Good morning, everybody. Thanks for joining us for the 2026 Citizens Life Sciences Conference. My name is John Wahlbon, analyst here, and pleased to have MBX Biosciences with CEO Kent Hawryluk and Salomon Azoulay, Chief Medical Officer.
We launched coverage on MBX, I think early last year. You guys had a heck of a 2025, and I think 2026 is gonna be another great year. One of our top picks, so I'm excited to have the team joining us here today to talk a little bit about the programs and everything to come. Thanks for joining us today, guys.
Well, thank you, John Wahlbon, and the Citizens team for the invitation to participate in this great conference.
Before I grill Ken, he's gonna walk us through a couple overview slides, and then we'll get into a discussion.
I'd be remiss if I didn't put up the forward-looking statement slide. Just remind everyone, we will be making forward-looking statements and encourage everyone to review our risk factors and other disclosures in our SEC filings, which are on our website. To lead off, MBX Biosciences is pioneering Precision Endocrine Peptides, or PEPs.
Our passion is to bring freedom to patients through therapeutics that are precise and convenient, and we're focused in the areas of endocrine and metabolic disease. This is a really important week for patients with hypoparathyroidism, HP, because this week we announced, just yesterday in fact, we had a successful end-of-phase two meeting and aligned with the FDA on our phase three pivotal study.
This is really significant because the FDA was supportive of our approach for this phase three, which is a confirmatory study with a primary endpoint that's very similar to our phase two endpoint that was so successful and reported last year. It keeps us on our original timeline for initiating the study in phase three and enrolling on time.
We're totally on track. The other aspect will be including our intended commercial device in the phase three, and there's just so many ways to differentiate with the design of the study versus a once-daily competitor that is establishing the market, which our once-weekly Kenvuparatide can capitalize on.
Just to a little walk down memory lane for a second, our phase two last September, we reported a 63% responder rate for the 12-week primary endpoint, which I think exceeded a lot of folks' expectations and was really clinically meaningful. That actually grew to 79% at the six months readout in the open label extension.
We're obviously very excited about this phase three and think it'll be really transformative for the company. Another aspect of this phase two trial that was successful last year, it validated our PEP platform, where we take peptides, which are miraculous molecules, but we know they don't last long, and we apply our PEP technology to have slowly rising and really steady exposure. This PK profile is super important in many endocrine and metabolic disorders, including obesity.
There we have a very growing and important portfolio. It's led off by MBX 4291. This is a GLP-1 GIP co-agonist. These are the two gold standards in Zepbound, which is the market leader and keeps winning head-to-head against other obesity agents. We have a 12-week readout, a 12-week MAD study that's reading out in Q4 in the target population of adults with a BMI of 30 or above.
In this 12-week study, we intend to show monthly dosing and believe that we'll have improved tolerability due to our very unique PK profile through the PEP approach. Also this year in Q2, we are going to declare an amycretin. This brings in another important mechanism in obesity, amylin or DACRA.
What's more, in Q3, we have another development candidate we intend to declare a triple G, GLP-1, GIP, glucagon, with glucagon to really supercharge weight lowering. You see that we are committed to serving the full spectrum of the obesity disease, and it is a very heterogeneous population where we need many tools in our toolbox to treat it.
We have funding to support all of these critical milestones, completion of our phase three, significant pre-commercial activities. We're planning on success with the phase three, so already planning our commercial launch and recruiting a CCO this year. The obesity portfolio, 12-week POC readouts in all three of these programs are funded, and we're also planning our phase two and conducting phase two enabling activities for MBX 4291. We had cash at $373 million year-end 2025.
We reported that will support our operations into 2029. Well, last month, we completed a successful ATM sale of approximately $87 million just to further reinforce our balance sheet and give us optionality on how we advance these programs to patients.
Well, that's a lot going on, Ken, and that leads me to take a big step back and want you to talk a little bit about your half-life extension technology, the PEP platform, because I think what's really nice here that resonates is you're going after diseases with known biology, you got known targets, you're finding amenable peptides, and you're able to extend them with your technology. The pipeline chart didn't look like this last year. Should people think of you as a platform or an asset company? And what's the basis of all this technology?
