Yeah, no problem. So we're a company focused on rare fibrotic diseases. Our specialty to date has been integrin inhibition for fibrotic diseases, and we've put four programs in the clinic so far. So the most advanced of those is bexotegrast. That's been tested in IPF as well as PSC. IPF is our most advanced indication. We've put out several readouts from our phase IIa program, latest of which was last year, with some additional one single site phase II that we reported on this year. We've also tested that drug in PSC, as I mentioned. We have phase IIa data that the final readout was earlier this year in that indication.
Right now, the company's focus with Bexo and IPF, so we're in the middle of a phase IIb, phase III seamless, registrational study, which is ongoing, enrolling very well. We will have that trial completely enrolled by first quarter next year, with data mid-2026, most likely. So we're all hands on deck for that trial right now. That's the main focus of the company is IPF and with Bexo. We've also got a couple early stage programs, an oncology program, that we are in phase I with, that's going well. We'll have data out of the oncology program late this year, early next year.
And we also have a CTA approved for DMD indication, and that's a program that we haven't entered the clinic yet 'cause we're still doing some preclinical work, but we can enter phase I anytime we want to with that one. So we got a lot of irons in the fire, but really the focus at this point is on IPF.
So, BEACON-IPF, the phase IIb/III, was originally a IIb.
Mm-hmm.
Maybe you can talk a little bit about what was really kind of the drive to transition that over to being a IIb/III. As an analyst, I'm thrilled that that was the case of it. Maybe you could just give some rationales to why?
Sure.
Yeah, I mean, I can say that we've always wanted to pursue that type of design for our late-stage program because it does give you the advantage of eliminating the gap between phase IIb and III, so you save a lot of time. We estimate about two years to phase III data-
Mm-hmm.
- and NDA with the seamless phase IIb/III design. And yeah, so we this is how we had initially thought about conducting the program, and certainly very excited that the most of the regions that are participating to the trial and in the countries are actually on the seamless protocol. So that will expedite our timelines in a significant way. So yeah, I mean, for the U.S., we're still you know really continuing to engage with the FDA to see if there's an opportunity to fold them into the seamless, and I think it's fair to say that at their relatively conservative, conservative division, they haven't entertained seamless trial designs for IPF in the past.
So we're definitely going to continue that, but just, you know, really excited about the fact that we will be saving a lot of time with the seamless being conducted worldwide.
Got it. So yeah, 'cause normally we're seeing the IPF trial phase IIIs are usually much larger, typically two trials, correct? But the... So how would that work with the agency? You were expecting them to allow just the one phase IIb/III, or how?
Yeah, so we've-
What's the wish list?
- been very thoughtful. It's a great question. We've been thoughtful about that because we wanted to really treat the phase IIb part as a, as it could be a pivotal study.
Mm-hmm.
And for that, we chose the pivotal endpoint, which is that absolute change in FVC. We have the 52-week time point that is really the time point for evaluation for all the phase III programs, and we've powered the study for at least 80%. We had an interaction with the FDA last year on the seamless, the potential for them to be part of the seamless, but they provided a lot of comments on the phase IIb-
Mm-hmm
... part that they viewed as really, being a robust effort, that they really, it was a tap on the back, if you wish, from them to say, "This could be-
Mm-hmm
... a pivotal study." But of course, they're never going to say that-
Right
... until they see the data, or that's a decision they'll make later. But, we believe that really what we've done with BEACON is we have two independent, confirmatory studies in one-
Okay
... that could serve for the NDA package, for example. So regardless of where I would say the FDA land in terms of their appetite for the seamless, we do have, you know, two independent studies that are being conducted in a seamless fashion.
And when you say seamless, so how exactly does that work from the IIb with regards to patients? Because the III will not contain the same patients as the IIb.
That's right.
It will not. And then the IIb will inform as to the dose for the Phase III, is that correct?
So exactly right. I mean, the seamless part is really about. It's an operationally seamless study in the sense that it has two independent components. What's really different is that you, the enrollment for both these studies is continuous. So as soon as you've finished enrolling your phase IIb part, then your study, then you continue on to enrolling phase III patients.
Mm-hmm.
So you eliminate that gap, that pause for sites, for example, reinitiating a phase III trial. So that's pretty efficient. And I lost the... Sorry, the last part of your question, because I wanted to make sure I addressed the whole-
Now, I've even forgotten what my question was. Sorry. That was my main thing, just wanting to know, to make sure that they were completely different.
Yeah
... and that you were seeing one as a leading in with the dose-
Yeah
... for the other, for the phase III.
Yeah, exactly. Oh, that's, that's the second part that I remember now. So yes, it will. So, it will. Phase IIb will inform on the phase III trials.
III, right.
But it will also inform on the final sample size for the phase III trial. Because once we have our phase IIb readout.
Yep.
