Conference Transcript - MBX 2026-06-03

Fiona, Analyst — Jefferies (Moderator)

Good morning, everyone. Thanks for joining us. Welcome to day one of Jeffrey's Global Health Care Conference. My name is Fiona. I cover spring cap biotech companies at Jeffrey's, and it is my greatest pleasure to welcome to the stage with me MBX Bioscience CEO, Ken Harlock, and CMO, Dr. Sam Osley. Welcome gentlemen. I believe before I put you guys in the hot seat, Kent is gonna give us some overview of the setup for MBX. First I'd like to thank Fiona

P. Kent Hawryluk, CEO

and the Jefferies team for inviting us to participate in the Jefferies Global Healthcare Conference. MBX is pioneering a novel platform technology we call precision endocrine peptides or PEP and we use this to design therapeutics to provide tailored and precision treatment of metabolic and endocrine diseases, ultimately to help patients live fuller and healthier lives. And this is our most catalyst-rich year. We are experiencing a lot of excitement following our recent obesity day, where we pointed the way toward our exciting 12-week MAD data for our once-monthly GLP-1 GIP coaginus prodrug in Q4. Additionally, next quarter, we are on track to expand our obesity portfolio by selecting our third obesity candidate, a GGG, GLP-1, GIP, glucagon, prodrug, and again, once monthly. So this is supporting our aspiration to become a global leader in obesity. Additionally, we have an exciting event coming up next week. We are presenting Avail Phase II data and one-year OLE follow-up data at Endo. And for investors who aren't able to attend in Chicago, we'll make available a conference call. And very excited about that. And we're on track to initiate our Phase III next quarter. I'll mention that I'll be making forward-looking statements, and Sam Azule as well. So, please refer to our risk factors and other disclosures and our SEC followings on our website. So, we're in an enviable cash position with cash into 2029. And that funds the advancement of all of our programs to key milestones. Great. So, we, just as an overview, we have multiple clinical stage programs. these are designed to address multi-billion dollar markets they are leveraging this PEP platform with extended duration of action the consistent drug exposures and less frequent dosing and you'll see that reflected in our some of the data we're sharing in obesity additionally we're on track for the phase three study and the phase two that we reported last September is really best in class we believe and in fact our phase three study we view as a basically a building on the phase three confirmatory. We have an expanding monthly obesity portfolio I mentioned in the PEP platform is clinically validated. So getting into canvuparatide, our lead program, let's just reflect that hypoparathyroidism is a serious rare disease that many are aware of because it affects over 250,000 people in the U.S. and Europe. And it is caused by a PTH deficiency, which is the key regulator of hormone, or rather of calcium. And the standard of care today is absolutely antiquated. It's very burdensome pill supplements, which are taken throughout the day and night and do not address the underlying cause of disease and importantly, leave the patients at risk of serious long-term complications affecting kidneys and other organs. So there is a sea change coming with the advent of PTH replacement therapies once daily. And where we're different is that we have a once weekly PTH replacement therapy prodrug. And in our avail phase two study, we demonstrated that it served proof of concept as it was designed using our PEP technology. We achieved 63% responder rate at 12 weeks. That met the primary endpoint with statistical significance. And that only improved at six months to 79% in the open label extension. We had a very high rate of opt-in for the OLE, 94% of the patients completing the Phase 2 elected to enter the OLE. We view that as a very encouraging indication of how patients are feeling on the drug and their interest in a once weekly. We also saw that we had excellent safety and tolerability and believe that the trial is on track to initiate in the third quarter, as I mentioned. The Phase III study, as I said, confirmatory. We say that because it's designed quite similar to the Phase II study with a key difference that it is 26 weeks versus 12 weeks for the primary endpoint. So we have a four-week fixed-dose period where the starting dose is the 600 microgram, which was the middle dose from our phase two. This had the optimal balance of safety and tolerability. And then there is additional 18 weeks for the patients to titrate and achieve their optimal dose. There is another twist. We have a key secondary endpoint of urine calcium. We think this is important as we have conversations with doctors and patients. This is something that That is not in the once daily label and we believe could be transformative in terms of our differentiation if we achieve this key secondary endpoint of reducing urine calcium while maintaining normalization of serum calcium independent of the standard of care I mentioned. The study will kick off next quarter with an enrollment target of 160 patients which is overpowered for our primary endpoint. However, it's appropriately powered for this key secondary endpoint that we aim to achieve. We have invested already quite a bit in our pre-commercial activities. I'm joined here today by Mark Swade, our relatively recently added chief commercial officer previously head of US for Alnylam and he's giving extra focus on this area in building on our efforts to be commercial ready we know that patients are very interested in a once weekly PTH replacement therapy and we don't want to lose any time in getting this to patients once it's hopefully approved so more more updates to come next week at at endo hope to see you

