Good morning, and thank you for joining Pliant Therapeutics' conference call. At this time, all participants are on a listen only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one one on your telephone.
You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would like to turn the call over to Christopher Keenan, Pliant Therapeutics Vice President, Investor Relations. Mr. Keenan?
Thank you, Shannon, and good morning, everyone. Thank you for joining us for Pliant's presentation of 24-week data from the INTEGRIS-IPF trial, our phase 2a clinical trial evaluating bexotegrast, formerly PLN-74809 at 320 milligrams in patients with idiopathic pulmonary fibrosis. Yesterday, we issued a press release that will be referenced during this call and is available under the investor and media section of our corporate website.
The slides accompanying today's webcast are also available in the same section. During today's call, we will be making forward-looking statements, including those related to the therapeutic potential of bexotegrast and our plans for the future development of bexotegrast. Forward-looking statements relate to the future, they are subject to inherent uncertainties and risks that are difficult to predict and many of which are outside of our control.
Important risks and uncertainties are set forth in our most recent public filings with the SEC, which are available at sec.gov. Pliant undertakes no obligation to update any forward-looking statements, whether as a result of new information, future developments or otherwise. Joining me today with prepared remarks are members of the Pliant management team, including Dr. Bernard Coulie, President and Chief Executive Officer, Dr. Éric Lefebvre, Chief Medical Officer, and Dr. Greg Cosgrove, Pliant's Vice President of Clinical Development and our Head of our IPF program.
We will be joined by Dr. Toby Maher, a Professor of Medicine and Director of Interstitial Lung Disease at Keck School of Medicine, University of Southern California, Los Angeles. Dr. Maher has spent the last 20 years specializing in the management of all forms of pulmonary fibrosis and orphan interstitial lung diseases. Dr. Keith Cummings, Pliant's Chief Financial Officer. Scott Turner, our Senior Vice President of Research, and Dr. Christopher Barnes, our Head of Biostatistics, will join us for the question and answer portion of the call. With that, let me turn the call over to Bernard.
Thank you, Chris. Good morning, everybody, thank you for joining us. It's a great pleasure for us to be with you and share the compelling data that we announced yesterday from our INTEGRIS-IPF phase 2a clinical trial of our lead asset, bexotegrast. As you know, bexotegrast is an oral small molecule. It's a dual selective inhibitor of αvβ6 and αvβ1 integrins.
It's currently in clinical development for idiopathic pulmonary fibrosis and primary sclerosing cholangitis. Today's 24-week results from the 320-milligram dose cohort of INTEGRIS-IPF again exceeded our expectations. Today's data build on the strong and favorable 12-week data that we presented in January, with the 24-week data from this cohort highlighting the long-term safety as well as the durable improvement in patients with IPF.
At Pliant, our focus is to drive innovative science to develop potentially life-changing drug candidates for patients in need. I believe the results from the INTEGRIS-IPF trial have taken us another and important step closer in our mission. Let me provide some background on why we evaluated this dose group and give a high level set of key takeaways that we will share with you today.
On slide three, you will see that the purpose of this study was truly to evaluate long-term treatment with bexotegrast 320 milligrams. We wanted to evaluate long-term safety of this top dose, which is planned for late stage development. Same time, we want to evaluate durability of the treatment effect that we saw before in FVC, but also looking at symptomatic improvement, potential symptomatic improvement with a focus on cough.
Also, we wanted to assess the long-term effects on pulmonary fibrosis as measured through imaging using Quantitative Lung Fibrosis. The key takeaways from the trial, clearly, and we will show you the data after this in a minute, that the key takeaways are that bexotegrast continues to demonstrate a favorable safety and tolerability profile.
It demonstrates durable improvements, not only on physiologic measures such as FVC, but also on fibrosis as measured by QLF and even on symptomatic assessments using a cough score, all versus placebo. We are convinced that these data provide strong support to advance bexotegrast into the next stage of development.
Today's call will have Eric beginning with an overview of the INTEGRIS-IPF trial and then turning it over to Greg to review the safety results and findings from the trial's exploratory efficacy endpoints. Eric will discuss the next steps of the bexotegrast clinical development program. Following this, we will hear from Toby on his thoughts on these results before I conclude and open the call to questions. Let me turn the call over to Eric.
Good morning, everyone. I'd like to first start by introducing the study design for INTEGRIS-IPF. This was a dose-ranging, double-blind, placebo-controlled study that evaluated four doses of bexotegrast. Here, the focus of this presentation will be on the top dose, the 320 milligrams that we plan to evaluate in our program.