We will select the dose, but we will also have an accurate assessment of our treatment effect, and then we'll be able to determine the total sample size for the phase III evaluation.
How many patients per, roughly?
Yeah, we haven't provided-
Okay.
guidance on phase III right now.
Okay.
-just because we'll need the-
Yeah
- phase IIb data to really-
To give an idea. Okay. But would we expect that the total number of patients at the end would be about what we would normally see in a traditional, like a TETON or a FIBRONEER study for IPF?
I believe it should be in the same range.
Okay. Okay, great. And then the phase IIa INTEGRIS-IPF did not show a dose-dependent effect on FVC change in the modified intent-to-treat analysis. 80 milligram looked better than the 160 milligram. So is it likely that the 320 milligram will be the final dose, as it seemed to show the strongest separation?
Yeah, yeah
-from baseline?
We think the 320 milligram has a good chance to make it to Phase III, but we also think it was more prudent to introduce the 160 milligram dose because we also had the best results. Maybe in terms of the absolute change in FVC-
Mm-hmm
... and in milliliters-
Mm-hmm
... that endpoint, the 80 did do better than the 160. But if you look at, for example, FVC percent predicted of greater than 10%, so that's a categorical endpoint for FVC, and then you also had QLF-
Mm.
the biomarkers, and even, what's the other one I'm missing out on?
Mm.
But the two, the 160 and the 320 were really the best doses overall.
Okay.
So, you know, we wanted to certainly have, we'll have about at least 30% of our patients in BEACON that are not on background therapies.
Mm-hmm.
That's also an additional opportunity to see which dose performs the best in monotherapy.
Got it. Okay. And could you talk a little bit about, the safety of the integrin class and just, just kind of what gives you guys confidence that there are no issues associated to date that you've seen?
Yeah. I mean, there have been some issues in the past. I mean, you're talking about Biogen-
Mm-hmm
... and the AbbVie-Morphic program, likely. Those were programs that Biogen specifically saw these issues in preclinical models, as well as their chronic tox and prechronic subchronic tox. The Morphic program never made it to the clinic. That was killed in 28-day tox. So, those programs, you know, definitely had their issues. What we've seen, though, preclinically and clinically, is we've not seen any of the pulmonary infiltrates that Biogen saw, the signal that the AbbVie-Morphic saw. We haven't seen any of that preclinically. We've done our chronic tox in 9 months in monkeys, 6 months in mice. That's all complete. That was clean.
By clean, I mean the NOAEL was set at the highest dose we tested, so completely clean. And we've been in over 700 patients to date with bexotegrast and haven't seen any dose relationship to AEs or and really no specific AEs to mention. So we feel very good about the tox profile for Bexo. And, you know, I think we've, that's been borne out in the data so far.
So with this, this seamless IIb/III, I guess, would this be the first time that you would think that the agency has potentially entertained the idea of potentially considering this as a pivotal trial? Just looking at some of the historical drugs that have either been approved or the ones that are in late-stage development, just to get an idea.
I mean, it's hard to say if other sponsors have proposed these types of design-
Without knowing
We'll never know. But you know, I think that good data always is the trump card for these agencies, right?
Mm-hmm.
I think that if we're able to show great data in both, and both studies meet their pre-specified endpoints, and by that I mean the phase IIb part and the phase III part, regardless of whether FDA has said yes to the seamless or what have you, it's still, or they, they would still be two independent, well-powered studies that could be confirmatory, right?
Right.
It would be difficult for them to look away from good data-
Yeah, yeah
-that's positive.
Yeah. So we obviously know the shortcomings of the two approved therapies out there for IPF. And then now we've got, you know, these programs like FIBRONEER and TETON trials are ongoing. Can you talk a little bit about that, about that competitive landscape as it's evolving now, and from the data that you've seen from those other programs, and how you see bexotegrast kind of fitting in with that?
Yeah, I mean, we hope these trials work. I mean, we need agents in the space. I think the more products that doctors have to choose from, the better for everyone. As far as specifically thinking about the phase III agents, the BI agent, they had, you know, interesting phase II data. They did have a diarrhea signal, so we'll have to see how that goes, if it's in combination with nintedanib, which also has a diarrhea signal. That's not a known antifibrotic mechanism as well, so we'll hopefully that bears out in the long-term data, but we'll have to see.
The United Therapeutics inhaled Tyvaso, you know, they saw an effect in phase II, but it was mostly in patients that had pulmonary hypertension as well as IPF, and you had to achieve a certain number of inhalations a day, which was difficult for patients. IPF patients cough a lot, and it's hard for them to do these kind of administrations. So, we'll see how that one goes as well. I mean, the other phase III that you didn't mention is BMS, and their IPF study with their LPAR1. That was a pretty modest effect that they saw in phase II. We know that they've initiated a phase III there in IPF, as well as progressive pulmonary fibrosis. So we'll see how those go.