Sam Azoulay, Analyst — Other

there. Thank you Kent. So I'm going to now go through the obesity pipeline and really at MBX we believe that there is a great opportunity for monthly administration with improved tolerability and with this in mind we have developed a TPP a target product profile which is described here that's a green curves green curves that's what kind of expectation we can get from our PK profile And as you can see, as compared to Tirzapetide in red and Met097i in black, it's a very different curve. You see that both Tirzapetide and Met097i have an abrupt raise to the C-Max as compared to our target product profile, where we want to get a really smooth raise to the T-Max. and we know that this burst of effect is related to GI intolerability. So again, if you look at the green curve, we want to get a flat curve with no peak, very flat and going down slowly to cover the months. And covering the months, you see the difference with stear's hepatite, which is given weekly, and we also know that the cycle in terms of PK, the cyclic change in concentration, are related to GI intolerability. And if you look at and compare with MET097i, they're claiming that the time to reduce C-max by half, the type T half C-max, is around 20 to 21 days. And we are aiming for 26 days. So that's our target product profile. Now, with this in mind, I'm going to talk about the phase one study, which is ongoing and still blinded. And I don't know the full data, but I'm going to share some preliminary data. So it's a phase one study, but it's a target population of patients with BMI at or greater than 30. So the target population. The study is divided in three parts. The SAD, single ascending dose. The MAD, multiple ascending dose. And the last section, which is a multiple administration, over 12 weeks. And each step informs the next. So we are progressing as we learn from each step. So going fast, we have five doses that will be explored with the SAD, three doses regimen with the MAD, with the potential for even a monthly administration. And we have the 12-week, that will be the most important part, which has not yet started, but we know that one of the cohorts will be on the larger population of 30 subjects, 20 treated, 10 placebo, will be a weekly administration for four weeks, followed by a monthly administration, likely to be two monthly administration. So, and this part, which has not yet started, is on time to have the results released and presented by the fourth quarter of this year. Okay, and we have another cohort we are planning, but again, we learn as we go. And the objective of these studies are clearly safety, tolerability, pharmacokinetic, and pharmacodynamic, which is a weight loss, and clearly also to prepare for phase two. So next one, which is the initial results. That's already ahead of the game. Okay. That's the initial results. That's a delay time to maximum concentration. What you can see here is that if you compare the 60 mg and the 90 mg single-dose MBX, right, our product, in respectively blue and green, you have exactly a PK profile which looks like the target product profile, the one we wanted to get by design. And here we have the smooth rays to the Tmax, right, exactly as you wish. You have a plateau when to get the drug stays constant, the concentration stays constant. Very importantly, the Tmax for both stearzepatide and Med097I is around two days. That's a burst of effect, right? That's when it gets really quickly to the Tmax. when RTmax is 13 to 14 days. So that's a big difference and also aligned with what we would expect in terms of the opportunity to reduce GI and improve tolerability. Here you can see that the self-titrating PK profile, which is, as I said, supposed to improve tolerability. So here, that's a multiple dose already. So that's a multiple dose in this slide. What you can see here is what we call the B1 cohort. That's a green, the green curve. Keep in mind the green curve. The green curve is a 60 milligram given weekly, a 30 milligram given weekly, sorry, 30, 3-0 milligram weekly, weekly, followed by 120 milligrams, four times the initial weekly dose, so four times. And you can see in this curve how smooth the rays even up to the fourth administration. And here, even when you give the 120 milligrams, you have again this smooth rays to the Tmax, really exactly what you want to observe. The comparison here is with 180 milligram in orange given as a single dose, which was a maximum tolerated dose. And what you can, in terms of nausea, vomiting, et cetera. And what you can observe here is that you reach the same concentration than the SAD, right, The single dose at 180 milligrams, but with a very, very different tolerability profile. And I'm going to anticipate a little bit. On the left, the orange curve, the SAD 180, give nausea, vomiting, and diarrhea. On the right, the multiple administration of 30 followed by 120 gives almost no GI effect. And I will show you later. So now what we have here is the safety and tolerability of this MAD, the multiple administration I was talking about. Look at, in the tolerability section, one event only of diarrhea. In fact, it was two days of loose stool and disappearing after the initial administration. No nausea, no vomiting and reaching this type of Tmax. I mean, if you look also, it's blinded. I remind you, it's blinded, so I can tell you that the weight loss is at 7%, all patient or all subject included in this analysis. And the range is between 0% and 16%. So very exciting result in terms of both. tolerability, demonstrating the monthly administration. I didn't tell you but the time to reduce the half C-Max is 26 days following the repeated administration. So we have demonstrated the three pillars of what we were expected monthly, tolerability, and really good potential for weight loss. Now I'm

