Conference Transcript - MBX 2026-03-11

Ellie Murrow, Analyst — Barclays

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 Murrow, one of the biotech analysts here at Barclays. Joining us from MBX is Chief Executive Officer Kent Harluck, Chief Medical Officer Sam Azuli. 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.

P. Kent Hawryluk, CEO

Well, first of all, thank you, Ellie 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 and our STC 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 the drug exposure through slow release. And we're able to address that with the technologies we call PEP for short. And 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 two meeting with the FDA, and it's all systems go for our phase three starting in Q3 of this year. So excited to be a phase three stage company and to bring a best-in-class once-weekly PTH replacement therapy to patients with HP. Also, the significance is this validates our PEP platform that is also being applied in a very exciting field, obesity. So, we have an obesity portfolio that is expanding and advancing. It leads off with MBX 4291, which is a GLP-1 GIP coagonist pro-drug with, we believe, once monthly dosing and should have better tolerability through this PEP approach, slowly rising and steady drug exposure. And we have a 12-week multiple ascending dose readout in Q4, which we think is just a major catalyst for the company, and it will also support our overall obesity portfolio, which includes a amicretin, single peptide with incretin, as well as the amylin or Dacra mechanisms, and a single peptide, also once monthly, and potential better tolerability. And that candidate selection will be in Q2 of this year. We're a triple GLP-1 GIP glucagon agonist, development candidate in Q3, copy-paste, once-monthly, better tolerability. So we have cash to support all this, support our operations into 29, 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.

Ellie Murrow, Analyst — Barclays

Great. Maybe starting with the news this week, after you met with the FDA and aligned on a phase 3 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 3.

Sam Azoulay, Analyst — Other

Yeah, it was. 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. And very importantly, we agreed on the primary endpoint, which is a responder rate and the responder definition, which is a composite endpoint. So no surprise there, but it was good to validate this agreement. But 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. So that was an important agreement. So it will be, as I said, six months, followed by an open label extension study, 78 weeks. So very important meeting with the FDA.

Ellie Murrow, Analyst — Barclays

Absolutely. And can you compare the design relative to Ascendis's Phase 3? What are the key differences that you would call out?

Sam Azoulay, Analyst — Other

Yeah, as I said, the good thing is Ascendis opens a path with regulatory requirements. which was good, so we didn't need to recreate the wheel. So we agreed on the main component of the design. But as I said, the urine calcium will be a key differentiation. And Yorvipas didn't have the urine calcium in the key secondary endpoint. It was, in fact, a safety endpoint. And opposite to us, where we are planning its predefined endpoints, pre-specified endpoints, which usually is 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.

Ellie Murrow, Analyst — Barclays

Got it. That's helpful. So, you know, turning to hypoparathyroidism in the market overall, curious where you see the unmet need. We see pretty high efficacy from your Vipath, but maybe speak to sort of how you see the opportunity.

P. Kent Hawryluk, CEO

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, a 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. and they want a PTH replacement therapy and the endocrinologists are supportive of that. So 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 HypoPara International meeting last fall. Sam and his colleagues presented our avail phase two data. I think they were treated like royalty, and there was just a lot of excitement. Can you elaborate on that?

Sam Azoulay, Analyst — Other

Yeah, so we had a very, very positive feedback from the hypoparathy 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 your Vipass 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, but coming up with a weekly administration and patient can, I mean, we have patients And with patients also coming to our company, think that they are taking up to 60 pills a day, including at night with alarm clock every 90 minutes. So it's not the quality of life, right? Beyond the complication, beyond the CKD, et cetera. So having something that you can take weekly and they can forget about the disease the rest of the time. Could be a fantastic progress. And if we get in addition and back to urine calcium, so that means preventing the complication, long term of complications through stone, et cetera, will be, again, something like an addition to the weekly.

P. Kent Hawryluk, CEO

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. And 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. And 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. And 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.

Ellie Murrow, Analyst — Barclays

mm-hmm and can you walk us through the data you've seen so far in phase two and you know specifically an investor question that we get a lot is how do you compare the data versus the ascendance data when we see such different responses in the placebo in your study versus ascendances phase

Sam Azoulay, Analyst — Other

two and phase three so yeah so let's start with rapidly the first the study was divided in two parts the first one which was a double blind placebo control 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 extension, at the end of which, at six months, we got 79% response. So let me get back to this question about placebo, because we are not that different from ERV-PASS. The ovipath in the ITT, intent-to-treat population, got 27% placebo, and we had 31% placebo response. So, similar. So, we looked at also our data. We looked at sensitivity analysis, what could have influenced, et cetera. And we looked at the level of endogenous PTH, which could have influenced the results. And for the phase three 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.

P. Kent Hawryluk, CEO

Also, it's notable that with your V-Path, that placebo rate went down from the phase two to phase three 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. So we're confident that we'll see that trend as well, but very well-powered to reach our primary point, rest assured, in our phase three.

Ellie Murrow, Analyst — Barclays

Great. And so we have the one-year data just around the corner in 2Q. Can you walk us through the additional data we can see and what your expectations are for what good data could look like here?

P. Kent Hawryluk, CEO

We're going to provide an update on our avail phase 2 in Q2 at a major medical meeting, and that will include one-year follow-up data. Sam, maybe you can share more in store.

Sam Azoulay, Analyst — Other

So, yeah, so we'll look at, 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. You'll be looking at urine calcium, bone biomarker. But we will be also be releasing the BMD, the bone mineral density. I'm sure that following the good results and the good response we got on the bone, such as the bone back into the game, the turnover, the bone turnover, and translated by an increase in the two bone biomarkers, CPX and P1NP, catabolism and anabolism. How is it translated in BMD? So what we would expect is to see a decrease in the BMD, because this population starts high in BMD. But when decreasing, it will still be within the normal value of the BMD when you match this patient with a population of the same age, same gender, same ethnicity, et cetera, when you compare able to able. So that's what we would expect. We'll be looking also at safety and tolerability. So a good time point to release a lot of that.

