All right. Welcome, everyone, to Jeffrey's London Healthcare Conference 2025. My name is Roger Song, one of the senior analysts covering Semi-Cap Biotech in the U.S.. It is my pleasure to have the fifth session with MBX Biosciences. Welcome, Ken and Sam.
Thank you, Roger. I really appreciate the invitation to participate in this great conference. I will be making forward-looking statements, so I encourage you to look at our disclosures, which are available on our website. For those of you who are new to the story, I just wanted to first start by sharing a bit of background. It really is MBX's aspiration to build a global leader in endocrine and metabolic disorders. We have three clinical-stage programs advancing, which have the potential to be best in class and overtake multi-billion-dollar markets. The underpinning of our company and pipeline is this precision endocrine peptide, or PEP, novel technology. What that enables us to do is design peptide therapeutics that are best in class and differentiated in terms of providing consistent drug exposure, longer time action, and convenient, less frequent dosing.
This includes our once-weekly canvuparatide, where just last September, we presented really outstanding phase II top-line results. In what we hope to be the first PTH replacement therapy that's once weekly. We also have a once-monthly GLP-1 GIP co-agonist prodrug, which is in the clinic and on track to have top-line results for a 12-week proof-of-concept study in the target population, once monthly, being obviously very differentiated in the field. We have value inflections in each of these three programs throughout 2026. We have funding, which will support our growth into 2029. That includes completion of our phase III study in HP, hypoparathyroidism, and pre-commercial activities to support our expected launch of the once-weekly canvuparatide pending approval. A lot of catalyst activity for 2026. Let's just take a closer look across our pipeline.
In once-weekly canvuparatide, in the first quarter of 2026, we intend to conduct end-of-phase II meetings with the FDA and EMA scientific advice. In Q2, important catalysts, additional data, the AVAIL presentation at a major medical meeting, and one-year follow-up data from our two-year open-label extension study. In the obesity candidate that I mentioned, the important catalyst there is this 12-week proof-of-concept study, where we intend to demonstrate once-monthly dosing during the 12 weeks and improve tolerability. Our third clinical program, once-weekly MBX peptide, we are expecting to report top-line results from our phase II A proof-of-concept study in PBH patients. Q2 2026. You see how these are spread out throughout the calendar year. We will have additional updates on our robust obesity discovery activities, again, applying this clinically validated PEP platform technology to targets of interest in obesity.
All right. Good. Thanks for the overview. I think it's an exciting time for MBX. You just reported very impressive phase II data and supporting the next step into the phase III. Maybe, Ken, if you can just give us some of what you have been hearing from the investigator and the physician in terms of the profile you've been showing, because some of the components are a bit more nuanced, and you just highlight two people and two focus.
We've received really amazing feedback to our phase II results that we presented in September. I would think it's fair to say the 79% treatment response at six months surpassed all or most expectations, very clinically meaningful. We feel that's consistent with a best-in-class profile in HP. Sam, I welcome you, your observations.
Yeah, so I'm going to give thanks, Roger. I want just to highlight again the excellent transition rate. A patient coming from the double-blind placebo control going to the open-label extension, we had 94% of patients. I mean, this number speaks by itself. I mean, just express the content of happiness of physicians, but also patients. And the most important thing is the patients. We went also to the Hypopara Association meeting. I think it was last October. I mean, we received really great feedback and I would say enthusiasm from the patients again about participating to the studies, the phase III studies. Overall, physicians and patients seem to be very happy and expecting the weekly administration as being a game changer.
In addition to the feedback that we've received directly from being out and about in the HypoPARA community, we commissioned primary market research, and we used ClearView to interview 27 physicians who treat HP patients. What we heard emphatically is that with comparable efficacy to the once daily and once weekly, that will drive category leadership. That is in terms of switching from patients who may be on a once daily PTH replacement therapy in the preferred drug of choice for new patients and in a potential to expand the market as well. This was really quite validating, not surprising, very consistent, again, not only with what we've heard directly from the patients and physicians, but what we observe in other endocrine indications when you transition from a once daily, if you will, first-generation therapy to a once weekly. You have rapid adoption of the once weekly and typically expansion of the market as well.