P. Kent Hawryluk, CEO

to hand over to Kent. Thank you, Sam. The great part about that preview that we shared with the community a few weeks ago and are today is that this is the PEP design now demonstrated proof of principle in the target population of obese adults where you have this slowly rising and steady exposure. And this translates to our obesity portfolio that is growing. We also a few weeks ago declared our imicrotin. We use this term to describe our molecule that combines four plus mechanisms in a single molecule. The dual incretin agonist plus a taste of glucagon, so not as strong as the other mechanisms, and then DACRA, which is calcitonin and amylin. We believe that we will have monthly, you know, true monthly dosing, as well as this improved tolerability versus others in the Omicrotin class. So we are excited to move toward the clinic in there with this program, and the data so far as showing, this is a non-human primates, that we have this very flat exposure, similar to what we've seen in the humans. Whereas the omicritin that is designed for weekly administration, you see first of all you have the burst effect which leads to a GI intolerability and then it doesn't have the exposure to cover a month. It has to be provided with dose weekly. So more to come and off to a great start. We demonstrated that in non-human primates, we've seen a leading weight loss with persistence, noting that non-human primates turn over albumin three times faster than humans. And importantly, there was no nausea, vomiting, and diarrhea that you typically see with the drugs in this species. So I've covered these catalysts. I just would note that I believe MBX is unique in having multiple clinical stage programs in blockbuster markets, all supported by this clinically validated PEP platform and the cash to take these through meaningful value inflection points. Thank you, Fiona.

Fiona, Analyst — Jefferies (Moderator)

Thank you. There's certainly a lot to unpack there. I want to maybe just ask a few pointed questions on CanVoo and also your OBC franchise, which are turning out to be the two pillars of the MBX portfolio. So starting from CanVoo, we're just a week away from endo data, data, which is highly anticipated, and a lot of people are building expectations, particularly on the durability. So what type of durability data should we be expecting? And based on your conversation with the KOL, what type of profile is considered competitive?

P. Kent Hawryluk, CEO

Let's start with the PTH replacement therapy. This is very known biology. As I said, PTH is an established mechanism. It's the deficient hormone. So we've already established in our phase two that we have a full week coverage. We have the expected PTH biology. And obviously, we met our primary endpoint. So I also focus on the retention as well as durability. We had 94% entering the OLE. At six months, we had retained most of them. There was a few that for feasibility, they elected not to continue in the OLE. And we will look at one year at how the patients are retained in the study. We think that's a really good measure. And we'll look at other markers as well to demonstrate the overall biology of the disease. Now, you mentioned durability. Let's note that when we spoke to KOLs, to patients, to our own engagement through primary market research, working with third-party firms, the consistent message is that if we are in the ballpark of the once daily with our once weekly, that is a best-in-class profile. So just in the ballpark of efficacy, that means it's the choice for PTH-naive patients. and in a large majority, it will drive switching, right? So once weekly really matters. These patients are kind of done with the standard of care, pills every day. They want a convenient weekly drug that fits their lifestyle and makes them function normally. So that's really what we're looking at in the phase three to demonstrate the overall biology that we've established with our once weekly PTH replacement therapy.

Fiona, Analyst — Jefferies (Moderator)

That's very helpful. Definitely looking forward to the data. And as you, as Cam was heading into phase three, just around the corner, tell us more about this design, because you have some very interesting components, particularly on the urine calcium, which is the secondary endpoint. Just tell us how important that is to have that in the label for HP patients and how much of an advantage it can offer you.

Sam Azoulay, Analyst — Other

Yeah, happy to answer. The urine calcium is a very, very important parameter in hypoparathyroidism, and addressing this issue for patients will prevent CKD in the long term. So that's why we thought it was very important to focus on this endpoint. So in this design, obviously, we are going to look at the responder rate as usual, but in addition, we'll be looking specifically at the population of patients with elevated urine calcium at baseline who normalize both urine calcium and serum calcium. And it's a very important point that the study is designed with this purpose. That means it's a pre-specified endpoint. We have calculated the power of the study accordingly. And during our meeting with the FDA, they didn't have any comments on our goal and objective. So if everything works well, and if we meet our expectation, we can expect to have this differentiation in the label, and that would be a big change for physicians.

P. Kent Hawryluk, CEO

building on that when we conducted this primary market research I referenced it came through that going beyond weekly if we're able to achieve this primary endpoint which is not in the label for the once daily PTH that would be and they use this term transformative differentiation so we're very excited to see how that plays out and we've powered the study appropriately for it

Fiona, Analyst — Jefferies (Moderator)

It's going to be a very powerful analysis. Let's assume everything goes well and then CAMU gets approved. Based on your KOL interactions and the market research, what type of patients do you think are the most easily accessible and what other layers of patients can potentially convert from daily PTH to CAMU?

