MBX Biosciences, Inc. (MBX) September 2026 Conference Transcript

Okay, great. Good morning, everyone. Welcome to day three. We're saving the best for last here at the Morgan Stanley Conference. I'm Jason Russell, and it's a pleasure to welcome MBX to the stage, so CEO Steve Herter, as well as Dr. Sam Azoulay, who is the chief medical officer. MBX's first time here at the Morgan Stanley Conference. We're pumped to have them with us. Just as a quick overlay for those that don't know, MDX is developing long-acting precision peptide therapeutics, lead in the clinic, late-stage cambuparatide, now I think officially started in Phase III for chronic hypoparathyroidism, and a very exciting MBX 4291 potential true once-monthly GLIP-GIP pro-drug for obesity with, I think, some data expected later this year. So, 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 Desfera 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. And just to set the stage, Jason, and by the way, thanks for the invitation to join for the conference. And we'll talk about this, I'm sure, during the course of our morning together, or a time together this morning, but we reported earlier this year 12-month open-label extension data from the Phase II avail study of canviparatide and 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 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 three 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 is reported now a billion-dollar run rate in revenue, and we believe that our once-weekly Canva Paratide 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 Canva Paratide 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 Canva Paratide. 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 one 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 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 cambuparatide 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 MBX 4291, 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 is a fundamental, 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, incredibly exciting time to be joining the company in an 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 it's very much in front of us. But it all comes back to this kind of foundational 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, you know, maybe some history around how that came together.

Sure. So the company was founded in 2018 by Richard DeMarkey, our scientific co-founder, and by Kent Harlick. 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 the work that he's done over the years, he's a co-inventor, I think, on about 100 patents, has 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 Lily's trisepatide. And he's been really sort of the father of the field, if you will. And so his work and his founding at MBX 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 prodrug technology. And so this allows us to deliver a very simplistic prodrug, 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 coagonist 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.

Yeah, that's exciting. I mean, obviously, anyone who's following either the endocrine phase 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's just entered Phase 3. let's go back to the Phase 2 data. You had the initial Phase 2 avail data. You put out earlier this year the one-year extension data, I believe in June. What are the two or three, I don't want to limit you, if there are ten 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 3?

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, etc. 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 six months, and as you said, we confirmed also this result at one 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 stone. 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. and released calcium. When we released the one-year data, we confirmed the effect on urine calcium excretion, so we saw benefits, and 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. So I would say that after So one year, we confirmed the total package of the PTH replacements 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?

Yeah, 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 cambuparatide, 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 cambuparatide, the majority of patients on cambuparatide who were PTH replacement therapy naive, and that physicians would also switch patients. So it was a high indication of a desire to switch patients 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, you can comment on what we hear anecdotally from physicians and investigators.

Yeah, so they are very, very encouraged by seeing that the weekly is coming and so that we will be having weekly administration as compared to the heavy, very heavy administration of calcium supplements, vitamin D, et cetera. They have today a daily product, but I don't think it's a full story. They need really the weekly administration. And we go to the Hypopar Association. We go to the investor meeting which we held two 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, the 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 III program that we would like to, we are aiming to demonstrate the benefits in patients with elevated urine calcium. and we target this population because they're the ones that need the improvement if you start with normal but that needs improvement and we will have two 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 a daily. Is there a presumption that there's a life cycle 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 Canvoo 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 three 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's based to our platform. And what we showed in the patient population, our POP-PK showed that the peak to trough, the concentration of the peak as compared to the trough, was 1.3. And when you compare this with a daily, it's 1.3 to 1.6, but on a daily basis. And on 1.3, it's on a weekly basis. And why is it important? It's because it's correlated to maintaining the serum calcium within the normal value of a time.

Yeah, no, 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, great. Well, obviously, that's going to take some time. It's something that is going to play out here over the course of the next two, two and a half 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 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, and how did that establish the confidence level for what we're running into here towards the end of the year?

Yeah, this is a good question. So through the PET 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 part to the burst effect, right? And you see it very well with tears, hepatitis, Medsera, CompatMET 907I. So you see it. So here, from a target product profile, what we wanted is a slow raise to the T-Max or to the C-Max and stay as long as possible at this level, right, and show a time to have the C-Max 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 have the CMAX was 26 days when MET-SERA, the MET-907I, is showing 20 to 21 days, and a relatively flat concentration, sustained concentration at the C-max and slowly going down. So the PK profile we got in this population was exactly aligned with the TPP, which was a consequence of the PEP platform. So very, very nicely. So the beauty of this concentration slow raise, it's related to one thing. The slow raise is related to the accumulation of the drug, slow accumulation of the drug that leads to a slow raise, no burst effect at all. What's the consequence is that we didn't get that many adverse events related to GI. And especially at the dose we presented, the doses, Those regimens, which was 30 milligrams four times weekly, followed by 120 milligrams 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, so just to think about the design here of both the phase one 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 the design for, is that what we see? Is it four weeks and then two monthly doses? And that's kind of how the data we'll see later this year.

