MBX Biosciences Stifel 2026 Virtual Cardiometabolic Forum

Hi. Good morning, everyone. It's our pleasure to have the management of MBX Biosciences here with us today. I have to apologize for the delay. We had some linking problems. We have newly appointed CEO, Steve Hoerter, with us, as well as the Chief Medical Officer, Salomon Azoulay. As you know, MBX has a precision endocrine peptide technology that's allowed for customization of peptides for both potency and durability. Maybe we can start with a quick overview of rare endocrinology and then transition quickly to obesity, which is driving a lot of the excitement today or right now. Steve, maybe you can talk to us about what drove the management transition and where you want to take the company today.

Yeah. Sure, Annabel, and it's great to see you, and thanks for the invitation to join for the virtual symposium today. Sam and I are delighted to be here. Maybe what I'll start with, Annabel, if you don't mind, is just a brief overview, and then we can dive into that exact question about the management change. Happy to address that. For those who are joining who are less familiar with the story, we're a clinical-stage company, and we're focused on the discovery, development, and eventual commercialization of our novel peptide therapies that we have now in the clinic, and we, of course, have a robust early pipeline in IND-enabling studies at the moment. The company's Scientific Co-Founder, Dr. Richard DiMarchi, is a pioneer in the field of peptide chemistry, and so he's the architect of the platform, which we refer to as a precision endocrine peptide platform.

As you noted, Annabel, the platform was designed to overcome some of the key limitations of peptide therapies and to improve clinical outcomes. We do that by engineering peptides to have optimized pharmaceutical properties to extend the time action, and really importantly, to deliver a PK in humans that has a low peak to trough ratio. So it's almost like an infusion-like PK that we see with our engineered peptides. What that allows us to deliver is a very differentiated PK profile, as I just noted, but that translates into a differentiated PD profile for our programs. The lead asset is canvuparatide, which we're developing for the treatment of chronic hypoparathyroidism. We'll talk about this, I'm sure, later. We just initiated the phase III clinical study for canvuparatide in this disease. Then we have a really robust obesity portfolio.

The lead program, MBX 4291, is a true once-monthly GLP-1/GIP co-agonist. This is now in a phase I study, and we're on track to deliver unblinded data from cohort C1 of that study in quarter 4, so we're looking forward to that milestone. Then we have two additional obesity programs that are in IND-enabling studies, MBX 5765, which is an amycretin, and then our triple G, our version of retatrutide which is MBX 6180, and that is also in IND-enabling studies. So two programs that we expect will advance to the clinic next year.

Great. So we have this robust portfolio, all wholly owned.

And we're very well capitalized. As of the end of Q2, we had about $420 million in cash. That gives us a runway into 2029, and the opportunity to deliver on a number of what we think will be value-creating milestones for the company and for shareholders.

Excellent. First wanted to talk about canvuparatide and HP. Obviously, the phase II Avail study was very successful, delivering once-weekly PTH with good clinical meaningfulness and safety. So what are the key takeaways from that trial that you want to pull out, and what you brought into the phase III?

Let me, thanks, Annabel, and very pleased to be here. Yeah. We were very excited by the results of the phase II studies, the Avail study, that showed a benefit with the response rate of serum normalization of serum calcium with independence of supplement calcium and vitamin D versus placebo in the initial 12 weeks. We confirmed this result at six months, at 12 weeks, so durability of effect. But very importantly, it's also the target organ. What we saw is that there is an improvement in urine calcium excretion, especially in patient with elevated urine calcium at baseline. And that's a target population because that's a population which is the most prone for CKD. So that's very encouraging result.

The last part is the bone, that like reactivating the bone turnover with an increase in biomarker, as you would expect, and confirmed by normalization or normal BMD. Everything as a PTH replacement therapy, as you would expect, so great potential for having a best-in-class weekly PTH replacement therapy with canvuparatide. Learning. We learned that the 600 microgram is really the weekly starting dose, and we will be starting the phase III program with 600 microgram. The dose range that we are offering has been confirmed 400 to 1,600 microgram with a dose titration as usual. That's a learning from the phase II.

Okay. Great. There was also quite steady delivery, with PTH concentrations that were in a very narrow band. Maybe you can talk about the significance of that.

Oh, that's a great point. Steve alluded to it through the platform, that having an infusion-like profile, and that exactly what we showed already in phase I with the peak to trough concentration, which were very similar after one week, to the daily administration of YORVIPATH. Very good. We confirmed in the pop PK, we confirmed this result in the target population of patient with hypoparathyroidism with a peak to trough ratio of 1.3, which is really great over a week. What's the implication? Implication is maintaining the serum calcium within the normal value over time. The more stable your concentration is over time, the better it is in terms of control and less excursion in hypo and hypercalcemia. So great PK profile. Okay, excellent.

Just to clarify one point, you're starting at 600 micrograms, but your range is from 400 to 1,600. So patients will be able to titrate up and down by 200 micrograms as necessary.

Exactly right. So that we have confirmed that we want to get the titration up, with exceptional case where you can titrate also down, that's always offered. But the 600 microgram is really a good starting dose that combine efficacy and safety. So that's really the dose that we are aiming to start with. Then you titrate up according to the response in terms of serum calcium that you want to stay normalized while decreasing the supplement. So it's like playing with the supplement and the drug dose, and we offering this large, broad range that we should cover the entire hypoparathyroidism patients.

Okay, great. And so feedback from the physician community regarding what they want to see beyond just weekly convenience. What is the most important feature here that they want to see come out, and how is phase III capturing that?