Okay, great. Good morning, everyone. Welcome to day three. We are saving the best for last here at the Morgan Stanley conference. I am Jason Russell, and it is a pleasure to welcome MBX to the stage. CEO Steve Hoerter, as well as Dr. Sam Azoulay, who is the Chief Medical Officer. MBX's first time here at the Morgan Stanley conference. We are pumped to have them with us. Just as a quick overlay for those that do not know, MBX is developing long-acting precision peptide therapeutics lead in the clinic, late stage, canvuparatide now, I think, officially started in phase III. That is right. For chronic hypoparathyroidism, and very exciting, MBX 4291 potential true once-monthly GLP prodrug for obesity with, I think, some data expected later this year. Steve, Sam, welcome. Thank you for being here. Thank you. Yeah, thanks for the invitation. Maybe we'll start with some high-level perspective. I mean, Steve, you took the CEO job recently, stepped in from the board, and I think in July, at a very important moment for the company. I already talked about where we are in the clinic. You have a very unique operating experience having transitioned Deciphera into a commercial stage company and a successful exit. So, maybe starting with your priorities as the CEO, what are the things that, if we step back 12 months from now, that you think investors should judge you and the team's performance on? Yeah. It's been a really transformative year for the company in 2026. Just to set the stage, Jason, and by the way, thanks for the invitation to join for the conference. We'll talk about this, I'm sure, during the course of our time together this morning, but we reported earlier this year 12-month open label extension data from the phase II Avail study of canvuparatide in chronic HP, demonstrating sustained clinical benefit for this once-weekly injectable, this once-weekly PTH replacement therapy. As you referenced, we've now moved into a pivotal phase III study, having dosed the first patient just a matter of a couple of weeks ago. So we are well on our way now with the phase III and have clear line of sight to the potential to be a commercial company. So we're starting to do all of the work that we need to do internally to prepare for eventual future commercialization in what is a market that is now clearly being validated as a multi-billion dollar peak revenue potential market, where there's a daily injectable that's on the market, which has reported now a billion-dollar run rate in revenue. We believe that our once-weekly canvuparatide has the potential to be best in class and to take the lion's share of that market. So if we think about the canvuparatide part of the business, it's a really exciting point in time and moment as we cast our vision to the future to be a commercial stage company with canvuparatide. Then at the same time this summer, in fact, earlier in the summer, we gave a sneak peek at some blinded data from an ongoing phase I study of MBX 4291, and this is a true once-monthly GLP-1/GIP co-agonist that we're exploring, obviously, for the treatment of obesity. The early data was very encouraging. We showed PK data that demonstrates true once-monthly dosing. We showed early weight-lowering data, which was encouraging, and in addition, we showed that our prodrug technology, which delivers not only an infusion like PK, but allows us to control the release of active peptide to a slow and steady rise to Cmax. We showed that there's the potential for that technology as it relates to the co-agonist to deliver improved tolerability. So as I think about priorities and what is to come in the next 12 - 18 months, it is really about canvuparatide getting to full enrollment in that pivotal study, which we expect in the second half of next year, and then doing all of the work we need to do to prepare for eventual future commercialization. As it relates to MBX 4291, it is about our Q4 disclosure, which will be from part C of the study, cohort C1, where we will have unblinded data for the first time with a goal being to deliver on this TPP of competitive weight loss, improved tolerability, and true once-monthly administration. I think if we are able to achieve that, this has the potential to be a fundamental frame shift in the obesity landscape because I think the field knows that less frequent administration is preferred by patients, and certainly, our ability or the potential to have a better tolerability profile with a co-agonist, I think is highly attractive to patients. That is great. We are going to peel the onion back on all of that. Incredibly exciting time to be joining the company in an operating capacity. Let us step back and just talk about the foundational capabilities for a minute. When the company went public a number of years ago, obesity was kind of out there as a dream at that point. Now it is very much in front of us, but it all comes back to this kind of foundational capability on PEPs or precision endocrine peptides. Maybe just give us a little bit of perspective around what the unique capabilities are for MBX, maybe some history around how that came together. Mm-hmm. Sure. The company was founded in 2018 by Richard DiMarchi, our scientific co-founder, and by Kent Hawryluk. Richard is a thought leader in the field of peptide chemistry. He