This dose level was different from the other dose levels because it had a longer duration. It went to at least 24 weeks of treatment, and this cohort had a 3-to-1 randomization ratio for active and placebo. The patients that were first enrolled in the study went out to a longer duration, which is approximately 40 weeks.
The primary and secondary endpoints for this study were safety, tolerability, and PK. Exploratory endpoints were change in forced vital capacity over 12 and 24 weeks, biomarker imaging using the QLF score, which is based on high-resolution CT scan, patient-reported cough severity, and effect on selected biomarkers. I'd like to stress that the data from this cohort alone were used to inform the MMRM model that was used to come up with the changes in FVC.
Pointing out that in terms of biomarkers, the active arm was compared to the placebo patients that were in this study alone, in this cohort alone, because none of the other cohorts went beyond 12 weeks. Now I'll pass it on to Greg to give you the results.
Thank you, Éric, good morning to everyone. The INTEGRIS-IPF 320 mg cohort identified that bexotegrast 320 mg was well-tolerated over a long-term treatment up to 40 weeks, with most treatment-emergent adverse events being mild to moderate in severity and not related to study drug. There were no discontinuations due to treatment-emergent adverse events from week 12 to week 40, and no drug-related serious adverse events.
A durable treatment effect was identified on FVC over the 24-week evaluation period. It identifies a continued improvement in FVC versus placebo from week 12 to week 24. In those bexotegrast treated patients, they experienced an increase in FVC from baseline to week 24, and 89% of those participants on bexotegrast maintained that increase at week 24.
Quantitative Lung Fibrosis or QLF strongly supported bexotegrast's anti-fibrotic mechanism, demonstrating stabilization of fibrosis in the bexotegrast treated patients, while the placebo participants, of which 80% were on either nintedanib or pirfenidone, had clinically meaningful progression. At week 24, bexotegrast treated participants were twice as likely to show stabilization or improvement of fibrosis compared to placebo.
Lastly, there was evidence of a treatment effect upon signs and symptoms experienced by patients in IPF. Cough, notably a common symptom in IPF and a debilitating one, was identified to be reduced in severity in those treated with bexotegrast compared to the placebo group, which all worsened. To give you a general overview of the disposition in the study, we see that INTEGRIS-IPF was an efficient, efficiently enrolled and operated study with minimal discontinuation in both arms.
As I mentioned, 80% of participants were on either pirfenidone and nintedanib, and approximately 50% were on pirfenidone and 50% were on nintedanib. The baseline demographics were similar between the bexotegrast-treated participants and those in the placebo cohort. Minor differences in the distribution of female sex were identified in the placebo group.
That comment is relevant if we look at the baseline physiologic characteristics, where we see a slight decrease in the absolute volume measured for FVC. If we account for gender, height, and ethnicity, normalizing for percent predicted FVC, we see that those distributions become quite similar at 77.5 and 75.5. As previously mentioned, the safety profile of bexotegrast 320 milligrams remains favorable.
We saw no drug-related serious treatment-emergent adverse events. There were no discontinuations after week 12 in the bexotegrast treatment group. The most frequently reported treatment adverse event was diarrhea. It was comparable between the bexotegrast treatment group and placebo, notably with participants in the vast majority of instances on background therapy.
The other adverse events identified are consistent with the underlying disease IPF and not related to study medication. The change in FVC from baseline to week 24 is identified in the ITT population and in the subgroup on standard of care in the two graphs. What we identify here in the left graph is that bexotegrast reduced the FVC decline by 67% relative to placebo at week 24. In that subgroup analysis on standard of care, that effect was additive up to 80% relative to standard of care alone at 24 weeks.
To identify what we consider the average effect of bexotegrast, we performed a trimmed mean sensitivity analysis where we removed the best and lowest performing participants in the bexotegrast arm. In doing so, we see a more pronounced effect with a 92% relative reduction versus placebo in that overall population, the ITT population, and a 96% relative reduction compared to placebo in the standard of care subgroup.
Consistent with these data, we see a 68% relative reduction in the FVC % predicted comparing the 320 milligram bexotegrast treated group to the placebo group. The effect of bexotegrast was durable throughout the study from week 12 to week 24. On this slide, we identify the proportion of individuals with an improvement in FVC compared to those with a reduction or decline in FVC.
What is evident is there's a durable treatment effect in the bexotegrast-treated participants from week 12 to week 24, with 89% of those in the bexotegrast-treated group with an increase were maintained at week 24. In contrast, in the placebo group, none of the participants after week 12 were identified to have an improvement, all dropping below their baseline values.
