The biggest issue with this compound was it had an off-target toxicity that, at that time, back in 2011-2012 timeframe, was not screened. This BMS-986020 issue off-target led to cholecystitis, and that trial was discontinued. They saw some liver improvement. That was probably the biggest issue there. The data there was pretty good. It was those—the start of those data, along with BMS-986278, which now is called Admilparant, I'll screw up the pronunciation of every—that convinced us that the right phase II study to do would be 2016. BMS went forward with Admilparant, BMS-986278 in a phase II study, both in IPF and then a second ACTF. The BMS-986020 issue was washed out. Every clinical stage LPA1 separate antagonist that's out there has washed that concern out. Where that program stumbled a little bit is there was a dose response, but at their lowest dose tested, they showed nothing different than placebo. As we saw the 60 mg BID data, we saw that it definitely had an impact because there was a change in FVC of about right around 46%-47% in their phase II study. It certainly was not maximal. What we thought is that they missed their phase II dose. I think based on the status of their phase III, they agreed. They have eliminated their 30 mg BID dose, and now they've added 120 mg BID as well. That is not really pharmalike behavior adding a previously untested dose into a phase III. There is also a potential signal with the BMS-986278 molecule around that. That is being studied in the phase III program as well. For us, what we really wanted to do was, first of all, get a molecule that's QBT. In this patient population, we think that's pretty important. The differentiating factor that we have with type 791 is the pharmacokinetic profile of it. It has a very slow on-and-off rate that allows for prolonged target coverage. We believe that we'll be able to achieve 90+% receptor occupancy with the dose that we test in our phase II. That should drive a benefit in—a potential benefit in the outcomes for patients. Given the other properties of low peak trough, we think that we can mitigate some of the potential challenges that BMS and others have from safety and tolerability. Okay. And then speaking of receptor occupancy, I know we're coming up on data fairly soon from your PET receptor occupancy studies for 791. Can you tell us more about that? What's the latest timeline? How extensive will these data be? And what are you guys looking for to demonstrate, I guess, what the proper doses will be for phase II and then ultimately phase III for both IPF and MS? I know we're going to see some healthy volunteer data, some patient-level data. There's some differences in how to interpret brain versus lung receptor occupancy. So maybe talk us through what we should be looking for, what's a good result. Yeah. As we've mentioned, there are a number of companies working on LPA1. We will be the first company to actually put out PET data. We had a very good sense as to what doses we would be bringing into the phase II even before running. We wanted to validate that and put some additional information out there in the community. Our timelines have stayed consistent. We plan to release data before the end of this quarter. What we hope to be able to demonstrate with these data is maximizing the receptor occupancy. I think that is a key differentiating feature as we continue to develop the program. We know that there are challenges in brain versus lung. We're in a unique position that we have a brain penetrant molecule. We have a PET probe that can interrogate the brain as well as the periphery. We know that LPA1 expression is very low in healthy lung. As Andy Pager showed, when an injury happens, that is when LPA is upregulated and you get further expression. That being said, we are aiming to get patient data in this study as well. As a surrogate, we know from our preclinical work and other data that there is a very tight correlation between brain and lung with respect to LPA1. From a plasma and from a receptor occupancy standpoint, the brain can serve as a surrogate. 90% is the goal. 10-plus is the goal, yes. Okay. You recently brought in a new Chief Medical Officer with considerable experience in IPF and in INI overall. How will his perspective shape the go-forward path? What is your latest thinking on the next steps once you get these PET or receptor occupancy results? We recruited Tim Watkins out of Gilead, previously Vice President of immunology there, also a pulmonologist. As we look at the way our portfolio developed and assess the risk of each of the different assets in our portfolio, there's an intensified focus. Tim has a long layer of experience there, running studies, regulatory programs throughout his career at CRIS. His background gives us a lot more confidence in the ability to execute within IPF. Basically, they're not a trivial study. There's a lot of complexity in the right sites, the right investigator. While FVC is the primary endpoint that FDA looks at for approval, it is not the most consistent across patients. We want to make sure that with Tim's expertise, that we are recruiting the right site for the right patients, to make sure that the data is interpretable and comparable to what we see in the market. How are you thinking about next steps? Will this be a 26-week FVC-focused