is at Indiana University currently, but spent 20 years of his post-academic career at Eli Lilly and Company, and then subsequent to that, spent time at Novo Nordisk. His insights into, and the work that he has done over the years, he is a co-inventor, I think on about 100 patents. Has published over 300 times in the peer-reviewed literature. His work at Lilly, for example, was instrumental in the first rapid-acting insulin at Lilly, FORTEO, other innovations. His work on peptides generally has really formed the foundation for the now multi-agonist approach with peptides like Lilly's tirzepatide. He has been really sort of the father of the field, if you will. His work and his founding at MBX, scientifically, really centered on three pillars as it relates to peptides. One was being able to design peptides with improved pharmaceutical properties. The second related to the ability to utilize a fatty acylation, of course, for extended time action. The third, and probably most important, is the prodrug technology. This allows us to deliver a very simplistic prodrug in a way to patients that then regulates the release of active peptide. As you think back to whether it is canvuparatide in the case of HP or very importantly, MBX 4291, the co-agonist for obesity, we are able to engineer a rate of release for the active peptide that then delivers, we believe, a differentiated PD profile. That is what is so exciting about the PEP platform and the work that Richard DiMarchi has done that is really instrumental and ingrained in all of the clinical programs that we have. Yeah. That is exciting. Obviously anyone who is following either the incretins or obesity understands the importance of why that profile might have significant lag. Maybe to dive into the portfolio a bit, Sam, maybe I will direct this to you. Let us start with canvu. Its latest stage, it is exciting, interest center phase III. Let us go back to the phase II data. You had the initial phase II Avail data. You put out earlier this year the one-year extension data, I believe in June. What are the two or three, I do not want to limit you, if there are 10, you can give me those. The two or three most exciting things that you saw in that data set that really gave you the conviction to push aggressively into phase III. Yeah, thank you. What is very exciting is when you get the results you are expecting. When we started this study, it was a double blind placebo control, et cetera. It was initially 12 weeks, and we show exactly what we were expecting in terms of responder rate, and the response rate was based on serum calcium. We confirmed this result at six months, and as you said, we confirmed also this result at one year. It is like a package, especially for PTH replacement therapy. You look at serum calcium, but you look also at the other target organs, such as kidney. Urine calcium excretion in this type of patient is extremely important. They excrete too much calcium. They cannot reabsorb the calcium. As a consequence, they get kidney stone, they get CKD, chronic kidney disease, right? The other target is the bone, because in terms of remodeling, they don't have any turnover. The bone doesn't turn over as it should and release calcium. When we released the one-year data, we confirmed the effect on urine calcium excretion, so we saw benefit. On bone, we saw that the bone biomarkers were high, but started to plateau, and the BMD, as a consequence, were exactly where we wanted to be. Slight reduction, but within the normal value. I would say that after one year, we confirmed the total package of the PTH replacement on serum calcium, urine calcium, and bone biomarkers and bone mineral density. Great. Helpful context. I think as you fast-forward to the learning, or you think about the learnings out of that trial and you take that back to the physician community, I'm sure you're doing already survey work with patient groups. What are the things that in a real-world setting are going to be most impactful and that you're hoping to pull out of the pivotal data set? As it relates to the work we've done with HCPs, with physicians, prescribers, and also with patients, we've tested the product profile of canvuparatide, a blinded profile with HCPs and with patients, as I said, to better understand how they view the data and what that means and what that could translate into in a commercial setting. What became very clear in the market research is that physicians and patients both prefer the profile of canvuparatide based solely on convenience. All other things being equal clinically, this is about less frequent administration for patients, which speaks to convenience, and then for patients not having to think about their HP on a daily basis because they simply take a once-a-week administration of canvuparatide and then they can forget about the rest. That in and of itself is very attractive and what we heard from physicians is that they would initiate more patients on canvuparatide, the majority of patients on canvuparatide who were PTH replacement therapy naive, and that physicians would also switch patients. It was a high indication of a desire to switch patients from, for those who were treated with a once daily, for example, over to a once weekly. That was all very encouraging to hear from the blinded