MBX Biosciences, Inc. (MBX) Earnings Call Transcript & Summary

Ladies and gentlemen, greetings, and welcome to MBX Biosciences Conference Call. Today's call is being recorded. [Operator Instructions] As a reminder, this conference is being recorded. It is now my pleasure to turn the call over to MBX Biosciences Senior Director of Investor Relations and Communications, Jim DeNike.

Thanks, Rob. Good morning, and thank you for joining us this morning to review the exciting top line results from our Avail Phase II clinical trial. I'm very pleased to report that earlier this morning, we issued a press release announcing positive results from our Phase II trial of once-weekly canvuparatide in patients with hypoparathyroidism as well as six months results from the ongoing open-label extension study. The press release and presentation slides are available on our website. So, before I turn the call over to our speakers, I want to remind everyone that this presentation includes forward-looking statements. These statements are based on current expectations and projections and are subject to risks, uncertainties and assumptions. I encourage you to review the risk factors and other disclosures outlined in our most recent SEC filings, all of which are available on our website. Joining me on the call today from MBX are Kent Hawryluk, CEO and Co-Founder; Dr. Sam Azoulay, CMO; and Rick Bartram, CFO, who will be joining for Q&A. I'll now turn the call over to Kent.

Thank you, Jim. Good morning, and welcome. Today, we are thrilled to share positive top line results from our Avail Phase II trial. The results exceeded our expectations and reinforce the potential of once-weekly canvuparatide as a best-in-class treatment for hypoparathyroidism. We took a peptide PTH with a natural half-life of an hour and engineered it into a therapy that can be given once weekly. This is a powerful demonstration of our Precision Endocrine Peptide or PEP platform technology. Today marks a seminal moment for the company and the patients we serve. We committed to provide 12-week results this quarter. Due to the rapid enrollment of the trial and the high rate of patients choosing to continue into the extension study. In today's update, we are able to include six-month results alongside the 12-week double-blind portion. These data offer a comprehensive picture of once-weekly canvuparatide's clinical profile and provide a strong foundation as we plan for Phase III and ultimately registration. I know you're eager for the data, so let's begin with the top line results shown on Slide 4. These results are exceptional, and they redefine what's possible for patients in our PEP platform. At week 12, 63% of patients receiving once-weekly canvuparatide achieved the primary composite endpoint compared with 31% who responded on placebo, representing a statistically significant difference. Importantly, every patient completed the 12-week study and 94% chose to continue into the open-label extension. We view this exceptionally high rollover as a clear testament to patients' enthusiasm for continuing their once-weekly treatment. In the ongoing open-label extension, overall responder rates increased to 79% at six months, highlighting the consistency and potential durability of response with once-weekly canvuparatide as doses are optimized over time. At week 12, urine calcium excretion was reduced in canvuparatide-treated patients with elevated baseline values, highlighting the therapy's ability to help restore calcium balance. We also saw increases in bone biomarkers in canvuparatide-treated patients at week 12 with continued improvement at six months, which is consistent with reestablishing normal bone physiology. Once weekly canvuparatide was well tolerated in the 12-week trial with no treatment-related serious adverse events or discontinuations. Together, we believe these results underscore the potential of once-weekly canvuparatide to establish a new standard of care for adults with hypoparathyroidism and strongly support advancement into Phase III development. Before diving deeper into the results, let's review the disease background. As shown on Slide 5, HP is a chronic condition with significant unmet need that affects over 250,000 people in the U.S. and Europe combined. The disease is caused by a deficiency of parathyroid hormone or PTH, most often due to inadvertent removal of the parathyroid glands during neck surgery. Because PTH is responsible for maintaining calcium homeostasis in the blood and in tissues such as nerves and muscle, its absence disrupts multiple systems. It is important to note that acute symptoms and long-term complications, which include kidney stones and chronic kidney disease arise both from PTH deficiency itself and from the standard of care. Turning to Slide 6. Due to the limitations of existing treatment options, patients on standard of care do not have restoration of the body's natural physiology and may experience large swings in serum calcium. Conventional therapy is burdensome, requiring patients to take pill supplements frequently throughout the day and night. A PTH replacement therapy was approved in 2024, but requires an injection every day. In contrast, canvuparatide is designed as a potential once-weekly best-in-class, long-acting PTH replacement therapy with continuous infusion-like PTH exposure. Increasingly, we're seeing in multiple therapeutic areas such as type 2 diabetes and obesity that patients and prescribers rapidly adopt the weekly treatment option for both its convenience and its improved real-world outcomes. We believe once-weekly canvuparatide can offer these same advantages. I will now turn it over to Sam to go over the results from our Phase II Avail trial and ongoing open-label extension study.

