MBX Biosciences, Inc. (MBX) November 10, 2026 Conference Transcript

All right. Well, welcome, everybody, and thanks for joining us here at Guggenheim's Healthcare Innovation Conference. I'm Seamus Fernandez, one of the Senior Biopharma Analysts here at Guggenheim, and I'm really pleased to be joined again this year by MBX Biosciences. To my immediate left is CEO Steve Hoarder. To his left is Sam Azoulay, Chief Medical Officer. And to Sam's left is John Smither, CFO. So, you know, maybe just to level set the playing field, thanks for joining us, of course. But Steve, you stepped into this CEO role in July after serving as Executive Chairman. And maybe just talk about where MBX is today, your, you know, top priorities for the company, and, you know, the next phase as, you know, both a late-stage rare endocrine drug company, but also a company with potential best-in-class long-acting obesity assets in the portfolio.

Yeah, thanks, Seamus, and thanks for the invitation to join the conference this year. It's always a great conference. And Sam and John and I and the rest of the team are really delighted to be here. And it's been a transformational year for MBX. So if you think back to the summertime, we had the one-year, the 12-month open-label extension data for Canvu Paratide from the Phase II AVAIL study demonstrating sustained clinical benefit for Canvu in patients with chronic hypoparathyroidism. And now, as we are in Q4, we've started the phase three study of Canvu Paratide in chronic HP. We're really excited about physician receptivity to that study and patient enthusiasm, and we're on our way to the potential to become a commercial stage company. So we're really excited on the Canvu front of where we are with this potential best-in-class therapy for patients. And then earlier in the summer, back in May, as you'll remember, we reported early blinded data from the Phase I study of MBX-4291, and this is our long-acting coagonist, GLP-1-GIP coagonist, for the treatment of obesity, again, leveraging the platform technology that we've built that's part of MBX, the same pro-drug technology that we use in Canva Paratide, for example. And in those early data, we were really excited about what we saw, even though blinded data, relatively small n. And so now as we, you know, fast forward, we'll talk about the balance of the year here in a second, but we're excited about the progress we're making with 4291 and the potential for that to really be fundamentally game-changing in the field of obesity. So, you know, I think in terms of the priorities that we have for this year, it's really about continuing to execute on enrollment in the Phase III canviparatide study in HP, while we also advance the rest of the obesity portfolio, including 4291.

Great. So... At your obesity day, the, you know, you shared this initial blinded phase one data for 42.91, you know, maybe just the key takeaways that you would encourage folks to really key into that informed, you know, views on weight loss and tolerability and what you really kind of see as the target product profile for that asset.

Yeah, thank you, Seamus. Yeah, so let's start with just reminding, a reminder about the dose that was a dose titration, right? It was an eight-week period during which a patient were exposed to 30 milligram weekly for four weeks, followed by 120 milligram. So, I'm going to start with the PK, which is probably the most important learning because it's directly related to the platform, the PEP platform. So, if you look at the curve, the concentration of the active MBX 4291, you have a slow race, smooth race to the C-max, right? And we know that this race, most of the case, with other product, create a burst, and the burst is related to the GI intolerability. So here it's a smooth. Then the concentration is sustained and with time to halve the C-Max of 26 days as compared to Medsera, which was 21 days. So here you have a really already a confirmation for the monthly administration, right? So now looking at the weight loss, it was blinded, still blinded, and we had 7% weight loss at eight weeks. Again, with a range from zero to 16%. And if you look at the tolerability, again, excellent tolerability profile with this limited number of subjects, but nevertheless, we had only one episode of diarrhea. So back to the PK curve, how to explain this good tolerability also is the way, the race to the Cmax, right? The sustainability with a lack of fluctuation, and that explains why we got this tolerability. So good learning from this initial dose regimen. Perfect.

And, you know, Steve, maybe you can talk about the upcoming data and what you see as kind of the target product profile. And maybe following on to that, Sam, do you believe cohort one is sufficient to kind of predict an ability to move forward with confidence into phase two?

