MBX Biosciences, Inc. (MBX) Earnings Call Transcript & Summary

Thank you. Okay, great. Good morning, everyone. Welcome to day 3. We've been saving the best for last here at the Morgan Stanley Conference. I'm Jason Russell, and it's a pleasure to welcome MBX Biosciences to the stage. So, CEO Steven Hoerter, as well as Dr. Salomon Azoulay, who is the Chief Medical Officer. It's MBX Biosciences' first time here at the Morgan Stanley Conference. It's a pleasure to have them with us. Just as a quick overlay for those that don't know, MBX Biosciences is developing long-acting precision peptide therapeutics. Their lead in the clinic, `Canvuparatide`, now I think officially started in Phase 3. That's right, for chronic hypoparathyroidism. And a very exciting `MBX4291` potential, a true once-monthly GLP-1 GIP pro-drug for obesity, with I think some data expected later this year. Welcome. Thank you for being here. Maybe we'll start with some high-level perspective. And Steve, you took the CEO job recently, stepped in from the board 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 `Desferal` 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?

Yes, thanks again for the invitation. It's been a really transformative year for the company in 2026. And just to set the stage, Jason, and by the way, thanks for the invitation to join for the conference. We will 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 2 `AVAL` study of `Canvuparatide` in chronic HP, demonstrating sustained clinical benefit for this once-weekly injectable, this once-weekly PTH replacement therapy. And as you referenced, we've now moved into a pivotal Phase 3 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 3 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. There's a daily injectable that's on the market which has reported now a billion dollar run rate in revenue, and 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 it's an exciting, 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 1 study of `MBX4291`. And this is a true once-monthly GLP-1 GIP co-agonist that we're exploring obviously for the treatment of obesity. The 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 pro-drug technology, which delivers not only infusion-like PK, but allows us to control the release of active peptides, so 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's to come in the next 12 to 18 months, it's 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. And then as it relates to `MBX4291`, it's 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. And I think if we're able to achieve that, you know, 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's great. We're going to peel the onion back on all of that. It's an incredibly exciting time to be joining the company in operating capacity. Let's step back and just talk about the foundational capabilities for a minute. So when the company went public a number of years ago, obesity was kind of out there as a dream at that point, and now is very much in front of us. But it all comes back to this kind of foundational capabilities capability on PEPs or precision endocrine peptides. And so maybe just give us a little bit of perspective around what the unique capabilities are for MBX Biosciences, you know, maybe some history around how that came together.

Sure. So the company was founded in 2018 by Richard DeMarchi, our scientific co-founder, and by Kent Harlow. And Richard is a thought leader in the field of peptide chemistry. He's 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. And so his insights into and the work that he's done over the years, I think on about 100 patents, is published over 300 times in the peer-reviewed literature. And his work at Lilly, for example, was instrumental in the first rapid-acting insulin at Lilly, `Forteo`, other innovations. And his work on peptides generally has really formed the foundation for the now multi-agonist approach with peptides like `Liraglutide`, at least, `Tirzepatide`, and he's been really sort of the father of the field, if you will. And so his work and his founding at MBX Biosciences scientifically really centered on three pillars as it relates to peptides. So 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. And then the third and probably most important is the pro-drug technology. And so this allows us to deliver a very simplistic pro-drug in a way to patients that then regulates the release of active peptide. So as you think back to whether it's `Canvuparatide` in the case of HP or very importantly `MBX4291`, the co-agonist for obesity, we're able to engineer a rate of release for the active peptide that then delivers, we believe, a differentiated PD profile. And that's what's so exciting about the PEP platform and the work that Richard has done that's really instrumental and ingrained in all of the clinical programs that we have.

Yes, that's exciting. I mean, obviously anyone who's following either the endocrinopathies or obesity understands the importance of why that profile might have significant lag. So maybe, and to dive into the portfolio a bit, and Sam, maybe I'll direct this to you, let's start with `Canvu`. It's the latest stage, it's exciting, it just entered Phase 3. Let's go back to the Phase 2 data. You had the initial Phase 2 `AVAL` data, you put out earlier this year the one-year extension data, I believe in June. What are the 2 or 3, I don't want to limit you, if there are 10 you can give me those, 2 or 3 most exciting things that you saw in that data set that really gave you the conviction to push aggressively into Phase 3? Yes, thank you.

Thank you. What's very exciting is when you get the results you are expecting. And when we started this study, it was a double-blind placebo control, et cetera. It was initially 12 weeks. And we showed exactly what we were expecting in terms of responder rate. And the response rate was based on serum calcium. And we confirmed this result at 6 months, and as you said, we confirmed also this result at 1 year. And it's 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. And 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 stones. They get CKD, chronic kidney disease, right? And 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. It should release calcium. When we released the 1-year data, we confirmed the effect on urine calcium excretion. So we saw benefit. And on bone, we saw that the bone biomarkers were high, but started to plateau. And the BMD, as a consequence, we were exactly where we wanted to be, slight reduction, but within the normal value. So I would say that after 1 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 kind of 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, you know, survey work with patient groups, you know, what are the things that in a real-world setting are going to be most impactful and that you're, you know, hoping to pull out of the pivotal data set?

