perspective of NDA reamendment versus NDA for indication expansion with regards to tentatively approved drugs? Do we have any precedence there? Thank you.
Roger Jeffs: Yes, I think both of those questions are in Rusty’s court. So, if you wouldn’t mind, Rusty.
Rusty Schundler: Sure. So, on the first question for the 327 patent, so there is a briefing schedule on that. United Therapeutics has filed their brief requesting – in support of their request for a preliminary injunction. Our response is currently due on April 5th. Their reply then would be due April 19. The thing I’d – and then from there, the court either schedules a hearing or not and makes a decision. The thing I’d remind you though is that, again, the default is that if there’s no preliminary injunction in place, there’s nothing that blocks us from moving forward, getting approval and launching. So, the burden is on United Therapeutics to get a preliminary injunction before that happens. So, we’ll see if they try to accelerate the proceedings or what they try to do on that front, but that’s the timeline that’s currently in place on that.
As far as the FDA position on amendments versus supplements, again, I think if you look at the FDA existing guidances, so there’s a 2004 non-binding guidance, that is what United Therapeutics was pointing to, which they claim stands for the proposition that you can never add an amendment to a pending NDA – or I’m sorry, never add an indication to a pending NDA. However, the 2016 regulations and the cited 21 CFR 314.60 subsection F, expressly contemplates situations where new indications could be added to a pending NDA, including a 505(b)(2) NDA like ours. So, again, I think clearly the FDA is contemplating that there are at least circumstances where indications can be added to NDAs as evidenced by the regulations.
Roger Jeffs: And if I may add, Kambiz, I think the guidance that United Therapeutics is pointing towards is the bundling guidance, but that’s really more specific. If you’re changing route dosage form or formulation and providing new data, that should be submitted separately, and it’s a way to make sure that the agency gets their review fees. We’ve done none of that. So, it’s the same route, same dosage form, same formulation and no new data. So, we think we’re well within the statute that Rusty just described. Great. Operator?
Kambiz Yazdi: And then I guess one other follow-up is on the ASCENT trial. What kind of patient populations are being studied and how is enrollment proceeding there?
Roger Jeffs: Yes, great question. Appreciate that. So, Rajeev, if you wouldn’t mind.
Rajeev Saggar: Yes, thanks, Kambiz. So, once again, the ASCENT study is something that we are extremely excited about. More importantly, this is a study that’s absolutely needed in the literature and has actually been desired by the KOLs across the entire region of the United States, requesting that patients that have been recently diagnosed with PH-ILD that are naïve to any therapy, are then placed onto YUTREPIA, which really will highlight three pillars that we have continued to suggest that are very important to this patient profile. The first thing is tolerability and titratability. These things are going to be led by our PRINT technology and therefore our formulation. The combination of those two allows us to use a very low resistance off-the-shelf inhaler which has the simplicity that is needed for patients that have impairments in lung function, but can deliver the dose profiles that we believe are going to be required to not only achieve the minimum therapeutic goals of equivalency of 10 to 12 breaths four times a day of inhaled Treprostinil, but more importantly, lead to actually more improvements in clinical outcomes and efficacy standards that are used, such as walk distance and actual overall clinical outcomes.