Quantitative Lung Fibrosis and its change from baseline to week 12 and 24 identified here, which demonstrates stabilization of fibrosis in contrast to the placebo group, which identified a clinical meaningful progression at weeks 12 and 24. This is identified as the dashed line across the horizontal axis indicating MCID. That 2% threshold, which is passed at week 12 and at week 24 in the placebo cohort, suggests the radiographic progression of fibrosis, which is linked to clinically meaningful measures.
In a similar analysis looking at the proportion of individuals that either, you know, stabilized or improved in their QLF score versus those that have worsened is identified in the current graph, suggesting that individuals treated with bexotegrast were twice as likely to have stabilization or improvement compared to the placebo at week 24.
As Bernard had mentioned, we also identified symptomatic changes in participants in the study where cough was reduced in the 320 milligram cohort, both at week 12 and at week 24. In contrast, in the placebo cohort, we saw worsening of cough at both those time points. As I mentioned, cough is not only a symptomatic manifestation of IPF that is debilitating in many patients, but it is also a predictor of disease progression and mortality.
Therefore, we are excited to see the impact upon cough in patients with IPF matched with the change in FVC. The change in FVC % predicted and QLF, they are further complemented by changes in circulating biomarkers integrin beta-6 and PRO-C3, both of which show reduction at week 12 and week 24.
Both of these markers are suggestive of progression in interstitial lung disease and therefore, the consistent reduction in these and in other metrics of the study suggest a physiologic, a radiographic, and a symptomatic improvement in the setting of treatment of bexotegrast. These data provide confidence as we move forward to our late-stage planning. I'll turn it over to Eric to describe future plans for bexotegrast.
Thank you, Greg. It's with great pleasure that we communicate on our study designs for the BEACON-IPF study, which will be our phase 2b evaluation of bexotegrast. This will include approximately 270 patients. We will evaluate two doses, the 320 mg, 160 mg, and that will be compared to placebo. The treatment duration will be at 52 weeks, and the study will be stratified.
We'll have two stratification factors. One will be the use of background therapy, which is nintedanib or pirfenidone, and the other one is the GAP index. The GAP index is a marker of disease severity and also is associated with increased risk of mortality for the highest GAP index scores.
Our primary endpoint will be the change from baseline in an absolute forced vital capacity at 52 weeks. Secondary endpoints will include time to progression of disease, which will include a 10% or greater absolute change or decline in FVC % predicted from baseline, respiratory-related hospitalizations or all-cause mortality.
We will also evaluate the change from baseline in absolute FVC in participants on and off background therapy, looking at the change from baseline in a PRO, or patient-reported outcome, named the Living with Pulmonary Fibrosis, which also evaluates cost, and then also safety and tolerability. It's with great pleasure now that I introduce Toby to provide some color on these findings. Toby?
Yeah. Well, thank you for inviting me to have the opportunity to comment. Congratulations to all of your clients for producing another very nice set of data. I think for me, looking at these, I think there's a lot of reassurance to be had.
You know, albeit it's a relatively small cohort that have gone through to 24 weeks, I think the fact that you're seeing a sustained benefit in terms of FVC, but also importantly, you're seeing that together with supportive imaging changes, supportive symptomatic changes with cough, and also the supportive biomarker changes makes this, to me, a very compelling set of data.
I think added to that, of course, the consistent safety effect with that that you've reported in the short studies, also provides further reassurance that the drug has a good and sustained safety and tolerability profile. From my point of view, this looks like an excellent set of data. You know, with the caveat that it's a small cohort, I think this provides excellent support for moving forward with the planned phase 2b trial.
Thanks. Thank you, Toby. Your valuable perspectives throughout the INTEGRIS-IPF program are very much appreciated. Today's data brings our INTEGRIS-IPF phase 2a clinical program to a close. This was a very successful trial that was well executed and produced very strong results that allow us to move with confidence into later stage development and take another, an important step closer to delivering a potentially transformative medicine to IPF patients in need.
We are pleased to see an increased interest in our program, as well as general interest in respiratory diseases, including recent acquisitions. I would like to personally thank all the members of the team at Pliant who worked tirelessly for this trial's initiation during the pandemic to delivering strong data from this important program over the last several months.
Of course, central to this success is the commitment and dedication from our clinical trial participants, their families and support networks, as well as the physicians. Thank you all for joining us today, and I trust you share our excitement with these data. With that, I will open the call to questions. Chris?
Shannon, please open the call to questions.
Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Yasmeen Rahimi with Piper Sandler. Your line is now open. Yasmin, your line is open. Please check your mute button. Our next question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is now open.
Hey, good morning. Thanks for taking my questions and congrats on the data. Two questions from me if I may. I guess first off, the effect size here, when you look at FVC slope and QLF, look maybe a little bit less robust in the second three months versus the first three months of treatment. I was wondering if you could maybe help us disentangle that a little bit.
