Hi, everyone. Good afternoon. Thanks so much for joining us here in Miami for the Barclays 20th Annual Global Healthcare Conference. Very happy to have MBX here with us today. I'm Ellie Merrill, one of the biotech analysts here at Barclays. Joining us from MBX is Chief Executive Officer Kent Hawryluk, Chief Medical Officer Sam Azoulay. Apologies if I butchered your name. Feel free to correct me. Perfect. Perfect. Really? Okay, great. Thank you both so much for the time. A lot of exciting things to talk about in your pipeline, but maybe first, you know, I'll pass it to you to give an overview of your platform technology and clinical programs. Well, first of all, thank you, Ellie Merrill and the Barclays team, for the invitation to participate in this conference. Also, a reminder to everyone that we will be making forward-looking statements and encouraging you to review our risk factors and other disclosures in our SEC filings you can find on our website. MBX is pioneering precision endocrine peptides or PEPs with a passion to bring patients freedom through convenient and precise therapeutics to treat their endocrine and metabolic diseases. This PEP platform you can think about is to kind of do better than nature with peptides, which are miraculous molecules, but they don't last very long. It's very important to extend their time action, but also to manage it, the drug exposure through a slow release. We're able to address that with the technologies we call PEP for short. This is an important week for MBX and for patients with hypoparathyroidism because we announced on Monday that we cleared an important regulatory milestone. We had a successful end-of-phase II meeting with the FDA, and it's all systems go for our phase III, starting in Q3 of this year. Excited to be a phase III-stage company and to bring a best-in-class once-weekly PTH replacement therapy to patients with HP. The significance is this validates our PEP platform that is also being applied in a very exciting field, obesity. We have an obesity portfolio that is expanding and advancing. It leads off with MBX 4291, which is a GLP-1/GIP co-agonist prodrug with, we believe, once-monthly dosing and should have better tolerability through this PEP approach. Slowly rising and steady drug exposure. We have a 12-week multiple ascending dose readout in Q4, which we think is just a major catalyst for the company. It will also support our overall obesity portfolio, which includes a amycretin single peptide with incretin, as well as the amylin or DACRA mechanisms in a single peptide, also once monthly and potential better tolerability. That candidate selection will be in Q2 of this year. A triple GLP-1 GIP glucagon agonist development candidate in Q3, copy-paste once monthly, better tolerability. We have cash to support all this, our operations into 2029, which is quite a unique position to be in, and just a tremendous amount of optionality in terms of how we advance these potential best-in-class programs. Great. Maybe starting with the news this week after you met with the FDA and aligned on a phase III design for hypoparathyroidism, walk us through sort of the conversation with the FDA and, you know, the study design that you'll be doing in phase III? Thank you. It was a really good meeting with the FDA confirming the study design. It will be a placebo-controlled study for six months. Very importantly, we agreed on the primary endpoint, which is a responder rate and the responder definition, which is a composite endpoint. No surprise there. It was good to validate this agreement. Very importantly, also, we proposed a key secondary endpoint, which was normalization of urine calcium in patients with elevated urine calcium at baseline. That was really important because if we confirm through the results and we get the response we want, we are looking for, it will be a key differentiation with the main competitors, a daily PTH replacement. That was an important agreement. It will be, as I said, six months, followed by an open-label extension study, 78 weeks. Very important meeting with the FDA. Absolutely. Can you compare the design relative to Ascendis' phase III? What are the key differences that you would call out? Yeah. As I said, the good thing is, Ascendis opened the path with regulatory requirements, which was good, so we didn't need to recreate the wheel. We agreed on the main component of the design. As I said, the urine calcium will be a key differentiation. Yorvipath didn't have urine calcium in the key secondary endpoint. It was, in fact, a safety endpoint. Opposite to us, where we are planning its predefined, pre-specified endpoint, which usually how the FDA looks at this endpoint. If you pre-specify, they are more open to look at them and put them in the label if you get the results they are looking for. Got it. That's helpful. You know, turning to hypoparathyroidism in the market overall, curious where you see the unmet need. We see pretty high efficacy from