Great. We're going to get started with our next presenting company. My name is Ted Tenthoff. I'm a senior biotech analyst at Piper Sandler. And before I begin, I'm required to point out certain disclosures regarding the relationship between Piper and our next presenting company, Regulus, which are posted in the back of the room and also at the registration desk. What an exciting time for the company. Victor Ambros and Gary Ruvkun were awarded the 2024 Nobel Prize for Medicine for the discovery of microRNAs. Regulus recently reported positive phase I data on RGLS8429 in autosomal dominant polycystic kidney disease at ASN. There's just a lot going on with the story. Jay's going to be better at telling you it than I am, so I'm going to hand it over to him. Thanks, Ted, and thanks, everyone, at Piper for having us. We appreciate the opportunity to present. This slide indicates that my colleague, Dr. Preston Klassen, a board-certified nephrologist, would be presenting with me, but he's ill, so you're stuck with me instead, so we'll keep the Q&A to a minimum. I will be making forward-looking statements. Actual results may vary materially from those expressed or implied. I encourage you to read our risk factors and our SEC filings, so Regulus, we are a leading antisense oligonucleotide company. We were founded as a joint venture between Ionis and Alnylam, where we are their exclusive licensee to all of their technology and intellectual property to design oligos directed against microRNA, and they keep their respective rights in designing oligos against mRNA. That relationship, while it involved them owning the majority of the equity, the company is now based solely on small single-digit royalties for anything that's commercialized. We're amidst a phase I study, wrapping it up, actually, early next year with our lead molecule dubbed RGLS8429. It's an antisense oligo directed to inhibit miR-17 or microRNA-17. And it holds the potential to be the first disease-modifying approach for the treatment of autosomal dominant polycystic kidney disease. We'll get into the disease in a minute. Our platform, though, we've evolved over time since our inception to discover a motif that is preferentially distributed to the kidney, specifically what we call short miRs. And because we only need eight nucleotides to recognize and bind the seed sequence of a microRNA, we can make short oligos. And it turns out that they preferentially distribute to the kidney, and we're pursuing a kidney disease. We'll show you some of the distribution data in a bit here. We have earlier stage development programs and research targeting additional kidney and CNS disorders, all based upon the assumption around haploinsufficient disease. And our team is quite experienced in nephrology drug development. In addition to Preston, several of our leaders in the company have significant experience in the space. So in terms of just quickly, high level, what we've seen to date, 8429, importantly, in this phase IB study in patients as well as healthy volunteers, was safe and generally well tolerated at all dose levels tested that we've completed. We've completed one, two, and three milligrams per kilogram and have seen the most consistent biological activity in terms of target engagement and polycystin production at three milligrams per kilogram, reaching statistical significance compared to placebo. We also, surprisingly, saw mean reductions in kidney volume at the two and three milligram per kilogram levels when dosed Q2W for three months of dosing. We're set to report out on roughly half of the 26 subjects enrolled in our fourth cohort, which is an open-label cohort, looking at a fixed dose. The reason for this is we want to migrate to our commercial presentation because our next study could be pivotal, and you need to introduce that in order to incorporate it into your NDA. Final data from that full fourth cohort, we would expect late Q1, early Q2, prior to initiation of the pivotal program. We're on track to meet with the FDA here before the year end, so you can imagine it's scheduled. We're looking forward to it, where we hope to align on the design of the pivotal study and get the clearances needed to move into a chronic study. Importantly, the chronic mouse studies have been completed, and the monkey study has been completed as well. The mouse NOAEL top dose of 300 milligrams was the NOAEL. We await the results from the non-human primate, but there's been no findings of concern to date. And with the financing we completed in March of last year, raising a $100 million and oversubscribed deal, we've initiated the phase II readiness activities, including the CMC activities to prepare for the prefilled syringes. So what are microRNAs? These are short, non-coding RNAs that bind to target message and control translation. Their involvement in disease is driven through aberrant expression. So you see an over- or under-expressed microRNA, it's going to lead to downstream dysregulation of specific gene networks that they're designed to address. So our approach is to then target that with simply steric binding and enable