Yeah, so the milestone coming up for 4291 is, you're exactly right, is the unblinding of the study, and specifically with a focus on cohort C1. And Sam just described the dose and schedule from B1 that we had as blinded data at the Obesity Day event back in May. And the schedule, the dose and schedule for this cohort C1 is 30 milligrams once weekly times four, followed by a monthly dose of 120, followed by another monthly dose of 180 milligrams. And so the TPP that we're trying to achieve is competitive weight lowering, and when you look into the landscape at whether it's terzepatide or SEMA or Barrow from Pfizer, what you see is a 6% to 8% weight loss at that 12-week time point. So we aim to be competitive with that. The second part of the TPP is around having a true once monthly, and we think this is now fundamentally differentiating, even based on the data we showed, the PK data we showed back in May. There just are no other coagonists or monoagonists that offer true once-monthly dosing. So that's the second pillar of the TPP. And then the third, as Sam described, based on the PK profile and this slow rise to Cmax, is to differentiate based on tolerability. And we can talk about, you know, relevant measures of that, Seamus. Vomiting is probably the easiest one. So GI intolerance generally, but vomiting specifically. And when you look at trisepatide data, phase three data, what you see, depending on dose and depending on study, is a range of anywhere from 8% rate of vomiting with low-dose trisepatide up to 18% rate of vomiting. So we think we have the potential to improve upon that based on the differentiated PK profile. Great.

And Sam, just following on to what this is going to help predict, do you need C1 to be able to advance as well? Or is B1, from your perspective, enough to really predict an ability to move forward into phase two?

C1 is a continuum of B1, right? It's a longer period with an additional monthly dose of 180 milligram, larger population exposed to the drug. So learning will be coming from C1. But really, when you want to move a program forward, you look at the totality of evidence, everything which will have generated in this phase one to a study that will help us moving the program forward. Okay. Got it.

And, you know... I think if we were to say the competitive weight loss profile at 12 weeks, obviously, is a key point. But you've stated kind of 6% to 8% is the competitive range. Is that, you know, rather than kind of get confused, I think we've already seen in the blinded weight loss data 7% at 8 weeks. I don't want to confuse people and think that that's kind of a reversion with the next dose. So how should we think about the data itself and your kind of positioning of that 6% to 8% as part of the discussion?

Yeah, it's a good question, Seamus. So you're right. When we had the disclosure of blinded data, we showed 7%. That was an N of 8, 6 on active, 2 on placebo. So very encouraging weight-lowering, especially at the 8-week time point. What we don't yet know, but I think the further data that, once we unblind and disclose, may help us to better understand is whether the unique PK profile of MBX 4291 translates into a differentiated PD profile. As you know, we get an infusion-like exposure with 4291 over the month period. When you look at the PK for the weeklies, you know, it's, as you'd expect, it's intermittent peaks and troughs over a weekly basis. So we get very good coverage, very good exposure with 42-91. So there at least is the potential for that to translate into differentiated efficacy and weight lowering. But nonetheless, what's still relevant is the competitive set. And the competitive set data is very clear at 6% to 8% when you look across SEMA, Trisepatide, 097i. And we think delivering on that would be an important component of our TPP, despite the fact that we might have the potential to do better than what's seen in the competitive set. But clearly, the benchmark is the competitive set weight lowering.

What you're communicating is, don't get over your skis. These data could be, you know, potentially better than expected, but the best point to focus on is, even if it were better than expected, phase threes kind of can dial back at the same time. Phase twos can dial back. This is still early exploration.

It's certainly still early, and I think the competitive set weight lowering is the relative and important, relevant, I should say, relevant benchmark for what we need to deliver. So, you know, as we've talked about, it's an N of 8 from May, which was early. We'll have a total of 30 subjects from cohort C1, 20 on active, 10 on placebo. So still relatively small numbers, but we believe it will be adequate for us to really understand the profile of 4291 and the potential for us to achieve that TPP that we just talked about. Great.

Perfect. And, you know, in terms of what will be sort of revealed in the fourth quarter, will that include B1 only, or should we expect it to include C1?

So the disclosure is absolutely the C1 cohort from Part C of the study. And we haven't talked yet about exactly the contours of the disclosure. But our goal here is to have adequate data and to share an adequate level of information with key stakeholders, with investors, so that we understand the profile of 4291. And I think Sam's going to be in a position at that time to also talk about how we're thinking about the next step in the development process for 4291. The team is very actively working, planning for success on getting ready to launch a phase two study next year. But we'll have more that we can share about that and our thinking when we get to the data disclosure.

Great. And any additional learnings from the C2 cohort in particular, other than replication?

Yeah, we disclosed that C2 existed, if you will, back in May. So that was when we talked about both C1 and C2. These are cohorts that have not been enrolling exactly concurrently. But nonetheless, I think the totality of the data from the study will be important for us as we think about the profile and as we think about the dose and schedule or doses and schedules that we might take into a phase two.

