Thanks for joining us here at Guggenheim's second annual Healthcare Innovation Conference. Really thrilled to have MBX Biosciences here with us again. To my right is Kent Hawryluk, the President and CEO of MBX, also a founder, and Sam Azoulay, the Chief Medical Officer as well. Just to kind of orient us to the MBX story, Kent, Sam, again, thanks for joining us. Can you just orient us to the story, give us just a couple of minutes, brief overview of MBX, and where you're headed in the next, let's call it, 12 months - 18 months?
Thank you, Seamus. I would also like to thank the whole Guggenheim team for the opportunity to participate in this Healthcare Innovation Conference, right, two years running. It has been great. I will be making some forward-looking statements, so I would encourage you to look at our risk factors and other disclosures in our SEC filings. MBX aspires to be a leading endocrine and metabolic disorder company. We have three clinical stage programs which have the opportunity to overtake multi-billion dollar markets. Our pipeline is fueled by a novel platform technology we call precision endocrine peptide, or PEP. This delivers consistent drug exposure, longer time action, and convenient dosing regimens.
As an example of what we can do with our technology, MBX 4291, which is our first obesity PEP candidate in our obesity portfolio, is designed to be once monthly with better tolerability through gradual controlled release of the active drug. That study is, or that program has a 12-week readout in Q4 of 2026. The company is really well funded now. We did a follow-on financing last month, about $200 million in proceeds, and we had $392 million cash in equivalents at the close of last quarter, which supports our operations into 2029, I should say. That includes our phase III readout and our lead once-weekly Canvu program in hypoparathyroidism, as well as significant pre-commercial activities for that program, as well as advancement across our pipeline.
2026 is set up, you ask about the next 12 months, really a catalyst-rich year across value inflection points across all of our programs. I am really excited to talk more about where we're headed.
Great. Maybe just to start us off with the lead program, Canvu paratide, despite all of the movements in the stock on the day or after, if there was one data set that we have seen that we are particularly excited about, I would say this is one of the ones that we have seen this year. Maybe help us understand a little bit of what excites you most about the phase II avail data, and just remind us not just the unmet need, but also what you are learning in your own research, your own market research around this program.
Thanks, Seamus. We're really excited about this data set as well because, first of all, it was very validating for our platform technology. So clinical validation for our PEP platform. The translation was just spot on from design to preclinical to phase I and now phase II in HP patients. And the results were as expected and really supportive, we believe, of best in class. This is a significant unmet need. We look at the prevalence in the U.S. and Europe. It's over 250,000 combined. So a chronic disease with a very large impact on quality of life. And think about the standard of care now. Conventional therapy is a high pill burden and really one of the last major endocrine diseases where hormone replacement is not the standard of care. But that's changing.
There is now a once-daily approved PTH replacement therapy that is validating the market and getting patients on a PTH replacement therapy, which is great for the patients. What we have seen is that we have a real differentiation. We did some market research. We had a market research firm interview 27 endocrinologists who treat HP patients. We presented a blinded profile for the approved PTH replacement therapy, once daily. We showed them on a blinded basis our profile with once weekly. The conclusion we heard back was that with comparable efficacy to the once daily and a once weekly profile, that is going to command category leadership. That profile that I described drives switching for experienced patients and will be the drug of choice for new patients. That was not surprising to us. It is what we have been saying.
It's consistent with what we've seen in other indications in endocrine where you go from a once daily to a once weekly and you have a really rapid adoption of the once weekly and not only switching, but an expansion of the market. That is where we see the path forward. It's also consistent when we are just traveling out in the HP circles. Like Sam and I were at the Hypopara International Conference last month in Dallas with Zach and some others. In fact, any reflections on that and some of the patient experiences we've heard?