Thank you, Kent. But let me start first by telling you how excited I am to share these results with you. I will begin with an overview of the Avail Phase II trial design and open-label extension study. The Avail trial was a randomized 12-week double-blind, placebo-controlled Phase II study designed to establish the optimal dosing range and titration strategy for Phase III while also assessing the efficacy and safety of once-weekly canvuparatide. Eligible patients were adults with a confirmed diagnosis of HP for at least six months who required conventional therapy consisting of active vitamin D plus calcium above prespecified minimum threshold levels. After an optimization period, a total of 64 patients were randomized and equally distributed into one or four treatment arms, once weekly canvuparatide starting at 400, 600 or 800 microgram or placebo. The 12-week blinded treatment period consisted of a four-week fixed-dose period, followed by an eight-week dose adjustment period where patients could adjust their dose every two weeks in a 200-microgram increment up to a maximum of 1,600 micrograms depending on their starting dose. Throughout the 12 weeks, patients could also receive conventional therapy as needed to maintain normal serum calcium by following a prespecified titration algorithm. The primary composite endpoint was a proportion of responder at week 12, which is defined on the slide. Select secondary and exploratory endpoints are also listed and will be discussed in more detail today. All 64 patients completed week 12 and 60 elected to continue into a two-year open-label extension study. We view this as a strong indication of both patient interest in remaining on the once-weekly canvuparatide and the favorable profile observed in the study. The objective of the open-label extension is to evaluate the long-term safety, potential durability of effect and optimize dosing of once-weekly canvuparatide as patients continue treatment beyond the initial 12-week study. Turning now to Slide 9. We will review the patient demographics and baseline characteristics. Overall, the group were well balanced across the four treatment arms. The median age was 49 years and female made up 80% of the study population, which is typical for this indication. Race and ethnicity were well balanced across group. Similarly, on Slide 10, we have the baseline disease characteristics. The mean duration of HP for the total patient population was approximately 10 years. About 90% of patients had chronic HP in the postsurgical setting, which was one of the two stratification factors, while the remainder had HP from other causes, including idiopathic, genetic or autoimmune. At study entry, the median daily calcium dose was 2,000 milligrams with a wide range from 800 to 13,500 milligrams per day, while the median active vitamin dose was 0.75 microgram per day ranging from 0.5 to 2.5 microgram. These numbers illustrate the high treatment burden patients were carrying at baseline. The mean baseline serum albumin adjusted calcium was 9.2 milligram per deciliter in all patients and mean serum PTH level range from 9.2 to 12.1 nanogram per liter across treatment arms with slightly higher level noted in the placebo group. This low PTH level were consistent with the disease. The other stratification factor was patients with 24-hour urine calcium or below -- above or below 250 milligram per day and fewer than half of patients in the trial had baseline urine calcium expression above 250 milligram per day. Overall, we believe our trial enrolled a very representative HP population, also similar to patients studied in other recent clinical programs. Let's now review the clinical results, which we believe highlight the exciting potential of the once-weekly canvuparatide. Here, on Slide 12 are the results of the prespecified primary composite endpoint. At week 12, 63% of patients across all starting dose of once-weekly canvuparatide achieved the primary composite endpoint compared with 31% of patients on placebo. This one -- this was a statistically significant difference. Patients met this endpoint in the full canvuparatide-treated group with zero contribution from PRN, demonstrated that responses were achieved with a once-weekly administration without the need for rescue therapy. When looking at the proportion of patients meeting each individual component of the composite criteria at week 12, all three showed a statistically significant difference between canvuparatide-treated patients and placebo. These results provide strong evidence of once-weekly canvuparatide's potential efficacy across these key measures of disease control. On Slide 13, we look at responder status at week 12 by starting dose group, which was a prespecified secondary endpoint designed to explore the dose response. As shown in the table, 50% of patients in the 400-microgram arm achieved responder status at week 12 compared with 69% of patients in the 600 and 800 microgram arms. With the 800-microgram arm achieving statistical significance. In addition, the 800-microgram dose was a median dose of responder at week 12. Overall, this data demonstrate that responder rates were generally higher at the 600 and 800 microgram starting dose compared with the lowest 400-microgram starting dose. This data not only demonstrates once-weekly canvuparatide dose response and wide therapeutic range across multiple dose levels, but also help inform dose selection for Phase III and increase our confidence in identifying the optimal dosing strategy moving forward. On Slide 14, we are showing the albumin-adjusted serum calcium level over 12 weeks. It's a key measure in HP patients since maintaining calcium within the normal range is a central goal of therapy. Over time, patients treated with canvuparatide consistently maintain serum calcium within the normal range at every visit. Placebo patients trended downward initially, but then leveled out through continued use of conventional drug. We'll take a closer look at supplement use later in the presentation. We believe these results support the profile of a once-weekly therapy providing stable control. Now let's turn to Slide 15, which shows the effect of once-weekly canvuparatide on the 24-hour urine calcium excretion, which is an important endpoint as elevated urine calcium is a well-recognized complication of conventional therapy and a major contributor to long-term renal risk. As expected with PTH replacement therapy, 24-hour urine calcium decreased in patients treated with canvuparatide with a more pronounced reduction in patients who entered the trial with elevated baseline levels. In this subgroup at week 12, urine calcium decreased by 203 milligram in the canvuparatide group versus 117 milligram in placebo. This reduction in the canvuparatide group occurred while maintaining serum calcium in the normal range with less reliance on conventional therapy compared to placebo. In summary, the 12-week results shows that once-weekly canvuparatide achieved the primary endpoint and helped restore the key features of PTH physiology. Now we are going to turn to the results from the ongoing open-label extension study. At six months in the open-label extension, 79% achieved responder status, an increase from 63% observed at week 12 in the blinded portion of the study, which is a terrific result. Patients who had already been receiving canvuparatide continued at their last assigned dose with the option for further titration if needed, while those previously on placebo started at 400 micrograms once weekly and follow the same titration algorithm to reach their optimized dose. Now I'm going to break it down by components. 