I think we're ready to get started here. Thanks again, everyone, for joining us at the Guggenheim Healthcare Innovation Conference again this year. I'm Bob Leduc, one of the biopharma analysts here, joined on the stage from the Guggenheim side by Daniel Krizay from the team. Pleased to have next up in this room is Rein Therapeutics, and with the CEO, Brian Windsor, joining us. Brian, thanks for joining us at the conference.
Thank you.
Maybe just for those who are less familiar with the Rein story, if you can give us a little bit of the overview, a background of the company, and then we'll dive deeper into the events that are coming up.
Sure. At Rein, we're focused on pulmonary orphan conditions. We've got two programs that are phase II ready, both in respiratory diseases. Idiopathic pulmonary fibrosis is really our focus. The Rein story, I've been with this company now just over 13 years. We started as a private company called Lung Therapeutics out of Austin, Texas. We did a reverse merger in October 2023 with Aileron Therapeutics. They had been cancer-focused, obviously didn't make it. Really liked our program in IPF, and then we rebranded to Rein early 2025 to kind of highlight our focus on reining in fibrosis, which we love to say.
Okay. You lead out, you have LTI-03, obviously, on this.
Yeah.
Moving forward here, maybe you can talk about this product, its mechanism, and why you think this is the right approach for IPF.
Yeah. It is a really amazing mechanism, and one that I think has been underappreciated, maybe because of the fact that it is missing in fibrosis. We are targeting, in a sense, caveolin-1. Caveolin-1, in addition to the structural role that it plays in cells, has a regulatory function, and it affects this regulation through a small 20 amino acid region called the caveolin scaffolding domain, and that domain interacts with a large number of proteins across multiple fibrosis pathways, and it really kind of promotes homeostasis in the cell. CAV1 is missing in a fibrotic state, not just in the lung. In any fibrosis, liver, skin, ocular, kidney, it is just missing. What we are doing is we are adding back a portion of that caveolin scaffolding domain region. We are basically supplying the regulation back to these cells that they normally would have.
It is impacting virtually every cell type in the fibrotic lung and adding back this regulatory capacity.
Okay. You are delivering it directly to the lung. Maybe you can talk about the approach here, the way it is administered, and why you think that could be an advantage, whether it is for in terms of getting enough local exposure, but also more of the systemic potential side effects.
Absolutely. So we use an off-the-shelf dry powder inhaler, and we get great local lung coverage without kind of commensurate systemic uptake. The reason that we wanted to do an inhaled approach was when we had an ad board very, very early on related to this program, every KOL in the space said, "We have got inhaled programs for COPD, for asthma, for other lung diseases. Why can't we get one for IPF?" These patients have enough inspiratory capacity, and that has been our experience, is that they really do. We saw that in our phase I-B study. So again, we get really good kind of local lung coverage without the systemic uptake.
Okay. So you have a phase II trial that is obviously ongoing now, started back in March, and now enrolling in the different countries. Maybe you can just give us an update on sort of where you stand with the execution of that trial and sort of the key upcoming events here.
Sure. Our RENEW study is a global trial, 24 weeks of dosing in IPF patients. We will do a CT scan to confirm diagnosis before the study, and then they also get one after the trial. We are looking at HRCT, we are looking at forced vital capacity. We announced earlier this year that enrollment was going great. We hit 25% faster than we thought. So enrollment is good across all the countries in the study. Now we are enrolling in the U.S., the U.K., Australia, Germany, Poland, and we just opened Bulgaria and Romania as well. So other countries, and so far, I think the study is going great.
In terms of the patients that you're looking at here, maybe you can talk about what types of patients are included in the criteria for the trial.
Sure. The criteria, really, they've just got to have a diagnosis of IPF, and we reconfirm that diagnosis when they get into the study, and enough lung capacity to be progressive in their disease. So just enough lung capacity so that they progress. We allow background standard of care, any standard of care. So nintedanib, pirfenidone, nerandomilast, anything that's approved, they can take, because we've seen benefit of LTI-03 basically on top of other compounds. So that's really kind of the key inclusion and probably the differentiator of this trial, is that we're allowing any kind of background standard of care.