Yeah, I think, first of all, thank you, Seamus. What excites me is the results. 63% after the 12-week double-blind placebo period, followed by 79% in terms of open label extension. That is exciting. Back to the Hypopara Association meeting, it was a lot of excitement around the weekly administration. A lot of interest in our program from the patients that recognize that so far there has been some improvement with the daily administration of the PTH therapy, but there is a large room for improvement and they are expecting to see this weekly administration to be on the market as soon as possible for them. It is a word that people are using.
Great. In terms of a little bit more of the details around the key findings, you guys have talked a little bit more about the OLE. Can you maybe walk us through what you're hoping to learn, not just from the OLE where it stands today, or at least what's presented today, but going forward as we go to more full-year data all the way to two-year data?
Sam, why don't you start with what we've seen at the six months and what we hope to continue to see at the one-year follow-up?
Yeah, that's what I alluded to, which is a 79% response rate we have in the OLE. Also, just one step back, the percentage of patients moving from the double-blind to the open label extension, 94% of patients wanted, were willing to stay in the study. In fact, wanted to stay in the study, which is really a good number. When we look at the OLE result, as I said, the 79%, but also beyond this, the improvement in all the symptoms, but also looking at the key organ, the kidney and the bone. In that way we see an improvement in terms of bone biomarkers that back to reactivating the bone turnover, that's what's missing in this population. The same thing what we saw at the end, it's not in the open label extension, but it's very important to highlight.
At the end of the double-blind period, what we see at the kidney level on the urine calcium in patients with a baseline, elevated baseline urine calcium at baseline, which was very remarkable. It means that PTH is back. That means these patients are back to almost normal.
Help us understand a little bit. There was some confusion around the data around the placebo effect, but you did a sensitivity analysis. Maybe just walk us through around that sort of initial placebo response and then what you did to better understand that placebo response in the different patients that you studied.
Yeah, we got a placebo response which was a little bit higher than we were planning for, but nevertheless, we get positive results. That is something very important to highlight. If you look back on the competition, what was shown in the daily administration, the competitive agent Natpara given daily, they show placebo response around 27, not around, at 27%, which means they had four patients who were placebo responders. We had five. We are in the same ballpark. Nevertheless, we tried really to better understand what was the rationale behind this. We consulted with experts in the field and they advised to look at PTH residual patients with residual PTH, which is PTH above 20 pg/mL. When you look at this population, we found eight patients who had an elevated PTH above 20.
We eliminated these patients from the analysis, initial analysis. In fact, there were three patients in the placebo arm, five in the treatment arm. The numbers became 60% responder in the treatment arm as compared to 15%, 15% in the placebo arm, highly significant, p-value 0.007. When we look at now six months in the open label extension and we said, okay, what's going on if we exclude these patients also from this analysis, it became 73%. Again, the sensitivity analysis is very reassuring in terms of the quality of the data we observed with the ITT analysis. What is the learning? The first learning is that we are going to, for the phase III program, to stratify these patients in order to make sure that the population with PTH above 20 is well balanced across the two groups in the phase III program.
That was one of the learnings that we'll be applying immediately to the phase III program.
Great. You already covered my next question, which was on the phase III learnings, but are there any other tweaks to the patient population that we should consider or perhaps to dosing that you think might be relevant between your phase II to phase III program?
Yeah, so that's a dose finding study, a phase II study, right? The most important for our phase III program is what will be the starting dose in your phase III program. When you look, you look at the efficacy, you look at the safety profile, and we are happy to see that at 400 and 600 micrograms, the Canvu paratide was very safe. We reported four adverse events of hypercalcemia, but in fact, when we looked really in detail, it was only one case across the 400 and the 600 micrograms, which is likely for the phase III. Between these two doses, we'll be selecting the starting dose between the two.
No changes to the timing of dose escalation. One question that I do have is, what is it in your understanding, or at least what's the opportunity to continue to dose escalate beyond where perhaps Natpara label in the United States limits it or may limit it? How might that be an advantage in your phase III?