90% of patients gained independence from active vitamin D, 81% gained independence from therapeutic dose of oral calcium and 95% maintained adjusted serum calcium within the normal range. The results of the individual components were comparable or higher that what we observed at week 12, providing highly encouraging evidence of the potential durability of once-weekly canvuparatide over time. On Slide 18, you can see changes in serum calcium level from the start of the Avail study through month six in the open-label extension. Calcium levels were in the normal range in both the canvuparatide and placebo groups before treatment. As we have already shown, canvuparatide-treated patients maintained normal serum calcium through 12 weeks. In the extension, those patients continued to maintain stable calcium at six months, supporting the durability of once-weekly canvuparatide beyond the initial treatment period. In the placebo group, calcium level declined early and remained low through week 12 despite ongoing use of active vitamin D and calcium supplement. However, after switching to canvuparatide in the open-label extension shown in light blue, serum calcium level in these patients increased to well within the normal range, demonstrating a direct effect of once-weekly canvuparatide in restoring physiological calcium control. This occurred while active vitamin D and calcium supplements were gradually decreased or discontinued, which we review on the next slide. On this slide, Slide 19, you can see the changes in the active vitamin D dose and total daily calcium dose from the start of the Phase II study through six months in the open-label extension. On the left, in the canvuparatide-treated group, active vitamin D dose decreased rapidly within the first two weeks and nearly all patients discontinued use altogether. In contrast, a substantial proportion of placebo patients were still taking active vitamin D during the 12-week period. Upon crossing over in the open-label extension at a starting dose of 400 micrograms of canvuparatide, those patients were able to decrease active vitamin D and ultimately discontinue. On the right, you see a similar pattern for calcium supplement with patients on canvuparatide reducing their daily intake, while placebo patients required higher dose until they transition into the expansion. Overall, these results demonstrate durability of effect of canvuparatide in both patients who started on therapy and those who switched from placebo, maintaining normal serum calcium while greatly reducing the heavy pill burden of conventional therapy. One final result I would like to highlight here on Slide 20 is the effect of once-weekly canvuparatide on bone health in patients with HP. As a reminder, in the absence of PTH, the skeleton cannot properly release calcium and phosphate. This leads to abnormally low bone turnover. Here, we are showing three markers of bone turnover and formation over the 12-week double-blind period and through six months into the open-label extension. CTx is a marker of bone resorption and overall turnover, while BSAP and P1NP are bone formation markers. The blue line represent patients treated with once-weekly canvuparatide and include patients who crossed over from placebo after 12 weeks. What we observed is a substantial increase in all three bone markers during the first 12 weeks in canvuparatide-treated patients in comparison to placebo. This upward trend continued through the six months. We are very encouraged by this finding. They show that once-weekly canvuparatide is restoring normal bone remodeling activity, both formation and resorption, which is a hallmark of reestablished PTH physiology and contributing factor to long-term bone health. Now let's turn to the safety. On Slide 22, we demonstrate that once-weekly canvuparatide was generally well tolerated. As you can see in the top row, 73% of canvuparatide-treated patients and 63% of placebo patients experienced treatment-emergent adverse events with rates that were fairly similar between all treatment cohorts. Importantly, the vast majority of events were reported as mild or moderate in severity and recovered without dose interruption. Approximately half of patients in the pooled canvuparatide group and approximately 40% of placebo patients experienced adverse events that investigators considered related to drug, and I will go into those details on the next slide. There was one serious adverse event in the 600-microgram cohort, a case of Bell’s palsy that was not considered treatment related and resolved without sequela. Finally, there was no study drug-related discontinuation, no study discontinuation and no deaths during the 12-week treatment period. On Slide 23, we provide additional detail on the most commonly reported adverse events. This table lists any treatment emergent adverse events that occurred in more than 5% of patients in any treatment group and at least 2% more frequently than in the placebo group. The most commonly reported events among canvuparatide-treated patients were headache, hypercalcemia, arthralgia and nausea. On Slide 24, we will take a closer look at adverse events of special interest. Starting with hypercalcemia. This was reported in approximately 13% of patients in the 400 and 600-microgram group and 31% of patients in the 800-microgram group compared with 6% or one patient in the placebo arm. Hypercalcemia is an expected outcome from PTH replacement therapy, and it was also observed more frequently in the highest dose cohort during the four-week titration phase, while patients were still titrating down from conventional therapy. Importantly, none of the cases required hospitalization. Hypocalcemia was reported in four treated patients, one patient in each of the 400 and 600-microgram group and two patients in the 800-microgram group compared with three patients on placebo. As expected, nearly all hypocalcemic events occurred within the first weeks of the titration period, again, while patients were still titrating down from conventional drug. None of the patients with reported hypocalcemia required hospitalization. We are also very pleased to see that injection site reactions were infrequent overall, occurring in 18.8% of treated patients versus 12.5% on placebo. Finally, I would like to close by highlighting safety data from the ongoing open-label extension, and that is so far to date, we are seeing similar trends as to what we observed in the double-blind study and we are highly encouraged by the favorable safety profile. Taken together with the efficacy results, we believe this data strongly supports the potential of once-weekly canvuparatide to become a new standard of care for patients with HP. And with that, I will hand it back to Kent.

