Hello, everyone, thank you for joining us today. I'm Trevor Allred, an analyst here with the life sciences team at Oppenheimer. Today, I have with us Kent Hawryluk, CEO at MBX Biosciences, and Samer Ali, the CMO. Welcome, team. Can you start off by giving us an overview of some of your recent updates and expectations for 2026?
Sure. Thanks, Trevor, for the invitation to participate. I'd like to remind everyone that I will be making forward-looking statements and encourage everyone to look at our risk factors and other disclosures in our SEC filings, which are available on our website. As background, for those of you new to the story, MBX is pioneering Precision Endocrine Peptides or PEPs, with a passion to give patients convenient and precise treatment of their endocrine and metabolic disorders. PEPs is a clinically validated platform, and it's really taking a peptide, which is a miraculous molecule that doesn't last very long, and engineering it to provide slowly rising and steady exposure. We see 2026 as a pivotal year for the company, with important milestones across our 3 clinical stage programs, as well as in our obesity discovery and preclinical development areas.
Looking at our once-weekly canvuparatide, we have an end-of-phase II meeting with the FDA this quarter, and coming out of that meeting, we'll be able to provide more information on our study design for the phase III. We have a phase II update, including 1 year data in Q2, and initiation of our global registrational phase III study in Q3. In our obesity portfolio, we anticipate 12-week data from our multiple ascending dose study in the target population for our once-monthly MBX-4291, a GLP-1/GIP co-agonist, and very excited about the opportunity for this study to show once-monthly dosing and potentially better tolerability. We have two other candidate selections in Q2 and Q3, which are targeting important new obesity targets, amylin and glucagon.
We have a cash runway into 2029 and a great deal of optionality in how we continue advancing our pipeline.
Great. Thanks for that overview, Kent. You know, for those not familiar, can you also tell us a little bit about the PEP technology and the potential applicability across molecules?
Great. It is the base of all of our pipeline programs, it's quite proprietary, differentiated, and unique in the sense that it provides this slowly rising and steady exposure. We do that starting with innovative peptides, which are designed to optimize potency, including the ability to have multiple mechanisms in a single peptide, à la our GLP-1/GIP co-agonist. We also optimize for shelf life, dose volume, and other attributes. Our programmable prodrug is what provides that slow release through an internal, very natural chemical process in the bloodstream, requires no enzymes. What this does is improve tolerability by reducing the burst effect for the drugs upon injection. As well, we use fatty acylation to extend the time in the bloodstream. This creates more convenience through less frequent dosing and extended exposure.
It's how we combine these different PEP technologies synergistically, to create the best-in-class molecules that's so differentiated.
Great. We saw 2025 as a pretty transformative year for MBX, with the initial hypoparathyroidism proving on the platform. Shares have really taken off from there. Our next update for hypopara will be the 1-year OLE data anticipated in 2Q. Can you give us any insight into what we might see on that update?
Well, we are very excited about 2025. Agree, it was just a spectacular year for the company. What's exciting is in 2026, we're very focused on execution around launching our phase III study and commercialization planning. To give a little background for folks who aren't as perhaps familiar with HP, hypoparathyroidism, this is really a devastating disease that currently has a very antiquated, insufficient standard of care. Quite prevalent, over 250,000 prevalence in the U.S. and EU, we hear from patients that they're taking large doses of pills throughout the day and night, and yet they're still not functioning well.
We know that patients are very excited about the potential freedom that comes with canvu because they don't want to have to think about their disease every day, and this can be a really major impact on the quality of life. What canvuparatide is, it's a once-weekly PTH replacement therapy using our PEP technology. We have a peak to trough over a week that's comparable to the once-daily YORVIPATH peak to trough over a day. I'll ask Sam to talk about some of our upcoming plans.
Yeah, sure. Thanks, Kent. I would like to go back a little bit to the phase II data. It was a 12-week placebo-controlled study. We observed at the end that the responder rate was really a tough endpoint because it was made of a composite of 3 components: normalization of serum calcium, it was no vitamin D at all, 0, and a calcium supplement within the dietary dose of at or less than 600 mg per day. A hard one. We observed 63% response rate at that time, which was significant versus placebo. Excellent results at this time. We had 94% of patients moving from the double blind to the open label extension, so really a great number.