research, and maybe Sam, you can comment on what we hear anecdotally from physicians and investigators. Yes. They are very, very encouraged by seeing that the weekly is coming. So that we will be having a weekly administration as compared to the heavy, very heavy administration of calcium supplement, vitamin D, et cetera. They have today a daily product, but I do not think that it is a full story. They need really the weekly administration. We go to the Hypoparathyroidism Association, we go to investor meeting, which we held two weeks ago, and there is a strong interest. But beyond this, there is also back to the urine calcium. There is something which is missing, is a demonstration of the urine calcium excretion that can improve in this population. We are so confident in this endpoint that it will be one of the key component, a key secondary endpoint in our phase III program that we are aiming to demonstrate the benefit in patients with elevated urine calcium. We target this population because they are the one that needs improvement, right? If you start with normal, but that needs improvement. We will have two parameters, which is first one, normalization of urine calcium and normalization at the same time of serum calcium. Okay. Maybe just to tie it back to the PEP platform. I mean, obviously reasonably obvious a weekly is much preferred if similar efficacy tolerability to a daily. Is there a presumption that there is a lifecycle management play to go to a monthly, or is there a limit? I am just thinking, is that something that might be possible under the platform? I think that suffice it to say there are a variety of, I think, options that we have from an LCM perspective. I think what we have heard from the prescriber community and from patients is that this level of innovation with canvuparatide going from a daily to weekly is exciting in its own right. That clearly is the focus for us today, is on prosecuting that opportunity, getting the phase III enrolled and such, and driving that to make it available to patients who need it. I would like also to come back to the PK. I mean, the PK for this product is so important, right? That is to our platform. And what we showed in the patient population, our PopPK showed that the peak to trough, the peak concentration at the peak as compared to the trough was 1.3. When you compare this with a daily, it is 1.3 to 1.6, but on a daily basis and our 1.3, it is on a weekly basis. And why is it important? It is because it is correlated to maintaining the serum calcium within the normal value over time. Yeah. No. That all makes sense and resonates. Maybe to the phase III, so oPTimize, I believe is the Yeah is the name of the protocol. You announced on August 27th that you have dosed a patient. Give us some perspective around anticipation, around enrollment cadence, site activation. Is there any guidance on expectation around the timing for that data or too early? Sam and I were just in fact at the North American Investigators meeting for oPTimize, which was exciting to attend to just hear the level of enthusiasm coming from investigators in the U.S. and in other parts of North America. Which I think is important by the way, because of course it is in the U.S. where a daily injectable is available, but nonetheless, there is considerable enthusiasm for participating in the study. And we are now, I think per clinicaltrials.gov, up to something in the range of 12 sites open for the study. We will of course, continue to open sites at a rapid pace for that study. And what we have said, Jason, is that we think it is reasonable to expect that we will get to full enrollment in the study by second half of next year. So in the second half of next year. We are excited to be underway with the protocol and to get patients on study and we are off on our way. Okay, great. Well, obviously that is going to take some time. It is something that is going to play out over the course of the next two and a half years. You have got something right in front of you, which I know people are very focused on as well. Let us switch gears from the rare endocrine side to the obesity side. You gave us some setup at the beginning around the thought process around MBX 4291. I think the investor community saw your blinded data back in the spring. Maybe the first question is what do you think you learned on the PK profile in those data that you shared with the market? How did that establish the confidence level for what we are running into here towards the end of the year? Yeah, this is a good question. Through the PEP platform, we already designed the target product profile without even knowing the results, right? From a PK standpoint. What did we want to get is we know that the GI effect of the intolerability, nausea, vomiting, et cetera, are related for a part to the burst effect, right? You see it very well with tirzepatide, Metsera compared with MET-097i, so you see it. Here from a target product profile, where we wanted is a slow raise to the Tmax or to the Cmax and stay as long as possible at this level, right? Show a time to have the Cmax as long as possible. That was our target. When we released in May last year, the Obesity Day, it was amazing to see how our PK in healthy volunteer, I mean, patients with a BMI above 30, otherwise