Great. And strategic path for the obesity franchise, you know, whether go it alone, partnership, how are you thinking about just the most reasonable time to consider, you know, whether it's potential partners or the aggressiveness to move forward?

Yeah, this, as you know, is now the world's largest pharmaceutical market. So we believe that we'll need to access someone else's balance sheet capabilities, if you will, to recognize full value for a drug like 4291. So we think getting to achieving clear evidence of differentiation is the important next step, whether that's from this Phase I, II study or a larger Phase II study. That will be, I think, necessary for us then to unlock potential for a future partnership to then fully maximize value.

And, you know, Steve, one of the things that I think is interesting is you've already got a preclinical profile for a redditrutide-like molecule utilizing the PEP platform and the prodrug. Can you just, you know, it's hard to sort of automatically say that something like that translates, but what did we learn from, or there's abstract data so far, not the full poster, so I don't want to, you know. Skate to the puck a little too soon. But how does that sort of translate for the platform, what you've seen so far pre-clinically, and your enthusiasm for the platform going forward?

Well, we now have very clear and convincing evidence that the platform can be leveraged to design peptides with a unique PK profile. So, you know, the pro-drug technology is now validated clinically with CanVu. We have the early blinded data from 4291, which adds further validation. We'll get to our unblind here in the quarter to add yet more data. And so now the task ahead for us is, you know, not to say that it's easy, but it's straightforward. Our goal is to apply the platform to other validated targets in obesity where we can create value and meet unmet needs. And so the Triple G is a great example of that. You know, as you alluded to when we disclosed our Q3 financial results yesterday, we also announced that we'll have preclinical data from 6180 at Obesity Week here coming up shortly. So we've applied the same project technology with the goal of getting to a once-monthly Triple G, also avoiding the burst effect. So all of the hallmarks of our platform, we'll do that with a Triple G. We have the potential to do that with our multi-agonist, where we look at a GGG construct together with a DACRA and other validated targets in obesity, with the goal then of building out a robust obesity portfolio that is fundamentally differentiated.

Great. And, you know, Sam, when you look at just sort of the data so far, how reliable and repeatable do you think the PEP platform is at this point?

Well, when we look back at Convu Paratide, we had already demonstrated in phase two. Now we are in phase three. So we have good arguments that Convu Paratide was behaving like a PTH replacement therapy. So we can say that the platform was translated into a good product from an efficacy and safety standpoint. And when we look at 4291, when we saw with the B1 cohort, it's already a good sign that we have something that would work beyond even these two assets. And the GGG, what we used to call amicretin, or the DACRA GGG, is also a good example where we can go.

Great.

Let's talk about campiparatide. Once weekly PTH replacement therapy for chronic hypoparathyroidism, the unmet need as you see it, what's kind of the unlock opportunity? with a weekly replacement therapy, and what do you think the addressable market is?

So this is a market where there remains clear unmet need. We have a competitor that was approved by the FDA in December of 2024. It has reported now six quarters of launch and is already on a $1.2 billion run rate in terms of revenue, which clearly validates the size of the opportunity in the U.S. for chronic HP. And for us, you know, we anchor to the extensive market research that we've done with both patients and physicians who tell us that the idea of having a once-weekly injectable instead of a once-daily injectable is incredibly attractive. So patients tell us that they would prefer a weekly over that daily, and we have the potential, we think, to compete not only for newly diagnosed patients, you know, upon a future approval, but also to switch patients from a daily injectable over to a once weekly. So it's a fairly straightforward commercial story. You know, as Sam commented earlier, the data from Avail is clear. The open label extension data at one year shows sustained benefit. So this is now just about the confirmatory execution of the Phase III study to deliver CANVU to patients who seem to prefer that profile. So we're really excited about this, and we think it's ideally suited to a company of our size in terms of being able to commercialize this on our own, most certainly in the U.S. and potentially even outside of the U.S.

Yeah. And, you know, in terms of just the what questions do you feel need to be answered in the phase three, in particular, will it be whether it be relative to avail or relative to the competitor? You know, and honestly, what do you think is the gap between sort of investor valuing this opportunity appropriately? We kind of feel like there's almost an order of magnitude difference between how we're thinking about it and maybe how you're thinking about it and where investors are.

Yeah, so maybe, Sam, you want to take the first part of that, and then I'll take the second.