Obviously, patients are starting off much better having taken beksa for those first three months. I'm curious what gives you the most confidence in the persistence of effect. Any mechanistic explanations, or outlier effects to consider? It sounds like there were some outliers, so it would help, I think, if you could further expand on that.
Maybe quickly for Dr. Maher, just curious, your views overall on, like what stands out most to you with these data? I think it would be helpful for everyone to hear what you think differs most here versus other developmental IPF drugs that maybe showed early signals but which didn't ultimately pan out. Thanks.
Thanks for your question, Brian. In terms of the second half of the study, basically between weeks 12 and 24, we did see good results, obviously with the durability that we presented with 89% of patients remaining above their baseline values at that time point, which of those were, who were already above it at week 12.
I think it was, you know, really a small sample size as many have described. In small sample sizes, certainly, one or two patients that behave a bit differently than the rest of the group can really skew the results. I think the trimmed mean sensitivity analysis that we performed, taking out the worst performer and also the best performer, really helped to inform the curve.
I would argue that this suggests more stabilization of disease, which is really something to strive for in IPF because so far this has not been addressed. The approved drugs only can slow the decline of FVC by about half on a yearly basis. For us, for myself, I find these data very encouraging and provide great confidence in what we could expect to see in the phase 2b study. Toby?
Yeah. I, you know, I, I think the durability of the effect over six months is clearly very important. I think with the three-month data, there's always an anxiety that perhaps we're looking at short-term changes and those effects won't be durable.
I think now having the six-month data has been very important. I think if we contrast this to other development programs, the combination of having the six-month data together with the very clean looking safety and tolerability profile, I think is a major strength.
Again, you know, it's early days and small study numbers, but the magnitude of effect also looks to be potentially very impressive. Fingers crossed that this can be replicated in a phase 2b. But it... You know, the potential is there that this is both better tolerated and perhaps has slightly better efficacy than existing treatments.
Thanks, and congrats again.
Thank you. Our next question comes from the line of Ritu Baral with TD Cowen. Your line is now open.
Good morning, guys. Thanks for taking the question. I just wanted to ask about BEACON, and the assumptions that you guys have designed into that study for both how placebo will act, I'm sorry, control, on standard of care. Just because that arm does seem to be behaving differently over different IPF studies recently and any factors that drive it. If you could also recap what your effect size assumption will be for that 80% powering of BEACON. Thanks.
Thank you, Ritu. Really the week 12 data that we presented in January was the one that was mainly influencing our sample size duration for BEACON-IPF. It's important to mention that because we don't have long-term data, the data from other programs that went out to 52 weeks were also informing this estimation for the sample size. You know, based on what we see here with an 80% reduction in FVC decline over placebo, this played a big part in the sample size duration.
Effect size?
Well, that's what I'm talking about here.
Okay.
If you see the drug on top of standard of care providing 80% further reduction in FVC decline.
Got it.
compared to standard of care alone, that played a big part.
That is.
Yeah.
Got it. Okay. Got it. Just a quick question just on the cough. Was PPI use balanced between the groups? Maybe I missed it on the background.
We did not control for PPI use in terms of prohibit nor mandate its use. It was real-world medical therapy at the discretion of the PI.
Got it. Thanks for taking the question.
Thank you. Our next question comes from the line of Pete Stavropoulos with Cantor Fitzgerald. Your line is now open.
Hi. Good morning, and thank you for taking my question, and congratulations on the data. For Dr. Maher, you know, can you talk about cough, you know, how it affects your IPF patients? You know, how does that, you know, difference between the bexo arm and placebo translate to your patients in terms of severity of cough and impact on quality of life?
The cough is an important and common symptom associated with IPF. About two-thirds of patients will report some cough, and about half of patients will have significant cough that has an impact on their quality of life, increases anxiety, increases depression. It's a major issue.
Actually in work that we've done looking at the cough VAS, the visual analog scale, we do find an association between patient-reported cough severity and mortality as well, suggesting that there may be a link between the coughing and disease progression. I think there are several important reasons to want to impact cough.
One is the simple fact of trying to improve quality of life for our patients and actually manage the symptoms that are most disabling for them. It may well be that the mechanical stress of coughing is also associated with disease progression, helping to alleviate the cough may in actual fact have other positive benefits for patients.
Thank you. In terms of other symptoms that you can see, you know, taking into consideration the mechanism of action of bexo, you know, is there any other symptoms you can see bexo addressing?