Okay. You talked about having an interim analysis here, I think by the end of the year. So maybe you can just talk about what will you be looking at, and then what do you plan to sort of share publicly on the back of that?
Sure. We just want to share kind of a snapshot of where the study is, at least by the end of this year. It will be a blinded snapshot, so we're not going to unblind the trial. We're not making decisions off of this. It's not futility. This is really to take a look at safety and tolerability to the point of 12 weeks of dosing, and then also, what do we see in terms of lung function? Do we see, even in a blinded way, do we see a spread in the data, or are all the data points kind of clumped up together?
We just want to get a snapshot of how things are doing at 12 weeks with some portion of patients, 20, 30, 40 patients, some portion of patients who have hit that 12-week mark, and then we will at least provide that snapshot for the public.
Okay. You mentioned people will be allowed to be on these background therapies, or they are allowed to be on them in the trial.
Yes. Yeah.
I guess, how are you thinking about that in terms of how it's going to impact the sort of control arm? What sort of, what's your assumptions around how they're going to progress, and then what sort of separation are you hoping to see from the drug side?
Sure. Of course, we stratify for all of the background therapies, in patients who are naive or on JASCAYD or nintedanib or pirfenidone. I think that other studies, the JASCAYD trials, TYVASO, they've also been on top of background therapy and really seen a lot of the benefit from those drugs, mostly on top of patients taking something else. I think for us, at least pre-clinically, we've seen that LTI-03 can provide benefit on top of a typical anti-fibrotic drug, and we expect to see the same thing in patients. So, at least pre-clinically, in all of the tests, we could see amelioration of some of the toxicity for some of these drugs and efficacy benefit above and beyond. Again, this is something that's going to be standard, as you know, in IPF going forward.
You're going to have to show a benefit on top of existing standard of care. That's what a couple of the drugs have done, and that's what we believe LTI-03 will do as well.
Okay. You mentioned, obviously, the inhaled therapy. One concern we always get around inhaled therapies is the ability to take it and cough and just the tolerability of the inhalant. Maybe you could talk about that. What has been the experience, and what do you hope to see in terms of the tolerability side beyond seeing the FVC benefit?
Sure. With a dry powder drug, cough is the big concern. I guess with any inhaled therapy, you just don't want to cause cough in this patient population. We've got a really easy dose for patients to take. Our low dose is 2.5 milligrams. It's inhaled BID. The high dose is 5 milligrams inhaled BID. It's two 2.5 mg capsules. The inhaler that we use, which of course I keep one all the time, is made for patients that have a low inspiratory capacity. It's called a high resistance, kind of a misnomer. It's for patients that don't have a lot of inspiratory capacity. So it gives great local lung deposition without, again, without systemic uptake.
Okay. You did release some biomarker data from phase I. Maybe you could talk through what you've seen on the biomarker side and why that gives you confidence on what you'll see in the phase II.
Yeah. We did a phase I-B study that I believe was probably the most robust phase I-B trial anyone's ever done in this space, and we recently had this study published in Nature Communications, so we were obviously thrilled to get it published in such a great journal, and a lot of great investigators who were in that study. The reason the study was different was because we're not just measuring safety and tolerability over two weeks in IPF patients, but we did take bronchoscopy samples before and after 14 days of dosing. So we used a technique called deep bronchial brushings, which is exactly what it sounds like. You stick a brush into the deep lung, you're able to get protein samples.
We wanted to measure protein biomarkers like interleukin-11, TSLP, galectin-7, ones that we had seen pre-clinically, LTI-03 can affect these proteins, can inhibit these proteins in cells, fibroblasts, say, from an IPF lung. Now we could see the same thing in patients in the clinic. So in just two weeks, we saw movement in the very same biomarkers. In fact, we had five that were statistically significant for one or the other dose, and some dose response between some of the biomarkers as well. So, with a dry powder drug, with a peptide drug, we always get the question of, "How do you know the drug is even getting to the lung?