healthy. If you look at our PK, that is exactly what we saw. We saw slow raise to the Cmax, especially after the multiple administration. The time to half of Cmax was 26 days when Metsera, the MET-097i, is showing 20 - 21 days. A relatively flat concentration, sustained concentration at the Cmax and slowly going down. The PK profile we got in this population was exactly aligned with the TPP, which was a consequence of the PEP platform. Very, very nicely. The beauty of this concentration slow rate, it is related to one thing. The slow rate is related to this accumulation of the drug, slow accumulation of the drug that lead to a slow raise, no burst effect at all. The consequence is that we didn't get that many adverse events related to GI. And especially at the dose we presented, the doses, dose regimen, which was 30 mg four times weekly, followed by 120 mg monthly, we got only one episode of diarrhea, and that was really aligned with what we were aiming for. To the accumulation phase and the comments, just to think about the design here of both the phase I and then thinking forward. So, there's a induction phase at a weekly basis until you get to certain levels and then switch to monthly. Is that what we see? Is it four weeks and then two monthly doses and that's kind of how the design, the data we'll see later this year? You're absolutely right. The cohort we disclosed, B1 cohort, was exactly as you described, weekly administration for four weeks followed by one monthly administration. And the accumulation, the benefit of the accumulation, back to your comment, is related also to almost a self-titration. So patient self-titrate is not really a self-titration in terms of increasing the dose, but self-titration of the patient and like a desensitization of the receptor for GI effect, the GLP-1 receptor. So that's really a nice thing. Back to your question about what the next steps, the C1 cohort, C1 will be disclosed by the fourth quarter of this year, will be the same starting doses, 30 mg four times every week, and followed by 120 mg monthly, followed by 180 mg monthly. Okay. With the expectation that the 180 mg, I guess we'll learn from these data. How many patients are we going to see? How many are It's just two arms, but yeah, maybe. The C1 cohort will have 30 patients, 20/10, 20 treated, 10 randomized, as compared to our B1 cohort, which had 8 patients, 6/2. As a reminder, when we disclosed the B1 cohort, it was still blinded. We still, as of today, we haven't unblinded the study. Right. Okay. Let's think about what good looks like. I think you've obviously noted that I think the most unique feature is probably the tolerability. But help us, in your minds, what do you want to see? Is there a weight loss bar at 12 weeks that you're trying to guide to? Is that even important today, given I mean, obviously it's important. It's the reason why we're doing this. But how do you see it? How do you think investors should position as they look forward to that data? I think there are really three, as you mentioned, Jason, it's kind of three pillars to the desired TPP, and what we hope to show in Part C of this study is competitive weight lowering. We think based at 12 weeks- How do you define that? We think based on the data, that's probably something in the range of 6%-8% of weight loss at 12 weeks. We want to be able to show and reinforce the PK data that we had in May, which is true once monthly. The third component is the potential to demonstrate improved tolerability based on the PK profile and avoiding the burst effect, as Sam Azoulay just mentioned. I think what's important, and it sort of was crystallized further this week, when you look at some disclosures as it relates to the potential for once-monthly administration of these co-agonists or mono-agonists even. We heard, two days ago that Novo Nordisk has discontinued the collaboration with Ascendis Pharma as it relates to using that older PEG technology to get to extended duration, which I think is notable. On the other hand, we see Pfizer with Metsera's MET-097i, trying to cover all bases by conducting both weekly studies, weekly administration studies, in addition to monthly. Our view is that this potential for a true ultra long-acting once monthly, that field, to us, continues to be wide open. We're very encouraged by the early data that we saw in May that we disclosed, and we're looking forward to the upcoming disclosure here in Q4. I think if we're able to deliver on that component of the TPP, that will be exciting in its own right, in addition to this potential to deliver improved tolerability. We couldn't be more excited about the program and the potential to deliver on those three pillars. Q4, you made that very clear. I'm going to try and you're not going to tell me, but is that October or December? You're going to plead the fifth on that one. That's right. Thanks for trying. We're going to stick with our Q4 guidance. There you go. That's all right. Thanks, Jason. And format of that disclosure, that's a press release and a call, presumably, or Oh, I'm sure. Yeah, I'm sure we'll do a call. We'll want to make sure that we have ample opportunity to go through the data in detail and share the context of how we think about it and what the next steps are. Okay, great. It's not