There were some AEs with the BMS program as well. I believe it was hypotension that they saw. So we'll see how that goes, but we, you know, we hope that these medicines get to patients.
So, what is it at the end of the day, is it still gonna see more like of a combination therapy, or would you see that docs are gonna maybe stick to the already approved drugs?
Yeah
and wait for those patients to fail or have issues, which always is the case, it seems, the two approved drugs, and then move on to something new?
It-
How do you see that?
It's a very good question. I mean, by the time we're If we make it to approval, by the time we get there, the approved agents will be generic. So we have to assume that they'll, they'll be heavily used. But we're designing our late-stage trials so that we can have the strongest label as possible to be in newly diagnosed patients, patients who are already on an approved therapy, who are tolerating it, but want then some, potentially some additional efficacy, and for patients who couldn't tolerate this approved agents and wanna switch. So those three broad groups, I think, you know, that's why we're doing a large number of patients who are not on standard of care-
Mm.
in the phase III, as well as those who are, so we can, you know, hopefully address the whole population.
What has been the feedback to date from physicians who've seen the data on bexotegrast?
I mean, they're excited about the program. Their first experience was basically the safety piece, right?
Mm.
So we had in our INTEGRIS-IPF study, we had a 3-to-1 randomization ratio from active to placebo. So in essence, they were seeing very good tolerability there, so they assumed that that drug was well tolerated because most patients were on active. And so that those were the early comments we've received. And then the data came out. I think people were excited to see the good safety being confirmed, and, and also, the efficacy signal, even though the trial was not powered for efficacy.
Mm-hmm.
We saw that effect on FVC, but we also had QLF, you know.
Mm-hmm. Yeah
... as a different imaging method to assess the changes there, the cough data, so that was intriguing. And more recently, I think what's gotten them really excited is the collagen PET data that we released, showing that 12-week treatment with bexotegrast, it was dosed at 160 mg in that study, was able to reduce collagen deposition over 12 weeks, in contrast to placebo patients who continued to see an increase. In that, and in that study, we also saw the improvement in FVC and also the effect on cough in patients that at baseline were coughing more than those in INTEGRIS.
So altogether, I think they're really excited about the program because of the results, but also because of all the understanding, you know, the translational aspects of our program that is beyond what they've seen with other programs as well.
Yep. But before we move on to PSC, I wanted to ask, just with regards to the current design, if the agency does not buy in to the current IIb/III, would the thought be to go and do the standard phase III, II phase III trials? Or how would that change as far as what you're doing? 'Cause it sounds like ex- U.S. , you don't have a problem with the IIb/III, but if the USA is, how would that change things for you?
Yeah, I mean, there, there is a possibility that we might fully enroll the phase III part of-
Mm-hmm
... BEACON, at the time that we read out on the dose-
Yep
From Phase IIb data. In this scenario, again, keeping in mind that these are two independent studies-
Mm-hmm
... that are well powered-
Yep
... the bulk of our enrollment so far in the Phase IIb part has been from the U.S. , because that's the quickest region to open. So we would have representative U.S. population in our program.
Mm-hmm.
It's hard for. This is my opinion, it's something that, you know, I want to disclose that-
Yep
... but it would be hard for the agency to see a positive Phase IIb and a positive Phase III and say, "Well, we want an additional one.
Yeah.
Because that would be an additional requirement that has not been made to other sponsors as well, considering the you know, the robustness of the phase IIb effort. So we do think there's a you know, there's a... In that scenario, it's hard to see that they would require an additional study.
Yeah. Yep. No, it makes sense to me as well. I agree. And just moving over maybe to PSC, I know IPF is clearly your- the main focus for the company, but just what is the gating factor as far as wanting to move forward on the PSC program?
Yeah, I mean, given our ambitions in the pulmonary world, and that being IPF plus plus expansion into pulmonary, progressive pulmonary fibrosis, that's where our resources are focused now.
Mm.
I think in order to move PSC forward, we need two things to happen. One, we need clear guidance from the FDA on a phase III design and endpoint.
Mm-hmm.
They've given us agreement on a phase IIb, but we still-
Mm.
It's still unclear about phase III. So we don't wanna go into a phase IIb blind to the-
Yep
... to what the ultimate path of approval is. And based on where our focus is now, we'd need additional capital to run the PSC program. So, I mean, from a competitive perspective, there's not a lot out there.
Yeah.
It's a pretty open space. The path to approval is what we really have to figure out.
Yeah, I was gonna say, even with the competitive landscape, I mean, it's, it's evolving more, but it's still not that many drugs that are out there, and they're very early stage. So it's... And with nothing approved for it, it just seems like a, a, a good primary area for you to be in as well, since it's fibrotic. But, obviously resource-
Yeah
... resources.