How do you know the drug is getting to the fibrosed part of the lung?" Well, these biomarkers come from cell types that are found in the deeply fibrotic part of the lung, and that was a big part of the test for us, is can we see the same thing dosing in the lungs of a patient? The short answer was yes.
And then you mentioned that there was a number of biomarkers you looked at. Are there certain ones that you're particularly interested in or that are particularly promising, or as we learn the story, it's always been a little bit unclear as to which ones are the ones to particularly focus on, if any?
Yeah. I like the totality of the data, I think is really what speaks to the effect of the drug in the phase I-B trial. But if I was to pick ones, I would say interleukin-11, IL-11, is obviously a real bad actor in IPF and one that a lot of people have focused on, even as potential therapeutic potential, just shutting down IL-11. That's one that we've seen consistently that we can shut down. IL-11, galectin-7 is only made in the aberrant basal-like cell that's found in the deeply fibrotic part of the lung. There's more coming out about GAL-7. And the surfactant protein D, which is a plasma biomarker that we tested, and SP-D now is on a panel that went before the FDA.
Biomarkers that are indicators of progression to lung transplant or death, surfactant protein D is the biggest indicator. And we saw great movement with that biomarker as well.
Okay. So maybe one more from me, then I'll turn to Dan, but just around the regulatory side. You do have Fast Track status. You're also orphan drug designation. How is that helping you in terms of planning forward? Assuming you get your positive results here, how is those interactions going, and what do you think would be the next steps, assuming positive data in the ongoing RENEW?
Yeah, it was really great to get Fast Track designation. I think it underscores the unmet need in IPF and the promise of LTI-03, and that the agency wanted to give us a Fast Track designation. For us, it just means more and better interaction with the FDA, and that is what we are looking for, is good communication, of course, with the agency. Having the orphan designation, as you all know, is great for potential barrier to entry once the drugs are approved. We have got orphan designation in Europe and the U.S., and I think the orphan designation also is something that just speaks to the real unmet need in this space. So, great for us to get these designations and the Fast Track in particular for more communication as we move this drug forward.
Okay. All right, let me turn it over to Daniel.
Yeah, great. As you touched upon, United Therapeutics, TYVASO, it did show that inhaled therapy can lead to benefit in these patients.
Yeah.
So I guess, what are your key takeaways from what we saw in that program, and how do you think your drugs are differentiated from TYVASO?
Yeah. Our CSO, Cory Hogaboam, and I were sitting in the audience at European Respiratory Society a year ago when they shared data on TYVASO, one of the TETON trials, the phase III studies, and we were excited to see this. Believe me, we're for anything that's going to help these patients. There's a really dire need. And it was great to see an inhaled therapy get a lot of traction. We get questions on ours being an inhaled therapy. I think an issue that you might find when you dig into TYVASO is there was a pretty high dropout rate. I think about a third of the patients dropped out in the study, and I think maybe it is causing some cough. We just haven't seen cough in our trial with our drug, at least our 1b trial.
We had mild cough, it was kind of the predominant AE, but not something that was really severe or serious. Inhaled therapies are great. I think you just got to, again, bring down the side effect profile for these patients.
Do you believe that there's like a meaningful difference between going with like a nebulized approach versus a dry powder inhaler approach?
Well, with the neb that they are using, patients have to be on that four times a day, I think, for total inhalations of 48 inhalations over that time. That's a lot of time to be on a device for any drug. And again, these patients are elderly. Quality of life is a big deal for this patient population. They want to feel better, they want to have a better quality of life. So having a dry powder where one or two inhalations and it's over, I think is a real advantage over a nebulizer. And our aerosol is a great aerosol. We've got great deep lung deposition, so very happy with that.
Okay, great. Outside of United, obviously there's other things. JASCAYD is currently launching, and admilparant had some positive data recently in one of their doses, and some other mid-stage readouts as well. I guess just overall, what are some lessons you draw from this, maybe in relation to trial design and where LTI-03 could potentially fit in commercially down the road in combination or monotherapy, or how you're kind of viewing all of this?
