Good morning, my name is Kent Hawryluk, and I'm the co-founder and CEO of MBX Biosciences. I would like to thank the Goldman Sachs team for the invitation to participate in this conference and to provide an opportunity to present an update on the company and what is promising to be our most important year in our company's history. With the data release next quarter of our available phase II data for the first PTH replacement therapy prodrug that's once weekly. I will be making forward-looking statements and encourage you to review our risk factors and other disclosures in our SEC filings, which are available on our website. For those of you who are new to the MBX story, MBX Biosciences is a clinical-stage biopharmaceutical company that's founded by global leaders in peptide drug design, development, and commercialization.
MBX's aim is to unlock the full potential of peptides through precision therapeutics that provide continuous infusion-like PK drug exposure and convenient infrequent dosing regimens. Applying our novel PEP technology, we already have two clinical- stage programs in indications with significant unmet need, including chronic hypoparathyroidism, or HP, and post-bariatric hypoglycemia, or PBH. We expect to have a third clinical- stage program soon in obesity. We have other programs in lead optimization to address obesity and comorbidities and plan to provide an update on those activities later in the year. This technology, which we call PEP, was invented by Dr. Richard DeMarchi, our scientific founder. He is a leading peptide chemist and the inventor of Humalog and the first GLP-1/GIP co-agonist.
Together, Richard and I have a more than 20 year history of successfully creating life science companies in metabolic disorder and endocrinology, which have yielded partnerships in M & A with Merck, Lilly, Roche, and Novo Nordisk. MBX is well funded. We ended last quarter with over $240 million, which we expect to support our operations into mid-2027, including a number of important value- creating milestones across all of our programs. Our team brings exceptional expertise from large pharma and clinical development stage companies, and we will continue to expand our team to support the ongoing development and commercialization of our product candidates. Our PEP technology is driving an ever- expanding pipeline of differentiated candidates. Our lead investigational drug, c anvuparatide, is a potential once- weekly PTH replacement therapy prodrug which has orphan drug designation in the U.S.
We published positive phase I data last year, and our phase II trial is fully enrolled and on track to read out data in the third quarter of this year. Our second compound, MBX-1416, is a potential once-weekly therapy for post-bariatric hypoglycemia, or PBH. We presented positive phase I results earlier this year, and we plan to hold an end- of- phase- one meeting mid-year, followed by a phase II in patients with PBH in the second half of the year to further optimize dosing. MBX also has an obesity portfolio of differentiated PEP candidates, including MBX-4291, which is a GLP-1/GIP co-agonist prodrug which we believe has the potential for once-monthly dosing as well as other benefits such as durability and greater weight loss.
We are on track to file an IND this quarter, followed by a phase I study in overweight and obese adults. This will include a 12-week study, which we believe will not only confirm the monthly time action but demonstrate some of the other potential benefits I mentioned. We are very excited about that program as well as the ongoing development activities and other programs in our obesity portfolio. You see that we expect to achieve proof of concept in the target population in each of our three programs in 2025 or 2026. I'll give you a little look under the hood of our PEP technology platform, which is driving the discovery of our candidates. When you think about peptides such as hormones, nature has optimized these for physiology rather than pharmacology. They have short half-lives.
Frequently their chemical properties are challenging, and often you need more than one mechanism to have effect. We start with our technology you see there on the left, with innovative peptides that are optimized for potency, stability, and solubility. We also have the ability to engineer multiple mechanisms of action in a single peptide, a la our GLP-1/GIP co-agonist. We have a novel programmable prodrug as depicted in the middle of this slide. This provides gradual, controlled release of active drug, which can improve clinical outcomes. This mechanism uses a prodrug extension that, under physiologic pH and temperature, converts and releases active drug. This does not require any enzymatic intervention. It is a very natural process. We also, as you see on the right, employ fatty acylation, which is the most preferred contemporary approach in peptides to extend time action.
It facilitates binding to the albumin protein in circulation. It's used by tirzepatide, semaglutide, and many other peptide candidates, and it's compatible with oral formulation. What is really unique to MBX is that we synergistically combine our programmable prodrug technology and fatty acylation to provide a unique PK profile that resembles continuous infusion- like drug exposure. Let's take a closer look at our lead program in chronic HP. Canbuparatide. Chronic HP is a serious condition that, although rare, affects over 250,000 people in the US and EU, and it carries a high burden of illness. Surprisingly, the standard of care today in chronic HP is not hormone replacement, but rather pill supplements, active vitamin D, and calcium. Notably, these do not address the underlying cause of disease, which, as shown on the left, is PTH, or parathyroid hormone deficiency.
These patients with HP have large fluctuations in their calcium, symptoms of hyper- and hypocalcemia. This includes brain fog, tetany, seizures, GI distress like nausea, constipation. The even worse for patients is that these fluctuations in calcium cause long- term complications affecting multiple organs, particularly the kidneys. The good news is that we're now at an inflection point in a transition in the standard of care. We now have, as of last December, a PTH replacement therapy that is available to patients in the U.S. However, there's room for improvement. This drug, Yorvipath, is administered once daily subcutaneously. It is only approved in the United States at half the dose range as in Europe.