Yes, so 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. And what became very clear in the market research is that physicians and patients both prefer the profile of `Canvuparatide` based solely on convenience. So 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. So 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 would be PTH replacement therapy naive, and that physicians would also switch patients. So 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. So that was all very encouraging to hear from the blinded research, and maybe Sam, what we hear anecdotally from physicians and investigators.

Yes, those are very, very encouraged by seeing that the weekly is coming. And so that we will be having a weekly administration as compared to the heavy, very heavy administration of calcium supplement, vitamin D, etc. They have today a daily product, but I don't think that it's a full story. They need really the weekly administration. And we go to the Hypopara Association, we go to investor meeting which we held 2 weeks ago, and there is a strong, 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. And we are so confident in this endpoint that it will be one of the key components, a key secondary endpoint in our Phase 3 program that we would like to, we are aiming to demonstrate the benefit in patient during calcium, and we target this population because they're the ones that need the improvement, right, if you start with normal, but that needs improvement. And we will have 2 types of populations, 2 parameters, which is first one, normalization of urine calcium and normalization at the same time of serum calcium.

And maybe just to tie it back to the PEP platform, I mean, so obviously, reasonably obvious, a weekly is much preferred if similar FC tolerability to it to a daily. Is there a presumption that there's a lifecycle management play to go to a monthly, or is there a limit? And I'm just thinking, you know, is that something that might be possible under the platform?

You know, I think, suffice it to say, there are a variety of, I think, options that we have from an LCM perspective. You know, I think what we've heard from the prescriber community and from patients is that this level of innovation with `Canvu`, 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 3 enrolled and such, and driving that to make it available to patients who need it.

I like also to come back to the PK. I mean, the PK for this product is so important, right? That based to our platform. And what we showed in the patient population, our PK showed that the peak to trough, the peak concentration of the peak as compared to the trough was 1.3. And when you compare this with the daily, it's 1.3 to 1.6, but on a daily basis and our 1.3 it's on the weekly basis. And why is it important is because it's correlated to maintaining the serum calcium within the normal value of a time.

Yes, that all makes sense and resonates. Maybe to the Phase 3, so Optimize, I believe, is the name of the protocol. You announced on August 27th that you've dosed a patient. Give us some perspective around anticipation around enrollment, cadence, you know, site activation. Is there any guidance on expectation around the timing for that data, or too early?

So 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's in the U.S. where a daily injectable is available, but nonetheless there's considerable enthusiasm for participating in the study. And we're now, I think, per clinicaltrials.gov, up to something in the range of 12 sites open for the study. We'll of course continue to open sites at a rapid pace for that study. And what we've said, Jason, is that we think it's reasonable to expect that we'll get to full enrollment in the study by second half of next year, so in the second half of next year. And so we're excited to be underway with the protocol and to get patients on study, and we're off on our way. Okay, cool.

Great. Well, obviously that's going to take some time. It's something that is going to play out over the course of the next 2, 2.5 years, but you've got something right in front of you, which I know people are very focused on as well. So let's switch gears from the rare endocrine side to the obesity side. You gave us some setup at the beginning around the thought process around `MBX4291`. I think the investor community saw your blinded data back in the spring. You know, maybe the first question is, you know, what do you think you learned on the PK profile in those data that you shared with the market and kind of how did that establish the confidence level for what we're running into here towards the end of the year?

Yes, this is a good question. So through the PEP platform, we already designed the target product profile without even knowing the results, right? From a PK standpoint. And 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. And you see it very well with `Tirzepatide`, [indiscernible], Compound `907i`. So you see it. So here from the target product profile, where we want it is a slow raise to the TMAX or to the CMAX and stay as low as possible at this level, right, and show a time to have the CMAX as long as possible. That was our target. And when we released in May last year, the obesity day, it was amazing to see how our PK in healthy, I mean patients with BMI above 30, otherwise healthy. But if you look at our PK, that's exactly what we saw. We saw slow raise to the CMAX, especially after the multiple administration. And then the time to halve the CMAX was 26 days when [indiscernible], the `Meta-907i` is showing 20 to 21 days. And a flat, relatively flat concentration, sustained concentration at the CMAX and slow. So the PK profile we got in this population was exactly aligned with the TPP, which was a consequence of the platform. So very, very nicely. So the beauty of this is that we have a very, concentration slow raise it's related to one thing, the slow raise is related to accumulation of the drug, slow accumulation of the drug, that leads to a slow raise, no burst effect at all. What the consequence is that we didn't get that many adverse events related to GI. And especially at the dose we presented the drug doses, those regimens, which was 30 milligrams 4 times weekly, followed by 120 milligrams monthly, we got only 1 episode of diarrhea, and that was really aligned with what we were aiming for.

To the accumulation phase and the comments. So just to think about the design here of both the Phase 1 and then thinking forward. So there's an induction phase at a weekly basis until you get to certain levels and then switch to monthly. Is that what we're is that the design for is that what we see? Is it 4 weeks and then 2 monthly doses? And that's kind of how the design will, the data.