Yeah, I think for that last part, LTI-03 impacts basically every cell type in the lung. The smooth muscle cell, the epithelial airway cells, endothelium, macrophages. These cells are necessary for normal lung function. Just focusing on the fibroblast, which a lot of these drugs target mechanisms in the fibroblast in particular, you are going to get a modest slowing of progression, but you're not going to get the ability to potentially make new lung tissue, to restore the lung, to have proper macrophage function. All of these that we've seen with LTI-03 can cause a benefit. So, I think with a lot of existing antifibrotics out there, what's missing is the condition for normal lung function or normal lung repair, and that's where LTI-03 can really provide complementary activity to some of these other drugs or work as a standalone drug.
But I do think, as they said at that ERS meeting for when they shared TYVASO data, that we're now in the era of multi-therapeutic approach in IPF. So, it would be good to complement these kind of strictly antifibrotics with something that allows the rest of the lung to heal.
Yeah. Okay. You touched on this at the beginning a little bit, but maybe beyond IPF, where do you see this CAV1 approach potentially playing a role?
Yeah. CAV1 is a phenomenal mechanism, a really unaddressed mechanism, and maybe because it's missing in the fibrotic state. It's not intuitive that, oh, we can put in a small seven-mer peptide and get kind of the activity of the protein that's missing. I get that, but that's absolutely how LTI-03 works. CAV1 is missing in a fibrotic state in the liver, in the kidneys, in the skin. Scleroderma is a condition that desperately needs therapeutic options as well. Ocular kind of fibrosis. CAV1 is missing in all of these fibrotic states, and we've seen a benefit when we apply a CSD, a caveolin scaffolding domain peptide approach to these. We see benefit in animal models of all these fibrotic conditions, heart, kidney, liver, skin. We think CAV1 is a real untapped goldmine in terms of potential for therapeutics approaches down the road.
Okay. Then maybe one more from me before passing it back to [inaudible]. You have another asset, LTI-01, I believe is phase II ready. How are you thinking about this one, advancing it, doing it alone versus partnering, or how do you view this program progressing?
Yeah. LTI-01 is a great drug. The market is not quite what an IPF drug is, so that's really kind of honed in our focus on LTI-03, but it is a very good drug. We had a good phase II study that unfortunately started right at the beginning of COVID. For pulmonary drug given in the hospital, not a good time to be doing a clinical trial. We really need to go back and do another phase II study, but we have an existing partnership with Taiho Pharmaceutical for Japan rights. I'm very excited about the partnership with Taiho. Then we're open to exploring partnering, or another study for this. I like the drug a lot. Would love to pursue it. We just don't have enough cash to do everything right now.
Okay. We have a few minutes left here, so maybe a couple last topics, more from a corporate perspective. One, just your current cash position, if you can share what's the latest publicly disclosed number there, and where does that runway take you through?
Yeah. I think the last disclosed number was about $40 million, back in June, July, and we have said that provides cash into the first quarter of 2028. So well past, hopefully, the end of the study. We continue enrollment, as we've seen, kind of initially, that should be well past the end of our current phase II trial. So we'll be able to get the readout with some cushion and cash into Q1 2028.
Okay. Just in terms of timing of the upcoming events, you mentioned this interim coming up soon. When do we expect that sort of disclosure to be made publicly in terms of what you saw in that interim? What should we expect next year?
Yeah. The interim blinded kind of summary will be before the end of this year. Then, with enrollment, as we had previously kind of disclosed, we're thinking last patient springtime-ish next year. All of it's coming up off of the holidays, it impacts enrollment, as you guys know. So we'll see how that will go. But last patient in kind of spring next year with data before the end of 2027.
Okay. All right. I think we can probably wrap it up there. Thanks, Brian, so much for joining us. Congrats on the progress. I look forward to seeing the updates coming up here.
Thanks for having me.