Yeah, so the phase three, in my view, it's a confirmatory trial. So that we want to see what we observed with the phase two EVAL study. And we, it was longer exposure, six months exposure, placebo control, et cetera. I mean, but really we are going to look at the response rate, the classical response rate. But there is another key secondary end point that would be a key factor for differentiation, which would be urine calcium. And urine calcium is key in this disease because that's creating CKD. That's the cause of CKD. And through the stone, et cetera, stone formation. So, if you reduce, urine improves, urine calcium excretion, you reduce the long-term chronic kidney disease. So, that will be a key factor of differentiation in our phase three. We are confident from what we saw in phase two that we can get there.

And then in terms of, you know, how the street, you know, might view the opportunity, you know, this is for us very, very clear in terms of the magnitude of the opportunity. I referenced earlier the competitor daily injectable and how that launch has gone, which has been super well, validates the market opportunity for us. And, you know, we view Canva Paratide as having best-in-class potential based on its profile, based on the market research that we've done. So I do think it, you know, it seems to be underappreciated by investors, the value that can be created with Canva Paratide on its own.

Yeah. I'm going to ask John a question. So what is it, and it might be a little bit unfair, but what brought Michael Jordan out of retirement, you know, back to join MBX?

Well, first of all, I was invited via the Frazier folks, but it became evident quite quite quickly that this was a great opportunity in terms of the drugs that we were working on, the pipeline, the quality of the people, and it got sweetened even more once Steve came on board and I had a chance to work with Sam. It was a no-brainer. They were well-capitalized, great programs, the data was strong, bright future, the ability to commercialize a product. It had all the ingredients I looked for in any of the situations I went into, and And it was a bit of a no-brainer for me.

Yeah. And just in terms of, you know, kind of capitalizing the opportunity and the capital needs, you know, where do we stand, you know, in terms of where the programs sit today, but also that ability to accelerate into phase two's, you know, larger obesity phase two programs. But you can get a lot of answers relatively quickly in obesity programs. So just wondering how we sit today on the cash runway.

So Cash Runway, our guidance is the same and has been consistent over the last few quarters, and that's into 2029. You may have noticed in our earnings we put another roughly $100 million on the balance sheet, which gives not only strengthens the balance sheet, but helps us continue to identify programs to put in the clinic, which we've disclosed. It also positions us well to complete our phase two around obesity and clearly to also complete our phase three and still be in a good spot from a balance sheet standpoint. So it all made complete sense. And as Steve pointed out. With respect to how we think about obesity strategically, the thought of going into phase three with obesity, that's a pretty big lift from a capital raising standpoint. And as we have discussed and continue to discuss what's the best outcome for investors in terms of unlocking value and providing that value to them, we think, you know, probably considering some type of strategic arrangement with somebody that's got the ability to really unlock that value and obesity makes sense. But in the meantime, our capital needs for launching around Canview Paratide are quite manageable, and we have the ability to do that.

Great. You know, Sam, I think there's one aspect, one point of interest that we're following very closely, which is this opportunity to use the PEP platform to improve upon something like a GGG. So what we see in the data for Red or True Tide is, you know, an ability to see extraordinary weight loss. But there are a lot of outstanding questions on tolerability. So what are you most excited about and what do you see as kind of the flexibility of the that the platform kind of brings to tolerability improvement could be as a weekly or a monthly?

I think you said it, Simas. We see the platform as the ability to address this unresolved question today, unsolved questions such as tolerability, but also the potential for monthly. So if you can get the same weight loss that Ritathritide showed and with a good tolerability profile and a monthly administration, I think there's a large segment of population who need a lot of weight loss that could benefit from this treatment. And the paid platform is the key. Yeah.

And Steve, from your perspective, it feels like... With this kind of increased execution mode that you're moving into, is the solution now just kind of replication and validation of the platform that we have an opportunity to see repeatedly over the next, you know, let's call it 12 to 24 months?

We're excited, Seamus, about the many ways that we have to win, whether it's with the Canvu Phase 3 results and validating Phase 2, but now, importantly, applying the platform technology, as Sam was just talking about, to high-value obesity targets. So we're excited about sort of the rinse-and-repeat opportunity leveraging the platform to deliver differentiated products and create a lot of value for shareholders. Great.

Well, it's fantastic having you here again this year. Looking forward to the upcoming, I guess, data reveal sometime soon. Thanks, Seamus. Thank you, Seamus.