Yorvipath, but maybe speak to sort of how you see the opportunity. Let's just start with the cause of disease here, PTH deficiency. The standard of care is quite antiquated, insufficient. It's pretty surprising that it's not hormone replacement. Probably the last major endocrine disease where the standard of care is not hormone replacement. But that's changing, which is really great news for patients with HP. We hear from patients that the standard of care, lot of pills, active vitamin D, calcium taken throughout the day for many patients throughout the night as well, very burdensome. But even if they manage to moderately control their serum calcium, they don't feel controlled or functioning well, and this is a hindrance in terms of brain fog, getting on with their daily life. They want a PTH replacement therapy, and the endocrinologists are supportive of that. We know that patients want to not have to think about their disease every day. What they tell us is a once weekly would be just a boon for them, so they can have freedom. And what underscored this was participating in the International Hypoparathyroidism Conference last fall. Sam and his colleagues presented our Avail phase II data. I think they were treated like royalty and there was just a lot of excitement. Can you elaborate on that? Yeah. We had a very, very positive feedback from the Hypoparathyroidism Association itself, but also patients and experts who were present, the endocrinologists who were present there. They see our program with weekly administration as compared to what's currently available or even with Yorvipath, as something really like a plus, a significant difference that can be offered to the patient. PTH replacement therapy by itself, it's a really great progress. From a medical standpoint, it's really a big difference with the standard of care. No question about this. Coming up with a weekly administration, I mean, we had patients there, and we had patients also coming to our company saying that they are taking up to 60 pills a day, including at night with alarm clock every 90 minutes. It's not a quality of life, right? Beyond the complication, beyond the CKD, etc. It's not the quality. Having something that they can take weekly, and they can forget about the disease the rest of the time could be a fantastic progress. If we get in addition and back to urine calcium, that means preventing the long-term complication through stone, etc., will be again something like an addition to the weekly. Building on that, when we conducted primary market research, interviewing endocrinologists and patients, uniformly, they said that once weekly would be their drug of choice versus a once daily. A vast majority, 80% of the endos, said they would switch their patients from a once daily to a once weekly. All the reasons Sam mentioned. Through those interviews, it came through that if we were to have urine calcium claims in our label, that would be transformative. Opportunity to increase switching, expand the market further. We do see in other indications when you transition from a daily to a weekly drug, you have a rapid adoption of the weekly and typically an expansion of the market and better clinical outcomes. Can you walk us through the data you've seen so far in phase II? You know, specifically an investor question that we get a lot is how do you compare the data versus the Ascendis data when we see such different responses in the placebo in your study versus Ascendis' phase II and phase III? Yeah. Let's start with the Avail. The study was divided in two parts. The first one, which was a double-blind, placebo-controlled 12-week study, at the end of which we looked at the response rate, and we got 63% response versus placebo, significant, statistically significant. 94% of the patients moved to the open label expansion, at the end of which, at six months, we got 79% response. Let me get back to this question about placebo, because we are not that different from Yorvipath. Yorvipath in the ITT, intent to treat population, got 27% placebo, and we had 31% placebo response. Similar. We also looked at our data. We looked at sensitivity analysis, what could have influenced, et cetera. We looked at the level of endogenous PTH, which could have influenced the results. For the phase III program, we have decided to stratify to make sure that this population with a little bit elevated PTH, but still sick population, right, are well distributed between the treatment arms and the placebo arm. Mm-hmm. It's notable that with Yorvipath, that placebo rate went down from phase II to phase III from 27% to 5%. It's just very hard for a patient with HP to get by without either standard of care or a PTH replacement therapy. Maybe they can get by four weeks, maybe 12 weeks, but at six months, very unlikely. We're confident that we'll see that trend as well. Very well powered to reach our primary endpoint, rest assured, in our phase III. Absolutely. Great. We have the one-year data