your only obesity program. No. You've got some additional- That's right. levers coming along the way. Talk to me about MBX 5765 and MBX 6180. Both, what are they, timing into the clinic. Maybe we will start there and I will follow up. Sure. We have disclosed now two development candidates that we have that are both in IND-enabling studies. The first of those that we disclosed is a multi-agonist prodrug that packs in multiple mechanisms into a single peptide. That was the first disclosure that we made. This is the so-called incretin or multi-agonist that we disclosed at our Obesity Day. That is moving forward toward the clinic. Our second disclosure on our most recent quarterly financial results was related to our triple agonist. This is a potential once-monthly triple agonist that we have now declared as a DC also in IND-enabling studies. In our experience, I think industry norm time from a DC to an IND is somewhere in the range of 12- 18 months, and we expect that we will be on that sort of timeline. There is at least the potential that we could be delivering two new INDs, all leveraging our prodrug and PEP platform with respect to those two candidates, that we could deliver those two INDs in 2027. I think we now have, as we mentioned earlier, clear clinical validation of the platform technology, not only in canvuparatide but in the early blinded data from MBX 4291, showing true once-monthly PK, showing this slow rise to Cmax. Our focus and goal now is to apply that same platform technology to other targets of interest in obesity, and that is exactly what you have seen us do this year. I am sure we will be continuing down that path further as we build out what we expect to be a robust portfolio of obesity medications leveraging the platform. Great. I missed one and I want to go back for a minute to MBX 4291. We have the data later this year. How should we think about the next steps on the other side of that without getting out in front of what you will ultimately say, but is this a traditional path that we have seen across the obesity landscape, where we are then going to go run a 26-week study in a phase II setting and then progress to a larger phase III? Is there a faster path? What are you willing to share in that regard today? Yeah. What I can say philosophically is our goal with the phase I program is to get to the right dosing schedule. It's really important, obviously, I think, in a phase I setting to understand the right dosing schedule to get to a profile that delivers on the TPP that we think will be a winning TPP. That's not to say that we may not choose to move into a phase II program as a next step. Yeah, we think doing the work early to understand dosing schedule is really important for obvious reasons. In part C of the study, as we've said, our milestone in Q4 is reporting on cohort C1. We've also disclosed back at our Obesity Day in May that we have a cohort C2 as part of that study. We're continuing our work to understand dosing schedule. That's how we think about future development. I think, Jason, the way to further think about it is when we get to the disclosure in Q4, I imagine we'll be able to put some more color around how we think about next clinical development steps and where we're headed with MBX 4291. Okay. Great. We look forward to that. Maybe just to wrap up here, a couple more minutes. You've been in the CEO seat for three months or so. I think we have a very clear understanding of what's in front of us in the near term and kind of over the medium term. Let's say we're sitting here 12 months from now, 18 months from now. Reinforce for us what you hope investors will have taken away that you've accomplished in the seat and both on the endocrine side as well as the obesity side. Well, we're excited about the way the portfolio is constructed, all based on the platform technology, and we think there are multiple ways that we can unlock significant value for our investors. So, on the one hand, we have canvuparatide, which is going to be entering this multi-billion dollar market, and our goal in the next 12- 18 months is to get to that full enrollment of that phase III study to put us on that trajectory, and we'll continue doing the work, of course, to be ready for eventual commercialization. So that's on the canvu side of the house. Then for the obesity portfolio, this is about getting to clinical data with MBX 4291 that shows in a clear manner that we have the potential to achieve that TPP that we talked about. That will include the Q4 disclosure, and I am sure by the time we get to the end of next year, we will be well on our way to the next steps in terms of clinical development for MBX 4291, all while we advance the balance of the earlier portfolio. By the time we get to next year, the end of next year, we think we are going to be a fundamentally different company even from where we are today with a fully enrolled registration-directed study for canvuparatide and a lot of progress on the obesity portfolio. Sam and I and the rest of the team are really excited to find ourselves in that place in 2027. Yeah, it is exciting times. I think we will wrap it there, Steve. Sam, thank you both. Thank you very much. for being with us. Good luck here over the coming months. Great. You too. Thank you, Jason. Thank you all.