At six months, we observed 79% responder during the open label extension. Now we are going to reach a 1-year time point, we would like to look at the retention rate, right? The response rate, the durability of effect, also other pharmacodynamic or biomarkers that we released at previous time points. The same thing, safety, tolerability. Very importantly will be the BMD, because it did not make any sense to measure BMD before 1 year. We release bone biomarkers, CTX, P1NP, which showed really an increase, that the bone turnover was back, right? Now it will be very important to see that the BMD that we'd expect to decrease, which is normal.
We saw it with the competition, but within the normal value, and at least when matched with age, and ethnicity, et cetera. That will be an important release at the 1-year time point.
Great. Yeah, it looks like you've got a potential best-in-class drug here. I mean, can you speak to some of the feedback you've had from the physician community following the top-line data?
Trevor, I agree with you regarding the best in class, and to give you some flavor, I had an opportunity to participate in the Hypoparathyroidism Association meeting last October, where our team presented our phase II data, and I was so encouraged to see the positive reaction to our strong data from the endocrinologists, from some of the study investigators. I saw endos lobbying Sam to participate in the phase III, and that will really help our enrollment.
That's a feedback.
Weekly really matters, and we see this across the board. I mean, when you look at even in type 2 diabetes, obesity, when you have a weekly enter the market, you have a rapid adoption and expansion of the market. This is suggested in some of the primary market research that we've conducted around a once-weekly canvu, and we heard overwhelmingly from physicians interviewed that they would pick canvu for new patient starts, and a vast majority, 80%, would switch their patients for a once daily. Sam, any other thoughts?
Yeah, I just wanted to add that the feedback from the current investigators is very, very positive. They want to participate in the phase III study. That, as you say, Trevor, it's a very strong we see a strong support for our phase III program. Really the weekly administration is really attractive for patients, but also for physicians.
Yeah. Yeah, absolutely. Yeah, we'll look to see more feedback from that with the one-year OLE data as well. I'm sure. Okay, let's move on to obesity, which is another, you know, primary thing that.
Yeah
... many investors are paying attention to. For those that are less familiar with the obesity targets and what optionality you have there, can you just discuss some of the advantages of your obesity portfolio? I'm just targeting incretin benefit over GLP-1. What are some of the added benefits of the triple agonist?
Well, I've been in the obesity field for over 20 years, and through that time I've been collaborating with our Scientific Co-Founder, Dr. Richard DiMarchi, who's a true pioneer in the peptide field, especially in obesity, where he was the inventor of the first GLP-1 GIP co-agonist and the first GLP-1 GIP triple agonist. We've been at the forefront of bringing change and benefit to patients with obesity. I just reflect on how far we've come from 20 years ago, where it wasn't accepted generally that obesity was a disease or that you could safely treat it therapeutically, and boy, how far we've come. We're now at a point where we recognize that it's a heterogeneous disease, and that we need an armamentarium of really different tools to address the individual patient needs.
We are approaching it with a portfolio and a quite robust and growing one. When we look at some areas that have remained to be solved, if you will, in obesity, tolerability looms large. With the incretins, they're highly effective, right? The GLP-1s and related GIP. However, we see some issues with adherence due to the GI side effects, nausea, vomiting, and we see discontinuation rates being pretty high. We know that dosing frequency matters because this is a chronic illness that requires lifelong treatment, and patients to the discussion on HP, want to take injections less frequently. We believe our PEP technology is uniquely suited to address these limitations.
This is through the slow rising and steady exposure, and this overcomes the burst effect and fluctuations that we know cause the GI side effects with the incretins. I think it'd be useful to compare against Metsera, obviously, was much in the news late last year. Their so-called ultra-long acting incretin zero nine seven I is focused on potency around the GLP-1 receptor. This is a mono agonist and also on time action. They, however, have a quite a fast rise to Cmax or Tmax, and as well, they have a time to half- Cmax of 20-21 days per their S-1. In our case, we have a longer Tmax, again, slower to rise, and we project a longer T- half Cmax.