What our goal is to be able to treat the anti-PTH HP population, patients with hypoparathyroidism, the anti. As you know, and as you alluded to, Natpara is limited to dose up to 30 micrograms daily. The rationale behind is related to the FDA did not allow them, did not grant them the dose above 30 micrograms due to the device. Our goal is really to be able, as I said, to treat the anti-population.
Maybe you can remind us on just dynamics around your end of phase II. Obviously, a government shutdown is not particularly productive in that regard to getting it scheduled, but maybe just you can provide us with a little bit of color along those lines.
We're very confident in being able to hold both our end of phase II meeting with the FDA and the scientific advice with EMA in the first quarter of 2026. We've really seen no change in our interactions with the FDA and excited about this first opportunity to engage with the EMA and believe those learnings will be really important as we initiate our phase III study in Q3. This registrational pivotal study will obviously be a major catalyst for the company.
Maybe just as a final question on Canvu, how would you kind of characterize the physician reception to the data, the desire to participate in a potential phase III going forward?
I would just go back to the conference we attended for the entire international Hypopara community. I felt very strong interest in joining the study and ultimately getting prescribed once weekly. You know, the patients tell us they do not want to have to think about their disease every day. Currently, many of them are setting their alarm clocks to take pills in the middle of the night, right? The calcium active vitamin D is a big burden. We want to give them freedom to get on with their lives and really live them to the fullest. KOL conversations were really supportive. They looked at our, of course, our responder results. They looked deeper. They looked at the secondary endpoints around urine calcium, the bone biomarkers like Sam described. They are really excited by what they see. There is the market research.
I think the stories really come together on this program. We're extremely excited about the opportunity to become leaders in a proven multi-billion dollar likely market that's fast growing.
If I may add, Sam, thank you. It is 94% patients who are willing to stay in the open label extension.
Two years.
Yeah, for a two-year study. I think that's the best marker if you want of how the patients want to stay with the weekly administration.
How it's working for them.
Yeah, exactly.
How it's making them feel.
Great. Maybe just one last question. In terms of sort of major medical publications, how are you thinking about the right timeframe for sort of the full data? Is it 26 weeks? Is it at the 52-week OLE? Or is it you'll have multiple, your view is multiple publications?
Multiple opportunities. We are eyeing a major medical conference in the second quarter to present the full avail results. When available, we'll look forward to presenting the one-year follow-up data also in Q2.
Okay, great. Let's shift gears to 4291. So this is your long-acting GLP/GIP asset. There's a lot of enthusiasm and a lot of strategic interest in this space. Maybe you can just describe for us 4291, what you're hoping to achieve with it and how you think it can potentially be a differentiated GLP/GIP in a market where we're starting to see more of these assets being funded outside of pharma.
Exactly. We have a long history in obesity, members of our team. So we're not sort of Johnny come lately here. Recall that our scientific founder, Dr. Richard DiMarchi, an inventor of our molecules, was the inventor of the first GLP/GIP co-agonist basically almost 20 years ago. So we've been following this space. And with MBX 4291, this is an opportunity to apply our most cutting-edge, strongest PEP technology to provide ultra-long-acting GLP/GIP co-agonist prodrug. What we hope to achieve is definitive once monthly time action. As well, we believe we will see better tolerability, better GI tolerability, specifically less nausea and vomiting. So why do we believe this? The design of the molecule is to gradually release the active drug. And we know from KOLs that it's the rate of rise, the C max for these incretins that's causing the GI distress.
This GI intolerability is causing the incretins, as powerful as they are, to underperform due to the adherence, some of the adherence challenges and high discontinuation rate. What we think is we combine the gold standard dual mechanisms seen in Zepbound and provide this sort of prodrug approach to show greater tolerability. We think all of this can be demonstrated clearly in our 12-week study where we plan to dose monthly in the 12-week study. You do not have to extrapolate or look at follow-up. Right there in the 12 weeks, we will see monthly.