Ellie Murrow, Analyst — Barclays

Makes sense. And 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 preclinically, both from an efficacy as well as a tolerability perspective?

P. Kent Hawryluk, CEO

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, major market opportunity, and huge unmet need where you're going to have a heterogeneous population with different therapeutic needs. So 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. We have, it's worth noting this Precision Endocrine Peptide PEP platform. The architect is Dr. Richard DeMarkey. 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 coagonist and first GLP-1 GIP glucagon triple agonist. And we decided to apply our PEP platform first to GLP-1 GIP. These are the two proven mechanisms in the current market leader, Zeppound. We also realize that one limitation with the Ingritins for all the weight lowering they have is side effects, nausea, vomiting. And, you know, this is chronic treatment for the rest of your life. And 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. So 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. And so 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. And 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.

Sam Azoulay, Analyst — Other

Yeah, sure. So I'm going to get back a little bit on how the drug was built with the ProDrag and the fatty acylation. And these two technologies which have been applied to this product had the goal to really, as Kent referred, to have a slow race to the C-max and also a lack of fluctuation when reaching the steady state. That's the goal. And why? It's because it increased or improved the tolerability, decreased, and the relationship has been made between the PK and the GI effect. So that's the goal. So we had a study in NHP, it was a tox study where we evaluated different doses of 4291, and what we showed, it's exactly what we were expecting. Slow raise to the Cmax, lack of fluctuation, in fact, really nice steady state, so 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, there was no vomiting, there was no diarrhea, and this NHP lost almost 20% of weight. So there was a weight loss around up to 20%, which was quite exceptional in this type of study.

Ellie Murrow, Analyst — Barclays

study. And so 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? And then we can talk about tolerability

Sam Azoulay, Analyst — Other

afterwards. So I think clearly the objective is to show a monthly, the 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 effect, the vomiting, nausea, diarrhea, etc. So that's really the objective. It's a GLP, a GIP co-organist, so you would expect to see something on the weight loss which will be competitive with So that's what's the goal. So just to insist on monthly tolerability and competitiveness on weight loss.

P. Kent Hawryluk, CEO

We know these mechanisms work. So given time, we fully expect to have exceptional weight loss. But this 12-week study, we really are emphasizing the monthly, which I'm going to feel with adequate tolerability. This is, I think, the nut that the ultra-long acting or the monthly, once monthlies have not cracked, but with our unique pro-drug slow-release approach, we can.

Ellie Murrow, Analyst — Barclays

How do we compare the tolerability across studies?

P. Kent Hawryluk, CEO

You want to start with looking at the other monthlies, that's sort of apples to apples. But in general, we believe that we should – we, you know, would look to see, as Sam alluded to, lower rates of the GI issues that you would see with, for example, trisepatide.

Ellie Murrow, Analyst — Barclays

Turning to your PBH program, can you give an overview of this program and the clinical timelines and data we can expect?

P. Kent Hawryluk, CEO

In PBH, we are looking to serve the overall spectrum of disease and obesity. 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. And unfortunately, a subset of the patients undergoing bariatric surgery developed 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. And so bringing a GLP-1 antagonist, in our case, imopexide, which is fatty-isolated, with a long half-life of 90 hours to treat these patients is interesting to us. And we have a phase 2A POC study in PBH patients reading out next quarter. Sam, you want to talk more about that?

Sam Azoulay, Analyst — Other

Sure. So this phase 2A study is evaluating the pharmacodynamic effects, such as the glucose nadia. how low glucose can go and how much is it correlated with insulin level. So for this, we have a study where we give mixed meal tolerance test, which is MMTT. So we have a baseline time point. We have a low dose of a single dose of MAPX died followed after washout period of higher dose. And that's what we want to evaluate is the increase in glucose nadir as compared to a decrease in insulin secretion. And that, if we reach to these evaluations, after evaluation, we'll have reached a proof of concept, and we'll be moving to a phase two, and why not phase two, three?

Ellie Murrow, Analyst — Barclays

Great. And how are you thinking about the competitive landscape?

P. Kent Hawryluk, CEO

Really strong differentiation. 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 to 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 want to 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. So we think a 90-hour half-life

Ellie Murrow, Analyst — Barclays

is important differentiation. Yeah, and what we should think about is good data in the second

Sam Azoulay, Analyst — Other

quarter? So I'm waiting for their data and I think that they should be positive. I hope that they will be positive because in these populations there is a need for a medical treatment. So there is a strong need. But again, coming up later with a weekly administration with our half-life of 90 hours, and what we expect better coverage, especially at night. So we hope that we are aiming for being even better.

Ellie Murrow, Analyst — Barclays

Maybe just to close it out in terms of hypoparathyroidism as we head into 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

Sam Azoulay, Analyst — Other

the phase three? Yes. So the phase three as I said following the agreement with the FDA we have adjusted up our study design according to the SBA the comments that the FDA made especially on urine calcium and so 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 YordiPath. It was not, there was no agreement with the FDA. So that would be very important for us. It was very important for us to match inclusion criteria and endpoints. So when we get the results, the response rate on the serum calcium and the composite endpoint, we have very similar composite endpoint. But again, key differentiation will be coming from the urine calcium.

Ellie Murrow, Analyst — Barclays

Great. Well, exciting year ahead with clinical readouts across all three programs. So appreciate you joining us today and sharing your insights.

P. Kent Hawryluk, CEO

Thank you very much.