Also, there is a sizable portion of the population, the HP patients using Yorvipath who in their phase III study showed that after one year and a year and a half needed to increase the dose due to waning efficacy. Room for improvement. We believe that Canvuparatide can provide once- weekly treatment for patients with consistent PTH exposure. Starting with once weekly, we see this as a tremendous advantage for patients. When we look at other indications like obesity, type 2 diabetes. When we transitioned from a once- daily treatment option to once- weekly, there was rapid adoption by the patients and the prescribers for the once- weekly initially for convenience, but you typically also see improved clinical outcomes.
In the case of canvuparatide, we believe that we have the potential for better adherence and compliance with a once- weekly, and also due to our continuous infusion-like PK profile, we believe that at maintenance we can provide more stability and less excursions into hyper- and hypocalcemia and reduction of those symptoms and the long-term complications they cause, just providing greater homeostasis, thereby making patients feel better overall. We conducted a placebo-controlled phase I study, single and multiple ascending dose, in healthy volunteers. The purpose of this study was to explore the safety, tolerability, PK, and PD of canvuparatide. I'm delighted that the phase I resulted exactly as we expected based on the PEP design. First, we achieved our primary endpoint. Canv uparatide demonstrated overall favorable tolerability and safety profile.
Additionally, we saw dose- proportional increases in drug concentration, and we saw this flat infusion-like profile with a peak to trough over a seven- day period comparable to Yorvipath over a 24- hour or one- day period, with an eight- to nine- day half-life that fully supports full week coverage with once- weekly administration. We saw as well the expected PD effects, dose- dependent increases in serum calcium and decreases in endogenous PTH, which is another marker of increased calcium. These results supported our dose selection for phase II and give us confidence in our ability to show a clinical effect in HP patients. In our phase II study last March, we were very pleased to announce that our AVAIL phase II trial was fully enrolled and that we had exceeded the original enrollment target with 64 patients randomized.
We view this as a testament to the strong interest from patients and the study investigators in a once- weekly treatment option. This phase II study is really well designed, we believe, to show clear and definitive clinical proof of concept as well as differentiation and ability to meet the unmet need in HP. The 64 patients that were randomized are evenly randomized across four cohorts: 400, 600, or 800 micrograms of canvuparatide given once weekly, or to placebo, and the 12- week treatment period is divided into a four- week fixed- dose period followed by an eight- week d ose adjustment period where the dose of canvuparatide can be increased or decreased by 200 micrograms every two weeks for a total potential increase of 800 micrograms.
If you take a patient who is in the 800 cohort for the four- week fixed- dose period, during the eight- week dose adjustment period, they could increase that potentially if needed to 1,600 micrograms. The primary endpoint of this study is the proportion of patients who eliminate active vitamin D and decrease calcium to 600 milligrams per day or less while maintaining serum calcium in the normal range. After 12 weeks of treatment with 64 patients randomized, we have 90% powering to show a statistically significant pooled treatment increase or pooled treatment effect of 55% versus 7% for placebo, or a 48% placebo-adjusted treatment response at 12 weeks, and our KOLs point out that this will be a clinically meaningful outcome and inform dose selection for the phase III.
We have an open label extension study so that all of the patients who complete avail have an opportunity to roll into the additional two years of treatment where everybody receives canvuparatide on an open label basis. We are very excited about this program and believe that if approved, canvuparatide can be a game changer for HP patients. I'll now turn to our second program in post bariatric hypoglycemia. PBH has a number of similarities to the chronic HP market opportunity. When we look at US prevalence we believe it's over 90,000 and there's currently no approved pharmacotherapy. The disease is chronic, it presents six months to three years after bariatric surgery and unfortunately the patient has it for life. We see with bariatric surgery remaining the gold standard for significant and sustained weight loss in the severely obese population, this unmet need continuing.
The cause is an excess in GLP-1, and this is due to the anatomical changes from vertical sleeve gastric bypass surgery and Roux-en-Y. This causes nutrients to quickly pass through the small intestine. The result of this is the potential for severe hypoglycemia and very significant neuroglycopenic symptoms like seizures, loss of consciousness, brain fog. This disease, PBH, is very disabling, disruptive to quality of life. Due to the unpredictable timing of the episodes of severe hypoglycemia, they can occur soon after mealtime or hours later, even in the middle of the night. The patients are advised to carry a glucagon injector as a rescue, which is typically given by a third party. This, as you can see, leads to social isolation, often an inability to hold a job, drive, et cetera.
Currently, standard of care largely rests on dietary interventions such as small, frequent meals that are low carb. This is very difficult for patients to maintain long- term. There's some off- label use of medicines, limited clinical data for these, and they're often poorly tolerated. In contrast to candidates in development, our aim is for MBX-1416 to be the first approved once- weekly treatment for PBH that provides full day and night coverage throughout the week to prevent hypoglycemia from occurring and relieving the need for rescue with glucagon, sort of eliminating that fear factor that PBH patients have today. Our molecule MBX-1416 utilizes a clinically validated mechanism in this disease, which is GLP-1 antagonism. We have a 100-fold more potent molecule than abexatide with a significantly longer half life. Abexatide has about a three hour half life and aims to be once daily.