My belief is that really great biotech companies are both platform companies and pipeline. It's really no good to have one without the other, in my view. My previous company before MBX, I was a co-founder of Avidity Biosciences, very proud of that company's success and the team's execution, and I would say we're really blessed with this clinically validated PEP technology or platform technology that's clinically validated through our phase two with Kenvuparatide.
Peek under the hood a bit, what we do is start with really innovative peptides. We focus on optimizing potency, and this includes multiple mechanisms of action in a single peptide. For example, our GLP-1/GIP co-agonist MBX 4291. We have a lot of history in being able to design these multi-agonists.
I would say that our scientific founder and key inventor, Richard DiMarchi, is, in many ways, the father, if you will, of these multi-agonists in the incretin field. He invented the first GLP-1/GIP co-agonist at our previous company, and as well, the first triple G. We have some experience. We've watched the field evolve in obesity over the last 20 years, and where we saw continued unmet need is in tolerability.
What we look at is applying our programmable prodrug, which slowly releases the active peptide. Under physiologic conditions, it's through a very natural chemical process that's designed into the molecule, into the peptide itself, and it requires no enzymes, just physiologic conditions in the bloodstream. After that slow release, the active peptide has long time action because it's fatty acylated.
Fatty acylation is known in the field, and we believe we have world-class know-how in applying fatty acylation, and you see that in semaglutide, tirzepatide, and others using albumin binding to extend time and circulation. It's really the synergistic combinations of these three elements of our PEP platform that allows us to create really differentiated pharmacokinetic PK profiles that should lead to not only greater convenience, and in chronic disease like obesity.
We hear from patients they really don't want to take an injection every week if they could take it every month. Tolerability is still a limitation with the incretins because many just feel bad every week, a certain time after they take the medicine, and we know that's because of the steep rise in exposure that these other molecules that are not prodrugs experience.
You really had stunning results with Kenvuparatide and hypoparathyroidism last year. Can you talk a little bit about that disease, the unmet need, and what you guys are trying to do there? Because I think people are starting to kind of recognize that as a real market with Yorvipex, I think, doing over $500 million in sales, just a really strong launch. W here can you guys improve upon what's available for patients?
Well, just leading off, and then I'll turn it to Sam, because I've been really gratified to see over the time we've been developing once-weekly Kenvuparatide a real shift in people's understanding of the unmet need and the market opportunity for PTH replacement therapy. T he patients are calling for it because even they tell us the pill burden, it's the standard of care, the supplements, it's antiquated.
It does not address their underlying cause of disease. Even if their serum calcium is roughly controlled, they don't feel normal or functioning well. T he brain fog, confusion, fatigue, they can experience tetany. Quite a bit of unmet need. It's now recognized in the treatment guidelines, PTH replacement therapy, so that's very positive for the field, and then you referenced it.
The fact that a once-daily is out there establishing a market. I've really witnessed the excitement, for example, last fall at the Hypoparathyroidism Association International meeting. Sam, maybe you could just give more flavor for what you're hearing from the patients and docs.
Yeah, patients are very, very interested in the weekly administration, replacing the daily administration, but also in terms of standard of care, the burden of standard of care. PTH replacement therapy replace what's missing. We should look not only at addressing the serum calcium, but also the long-term complication or even the daily complication, such as bone turnover.
I mean, there is no bone turnover in this population because they are missing the PTH. So replacing gets the bone back into the game, if I may say that. The bone is also participating to the homeostasis, calcium homeostasis. Look at the kidney. The kidney also has lost the ability to reabsorb calcium.
Now, putting a PTH replacement, the kidney not only can reabsorb calcium, but also participate to the homeostasis and prevents a long-term complication related to CKD. Back to the population, the Hypoparathyroidism Association, and the feedback from the patients, but also the physician, that's the reason why they are so excited by PTH replacement therapies.
Just yesterday, you guys put out some news that you had a successful end of phase three meeting. You gave some details on the phase three design. Can you talk a little bit about what you're gonna be doing with that trial starting in the third quarter of this year?
Yeah, we had a good meeting, very good meeting with the FDA. I mean, the regulatory path has been paved in terms of what kind of studies we should be doing. It will be a six months, a double-blind, placebo-controlled study, with a primary endpoint, which is extremely important, which will be a composite endpoint of, at least three components.