derepression to allow translation of downstream protein. And we'll walk you through some of those data. So just quickly on ADPKD, it's driven by mutation in either the PKD1 or PKD2 genes. And about 80% of the diagnosed population have a mutation in the PKD1 gene, which tends to be a more progressive disease, with patients advancing to end-stage renal disease in their mid-50s. PKD2 is a bit more benign, maybe two decades later before reaching ESRD. And in the middle, the cartoon is really designed to show that, in general, it's believed that you have this sort of linear expansion of cysts, both in terms of volume and number, over time, and ultimately leads to renal failure due to simply the physical space that the kidney is supposed to reside in. And obviously, you want to avoid having them get to the size that you see in the far right-hand column. A healthy kidney should be the size of a closed fist, and they can get to be 8-10 x the size of a normal kidney. About 160,000 diagnosed in the U.S., of which roughly two-thirds are considered at high risk of advancing to ESRD. So about 100,000 addressable patient population. I've touched on the other elements on the left-hand side, other than to say there's only one drug approved called tolvaptan that comes with a box warning for potential drug-induced liver injury. The more significant issue, though, really is its tolerability profile. We'll touch on that in a second. Despite that, in its, I guess, fifth full year of sales, it was launched in the middle of 2018, did $1.3 billion last year. We've recently completed a pretty significant market research study conducted in both the U.S. and Europe with about 100 nephrologists, as well as a number of payers. Just to get an understanding more deeply about the patient journey, tolvaptan utilization, and the opportunity for our program. Right now, you can see, if you can see that lighter color there, as I mentioned, about $1.3 billion grew about 30% year over year since 2022. But that represents less than 7% of the addressable patient population, less than 7,000 of 100,000 total. The uptake's been limited by both physician as well as patient product concerns, as well as tolerability issues, specifically the polyuria and the need to get a clean liver function test monthly. I touched on the middle bucket there. The size of the addressable population is estimated to be about 100,000 in the U.S. However, many epidemiologic studies suggest that it's significantly underdiagnosed, and it could be three to four times as high if we had more screening that was going on. So a little bit more in terms of market research. We do have good access in terms of tolvaptan coverage, almost 75% commercial coverage. And with a concentrated prescriber base, you can see really quick uptake in the first year of introduction. That's only a half year in 2018. Typically, a specialty nephrology sales force will call on 6,000-8,000 physicians. So it's a pretty concentrated base here relative to the total potential prescribing base. And you can see that the uptake really slowed quite a bit, driven primarily because of, again, tolerability issues and a growing number of non-repeat prescribers. But importantly, a pretty large market addressable with a very focused sales force. And the right-hand side is just a snippet of feedback. We tested a product profile with tolvaptan-like efficacy. What they showed in their pivotal program was they were able to slow the growth of the kidney by about 50%. So instead of 5.5% untreated in the placebo arm, subjects' kidneys grew at about 2.8%. And that translated into about a 35% improvement in the rate of decline in kidney function as measured by eGFR. That is the product profile, just slowing the time to end-stage renal disease that we tested. You can see the feedback from the nephrology community was quite enthusiastic with a drug that's safe and well tolerated with tolvaptan-like efficacy. You can anticipate significant utilization because really no standard of care exists. We make adjustments, obviously, for overstatement. Physicians tend to be zealous sometimes about new opportunities. Our drug is designed to block miR-17. We'll touch on the specifics around why we're doing this. I already mentioned we get preferential distribution to the kidney, and the half-life in the kidney enables every other week dosing. The safety and tolerability profile to date is quite encouraging, and we've had no related SAEs or notable adverse events of interest. And then lastly, with the dose response we've seen in the mechanistic biomarkers, we were really excited to see this early evidence of impact on kidney volume seen at both 2 and 3 milligrams per kilogram. The intent of our end-of-phase I meeting here is to align with FDA on the next study, which we've already confirmed with them is an acceptable endpoint, total kidney volume, for accelerated approval with the commitment to study GFR in the post-marketing setting. So I'm conscious of time. We've got seven minutes left. I got quite a bit of preclinical evidence. I'll try to move through it fairly quickly here. So miR-17, it's