Great. I guess some of the questions are, you've initiated the program. What we've seen with obesity programs is they tend to recruit at a blistering pace. I'm not asking you for recruitment updates, but in the context of timelines, how should we be thinking about the updates and what are the gating factors that you feel you need to be careful about with regard to maybe gate, I mean, I'm sure a study like this could recruit in minutes in some cases with enough sites, but you have to be careful about the drug development. Just trying to get a sense of how to think about what the gating factors are to getting you to those 12-week data.
Right. The key catalyst is the 12-week data. We've seen just how much enthusiasm 12-week data can generate for these ultra-long-acting molecules. Again, we believe ours should demonstrate best in class. It is a SAD, MAD, and then part C study. Sam, do you want to just give a little more color?
Yeah. So from the SAD, which we will establish, we will check multiple doses. And rapidly, you will see about the tolerability and how far you can go in terms of doses. And then you can also, starting with even the SAD, you can see what kind of PK you can get and how you get to the C max. So very informative. The SAD will be very informative. Then you follow by the MAD, which will be a four-week administration. I mean, we give the drug every week. And then the key will be the 12-week. The beauty of this study, we are directly in the target population. So all the extrapolation will be easy to make. And you can get at the end of this study, you will get information on the PK confirmation of the monthly, right? You will get the tolerability.
You can also get information about how far you can get into the doses.
Weight lowering, as you said.
Obviously, at 12-week, you can see how you fit with the competition in terms of weight lowering. It is a very, very informative study.
Great. Let's move to your, actually your next data program, which is Imipexatide. The PBH market opportunity is something that we've talked about quite a bit in our overall coverage of MBX and other companies as a multi-billion dollar market opportunity. Maybe just put your, how you see the opportunity for Imipexatide into context and the work that you're doing to really understand that profile of that product as best as possible.
I think you're ahead of the curve in recognizing this market opportunity, this profound unmet need. When we did our market research, we found a U.S. prevalence over 125,000. That's, I think, even a little below what our competitor talks about, but similar size to Hypopara and growing awareness, I would say, in it. It's chronic. It's severe, major impact on quality of life. The occurrence of these episodes of hypoglycemia are unpredictable. They can be postprandial due to the changed anatomy following this bariatric surgery that affects some of these post-op patients, but maybe not necessarily postprandially, but hours later or middle of the night. What we think is really important when you're building an ideal product profile for this is you want full day and night coverage throughout the week.
Of course, the convenience of once weekly, as we talked about with our lead once weekly Canvu program, we know physicians prefer and patients do. What we have demonstrated with our phase I is that Imipexatide has a 90-hour half-life, so very supportive of once weekly. We had good safety and tolerability. We even saw the PD signal, even though these were healthy volunteers. We saw an increase in endogenous GLP-1, which is what you would expect to see because our molecule is a competitive antagonist, right? It blocks the GLP-1 receptor. This large excess of GLP-1 in these patients cannot have the effect on insulin and then glucose to cause hypoglycemia. Now we are set up well for this phase II-A proof of concept PD study in PBH patients. You want to speak about that?
Sure. The goal of this study is to look at the pharmacodynamic effect. We'll be measuring the pharmacodynamic effects through the glucose nadir. You want to increase the glucose nadir. You're going to measure the insulin secretion and the C peptide. You want to see a decrease. We will be looking at a mixed meal tolerance test. That's how we're going to evaluate it. We will have a baseline. We'll have one dose and one higher dose. It will be single dose each time. The patient will be compared to himself. That's easy. A sample size of 10 patients is enough. At the end of this study, we'll have a good idea about the potential of two different doses to move to the phase II, phase III.
A similar study was conducted for the once daily, which has a two to three-hour half-life. Recall, that's quite a bit different from our 90-hour half-life. Even for once daily, I think you can see why we believe we'll have a better prevention day and night for these episodes.
Great. Unfortunately, we are up on time. Just 10 seconds left. Kent, Sam, thank you so much. Congratulations on a very busy year. Actually sounds like a busier 2026 ahead. Thank you again.
Thank you.
Thank you.