phase II B? How does it sort of tie in with your latest thinking on the overall regulatory path? I know we've seen some companies pursue IPF and PPF in parallel. What are your latest thoughts? Obviously, pending the RO data, but what's your sort of base case? There's really 2 sides of the coin. If you look at what Carmine Stengone did with, what should I describe it, Theran and Nolomast, they started their phase II, pretty small phase II, 100-some odd patients, single dose, and only IPF at 12-week study. We aren't really comfortable with the 12-week study. It seems like there's some anomalous results in smaller studies at 12 weeks. In their phase II, which they just reported at HVS earlier this week, they had successful phase III sample IPF. BMS took a different approach. They started with a 10-week study. They also did it as a power study. Upwards frequently in that phase II. Now they're in about a 20-week phase II, III, so they're looking at IPF and IPF. From our perspective, we'll be looking at a 26-week study at the moment. What's your latest view on the market, right? There are 2 drugs on the market currently. There is another drug that just got through phase III. We saw those results this week. What are some of the, I guess, what are some of the unmet needs in this market? How do you expect this to ultimately play out with perhaps having multiple drugs and even multiple LPA receptor antagonists on the market? Where does 791 fit in? I think that LPA1 antagonist in general can accommodate hepatitis, disappointed polycarbonate, different ways to attack fibrosis. The unmet medical needs there, I don't think the BI data that came out is certainly welcome. Welcome. Gears and gears. Let me shift gears Let me shift gears and talk about MS. Another indication that you're looking at with 791. What's your latest thinking there? I guess, how much do we know about how the LPA mechanism influences remyelination and inflammation in MS? What are your next steps there? How high of a priority is this relative to IPF? Our initial input in LPA1 is actually driven through the brain. If you look at the expression profile of LPA1, it's pretty broadly distributed in the brain. The areas that were of most expression had high expression on the ligand dendrocyte, as well as on microglia. By inhibiting that receptor, we can potentially have an impact on remyelination, the driver of disability, progressive as well as relapse-remitting MS, as well as neuroinflammation. Having an impact on paramagnetic rim leak potentially decreasing disability in that patient's pocket as well. We have guided to initiating a phase II study, probably a smaller study, IPF, by the end of this year. Really using that as a proof of principle to be able to demonstrate these areas of improvement. You've also started to look at, to explore the idea of this mechanism in pain as well. Can you talk a little bit more about that, maybe some of the scientific rationale that you've seen? And then maybe remind us of your phase I B chronic pain study design, what you're looking for out of the crossover study. Yeah. From a mechanistic perspective, this starts with the ascending pain pathway. When there is an injury, there is an activation in certain areas of the brain, the somatosensory cortex. This is driven through LPA again. An injury drives LPA production, and that activates the LPA1 receptor. This has both a central and a peripheral component. There is a demyelination component peripherally, and centrally, there is an activation. There is a fair amount of literature out there demonstrating LPA1 receptor antagonism in animals with positive impact. We took that a step further and decided, you know, rodent models, a lot of drugs work in rodent models that do not work in humans. We took the extra effort and ran a non-specific FMRI. An objective measure, this is not a foot tap model or anything like that. This is an objective FMRI while the animals are still going down chronic constriction injury models. And what we were able to show is with dosing of type 791, we have an improvement. We are currently running, this isn't an over-engineered study, so this is purely an exploratory study, 40 patients looking at both osteoarthritic pain as well as chronic lower back pain. If you. Tough indications. Tough indications for sure. This is not a powered study. It is placebo-controlled. We know if we did not placebo-control this and we saw an impact, no one would ever believe us. We decided to work that in. It is a 4 week study. The interesting thing here is when you look at these individual pain scales. With osteoarthritis, there is an upregulation in LPA in the synovial fluid. The level of that LPA is correlated with disease severity. Similarly with LPA and CSF. What we were able to demonstrate in-house as well, having both a central and a peripherally restricted LPA1 receptor antagonist, is that the CNS component to this is critically important. We have run that through models as well. We see an impact with a peripherally restricted compound, but the benefit is outsized once you have the central component as well. Those data we're expecting in the first half of next year. Any reason you chose to go after those particular chronic pain indications rather than a neuropathic pain indication? There is a neuropathic component to both of