just around the corner in Q2. Can you walk us through the additional data we could see and what your expectations are for what good data could look like here? We're going to provide an update on our Avail phase II in Q2 at a major medical meeting, and that will include one-year follow-up data. Sam, maybe you can share more. Sure in store. We'll be looking at the retention rate in the study, in the open label extension study at one year. We'll be looking at the response rate. We'll be looking at all biomarkers, the usual. We'll be looking at urine calcium, bone biomarker. We will also be releasing the BMD, the bone mineral density. I'm sure that following the good result and the good response we got on the bone, getting the bone back into the game, right? The bone turnover, and it translated by an increase in the two bone biomarkers, CTX and P1NP, catabolism and anabolism. Is it translated in BMD? What we would expect is to see a decrease in the BMD because it start. This patient population, this population start high in BMD. When decreasing, it will still be within the normal value of the BMD when you match this patient with other or with a population of the same age, same gender, same ethnicity, et cetera, when you compare apple to apple. That's what we would expect. We'll be looking also at safety and tolerability. A good time point to release a lot of data. Makes sense. Just in the interest of time, pivoting to obesity, where I think it's becoming increasingly a focus for your story. Starting with the GLP-1/GIP currently in the clinic, can you walk us through what you've seen so far pre-clinically, both from an efficacy as well as a tolerability perspective? Maybe I'll just start with a bit of perspective, having been in the obesity field myself for over 20 years and seeing the evolution from even questioning whether it was a disease or a lifestyle choice, and now to the point where we recognize it as the health issue of our time, a major market opportunity and huge unmet need where you're going to have a heterogeneous population with different therapeutic needs. There will be segmentation. It is our goal to be leaders in the obesity field, and I believe we bring the track record and the experience to do that. It's worth noting this Precision Endocrine Peptide, PEP, platform, the architect is Dr. Richard DiMarchi. It's hard to overstate his leadership in the peptide field, and particularly in obesity, where he was the inventor quite a few years ago in the first GLP-1/GIP co-agonist and first GLP-1/GIP glucagon triple agonist. We decided to apply our PEP platform first to GLP-1/GIP. These are the two proven mechanisms in the current market leader, Zepbound. We also realized that one limitation with the incretins, for all the weight lowering they have, is side effects, nausea, vomiting. This is chronic treatment for the rest of your life. Even if a drug causes you to lose weight, if you feel miserable on it, you're just not going to take it long term. We believe that by having the convenience of less frequent injections with patients, which patients routinely tell us they would like, and also better tolerability through the slower rise and steady exposure, we see differentiation. 4291 is, again, our first obesity asset. It's going to read out at 12-week in the target population of high BMI adults in Q4. We have a lot of confidence that we'll be able to see not only the monthly, but also better tolerability based on what we've seen, particularly in NHPs. Yeah, sure. I'm going to get back a little bit on how the drug was built with a prodrug and the fatty acylation. These two technology which have been applied to this product had the goal to really, as Kent referred to, have a slow rise to the Cmax and also a lack of fluctuation when reaching the steady state. That's the goal. Why? It's because it increase or improves the tolerability, decreases as opposed to, and the relationship has been made between the PK and the GI effect. That's the goal. We had a study in NHP. It was a tox study where we evaluated different doses of 4291. What we showed, it's exactly what we were expecting. Slow rise to the Cmax, lack of fluctuation. In fact, really nice steady state. Reproducing exactly the target product profile you were aiming for, but in non-human primate. In addition to this, we didn't observe. I mean, there was no GI effect. There was no vomiting. There was no diarrhea. This NHP lost almost 20% of weight. There was a weight loss around up to 20%, which was quite exceptional in this type of study. As we head into your initial data later this year, what are your expectations for what would be good data at 12 weeks on weight loss? We can talk about tolerability afterwards. I think clearly the objective is to show a monthly administration being translated in a PK which fits with the monthly. That's the objective. Kent referred to good tolerability. That's what you must have, which is a good tolerability in terms of lack of GI