Since our IPO one year ago, we set out to deliver on the promise of once-weekly canvuparatide. So it is particularly gratifying to share data that bring that vision to life. These results are very encouraging and reinforce our conviction that canvuparatide is poised to be best-in-class. The strong Phase II Avail data unequivocally demonstrate that once-weekly canvuparatide can generate high responder rates in treated patients. Data from our open-label extension study showed the potential of even higher responses on canvuparatide as patients are titrated to their appropriate doses. Our results are already competitive to historical studies of an FDA-approved once-daily injection. HP is a chronic disease and is a significant unmet medical need. We estimate the U.S. and the EU represent a multibillion-dollar market opportunity and once-weekly canvuparatide is well poised with a best-in-class profile. The reason we believe that once-weekly canvuparatide may grow to be preferred by both health care providers and patients is simple. highly competitive results to date, infusion-like PTH exposure with far fewer injections. Patients don't want to have to think about their disease every day, let alone inject themselves daily. Once weekly canvuparatide can provide freedom by relieving patients from the significant burden of current standard of care and daily injections. Going all in on this program, I wanted to share some of the upcoming milestones. First, we plan to debut our data at the International HypoPARAthyroidism Conference being held October 3 to 5 in Texas. We'll be scheduling our end of Phase II meeting with the FDA. Additionally, we will be presenting full Phase II data at a major medical conference and in publication. In 2026, we plan to report 52-week results from our open-label extension trial as well as begin dosing patients in our global registrational Phase III trial. Finally, I'd like to thank the patients and their caregivers, the investigators, partners and the passionate team at MBX who made all this possible. Now I'll turn the call back to the operator to open up the line for questions.