That's a good question. I, and the sort of the three main symptoms that patients report are breathlessness, cough, and fatigue. I think, you know, the effect on breathlessness will likely be related to the slowing of disease progression. Fatigue is something else that may well be benefited by a treatment that's having a positive effect on disease activity. I think it'll certainly be something to tease out in the BEACON study as we move forward.
Thank you. Question for the company. You know, as you look forward towards the phase 2b, you know, and a registrational study, I know you provided some secondary endpoints as AM, what additional secondary endpoints, you know, are you thinking about that can help differentiate bexo from current standard of care and other agents in development?
Yeah. Thank you. We have, I mean, disclosed the key secondary endpoints, right? As you go into later stage development, you want to start to, you know, being clear on the ones you want to evaluate. I would say that one of the things that maybe didn't come across as clearly is that we also want to be looking at, you know, increasing the proportion of patients that are not on standard of care in our phase 2b evaluation. That's something I didn't mention. 30% of patients will not be on background therapy. This will help us to really characterize the treatment effect of the drug as a monotherapy.
We believe that this compound has a really good chance to be used in first line, potentially without the existing agents. We wanna start building on that. Maybe the other endpoint that wasn't mentioned here is the QLF score. That will be evaluated also in phase 2b. This will benefit here from having, you know, many more patients, obviously, and also the longer duration to really tease out the treatment effects.
Right. Thank you very much, for taking my questions and, congratulations once again.
Thank you. Our next question comes from the line of Eric Joseph with J.P. Morgan. Your line is now open.
Good morning. Thanks for taking the questions. Maybe just a follow-up on that last point about assessing treatment effect with monotherapy. It looks like from the INTEGRIS data overall that patients on the placebo are not on background standard of care progressing more slowly that, than those that are on standard of care.
I guess I wonder whether there's anything sort of in the baseline demographics that would inform whether that trend is real, and if it is real, you know, how that feeds into your confidence level that you'd be able to detect a treatment effect with monotherapy in BEACON with adequate power. Secondly, just on dose selection here in BEACON.
You have good tolerability with 320 mg, but I'm just trying to understand the decision to include both or evaluate both 160 and 320. Is it, is there a potential hedge around safety that you sort of wanna curve against, or is it more about just identifying a dose that is the minimum, yet fully efficacious regimen? Thank you.
Thank you for your question, Eric. For the patient, the sample size of the patients not on standard of care in INTEGRIS-IPF, we didn't see any notable differences in baseline characteristics for these patients. I think that we, you know, we think that it could be a question of small numbers where these patients perform differently.
We think those differences probably will be alleviated by, you know, the BEACON study where you have a much greater number of patients not on standard of care, and hopefully we'll be able to, you know, to see what really, how they perform really differently than patients on standard of care? They should. We'll look at that.
I would argue that it's in this patients, this group of patients not on standard of care that you would have a better characterization of the inherent benefits that you can expect with bexotegrast alone. The fact that we see an incremental benefit on top of approved therapies is really, really encouraging in that sense because you would expect that group, the patients receiving background, to have, you know.
This is where you'd have the hardest opportunity to show a difference because they're already on approved agents, right? The fact that we see this really strong improvement in patients on background therapy with bexotegrast suggests that we should be able to see that also on patients that are not receiving these agents.
To your second question, the two doses we're carrying in phase 2b, we do believe that both of these doses had great results in the INTEGRIS-IPF study. The question, you know, for me, the broader question is if, for example, the 320 milligram would have a better effect in patients on monotherapy, meaning that patients not on background therapy. If that was true, then would it be as well tolerated as the low dose? Because ultimately, what we wanna bring forward is a single dose to phase 3. we need to make sure that this drug is also effective in the setting of monotherapy, but also well tolerated in the combination.
Okay, great. Thanks for taking the questions.
Thank you. Our next question comes from the line of Joseph Stringer with Needham & Company. Your line is now open.
Hi, good morning. Thanks for taking our questions. Just had a few quick ones on the phase 2b trial. For the 30% or so of patients that won't be on standard of care, will these patients be treatment naive or treatment experienced? How does that differ from the phase 2a trial?
We will include patients that are treatment naive and patients also that have experience with these agents, just as long as they're not taking them for at least three months, eight weeks. That's different. We will collect that information as we enroll patients into the BEACON study. Unfortunately, we didn't have that information for the INTEGRIS IPF study.
You know, we can't report on that, but certainly, we'll be on the lookout to see if there's any meaningful differences in the patient characteristics of, you know, and also the treatment effects in patients that have experience with background previously or whether they're purely naive. Obviously, the trial is not powered to look at these differences, but we'll be able to look at the subgroups.
Great. Thank you for taking our questions.
Thank you. Our next question comes from the line of Yasmeen Rahimi with Piper Sandler. Your line is now open.