These should be very important in creating a once monthly incretin that is better tolerated. I want to highlight that ours is a dual agonist, and we know that these two mechanisms are the gold standard, with Zepbound once again recently having head-to-head superiority against competition. Think about a once monthly, if you will, Zepbound, that is slowly rising to Cmax and then hold steady to support the monthly dosing. We're going beyond that. That's in phase I. You heard that we have a very exciting 12-week read outcome coming. We're going beyond that because, again, we know that patients have different needs. With our incretin, this combines incretin activity with a new, a newer obesity target, amylin, or DACRA, that is clinically validated.
It's a complementary mechanism to reduce weight and could have other potential benefits that have been seen preclinically. We'll look for that clinically, like potentially a lean mass preservation. Patients respond differently to different molecules, so it's important to us to keep providing new options. The third that we're focusing on this year is a Triple G, for short, GLP-1, GIP, glucagon. Glucagon is a mechanism that, again, Richard DiMarchi has pioneered in the field. It turbocharges weight lowering, a la retatrutide, from Lilly. That has been seen too, to have other advantages besides weight lowering in terms of reducing pain. You can see how we're bringing multiple options to help patients, which is truly our passion at MBX.
Yeah, absolutely. Sounds very exciting. You also have your GLP-1 antagonist, imapextide, for the treatment of post-bariatric hypoglycemia. We're expecting some competitor read-through data this year, as well as initial phase II-A data for imapextide. Can you frame some of your expectations for imapextide and how you expect competitor data to read through to imapextide?
Sure, as we look to address the spectrum of disease in obesity, we know that bariatric surgery remains a gold standard for many to lose a substantial part of their weight, 40%, 50%, which is not currently available with therapeutics. Unfortunately, a subset of this population develops this chronic complication, post-bariatric hypoglycemia, and there's currently no approved therapeutic. We are excited to be advancing our once weekly GLP-1 antagonist with a 90-hour half-life to support full day and night coverage, and help patients sort of reduce the fear factor, because they wonder when they are going to experience this very dangerous condition of hypoglycemia. Let Sam talk more about the study that's underway.
Yeah, sure. It's a phase II-A study, so it's in the patient population, show with episode of hypoglycemia, and they are known for having had post-bariatric surgery, so they're known patients. It's a pharmacodynamic study. We are going to look at two things following mixed meal tolerance test. We're going to look at the glucose nadir. In this disease, the glucose go very low, below 70 milligram per deciliters. We're going to see, and we know that the patient at baseline has shown a glucose going below, and we are going to check how much higher the glucose nadir can go and how much we can reduce the insulin secretion following two doses or multiple doses of our product, Imapextide.
That's a very simple study, and we will get the result, 2nd quarter of 2024.
Got it. Okay. What might we see from the initial phase I MAD data with 4291 and obesity? Is there anything you can share about what, you know, we might see with that initial look?
Well, I'll just highlight to start what an important study this is, because 12-week data with a once monthly is currency. In the case of Metsera zero nine seven I readout from their 12-week study last year, this was with 12 weekly doses, and then kind of extrapolating to what monthly dosing could look like. In our case, we're very committed to demonstrating once monthly dosing in the 12-week study, and this is in the target population of obese adults. I really believe this is a major catalyst for our company in Q4, and Sam can provide more details.
Yeah, it's a very, very interesting study, very important study. There are three different part in this study. The first one is a single ascending dose, we will be looking at evaluating different doses of MBX 4291. We will be looking at two things: the PK profile, right? Kent referred to the ascending to the the slope, ascending slope to and smooth slope to the Tmax, very important. Also we'll be looking from a PK standpoint at the potential for a monthly administration, Very importantly, we'll be looking at tolerability, how far we can go with the dose. The second part of the study is a MAD study. The drug will be administered weekly for four weeks.