The first one is normalization of serum calcium. Second one will be no vitamin D, active vitamin D at all, and calcium supplement with a maximum of 600 milligram, per 24 hours. The FDA is also requesting the patient to be stable during the last four weeks. That mean that you cannot change your dose and the serum calcium should stay within the normal value.
All this has been agreed with the FDA, and not only we are looking at a normalization of serum calcium, as I said, in terms of response, but we are also looking at improving urine calcium excretion, which will be a key secondary endpoint and a key differentiation with the competition, if we achieve our objective.
That would be extremely important to normalize serum calcium, especially in patients who start with elevated urine calcium at baseline. That's a patient who need it, right? You need to get back to normal. That will be a key secondary endpoint in our study design.
We perked up when we saw that yesterday in your announcement, the key secondary endpoint of normalization of urinary calcium. Can you talk a little bit about the population that may be at risk, where that could be a driver, and why your drug may work better there than what's available?
When you have elevated urine calcium, the risk is kidney stone. The kidney stone leads, and especially when they are very small and the patient does not necessarily know it, can lead to CKD. That's why it's extremely important to normalize the urine calcium, as I said, for two reason, complication, but also now the kidney is back to the homeostasis, can participate to the calcium, serum calcium homeostasis and reabsorb as needed calcium or excrete as needed calcium. That very, very important endpoint.
What did you show in phase two on urinary calcium?
In the population with elevated urine calcium, we showed a decrease of almost 200 milligrams in the urine, which is similar to what has been observed with other PTH. We are very enthusiastic about these numbers.
Mm-hmm.
If we can reproduce it in the phase three, which we are aiming for, so that will be extremely important for the patients.
Kent, you mentioned the phase two results out to six months. You're gonna have 52-week follow-up here coming soon. What are your expectations for that data? What do you want to show or need to show there to maintain your high confidence?
We do plan to have an update on the phase two Avail study in Q2. This will include one-year follow-up data. We had really excellent participation in the OLE. Recall that 94% of the patients who completed the twelve-week endpoint for the Avail study elected to enter the two-year OLE. By the way, all patients who started the twelve-week study completed it, 94% advanced to the OLE.
We'll look at retention in the study and responder rate. We are just really excited to show that we have a competitive profile. In our primary market research, when we spoke to doctors, when we spoke to patients, across the board, they say with, in the ballpark of efficacy to the once daily, the once weekly Kenvuparatide is their drug of choice. A vast majority, 80% of the physicians said they would switch their patient from a once daily to our once weekly. I think showing this one-year data in Q2 will be really exciting.
not only are you gonna have a more convenient drug, you might have differentiation on kidney risk and also comparable fronts on out of every other metric.
It's a really important point, John. We presented a comparable profile, and what we heard back is we would again choose the weekly. 80% said they would switch. They did point out that these long-term complications from urine calcium excretion does concern them, and if we had that in our label, it would be transformative. We just believe we can expand the market with once weekly and some other differentiation, including potential urine calcium claims.
I wanna jump to obesity, because obviously this is an area of high interest from investors and the general public. How do you think the market evolves? Obviously, you guys are going for long duration. You know, we're gonna have daily orals. We have one now, we're gonna have another later this year. How do you think patients' preference will shake out between what's available today, what we know, versus things that may come that are longer, versus orals? What do you think?
I've been following the field for over 20 years, been really blessed to see obesity go from not even being recognized as a disease to now being seen as recognized as the health issue of our time that can be addressed with medicines that are effective and overall safe. What we see is that peptides are the. I talk about them being kind of nature's key for the lock of the receptor.
You just have the most on-target specificity, the least chance of off-target toxicity, which you can have with small molecules, which are maybe more like picking the lock. I believe that we'll continue to see peptides being the mainstay in treatment, especially if companies like us are successful in delivering monthly, well-tolerated medicines.
You know, you take it when you pay your rent or mortgage, you don't have to think about your disease for the rest of the month. That is a real. That's freedom. You know, I think orals can have their place. The question is, will it be long-term safety, of course, as always with small molecule mimetics and just their efficacy. I firmly believe that with the convenience we now have for delivery, people are accustomed to taking painless, virtually painless subQ injections, we will be the mainstay. I truly believe that 4291 is potential best in class.