Yeah, I mean, we really like the indication. I mean, the patients really need medications there, and our data to date has been fairly stellar. You know, we saw a tremendous antifibrotic effect in those patients-
Mm-hmm.
which we think reads through to the IPF program.
Yeah.
As well as the safety.
Yeah.
We think that reads through as well. So, you know, we're really happy with the results we've seen in PSC. We just need to, you know, there needs to be a couple of shoes to drop before we can go forward.
Yeah. Under the whole umbrella of interstitial lung diseases, besides IPF, there's also, we're seeing more companies also starting to target progressive-
Mm-hmm.
- Pulmonary fibrosis.
Yeah.
What's kind of your thoughts there on that as another indication to go after?
Yeah, we think that's a post-Phase IIb data. Once we've fully proved, proven the concept, we think we can do that with a single Phase III. That's what BI is doing, that's what BMS is doing. So that is our ambition, and that's the next big value driver for the company after, after we get proof of concept in the IPF.
Got it. And then the oncology program, can you just talk a little bit about that? I know it's still early days there, but just what exactly is the... You know, tell us a little bit more about the program and the total addressable market that program would be addressing.
Yeah, I mean, I can give you some details on the trial itself. So it's a first-in-human trial-
Mm-hmm
-that we're conducting. It's an alpha v beta, alpha v beta 1-
Mm-hmm
integrin inhibitor, small molecule, oral. And, we are testing it right now from a safety and PK perspective in all comers, patients with that are known to be refractory to checkpoint inhibitors.
Mm-hmm.
We have five dose escalation cohorts. They're all multiple doses. Patients will. It's all in patients, so they start with two weeks of monotherapy. We assess the safety there, and then they add pembro from that point on, and then you know, we follow them for tumor response. But mainly, what we're trying to show here is, can we get to high exposures-
Mm-hmm
With the compound? Are we seeing good safety? Because it's an all comers approach and it doesn't include, for example, tissue biopsy, it's gonna be more of a circulating PD marker.
Mm-hmm.
It has the standard 3 + 3 design as well.
Mm-hmm.
So right now, we're in the third cohort, and so we hope to be able to report data later this year or early next year, from that study.
Too cool.
But Frank, to answer the other part of your question on the-
Mm-hmm
the size of the market, I mean, what we're... You know, based on the mechanism, we think that a large part of the resistance to checkpoint inhibitors is based on TGF-beta activation in the tumor microenvironment, and there's an anti-inflammatory effect there that excludes T cells. We think that by cutting off that activation of TGF-beta, we remove that anti-inflammatory effect and sensitize... Basically, it could be any type of tumor to a checkpoint inhibitor. So the market is very large, but we recognize how tough it's been for these adjuvant agents to find success. So, you know, the mechanism is well understood, so we think there's a lot of buy-in from pharma, you know, in that as a combo treatment, so that the market could be very big, but we recognize the challenges.
Yeah. And with IPF, we, you know, talked about the IIb/III being designed for worldwide study. Kind of what are the thoughts from a business standpoint with regards to partnering ex- U.S. ?
That's something we'll look at over time. We're not contemplating that today. I mean, if, you know... We're well capitalized.
Mm-hmm.
We're funded through 2026, so we have plenty of capital to get through the phase IIb data, and we're conserving capital to that end. So, you know, we'll get to the phase IIb data. We'll see sort of where we're at from an efficacy perspective, and I think that's probably the opportune time to start thinking about whether it's an ex- U.S. partnership or what have you.
Mm-hmm.
That is something we will look at, but, you know, we wanna get to phase IIb data first.
And then what about as far as earlier programs like the oncology program?
Mm-hmm.
Would that be something that-
Yeah, oncology is definitely a BD opportunity.
Yeah.
You know, that program was spawned from inbound interest from pharma-
Hmm
- wanting to look at that target.
Yeah.
We have a large library that we can pull from, and we started working on it and quickly had a development candidate. We think, you know, with combination safety PK data with some PD markers, that's the data that pharma would like to see on that mechanism, and once we have that data, we'll consider partnering that out as well.
Got it. And now, just, I mean, as we get to the end, maybe you can give us an idea of what we should be looking for over the next 12 months from Pliant?
Yeah. I mean, we will have the oncology data-
Yeah
- that's coming out. I mean, we expect to enroll the BEACON study by first quarter next year, so we'll be reporting on that as it's enrolled. And then we'll have some potential, you know, BD from whether it's oncology or more platform deals or what have you. The other thing we're looking closely at is the formerly known as our DMD program. We're looking closely at in some other tissues with that mechanism. We think it actually could have a applicability outside of muscle. And once we have some more data on that and we form our thoughts a little clearer, we'll talk more about that. So hopefully, there's some, you know, exciting stuff to talk about with some of the early-stage programs.
Fantastic. Thank you so much, guys, for joining us. We appreciate it.
All right.