upregulated in both disease models shown on the left-hand side in the red and blue graphs in PKD1 or PKD2 knockouts, and also evidence of miR-17 upregulation in patient kidneys when taken at the time of explant. And interestingly, on the far right, you can actually introduce a cystic phenotype in an otherwise healthy mouse by simply overexpressing miR-17, which is shown in the far right-hand column. You can see the cyst formation. So what happens here in terms of mechanistically is that due to the mutation, you have increase in proliferative signals, much like a cancer signal. And one in particular, c-Myc, is overexpressed. That directly regulates the maturation of pre-miR-17 to mature miR-17, which then regulates a number of downstream genes, and we'll touch on that. So our approach here is to simply bind miR-17, correcting these downstream gene networks. There's a complicated slide. On the left-hand side is the transcriptomic data showing hundreds of genes that are dysregulated in disease and that with treatment, you shift them to either up or to the right. And what you'd want to see with correcting these gene networks is a slope of negative 1. And the green dots are those that are hitting statistical significance in terms of correction with treatment with an anti-miR-17 in a diseased kidney versus healthy background. Those green dots, you can see the slope is pretty close to negative 1. If you zero in on specific pathways that others have targeted in trying to treat the disease, including mTORC as well as inflammatory signals and PPAR alpha in the mitochondria, you can see these pathways shown in comparing disease versus wild type on the far left-hand side of that color chart there. You can see a number of those genes are upregulated in disease. And then in a nice dose-dependent way, with treatment with anti-miR-17, RGLS8429, improvement in those pathways involved. So we have, by definition, a pleiotropic effect, including regulation of both PKD1 and PKD2. And why that matters is we've been able to show the protein product, if we target miR-17, we can derepress those genes and increase polycystin. So a little more validation. In a PKD1 knockout or PKD1 flox/RC knockout, if you also conditionally knockout miR-17 in those kidneys, you have a dramatic impact on cystogenesis as well as survival. This has been recapitulated with pharmacologic intervention here, both in a PKD1 flox/RC or a knockout model and in a non-orthologous model, pcy driven by a different mutation, but also a cystic phenotype. Just a bit on PK. You can see here in the green chart, the circles, about 10-fold higher exposure in the kidney than the liver for just a naked oligo, and that's important. Normally, if you had a larger oligo, you'd get equal distribution kidney and liver, and it traffics to the cystic epithelial cells, which you see on the right-hand side through labeling. The target engagement here with a single dose shows that two-week half-life of blocking miR-17 leads to that sort of optimal 80% target inhibition. And let's jump into the clinical development with the last couple of minutes here. So as I said, we're wrapping up this phase I MAD study here early next year and by end of Q1, early Q2. Next study is planned to be a single pivotal phase III, where we get approved at an interim time point on total kidney volume at one year with a follow-up at two years for GFR, much akin to the IgAN space. This is a quick snapshot of the study design. We had three weight-based placebo-controlled cohorts, and then the fourth cohort, fixed dose, to simply get experience with a fixed dose as we look to introduce that into our pivotal program. Their primary objective is really safety, tolerability, and recapitulation of the results we've seen at the earlier cohorts. Our patient population we've enrolled, overall, Mayo class 1C/D/E. That was the classification of high-risk patients. Kidneys are quite large and corresponding reductions in GFR. Generally safe and well tolerated, as I mentioned, and the ongoing fixed dose cohort, similar benign safety and tolerability profile. Here's the data on polycystin changes from baseline, and you can see a nice dose response. We anticipated that around 2.5 milligrams per kilogram would yield sort of optimal miR-17 inhibition. That's driven by all the non-clinical work we've done, where at 30 milligrams per kilogram, we get optimal efficacy. Pushing the dose much beyond that doesn't provide much. And the miR-17 inhibition through the polysomal shift assay is optimized at that level. So we're pleased to see that we're at the asymptotic part of the dose response curve and that the 3 milligram results, you can see the p-values there, reach statistical significance compared to placebo with the 2 milligrams just missing it. So just in terms of background, I think I touched on this, but 80 PKD patients experience around 5%-6% growth in their kidneys. It is a heterogeneous sort of evolution where patients with more severe truncating mutations can grow quite a bit faster, upwards of 12%, and those with more mild disease, around 2%. tolvaptan showed they could slow that