We conducted a phase I SAD MAD study in healthy volunteers. It was placebo controlled. Again, the purpose was to explore the PKPD safety tolerability. We achieved the primary endpoint. MBX-1416 demonstrated overall good tolerability with a favorable safety profile. We demonstrated that we have that full weekly coverage with a half-life of approximately 90 hours. We also saw a PD signal in the healthy volunteers that we believe predicts a proof of concept, a clinical benefit in the PBH patients. This was a mixed meal tolerance test conducted at two different times during the MAD study, and in both cases, in both mixed meal tolerance tests, we saw an increase in endogenous GLP-1, which demonstrates that our GLP-1 antagonist is competitively blocking the GLP-1, receptor. We again expect that to have an effect on PBH patients, and that's where we're heading.
We expect an end- of- phase I meeting mid- year followed by a phase II in the PBH patients to further explore dosing. I'll now cover our obesity portfolio. I mentioned earlier that our scientific founder is Dr. Richard DeMarchi, who invented the first GLP-1/GIP co-agonist. We've been working in the obesity field for decades, and it certainly evolves quite a bit. I think we now all realize that obesity is a global epidemic and a mega blockbuster market opportunity. We see the obesity population as being heterogeneous and needing multiple treatment options. As this field evolves, we see also key limitations of the current products and development candidates in obesity. First, it's the frequency of dosing. Today the dosing is once weekly. We aim to have less frequent dosing.
Also, these obesity candidates tend to have, in the incretin field, a pretty high incidence of GI side effects, nausea, vomiting. This results in decreased adherence and compliance as well as the quite high discontinuation rate, 65% according to JAMA for the incretins. We think there's an opportunity to do better. Using our technology, we aim to have this continuous infusion-like profile that should reduce the rapid rise to maximum concentration and the fluctuations in exposure that the endocrinologists, the experts, tell us account for the GI side effects in the incretins. I'll now describe our first obesity candidate, MBX-4291. As you see from the illustration on the right, we have a GLP-1/GIP co-agonist prodrug. The stopwatch represents the programmable nature of our prodrug.
It is set to release active drug at a precise rate, and that is important to flatten that peak to trough and provide that continuous infusion-like profile. Now, down in there you see that the active drug brings in both mechanisms of action, GLP-1 and GIP, as the gold standard obesity treatment today, tirzepatide, or Zepbound. We believe that we can unlock the potential efficacy of these compounds but do so in a way that is more sustained and potentially tolerable to the patients. I am very pleased to show some data, some preclinical data, including some data that has never been presented at the podium before. Let's start with PK. This graph shows dose concentration of our active drug for MBX-4291 following a single administration in normal non-human primates, cynomolgus monkeys.
What we see here is just what I described, that slow, steady rise to maximum concentration and then sustained, sort of this prolonged flat portion of the curve. We contrast, and that's with the blue empty squares toward the bottom. Now let's contrast that to tirzepatide, the market leader, which is the dark triangles. You see this rapid rise to C max, and then the concentration is coming down. This is why Tirzepatide is given once weekly. What we see here is that even in nonhuman primates, which have a three-t ime- faster turnover of albumin than humans, we see exposure out to three weeks. We believe this is predictive of not only once monthly, predictive of once monthly dosing, but also that flat PK profile. This is supported also by multiple- dose administration in, again, normal nonhuman primates.
What we see here with multiple doses on a weekly basis is that steady rise to CMax in week one, and then at week four we see accumulation, which is expected based on the long half- life. In addition to greater exposure, we see a further flattening of the peak to trough so that it's as flat as you can imagine. We are very pleased with this nonhuman primate proof of concept. We saw this PK translate to the expected PD effects and are very excited to present these data. What we're seeing is that, with the given dose of MBX-4291 once weekly in the nonhuman primates, we see a nearly 20%, or approximately 20%, reduction in body weight. This is significant and could be potential for, we think, better weight lowering compared to the competitive set.
Where we are today is having completed our IND- enabling studies; we're on track to submit an IND this quarter. Following that, we plan a phase I study in overweight and obese adults, our target population, which includes a SAD, MAD, and 12- week part C study. The purpose of this 12- week study is to demonstrate once- monthly time action as well as other potential points of differentiation for MBX-4291, such as better tolerability due to this differentiated PK profile, and if patients can tolerate higher dose levels, then we would predict even better weight lowering as well. We think multiple ways to win with MBX-4291, and we're very excited to get started with this phase I study later this year.
I think it's important to understand that MBX is unique in having a clinically proven platform technology, multiple high- value clinical- stage programs that address significant unmet need, with a number of near- term de-risking milestones that are value- creating. With cash to support our operations into mid-2027, an ability to accomplish not only these milestones for 2025 but additionally to initiate a phase III study with canvuparatide in HP patients, a registration study, and to complete the phase I and advance other obesity candidates besides MBX-4291. We look forward to providing more updates on the story as we move forward. Again, I want to thank the Goldman Sachs team for this invitation and all of you for attending today.