So you're absolutely right. The cohort we disclosed, the 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 comments, is related also to most self-titration. The patient self-titrates, it's not really self-titration in terms of increasing the dose, but self-titration of the patient and like a desantitization, desantitization of the receptor for GI effect, GLP-1 receptor. So that's really a nice thing. Back to your question about what's the next step, the C1 cohort, that C1 will be disclosed by the fourth quarter of this year, will be the same starting doses, 30 milligrams four times every week, and followed by 120 milligrams monthly, followed by 180 milligrams monthly.

With the expectation that the 180, you know, I guess we'll learn. How many patients are we going to see? How many are? It's just two arms, but, you know, maybe.

So the C1 cohort will have 30 patients, 20, 10, 20 treated, 10 randomized as compared to our B1 cohort, which had eight patients, six, two. And as a reminder, when we disclosed the B1 cohort, it was still blinded. So we're still, as of today, we haven't unblinded the study. Okay, so 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, you know, help us, you know, 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, you know, how do you see it? How do you think investors should position as they look forward to that data?

So I think there are really three, as you mentioned, Jason, kind of three pillars to the desired TPP and what we hope to show in Part C of the study is competitive weight lowering. We think based at 12 weeks.

How do you define that?

So we think based on the data, that's probably something in the range of 6 to 8 percent 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. And then the third component is the potential to demonstrate improved tolerability based on the PK profile and avoiding the burst effect, as Sam 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, what, two days ago that Novo has discontinued the collaboration with Ascendis as it relates to using that older PEG technology to get to extended duration, which I think is notable. And then on the other hand, we see Pfizer with Metzera's 097I trying to cover all bases by conducting both weekly studies, weekly administration studies, in addition to monthly. So our view is that this potential for a true ultra-long acting once monthly, that field to us continues to be wide open. And so 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. And 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. So we couldn't be more excited about the program and the potential to deliver on those three pillars. Okay.

So Q4, you've made that very clear.

I'm not going to 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 thanks Jason and format of that disclosure that's a press release and a call presumably or I'm sure we'll do a call we'll want to make sure 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.

That's your only obesity program? No. You've got some additional levers coming along the way. Talk to me about 5765 and 6180, you know, both what are they, you know, timing into the clinic. Maybe we'll start there and I'll have a follow-up.

Sure. So we've disclosed now two development candidates that we have that are both in IND-enabling studies. So 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 emicrotin or multi-agonist that we disclosed at our obesity day. So that is moving forward toward the clinic. And then our second disclosure on our most recent quarterly financial results was related to our Triple G. And so this is a potential once-monthly Triple G that we've 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 to 18 months, and we expect that we'll be on that sort of timeline. So there's 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 Canva Paratide, but in the early blinded data from 4291 showing true once-monthly PK, showing this slow rise to CMAX. and so our focus and goal now is to apply that same platform technology to other targets of interest in obesity, and that's exactly what you've seen us do this year, and I'm sure we'll 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 4291. So we have the data later this year, or how should we think about the next steps on the other side of that without getting out in front of what you'll ultimately say, but is this a traditional path that we've seen across the obesity landscape where we're 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 one program is to get to the right dose and schedule, right? It's really important, obviously, I think in a phase one setting to understand the right dose and schedule to get to a profile that delivers on the TPP that we think will be a winning TPP. So that's not to say that we may not choose to move into a phase two program as a next step, but yet we think doing the work early to understand dose and schedule is really important for obvious reasons. So, you know, 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. So we're continuing our work to understand dose and schedule. But 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, you know, color around how we think about next clinical development steps and where we're headed with 4291. Okay, great. We look forward to that.

Here, just to wrap up here, a couple more minutes. So 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, you know, 12 months from now, 18 months from now. You know, what do you reinforce for us? What do you hope investors will have taken away that you've accomplished in the seat? And, you know, 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, you know, on the one hand, we have Kanbu Paratide, which is going to be entering this multibillion-dollar market, and our goal in the next 12 to 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 Kanbu side of the house. And then for the obesity portfolio, this is about getting to clinical data with 4291, that shows in a clear manner that we have the potential to achieve that TPP that we talked about. So that will include the Q4 disclosure, and I'm sure by the time we get to the end of next year, we'll be well on our way to the next steps in terms of clinical development for 4291, all while we advance the balance of the earlier portfolio. So by the time we get to next year, the end of next year, we think we're going to be a fundamentally different company even from where we are today with a fully enrolled registration-directed study for CanVu and a lot of progress on the obesity portfolio. So Sam and I and the rest of the team are really excited to find ourselves in that place in 2027.

Yeah, it's an exciting time. So I think we'll wrap it there, Steve. Sam, thank you both for being with us. And good luck here over the coming months.

Great, too. Thank you, Jason.