Rein Therapeutics, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Yeah. We started as a private company called Lung Therapeutics, and did a reverse merger to get public in October of 2023 with Aileron Therapeutics. They had been cancer-focused. Obviously didn't work out for them, but they really like our program in idiopathic pulmonary fibrosis. We did the merger with them, a small pipe at the time that we did the merger, and then we rebranded to Rein Therapeutics early last year to kind of highlight our focus on fibrosis. As we like to say all the time, we want to rein in fibrosis. We have a small team, but kind of spread out across the country in a phase II trial presently, in IPF. We kicked off the study earlier this year. We announced that enrollment is going great, so very excited to be at this stage finally.

Yeah, it's a great question. LTI-03 is our drug for IPF, and the mechanism is pretty unique. This is a drug that mimics the protein caveolin-1. We're focused on caveolin-1 or CAV1, and CAV1 is a regulator of other proteins in the cell. We think of it as kind of an effector of homeostasis. It just promotes balance in the cell. It keeps pro-fibrotic proteins in check. It promotes things like ECM turnover, this sort of thing. But caveolin is lost in a fibrotic state, so all of this regulation that you get is also lost. Our drug is a small portion of the region of caveolin that binds other proteins, affects their phosphorylation, affects their trafficking.

We're kind of adding back a small part of that protein. I will say non-intuitively, when we put this peptide into a living system, it sort of mimics the activity of CAV1. We get the same sort of regulation. We get inhibition of pro-fibrotic proteins. We get protection of epithelial cells. It's really amazing. CAV1 is something that's needed not just in the lung. It's in the heart, the kidney, the liver, skin, eyes. Basically everywhere that you can have fibrosis, CAV1 is normally present in the body and missing in a fibrotic state. It's a pretty unique mechanism. We give the drug, LTI-03, by dry powder, simple dry powder inhaler, and we're dosing BID right now in our phase II study. It's a mechanism. We kind of describe it as a dual mechanism in that we are anti-fibrotic, like most of the drugs in the space.

We're inhibiting the scarring process, and I'm happy to kind of talk about IPF and what the problem is. But more importantly to us, we're preserving cells, causing preservation of cells in the lung epithelium that are the progenitor cell. They're called type 2 alveolar epithelial cells. These are progenitor cells. They can make new lung tissue. They make surfactant. They can restore lung function. We think this is something absolutely not seen in drugs in this space today.

Yeah, it's really both. You really need both. You've got to stop the scarring process or slow down the scarring process. But I think what's been missing from the disease so far in terms of developments of new agents has just been this protection of the lung epithelium. If you only address the fibroblast cell or the cells that are making the scar tissue, you really are not addressing the part of the lung that can restore new tissue, that can resolve fibrosis, this sort of thing. You've really got to have both, in my opinion.

Sure. We just had our phase I-B trial published in Nature Communications. We were thrilled that such a top journal would publish this article, and it highlighted the work that we did in a phase I-B study in IPF patients over a couple of years. This was a trial, of course, looking at safety and tolerability. It is a phase 1, but we did a lot of biomarker work, and to do that, we took lung samples before and after 14 days of dosing. Actually, the patients were willing to undergo bronchoscopy, and we used a technique called deep bronchial brushings, which was pioneered by Rob Kaner at Weill Cornell, and it is exactly what it sounds like. You put a brush into the lung. We are able to get protein samples.

The reason we did this is because we had seen the ability of our drug to inhibit a lot of pro-fibrotic proteins in preclinical studies. Does that translate to the lungs of IPF patients? That is what we really wanted to see. We were able to do eight different biomarkers from lung samples, and seven of the eight trended in the direction we were hoping they would go, four with statistical significance, IL-11, CXCL7, TSLP, and galectin-7. We picked these proteins because, again, we had seen preclinically that we could inhibit the proteins. We wanted to match that up. Now we also saw in the lungs of IPF patients, we are seeing the very same thing. This was important to us for a few reasons. One is that our drug is a peptide drug. It is a dry powder drug.

I would always get questions about, "Well, how do you know your drug is even getting to the lung, getting to the fibrosed part of the lung?" We took proteins like galectin-7 is only made in an aberrant basal-like cell that is found in the deeply fibrotic part of the lung. We looked at proteins that were deep in the lung. The other thing is that some of these proteins are indicators of lung function, FVC. Just for example, interleukin 11 or IL-11, the inhibition of this protein has been linked in the literature to positive changes in forced vital capacity or FVC. That is the lung function measurement that we will be measured on in this phase II trial in terms of efficacy and going forward. It is the lung function measurement that drugs get approved on.

We wanted to look at markers that were maybe indicators of how are we going to do in a phase II trial, how are we going to do going forward. We were thrilled with the results. In fact, you talked about physician receptivity, clinical receptivity. The KOLs that we work with, we got on a call with them. We showed them this data initially. I would say they were giddy. They were so thrilled. One of them said, "You couldn't have imagined that you'd seen anything better than this, could you?" It was extremely positive. We were fortunate to work with Phil Molyneaux, Nik Hirani, Andreas Günther, Teja Kulkarni, some great investigators, all of them on this publication. We just, as you mentioned, we highlighted this data at European Respiratory Society Meeting in Barcelona this past weekend. We had a poster there.

Phil Molyneaux was sharing with the audience about the phase I-B study. Lots of great questions, lots of interest. There's a huge need in this disease, so I think the receptivity was really, really good.