by about 50%, and they showed that with repeat MRI. That correlated with an improvement in GFR, which led the way to the adoption of the opportunity for accelerated approval with that surrogate endpoint of TKV. GFR generally declines around 3-4 mL per minute per body surface area, and tolvaptan reduced that by about 33%. You need many measurements given the inherent variability of GFR. What we saw thus far in our study, now looking at repeat MRI at baseline and then at four months. Three months of dosing, one month of follow-up. At the fourth month, we take the second MRI. Placebo behaved as you would expect. If it's 6% per year, then at four months, you'd expect 2%. That's what we saw. You can see at 2 and 3 milligrams per kilogram, while not powered for statistical significance, suggests evidence of an ability to arrest that cystic expansion. eGFR, we wouldn't expect to see any benefit on kidney function in a short-term study like this, but met our expectations for safety. You can see the slopes of eGFR and, importantly, the confidence intervals in the middle table that they're all overlapping here, and on the right-hand side, more sensitive measures for safety, seeing no significant issues there, chem or BUN. We look at creatinine as well and don't see any evidence of any issues, so summary of findings real quick. Dose every other week for three months, well tolerated, no safety concerns. We did see a nice dose response and 3 milligrams per kilogram delivering statistically significant impact versus placebo and early evidence of an impact on kidney volume, so just to summarize, this oligo designed to block miR-17, we believe, is addressing some of the key control mechanisms, cystogenesis and proliferation, offering the opportunity for disease-modifying therapy. We'll report out on data from cohort four after upcoming FDA meeting early next year when we get the meeting minutes and wrap up that fourth cohort, as I said, early Q1, excuse me, late Q1, early Q2. And we look forward to our meeting with FDA to confirm the protocol that we've proposed for accelerated approval. And there's a clear unmet need here that we're very excited about and that physicians and patients need an opportunity for innovation. With that, wrap it up. Thanks. Hello, everyone. Thank you all for joining us for the second day of Piper Sandler's annual healthcare conference. I'm Michael Mazzola, one of the associates on our biotech team. It's my pleasure to welcome KALA BIO and their CMO and head of R&D, Kim Brazzell. I'll hand it over to Kim, and he'll tell us more about the company. Thank you. Thank you, Michael. I'd like to thank the Piper team for inviting us to provide an update on KALA and remind everybody there may be forward-looking statements in what I have to say. KALA is a leader in the emerging field of mesenchymal stem cell secretomes. We have a focus on rare diseases and ophthalmology and have an ongoing phase IIb/pivotal trial with our lead product, KPI-012, for the treatment of persistent corneal epithelial defects, which is a rare sight-threatening condition with significant unmet need. Our ongoing trial, we are targeting top-line data in Q2 of 2025. And as we'll discuss later, we think this is potentially a $1 billion opportunity. We've made significant progress in the last couple of years in our development of the secretome program. We filed an IND in November of 2022 and was accepted within the normal 30-day period. We initiated our phase IIb trial in Q1 of 2023 with a small safety cohort that the FDA asked us to do before going into the efficacy portion of the trial. And then we started the efficacy portion of the trial mid-year of 2023. We've also made significant progress on our CMC and potency assay program and had a very productive meeting with FDA earlier this year where we gained alignment with the FDA on our program for CMC potency assay program for phase III trials and ultimately for BLA filing. We have a very experienced leadership team that's been together for a number of years, both on the R&D side and the commercial side, experience with rare diseases, and experience with secretomes and cell therapies. One second. We previously developed and gained FDA approval for two ophthalmic products, one for dry eye disease and one for ocular inflammation. A couple of years ago, we divested those to Alcon to focus on our new focus, which is biologics for rare ophthalmic diseases. As I said, KALA is a leader in mesenchymal stem cell secretomes, which is an emerging field that we think has significant opportunity. By way of background, secretomes are produced by collecting the biomolecules that are secreted by cells into the extracellular space. In our case, we start with human bone marrow-derived mesenchymal stem cells, for which we have a master cell bank. We culture those cells under controlled conditions for sufficient time to let them produce the vast array of biomolecules they normally produce to support the growth and viability of the cells. We then, again, in a controlled fashion, remove the cells and are left with an aqueous solution containing a variety of the.