Good morning, team, sorry for missing my call earlier. Congrats to the data. A few questions. I guess the first question is, when you look at the biomarker data, it seems sort of like a little bit, there's quite a bit of variability, but sort of it went down when we look at the plasma integrin and PRO-C3. Is it just a function of variability, or do you think how should we project these blood biomarkers to change over, you know, 52 weeks of treatment? Maybe we can start there and then two quick follow-ups.
Hey, Yasmeen. It's an excellent question. As you I think you nailed it right on the head. This is really a variability. These are changes from placebo, which is a very small group of patients, we wouldn't expect necessarily to not have variability as we go over time.
Okay, wonderful. Just for Dr. Maher, I think it would be great if you could put into perspective sort of how the placebo curves on standard of care and not on standard of care. How do they measure up with historical phase 2b studies or phase 3 studies that have been conducted, and whether the range that were observed, and obviously this is a small number, is consistent. If he's still online, I would love to hear his thoughts on that.
Certainly. I historically the standard of the patients not on any background antifibrotic treatments, our anticipation is that they will lose somewhere between 220-280 mils of FVC per year. I guess what we've seen in INTEGRIS is not that dissimilar for the patients who weren't on background standard of care. For the patients who are on antifibrotics, I think it's been a bit harder to predict. Obviously, if you looked at the pivotal studies for pirfenidone and nintedanib, you might anticipate that the background rate of decline would be half of what we see in the patients not on antifibrotics.
We've now seen four or five trials conducted in patients on standard of care, and in each of those trials, we've seen a rate of FVC loss that's very similar to the patients not on background standard of care. Our working hypothesis is that patients who volunteer to be in clinical trials when they're already on antifibrotic drugs are probably those patients who perceive themselves to be failing treatment.
We are probably enriching the antifibrotic group with patients who are deteriorating more rapidly than average, which I think is why we're tending to see this more rapid rate of decline than one might anticipate, certainly from the pivotal studies.
Although what we've seen in INTEGRIS is probably at the upper end of what we would expect in patients on background standard of care, it's certainly not out of the ordinary, that the rate of decline has been similar between those who are and are not on antifibrotic drugs.
Thank you, Dr. Maher. Maybe one last question directed to you is, we, as analysts and investors now look at the data, and we assign a probability of success of the trend in a phase 2b. I would love to hear your thoughts now as you have looked at the totality of the data and you've been involved with other clinical studies.
It's like, what are some of the strongest data points that tell you that the translation in a larger phase 2b study that is really well designed is gonna be very high? If you could just put it in the hierarchy of what you see, that could be really helpful for all of us, and then I'll jump back into the queue.
Yeah. I, you know, again, I've said this before, I think Pliant are to be congratulated for having conducted a rigorous series of clinical studies to date, not just with INTEGRIS, but also u sing their PET ligand study to show target engagement. You know, I think we can have confidence that bexo engages its target in the lung. We've got the PET evidence to show that.
Obviously we've got the FVC data and FVC, you know, remains the regulator's endpoint of choice. We've seen movement or we've seen a clear difference between treatment and placebo in terms of the regulatory endpoint of choice. As I've already alluded to, I think the fact that we are seeing changes in other parameters that are unrelated to FVC, so the imaging data, the biomarker data, and the symptom data all just provides extra support that what we're seeing with the FVC is actually genuine.
You, you know, I think it's very easy with these small studies to ascribe movements in FVC just to measurement noise in small numbers. I think the fact that we are seeing effects on different dimensions, for me, really builds confidence that we're looking at a real effect and not just a sort of a spurious or lucky effect with FVC in a relatively small trial.
Great. Thank you so much.
Thank you. Our next question comes from the line of David Lebowitz with Citi. Your line is now open.
Hi. This is Deepanjana, on for David. Thanks for taking our question. Our main question was that what should be the expectations for bexo going forward? Is it like improvement, from baseline or stabilization or like slowing of decline? Secondly, we were curious about the gender distribution, which appears somewhat skewed towards placebo for the 320 main cohort. We were curious how that might have influenced the FVC results that we are seeing. Thank you.
Well, I'll take the second question first. there were some subtle differences in the sex proportions in the 320 and placebo group, and that is why we also added the percent, the changes in percent predicted. to account for the physiologic differences between male and female, we assessed the percent predicted, which normalizes changes in height and sex differences in FVC.
W e saw a similar reduction in progression in the setting of bexotegrast in the absolute change in FVC. In the ITT group, it was a 67% reduction. In the percent predicted FVC, which normalizes that sex distribution imbalance, it was 68%. That suggests that those minor differences did not influence our data, and the consistency allows us to be confident that the treatment effect is consistent and there is no bias.