Excellent. Okay. This is a top line, 26, 16 week, and then the 26th week all the way to the open label. You will give us a little bit more detailed data first quarter next year and then also one-year follow-up. What should we focus on those data sets?
Thanks, Roger. We think these are major catalysts given the excellent results that we saw with the 12 weeks and the six-month follow-up and are looking forward to continuing to show this competitive profile and best in class.
Yeah, so what we will confirm is at one year, the retention rate associated with the response rate. We had a 79% response rate at six months, so we'd expect to stay within the same ballpark, and it would be important. We'll be looking also at each component of the primary endpoint. We will be looking at also the two organs, the key organ for hypoparathyroidism, such as kidney and bone. For kidney, we'll be looking at urine calcium in phase II. In the early phase during the double-blind period, we saw a really good difference with the placebo. There was a reduction of 200 mg per 24 hours in the treatment arm as compared to a little bit more than 100 in the placebo arm. Just confirmation of this effect.
Bone biomarker is extremely important, especially at that time point w e will get the BMD, we'll get the DEXA results at one year, so also important. In addition to this, we will have the classical biomarkers, but also safety and tolerability. A lot to come.
Excellent. In terms of the detailed data from the 12 months and the 6 months data, anything you will give us additional kind of color on the top line data you will have already seen?
One area we would expect to share that was not available from top-line results is population PK. What we saw, the observed PK findings in the phase II supported the really outstanding PK profile in the healthy volunteers. There is no reason to expect that the PK would be any different in the patients based on this prodrug and fatty isolation combination of these technologies from our PEP platform. What we really did see, again, in the phase I was consistent infusion-like PK profile and this very flat peak to trough over a 24-hour period that was comparable to the dailies over a day and eight, nine-day half-life fully supportive of once weekly.
Excellent. Okay. This is the phase II. It is not designed to address everything we want to see because you're learning from the phase II and the design of phase III. What are the key learnings from this phase II? You're thinking you can design our phase III with a higher likelihood of success and also maybe generate an even more compelling profile compared to the current drug.
I think one of the key learnings from this phase II, which is a dose-finding study, just it's a phase II study. We will find out what will be the starting dose for the phase III program, right? It would be extremely important to start at the right dose, which combines efficacy, but at the same time tolerability. Without revealing something extraordinary, I can tell you already that it would be between 400 micrograms -600 micrograms of choice because it combines really a low level of really low level of hypercalcemia combined with great efficacy. That is why we will be starting. We will be incrementing also by 200 micrograms as in phase II. It is also a learning that we can continue with the same dosing paradigms. That is also important. It will be likely to be a six-month double-blind placebo-controlled.
I think that really we are not going to recreate something which is unprecedented. We are going to follow the path. Regulators, FDA and EMA have already approved this type of protocol, phase III protocol. We will be continuing on the same path.
Yeah, for example, the primary endpoint that we used in our phase II dose-finding study was very similar to the phase III endpoint. In some ways, we look at our phase III study as a confirmatory study based on the great results we saw in phase II.
Yeah, the last point, which will be the execution, will be important. We would like to meet our timeline, as Kent was alluding to. It would be extremely important to deliver this product, this weekly product, as early as possible. Patients are expecting to see this weekly administration being available soon.
Absolutely. How about the patient baseline? I believe in the phase II, we see a little bit high kind of placebo effect, although you still hit a static. How are you going to make sure this effect size you will see even bigger?
I don't need to get into the detail, but what we can forget, we shouldn't forget that this primary endpoint in the phase II was at 12 weeks, and the primary endpoint in phase III is at six months. The placebo effect that we saw in our phase II study is very unlikely to be the same at six months. The reason is very simple. These patients are sick. They have hypoparathyroidism. They need calcium supplements. They need vitamin D. The placebo is not going to replace a PTH replacement therapy. At some point, you will see whatever you start, the placebo response you start with, it would likely be very low at the end of the six months. Having said that, we will take a buffer to make sure that we'll have no surprise.