effects, the vomiting, nausea, diarrhea, et cetera. That really is the objective. It's a GLP-1/GIP co-agonist. You would expect to see something on the weight loss, which will be competitive with tirzepatide. That's what's the goal. Just to insist on monthly tolerability and competitiveness on weight loss. We know these mechanisms work, so given time, we fully expect to have exceptional weight loss. For this 12-week study, we really are emphasizing the monthly, which some in the field with adequate tolerability. This is I think the nut that the ultra-long acting or the monthly once monthlies have not cracked. With our unique prodrug slow release approach, we can. How do we compare the tolerability across studies? You wanna start with looking at the other monthlies, that's sort of apples to apples. In general, we believe that we should, you know, would look to see, as Sam alluded to, lower rates of the GI issues, that you would see with, for example, tirzepatide. Turning to your PBH program, can you give an overview of this program and the clinical timelines and data we can expect? In PBH, we are looking to serve the overall spectrum of disease and obesity, and we recognize that bariatric surgery remains an important treatment for patients who particularly are morbidly obese and need to lose, say, 40%, 50%, and this is a quick and durable way to go about that. Unfortunately, a subset of the patients undergoing bariatric surgery develop this chronic complication, post-bariatric hypoglycemia, that's quite debilitating to their standard of living, their quality of life, the fear factor of when these hypoglycemic episodes could occur day or night. Bringing a GLP-1 antagonist, in our case, imapextide, which is fatty acylated with a long half-life of 90 hours, to treat these patients is interesting to us, and we have a phase IIA POC study in PBH patients reading out next quarter. Sam, you wanna talk more about that? Sure. This phase IIA study is evaluating the pharmacodynamic effect, such as the glucose nadir. How low glucose can go and how much is it correlated with insulin level. For this, we have a study where we give mixed meal tolerance test, which is MMTT. We have a baseline time point. We have a single dose of imapextide, followed after washout period of a higher dose. That's what we want to evaluate is the increase in glucose nadir as compared to a decrease in insulin secretion. If we reach to these evaluations, after evaluation, we'll have reached a proof of concept, and we'll be moving to a phase II, and why not phase II, III. Great. How are you thinking about the competitive landscape? Really strong differentiation. There's clinical validation for this GLP-1 antagonism approach. The competitor is once daily with a very short-acting GLP-1 antagonist, has a half-life of two-three hours. We know from our primary market research, talking to endocrinologists and patients that once weekly matters to them. It's not only the convenience of once weekly, though. Again, it's important they wanna have freedom from their burden of disease. It's also ensuring that they have prevention, coverage, drug coverage on board and prevention of the hypoglycemic episodes nocturnally while they're asleep, when they're most vulnerable. We think a 90-hour half-life is important differentiation. Yeah, what we should think about is good data in the Q2. I'm waiting for the data and I think that they should be positive. I hope that they will be positive because in this population, there is a need for a medical treatment, so there is a strong need. Again, coming up later with a weekly administration with our half-life of 90 hours and what we expect a better coverage, especially at night. We hope that we are aiming for being even better. Got it. Helpful. Maybe just to close it out, in terms of hypoparathyroidism as we head into, you know, more details on the data, if you could give us any more color on kind of how your dose titration scheme compared to what Ascendis studied and how we should think about that as we interpret the data. You mean in the phase III? Yes. The phase III, as I said, following the agreement with the FDA, we have adjusted our study design according to the SPA, the Yorvipath SPA, the comments that the FDA made, especially on urine calcium. How to include the patient in such a way that the FDA would agree with the interpretation of the results, which was not the case for Yorvipath. It was not the case for Yorvipath. There was no agreement with the FDA. That will be very important for us. It was very important for us to match inclusion criteria and endpoint. When we will get the results, the response rates on the serum calcium and the composite endpoint, we have very similar composite endpoint. Again, key differentiation will be coming from the urine calcium. Great. Well, exciting year ahead with clinical readouts across all three programs, so appreciate you joining us today and sharing your insights. Thank you very much. Thank you.