Yeah. Maybe to address your first question, I think that, you know, the results that we saw in our INTEGRIS-IPF study are very encouraging, where we saw this improvement and the maintenance or the durability of the improvement, you know, remains to be seen in longer and larger studies, you know, how that will play out.
I would argue that if we would see improvement and followed by stabilization disease, that would be a really big step forward for patients. Especially when you consider in our study that 80% of folks who are on standard of care agents, you would have expected at least a better control over disease. You know, stabilizing disease would suggest that, you know, these patients would be able to have better lung function over time.
Certainly, you know, it's too premature to talk about survival, but certainly, having a better quality of life because their lung function is maintained would be really important. That's, you know, hopefully that's what we will be able to show in the phase 2b setting.
Okay. Very helpful. Thanks.
Thank you. Our next question comes from the line of Tom Shrader with BTIG. Your line is now open.
Good morning. Thanks for taking the question. You have an imbalance in these GAP stage three patients. I'm curious if you could give us some background on how different these patients are. Maybe for Dr. Mair, is this what you would consider a natural cut of the data to remove the stage three patients? Are they really different enough that you would wanna see the data without those patients? Thank you.
Maybe I'll address that question. The GAP index is a predictor of hospitalization and mortality in IPF. It doesn't necessarily predict rate of progression, but it's a way to categorize and risk stratify patients. At present, other than the rate of decline of FVC, which isn't oftentimes available at the time of study entry, we don't have a predictive way to assess progression. We included these individuals in a small sample set. There were two versus zero in the placebo group.
The rationale for including a broad, diverse group of patients with IPF with mild, moderate, and severe disease is really to assess the treatment effect in all individuals with IPF, as we do not believe that our mechanism of action is contingent upon disease severity, but is really at the heart of the underlying pathobiology of the disease. We didn't. Yeah. The other comment is, Tom, we did not remove these individuals from any analyses.
Okay, thank you.
Thank you. Our next question comes from the line of Alex Thompson with Stifel. Your line is now open.
Hey, great. Thanks for taking my questions. You know, I think the first one, if you could clarify a bit on your statistical modeling here and you know why there are some discrepancies in the four, eight, and 12-week data points versus the prior data disclosure. Then maybe if you could talk a little about, you know, any trends on clinical efficacy and how many patients actually got out past 24 weeks. Thanks.
The differences between the previously reported results and this current results have to do with it's a different subset of patients. On the original analysis, we included all patients in all treatment groups. In this analysis, we're only including those that are in part D. The reduction in the placebo patients impacts the results of both the active and the placebo patients due to the models. It's just purely an artifact of the model.
Maybe the second question was about, you know, data beyond 24 weeks. You know, because of the rapid enrollment of this study, we had, you know, most really most patients had treatment exposure we had, let's say the average duration on treatment was 27 weeks. We have really just a handful of data beyond that time point in terms of efficacy. All data was included in the safety analysis. The data beyond 24 weeks is too small to make any meaningful conclusions.
Great. Thanks.
Thank you. I'd now like to open the line of Jeff Jones with Oppenheimer. Your line is now open.
Thanks for taking the question, guys. Just one quick one. In terms of the phase 2b study, will we be able to see interim data at the, say, 12 and 24 weeks on the way to 52 weeks? I guess one other, can you expand a little bit on the similar levels of efficacy seen in the patients in combination with standard of care, and not on standard of care? Thank you.
In terms of interim analyses, we're not planning to do any interim analyses for our BEACON-IPF study. One of the reasons why this would be important is, we do believe that this study will meet the criteria for what the FDA or regulators would see as a potentially as one of the two confirmatory studies required for an NDA submission. In the sense that we have the approvable endpoint as the primary endpoint, so that's the change in FVC.
We have a 52-week duration of the study, and that is the standard for phase 3 trials in IPF. Also we have at least 80% power to show the difference overall. So it... You know, depending on the data, it's possible that it could count as part of, you know, the registration package. If we had to do an interim analysis, that would take away that opportunity, so we prefer not to do that. Now, your other question, please remind me.
Let me get the question. Yeah.
Go ahead.
Sorry, it sounded like you had it, but it was looking at the similar levels of efficacy at 24 weeks in the Bexo alone and Bexo in combination with standard of care and how we should think about that.
I mean, I think, you know, really when you think about the proportion of patients who are not on background therapy in our study, there were four on active and two on placebo. These patients didn't, you know, they couldn't influence the curve so much as the larger subset of patients who are on background therapy. I think this is why both are very concordant. It's interesting that it's in the standard of care subgroup where we saw the greatest reduction in further, let's say, the 96% further reduction in ELF. Sorry, I'm speaking not clearly now.