The samples will calculate the sample size with enough power to be able to conclude even if the placebo response is higher than what competitors observed, which was roughly 5%.
Yeah, that's very critical. Yes, okay, got it. This is a timeline definitely. We see the historical study from four, 12 months-6 months, the placebo rate is a little bit different and the effect size is different. Okay. I think, Ken, you mentioned earlier in terms of market research, what are the addressable population? It seems you can use it pretty broadly kind of for the entire HP patient. Just give us a little bit more HP patients. Give us a little bit more flavor in terms of who will be the low-hanging fruit and then also who you will be a battleground compared to the current daily drug.
Thank you, Roger. This is a major unmet need. We have a U.S. population, U.S. and Europe combined, over 250,000. That's about evenly split, according to our research, between U.S. and Europe. The opportunity to provide the missing hormone with PTH replacement therapy. Standard of care is really quite burdensome for patients, and it does not address the underlying cause of disease, which is PTH deficiency. We see with our once weekly, what we believe is a best-in-class profile with the physicians and the market research confirmed was best in class. We see an opportunity to switch patients who might be on a once daily PTH replacement therapy and, importantly, go after treatment-naive patients. There is an opportunity to, I believe, address patients who may be relatively well tolerated on standard of care, but they're taking pills that are, again, burdensome and don't address their disease.
Physicians note that those patients would feel better on a PTH replacement therapy. We heard that from the physicians at the HypoPARA International Conference weekly. Some physicians in the research told us directly they would want to prescribe a PTH replacement therapy for all their patients. There is a subset of patients we should look at. In the United States, the once daily is only approved up to 30 micrograms per day. In Europe, it is double that. That is low-hanging fruit where those patients who require a larger dose would be not served currently.
Got it. Okay. Just to remind us, what's the timeline for the pivotal? You will report a long-term follow-up, one-year data, early part of the next year, and then you will have an FDA discussion, and then when you're going to start the pivotal, and then I'll communicate with the street in terms of the pivotal design.
We're going to have the end of phase I meetings in the first quarter, the additional data release or releases in Q2, initiate the phase III study. We'll continue to update as we look at enrollment rate and have an estimate of top-line results.
Excellent. Great. One of the things I don't want people to lose sight of is you do have this platform, right? So long-acting peptide platform. And then with this data is absolutely validating the underlying technology. That's why you have two other pipelines. Why not we just spend a couple of minutes on that as well? I cover obesity space quite closely. I think this is a very, very big place. And then, but we also have a GLP, GIP, and ultra-subtitle grade drug, and then you have other pipelines as well. How you design [audio distortion] to address some unmet need, and then what's the product profile you want to achieve for that program?
We are, let me be clear, not generally related to obesity. Members of our team have been in obesity as long as it's been a disease area for drug development. And our inventor and scientific founder, Dr. Richard DiMarchi, invented the first GLP-1 GIP co-agonist prior to tirzepatide. That was at our previous company, Marcadia Biotech. When we approached this, we looked at our technology and saw that the field was moving toward once monthly. We found a way that we could design a dual incretin that, when converted from prodrug to active form, would behave like tirzepatide as closely as possible, but with novelty. Applying our prodrug provides gradual controlled release. What's important here, the reason that's really meaningful, is you have a slow, steady rise to the maximum exposure.
We hear from KOLs that should reduce the GI side effects that's seen in incretins due to this, in their case, steep rise to CMAX. I think the last few weeks have been really interesting in the obesity field, to put it mildly. My key takeaway is that pharma has spoken and that a once monthly obesity agent is not just on their Christmas wish list, but it's on their must-have list. They need it, they want it, they will get it at very high prices. We are really focused on execution. I think this 12-week POC study is going to be a major catalyst, real currency, and we are already exploring ways that we could advance this based on successful data and have multiple options.