those. A lot of this was driven by the liver function. If we know that there is an upregulation in LPA and there are LPA1 receptors, then this is a good proof of concept. If we show nice results coming out of this, and this is going to be an individual patient-by-patient assessment, if we see a signal, then we will certainly broaden this out in the future. Good. Maybe in the last 5 or 6 minutes, we'd love to talk about your other pipeline program, 307, the muscarinic. You're looking at relapsing remitting MS in an ongoing study right now. Can you talk a little bit more about that study, maybe some of the key endpoints that we should be focusing on, and really what endpoints you think are going to be most sensitive to best illustrate early drug benefits in this study population? Yeah. Type 307 is currently in the VISTA study. This is a phase II study. The focus is on remyelination and relapsing remitting MS pain. There is clinical validation with this mechanism in this particular area. A study, a REBUILD study was the name from UCSF, demonstrated with a dirty anti-muscarinic that there can be an improvement in remyelination. The key metric that they used there was visual evoked potential latency. In patients with MS undergoing demyelination, there is a conduction velocity loss from the retina to the visual cortex. Really, what that is, is it's driven through demyelination of the optic nerve. What the investigators at UCSF were able to show is with M1 receptor antagonism, you can reduce that latency almost back to normal levels. It's been a pretty short study. They also showed a correlation between that VEP improvement and low contrast letter acuity. VEP latency studies over 180 to 200 patients are not really feasible. There is a lot of variability depending site to site. We chose as our primary endpoint low contrast letter acuity. We believe that any improvement here would be beneficial to patients. One of the big complaints that MS patients have is a loss of contrast sensitivity. Trouble driving at night, walking down the dark stairwell. What we are using in the study as the primary efficacy endpoint is LCLA with the goal of achieving a 5-letter change in these patients. It sounds like that study enrolled even more quickly than you had expected. Just remind us on the timelines and I guess how you're feeling about the conduct. I guess, how well do centers know how to administer these exams and endpoints? I'll address the second part first. It's a very common exam, especially with MS patients. There is a tight protocol for that. We congratulate our clinical team. We had expected to fully enroll the study in the middle of this year. We actually completed enrollment near the end of 2024, beginning of 2025, two quarters ahead of schedule. That allows us to accelerate what we think is an inflectional readout that'll occur in the second half of the year. Great. I know this drug is partnered with J&J. How's that partnership going? Can you talk to the extent you can a little bit about the idea of exploring this mechanism in depression and maybe what's guided the decision to move this into a rapid-acting depression study? Yeah. We signed a collaboration agreement with J&J in the first half of 2023. We are running the VISTA study. J&J is now running what is called the Moonlight One study. This is focused on MUB. There is, again, clinical validation for M1 receptor antagonism in depression. As luck would have it, one of the J&J investigators generated this data while he was at NIH. His name is Wayne Drevets. What he was able to show with scopolamine is that with a single dose, it can lead to a very rapid change in MADRS. That change is sustained over the period that they were testing with only 4 weeks. Scopolamine obviously is not a viable drug in a commercial setting. The goal here was to identify a selective M1 receptor antagonist to be able to drive that same effect. The rapid impact that was seen in scopolamine is what we are hoping to see with type 307 in the Moonlight One study. The way that this is crafted, and this is all on clinicaltrials.gov, there are 2 different dosing regimens that J&J is looking at. The primary endpoint is a change in MADRS by day 5. When might we expect to see those results? Sorry, I'm limited by confidentiality. Okay. Based on clinicaltrials.gov, J&J's estimates are in the middle of the year. Definitely looking forward to seeing those. Maybe just real quick before we wrap up, can you remind us of your IP position around 791 and 307 and 303? I know these are all internally generated compounds. Yeah. Everything that we have in-house is internally generated. The composition of matter for type 307 runs through 2040. The polymorph patent is 2042, and that's before patent from extensions. With 791, it is composition through 2042, and then an additional 2 years on the polymorph. Definitely opportunity for extensions. The last thing is we're actually in a nice position from a funding perspective, which in a tough environment, we're thankful to have. We have about $191 million in the bank as of the end of last quarter, and that'll fund us through the end of 2027. That's great. I mean, it certainly seems like it's going to be a very catalyst-rich next year or so. Looking forward to seeing how everything plays out. Thanks again for joining us. Thanks, everyone.