You have a really cool phase one design, and one of the issues we had over the past few years is when people have four-week data sets and weight loss looks good and we'd say, you know, "Pump the brakes," like, we know we need to see longer term data. With 12 weeks, how much confidence can you get? What do you need to show to, you know, get you and investors excited?
It is a well-designed study, Sam.
Yeah. Thank you. So the study is divided in three part, and each part informs the next. So we start with the SAD, and we are going to increase the dose and see what the tolerability is in terms of GI effect, nausea, vomiting. But we will have already an idea about the PK profile and the potential for monthly, 'cause really the goal of this study is two ways, tolerability and monthly.
So the MAD, the four-week administration, it will be a weekly administration for four weeks, will confirm how far you can go in terms of doses, and you get also the PK. The study will culminate with a 12-week part, which will be for now because it's a flexible study design.
For now what we are planning to do is to give the drug weekly for four weeks and then directly go to monthly. It will be during this 12-week, we'll have two monthly administrations, so that will be fantastic in terms of appreciating the tolerability profile, but really getting the real monthly PK profile.
Mm-hmm.
Obviously we'll get an idea. It's a GLP-1, GIP, you will get an idea about the weight loss.
Mm-hmm.
that we'll have the full picture, the TPP, the target product profile, realized in phase one, which is in the target population of patient with BMI above or equal or above 30.
We talked, we mentioned this tolerability is very important. When we think about the tolerability with the incretins today, it's I think fairly well understood it's a Cmax related effect, and you have peaks weekly. Can you talk a little bit about your technology and why if you're given a monthly dose that's going to sustain you, why you're not going to see really bad GI tolerability at first that may wane? Like are you just looking for lower incidence or lower severity or both? Like walk us through what you're seeing in the PK that gets you excited about the profile.
John, it's a little nuanced. It's less about the Cmax than the rate of rise to Cmax.
Okay.
We consistently hear that from the KOLs. If you look at the weekly competitors and many of the monthly as well, you have a steep rise to Cmax, and then it's trailing off. In our case, through this programmable prodrug, we are able to slowly release the active peptide and extend the time to Cmax or Tmax.
Mm.
That's really important. Then through the combination of the prodrug and the fatty acylation applied to the active peptide, we then have the steady exposure such that we've stated that we believe that for 4291 and our other programs in obesity, we expect to have a time to half Cmax, as you're coming down the exposure curve, of greater than 21 days. That's, I think gives us very high confidence in having not only monthly exposure, but a flat peak to trough that will improve tolerability.
You know, a lot to talk about. We got a few minutes left. I don't want to forget about talking about post-bariatric hypoglycemia, because you guys will have a phase two readout here coming soon as well. Can you talk a little bit about that candidate, the opportunity, and what you want to see in that data set?
Well, I mentioned earlier that we're committed to serving the full spectrum of patients with obesity, and we know that there are different treatment approaches needed for this very heterogeneous population. That includes not only, you know, the incretins, and by the way, you know, we're bringing in amylin and glucagon, so we're going to have three programs that address medicinally obesity.
There's remaining a place for bariatric surgery. There is continued demand for this approach. It's a durable effect. It's a rapid reduction in weight of 40% or more. Unfortunately, a subset of patients who undergo bariatric surgery develop this chronic, quite debilitating complication, and there is a known mechanism, GLP-1 antagonism, and we have an opportunity with our long-acting GLP-1 antagonist to treat patients with PBH.
It has a 90-hour half-life, and we have a 2A proof of concept study reading out in Q2 in PBH, which Sam can address.
Yeah, sure. This study is a PD pharmacodynamic study evaluating following mixed meal tolerance test and after single administration of Imapextide. Two things. The first one is a glucose nadir. In this population, glucose goes down too fast and too low, and the idea here with the GLP-1 antagonism is to increase the glucose nadir. Parallel to this, you should observe a decrease in insulin secretion. We will be looking at other parameters such as C-peptide, but really, the pharmacodynamic will be based on these two parameters.
Got it. My last question is usually remind me of what to look forward to and how much cash you have, but you laid this out nicely for me, Ken. You guys got a lot to do, so I don't want to steal too much more of your time. I want to thank you guys again for being with us today, telling us more about the MBX story, and we're looking forward to catching up with you as we get through all these milestones in 2026.
It's going to be a great year. Look forward to updating you all. Thank you for your interest.
Thank you.
Thank you.