Again, we will look at how far you can go in doses, but in this step you will be reaching a steady state, and you hope that some tolerance will be developed in terms of GI effect, right? That you can go higher than the dose that we will have or the concentration that we will have seen in the SAD. You will be looking at the PK profile, same thing. And most importantly, that the last part of the study, which is a 12-week study. For now, and we are flexible in our study in terms of how we can assess this period, but for now, we are looking at giving the drug for 4 weeks, right? Weekly, 4 weeks, followed by a monthly administration.
At the end of this 12 weeks, we can very important information in terms of PK, then it will be a PK following a monthly administration, real PK, right? You get a half-life, et cetera, everything related to your PK profile. You get your tolerability, and you get an idea also of weight loss. If we combine these three effects, good PK, good tolerability, good efficacy, you can imagine that the compliance will be good, and the long term will look fine, I would say. Really, really important study, especially for the 12-week period. Again, results by Q4 2026.
Yeah, absolutely. Kent, did you have anything to share?
One point, these results will also validate our entire obesity portfolio. This idea that we can improve tolerability with once-monthly dosing, with mechanisms that in obesity that just continually become more clinically validated through other competitors' programs.
Yeah, absolutely. Looking forward to the data. It sounds very exciting. Okay, yeah, so beyond, you know, what we've seen with the pipeline so far, do you anticipate building out the pipeline any further? If so, are there any therapeutic areas that you'd like to focus on?
Well, currently we're very focused on executing on our current pipeline. That does include these two new candidates, candidate selections in obesity in Q2 and Q3, getting those to patients, to people with obesity as quickly as possible. Beyond that, we have a robust discovery effort, currently focused in obesity, looking beyond these current targets that we've discussed today. That will certainly keep our team busy. Longer term, our PEP platform is very applicable in other areas. That creates just a lot of optionality and opportunity. At the current time, we're very focused on the task at hand, especially the current milestones we've discussed.
I would just add that as a public company, I'm very proud that we've accomplished all of our major milestones on time, and that will continue.
Yeah, absolutely. Looking forward to it. Okay, what aspects of the company... You know, we've talked about all the things you guys have going on, which is a lot. What aspects do you think are most underappreciated into 2026?
Well, I think the story's getting out and becoming well appreciated, and you highlighted our stocks really positive trend. I believe that MBX is truly unique in having this clinically validated PEP platform that's just so powerful. Also, three clinical stage programs that are potentially best in class and a track record in obesity, which is the major health issue of our time, incredibly large market opportunity, and an ability for us to become leaders. That's really our goal. I think that when you look at our milestones throughout the year, Q2 is a very busy one, so this is a timely discussion. We're gonna you know, have reasons to keep people excited throughout the year, with data releases and progress toward building a leading endocrine and metabolic-focused company.
Yeah. Great. Yeah, I think you also shared this earlier, but I guess could you briefly share, you know, how the balance sheet looks now and what you expect the runway to look like into the coming years?
The balance sheet looks really strong. We had a year-end cash balance of $373 million. We discussed that that supports our operations into 2029, including rather, the completion of the phase III study in canvuparatide in the pre-commercial activities, and as well as advancing all of the studies that we've discussed. We including proof of concept studies in our new, two new obesity programs. Now, recently, we successfully had a $87 million ATM stock sale. If you look at it on a pro forma basis, the year-end cash that would be $460 million. That just gives us tremendous optionality in how we advance our portfolio.
I would just highlight that we're already conducting phase II enabling studies and planning our phase II in MBX-4291, because we absolutely expect success and differentiation with this GLP-1/GIP dual agonist monthly. I highlighted pre-commercial activities for canvuparatide. We're getting ready. We anticipate a successful, we call it a confirmatory phase III, and we wanna be ready to market that product should we be successful in getting it registered, because we know that the HP patients are waiting. We're recruiting a CCO this year to supercharge those activities. Just a lot going on, and it's gonna be a thrilling year for the company.
Yeah, absolutely. Yeah, we're looking forward to a catalyst-rich year. Okay, yeah, we're coming up on time here today. I want to thank everyone for joining us. We'll see you all in the next event.
Thank you.
Thank you, Trevor.
Thank you, Trevor. Bye.