P. Kent Hawryluk, CEO

So we believe that we have a best-in-class profile, and when we conducted the primary market research, our Phase II data was presented on a blinded basis compared to the label for the once daily, and hands down, it was chosen. We believe that this means that we can become the market leader for sure, and I think it's interesting when you look at other indications where you move from a once daily to a once weekly. Not only does the once weekly become the leader, but it tends to expand the market. So perhaps patients who weren't ready to begin a therapy now come on therapy, and we look forward to serving as many of the PTH patients as possible.

Sam Azoulay, Analyst — Other

If I may add something, I think this population for now is treated for symptoms, right? And PTH replacement therapy offers the treatment of the disease. So it's not only targeting serum calcium, but also targeting bone and kidney. And we've seen this in our phase two. We'll demonstrate it in the phase three. And it's like treating the anti-problem instead of really treating the symptoms.

Fiona, Analyst — Jefferies (Moderator)

That's a perfect segue to, you know, obesity, which is also building on the long acting profile. So coming into this space, Kent, we know you have, you know, 20 years of experience before obesity was even a thing. Now, looking at this space from your point of view, what kind of, you know, theme or any meaningful gaps that you can identify?

P. Kent Hawryluk, CEO

Thank you for that question. We at MBX have team members who have been in the field for 20 years and more. I would include Richard DeMarkey, our scientific co-founder. we have anticipated that the next wave in obesity will be one on therapies that are once monthly that provide the convenience that patients really want. But what good is a drug that causes you to lose weight if it makes you feel lousy? So what's also important, in addition to being once monthly, is that we have improved tolerability as a monthly drug. So that is where I think the opportunity is. We know these mechanisms are very active, and we'll see the weight loss. It's not a race to weight loss. It's really sustained benefit. That's what the patients and doctors and, frankly, payers are looking for. So I'm pleased that we anticipated that, and we're already in the clinic. You've seen some of the data showing that this approach seems to be quite powerful.

Fiona, Analyst — Jefferies (Moderator)

Yeah, thank you for that. So looking at the blinded data, which is already very promising, and, you know, we did the math, if placebo behaved as it should, the weight loss will only look better. So looking into maybe longer term, how, you know, competitive do you think the weight loss needs to be to support a monthly drug?

P. Kent Hawryluk, CEO

Well, I would say that 7% mean weight loss at eight weeks with our very first MAD cohort was pretty impressive. So I go back to it's not a race. You want to see steady weight lowering that's sustained, that doesn't cause discontinuation, that supports adherence and long-term benefit. it because we know this is a chronic illness and that patients need to be on the drug really for

Fiona, Analyst — Jefferies (Moderator)

the rest of their lives. Makes sense. And now that you have multiple great assets in your arsenal, how do you see them, you know, complement each other? And then where is the direction that this

P. Kent Hawryluk, CEO

obesity portfolio is headed? We are seeing segmentation in the market. And that's recognizing that obesity is a heterogeneous disease, not all patients are the same, and so you need various treatment options, much the way you have in treating cardiovascular disease. So we're evolving towards that, and we've also anticipated that different mechanisms will give you different benefits in different individual patients. So we have our triple G coming next quarter, and we're excited about that because the data coming out of Lilly with redditrutide is promising in terms of the amount of weight loss that can be achieved, especially for really obese, highly obese individuals. But in the case of redditrutide, you see it comes at a cost of tolerability. And we think with our unique PEP approach that's been clinically validated, we can deliver the benefits of a triple G with improved tolerability.

Fiona, Analyst — Jefferies (Moderator)

Perfect timing as we head into ADA next week. I think you'll get a lot of recognition from that as well. We already touched on the cash position, which is very solid. It gives you a lot of opportunity and flexibility. Anything else you want to highlight to the audience?

P. Kent Hawryluk, CEO

Well, we are excited about INDO coming up next week. This is our flagship program. You can see that we have conviction that we have a best-in-class, once-weekly PTH replacement therapy. We've brought in the big guns, right, Mark Swade, and building out our commercial team because we want to deliver this to patients. And I think you'll see us continue to move down that path. And there's room for improvement, right, with the PTH. We're glad that a once-daily is available to patients, and we look forward to providing patients a better option if we're fortunate to get it approved.

Fiona, Analyst — Jefferies (Moderator)

Thank you, Ken, and thank you, the audience, for listening and watching. It's going to be a very exciting time for MBX.

P. Kent Hawryluk, CEO

Thank you.