It's in this subgroup of patients where we saw a 96% further reduction, a further reduction in the ELF decline compared to placebo with background in the trimmed mean sensitivity analysis. I think that bodes really well for what we can expect to see in phase 2b. There were too few patients really in the not on background therapy to make any meaningful conclusions on or interpret the data for this study. We will have more patients, as we mentioned, in the phase 2b evaluation and have a much more thorough evaluation of the treatment effect.
Thank you. In the interest of time, we ask that you please limit yourself to one question. Our next question comes from the line of Ed Arce with H.C. Wainwright. Your line is now open.
Hi, good morning, everyone. Thomas here asking a question for Ed. Perhaps a question for Dr. Maher.
If the profile of bexotegrast, to date that we're seeing, persists through latest studies, how would you likely select bexotegrast in your treatment algorithm for IPF patients, either as a monotherapy or on top of standard of care? How likely is it, bexotegrast can become the new standard of care? Thank you.
Yeah, good question. I think we probably have to be realistic that by the time bexo gets approved, if it does get approved, then both pirfenidone and nintedanib will be generic. My anticipation is that payers will expect pirfenidone, nintedanib to be used first line.
However, if we see, you know, replication of data that we've seen so far from INTEGRIS, and we see that play out across a phase three program with bexo being potentially both more efficacious and better tolerated than current standard of therapy, I think there will be a move to use either combination therapy very early, or for patients who are intolerant of standard of care, a move to very quickly get them off pirfenidone, nintedanib and onto bexo as monotherapy.
You know, I think it has, as we've said, the advantage of being a simple oral dosing regimen, and therefore it compares very favorably to some of the other drugs in development. I can see it, you know, competing for first line treatment status.
Thank you. Our next question comes from the line of Mike Kratky with Leerink Partners. Your line is now open.
Hi, everyone. Thanks for taking our question and giving us on the data. You mentioned seeing strong interest in the asset. To get to that point, what's the right time to start thinking about partnership opportunities for this program? How can you think about potential ex-US partnership? Thanks.
Thanks, Mike. This is Bernard. I think, from a partnership perspective, I mean, we have a very strong cash balance right now, as you know. Pretty close to $600 million at the end of the quarter. This will allow us to develop it through phase 2b with our own means. That's how we look at this, so as kind of a standalone. Obviously, with the data that we have seen at 12 weeks and now confirmed at 24 weeks.
Notably with the safety which obviously is top of mind of any strategic, I would argue, having those hurdles now cleared, you know, I anticipate there will be, you know, always inbound interest for this specific asset ex-US versus global kind of, you know, partnerships at this point in time, I think it's way too early to make any comments about that.
Thank you. Our next question comes from the line of Joel Beatty with Baird. Your line is now open.
Great. Thanks for taking the question. How many patients in the 320 milligram arm withdrew consent between weeks 12 and 24? For those patients, could you discuss why they withdrew consent and if their withdrawal affected the curves on the SVC endpoint, you know, in some similar way to how the dropouts for after AEs impacted the slope of that line from between weeks 4 and 8?
We had three patients in the bexotegrast group who discontinued due to withdrawal of consent. There were two inpatients on placebo. We don't believe these data impacted the 24 weeks results in a meaningful way. I mean, this is patient's decision to withdraw consent. We can't stipulate what the patient's motivation were for, you know, withdrawing their consent in the study.
Thank you. Our next question comes from the line of Ritu Baral with TD Cowen. Your line is now open.
Hi, guys. Thank you so much for taking the follow-up. Since this is the first drug, well, first IPF drug, where we actually specifically know how it works, and you've got biomarkers moving, are there any enrichment strategies that you're considering around the phase 2b or even phase 3 down the line?
I think, Thanks for the question, Ritu. We, you know, we've been using very broad inclusion criteria, very similar to what others have used in their other sponsors have used in their clinical trials. We plan to do the same moving forward. We, you know, even without enrichment, we were able to see these great findings in a relatively small study in phase 2a.
I would argue that, you know, keeping the population as broad as possible would also have a better chance to have a broad label around approval. That's something we have in mind so that the data from phase 2b and phase 3 should be generalizable. Having a broader inclusion criteria is usually what gets you there.
With the question and answer session complete, let me turn the call over to Chris Keenan.
Thanks everybody for joining us today. On behalf of my client team and my client colleagues, I hope you enjoyed today's call. We look forward to updating you on our progress in 2023, including the initiation of BEACON-IPF. Have a good day and week, everybody.
This concludes today's conference call. Thank you for participating. You may now disconnect.