Excellent. Let's talk about this upcoming data. What do you want to guide to the people? I believe you say it's weekly dosing right now, and then what you want to achieve there, and then maybe the PK profile can support a future monthly dosing because I agree monthly is one of the unmet needs there.
It's exploring both weekly and monthly, and I want to be really clear. We expect to demonstrate definitively once monthly dosing in our 12-week POC study.
Yeah, so the phase I study, and I think in fact we should rename it. It's a phase, some sort of phase IIA. It's a target population. We can go directly to the target population. We'll have three parts, which is SADs, and it will be an MAD, which will be weekly administration, and then the 12-week part. That will be extremely important. The ultimate goal is to demonstrate the monthly potential, so the real PK after one month's administration, and with great tolerability. That's what we want to achieve, monthly and good tolerability. If you get good tolerability, you can aim to increasing the dose, if potentially. Also from a compliance standpoint, it will be very beneficial. That 12 weeks, we will also have some weight loss data. We'll have the full picture following this last part, the third part of this phase I study.
Excellent. Great. Can you give us some teasers? You have multiple ways to move forward this program. How should we think, contextualize this, say, okay, what stage you will do what in terms of your standalone or maybe with a partner, et cetera?
I like the ability to pursue multiple approaches to create value for patients who are looking for a better treatment option in obesity, one that they will want to remain on for chronic use for the rest of their life and not discontinue like we see today. I think there will be plenty of interest and plenty of options for us to pursue it.
Okay. I know you have not much can discuss, but I think I understand the underlying strategy, and then you can find a way to find an interest party, and then kind of either you go along, or then you want to go together.
Everything's on the table.
Yes. Awesome. All right. Last couple of minutes in terms of the PBH. Where are you in that program, and then why you think this still will be a very attractive commercial opportunity given where a lot of people probably will be addressed by the GLP-1?
I'm really pleased to see increased interest in post-bariatric hypoglycemia, PBH for short. There are remarkable similarities between this rare disease and hypoparathyroidism, which is clearly better known and more closely followed currently. I think that's changing with greater awareness of PBH. You have unmet need. There's no approved pharmacotherapy here to treat PBH. It's chronic. It's serious. It massively impacts quality of life for these patients who live under the fear of a severe hypo episode where they could lose consciousness, need a glucagon rescue or ER visit. We see over 125,000 U.S. prevalence. Again, some similarities in TAM. GLP-1 antagonism is clinically validated to treat this disease. That's important because what we're bringing forward is a once weekly treatment option with 90-hour half-life. We think it's a, throw in rare disease pricing, a multi-billion opportunity.
Excellent. Great. Okay. You are running a phase II, and then you would have some data to Q2 next year. What is the expectation there?
Yeah, let's talk about this catalyst in Q2, the phase IIA. I refer to it as a POC study. Sam, why don't you share a little bit more info?
Sure. We are going to test two single administrations of our product, and we are going to evaluate the pharmacodynamic effect. The pharmacodynamic effect will be evaluated after mixed meal tolerance test. We will be looking at the glucose nadir, and we know that there is a direct connection between glucose nadir and the symptom, the clinical symptom of hypoglycemia. The second parameter we will be looking at is insulin secretion with C peptides. It should decrease, right? If we get this pharmacodynamic effect confirmed, which is a POC with a two dose, then we can, it opens a path to the phase IIB or maybe IIB3, right? Study can be an adaptive design. That will be the path to the next step.
Excellent. Great. Just lastly, to remind us the balance sheet and then how you think about the capital allocation across all the pipeline and the priority.
We were fortunate to end last quarter with $392 million in cash and equivalents, which supports our operations into 2029. We not only are advancing all of these programs through the value inflection points that I shared in 2026, we will fully be able to complete the phase three and the pre-commercial activities that are in full swing so that what we can hope to do is have a phase three seamless transition to launch following approval.
Excellent. Thank you so much, Ken and Sam, and thank you everyone.
Thank you.