[Operator Instructions] And our first question today comes from the line of Seamus Fernandez with Guggenheim Partners.

Congratulations on the data. So a couple of things to just clarify. We got a lot of questions on the placebo response here. And there's also a lot of questions on relative comparisons around that. Just hoping you could help us understand the 31% placebo response. Admittedly, I think the dose response that you see with the 600 and 800 microgram clearly suggests a very wide margin between placebo on your endpoint. But maybe you can just help us understand how you're looking at the data from a comparison perspective versus the Yorvipath Phase II data that we have. Really appreciate those data. And again, congratulations. I appreciate the OLE data as well. I think it's important to look at the characterization of the response when you kind of convert from the OLE. But last question is just what other opportunities might you have to improve upon the response rate in the Phase III? I think 79% in the OLE would suggest that, that's going to be a little bit challenging to improve upon. But how do you think about Phase III design? Is it identical to this Phase II? Or are there other nuances that you could bring to the table to perhaps improve the response or even improve upon what's already a great safety profile?

Thank you, Seamus. We are very happy with our statistically significant results at week 12 despite the placebo response. And as you point out, the fact that the response rate in the treatment group increased further at six months, we believe, confirms the potency of canvu in this patient population. And the placebo group was higher than originally planned, but it's not unusual, noting the small sample size. And also, there's a precedent in HP. The daily injectable showed a placebo response of 27% in Phase II, which reduced to 5% in Phase III, and we would expect that trend in our Phase III study. That said, it's an important question, and our team has looked very closely into it. So I'll ask Sam to provide some more color.

Yes. Thank you, Kent. We also checked our results with four experts and author of the hypoparathyroidism guidelines. After looking at the baseline characteristic and the responder rate across the different arms, we decided to perform a sensitivity analysis, including patients with PTH less than 20 picogram per ml before treatment. Patients with low PTH are usually considered as more severe than patients with inappropriately normal PTH. A PTH above 20 picogram per ml indicates some residual PTH secretion, also not sufficient to maintain serum calcium level in the normal range for a long time. So when you apply this criterion, we identified a total of eight patients, three in the placebo group, five in the treatment group that were excluded from this sensitivity analysis. Excluding these patients from both groups, the placebo response declined to 15%. And the canvuparatide pooled responder maintained a robust response at 60% at the 12-week time point, which is highly statistically significant with a p-value of less than 0.01. And the active to placebo difference was 45%. We also carried over this rule into the open-label extension study and excluded those eight patients, and our responder rate was still very strong with 76%. So we believe -- I mean, really this sensitivity analysis strengthens our primary analysis and confirm our conviction in our results. It's also a learning for Phase III in which where the patients will be stratified between treatment and placebo to ensure equal distribution. That was one of the learnings already from the Phase II.

And then just on the Phase III. The Phase III, the possibility, is it -- do you see any changes in Phase III that would be necessary other than just sort of the stratification you talked about? Is there a possibility of perhaps even titrating weekly? Or does that put too much of a burden on the clinical trial or the population? Certainly, I could see a faster response rate being achieved if you were to titrate or allow for a titration after four weeks that was a little bit faster.

We really don't see the need to change to a more rapid titration. At this time, we're evaluating the data, and we'll be finalizing our study Phase III study design following the anticipated end of Phase II meeting with the agency. I'd also like to point out the very high responder rate we got from the placebo after they, if you will, crossed over following the 12-week Avail study with 14 and 15 becoming responders by the end of the -- by the analysis we did at six months. So, we again, are really encouraged by these results.

Seamus, it's a dose-finding study. Seamus, it's a dose-finding study at this Phase II. So we'll be looking in every detail and apply the learning to the Phase III program just to make sure that here, we are delivering the top line results, but we'll be looking at all in order to optimize the Phase III program.

Congratulations. The sensitivity on the placebo was also super helpful. Appreciate that.

The next question comes from the line of Jessica Fye with JPMorgan.

I had a few here. First, can you please clarify the definition of PRN calcium used in the trial? I guess my specific question is, if a patient had reached a daily calcium dose of zero and then they took 300 milligrams of calcium, would that be a PRN event even though the daily dose was still under 600? And does the same definition apply to the six-month open-label extension data? And what, if any, was the contribution of oral calcium to the six-month open-label responder rate? And I have a follow-up.

So, the PRN was initially defined as that more than one day of use of any vitamin D or calcium supplement for a total dose of more than 600 milligram a day. However, we went one step further and we look at any use of anything during the week of the evaluation and patients didn't take any additional calcium, any vitamin D during that period. So we went -- it's really going -- being very, very conservative and going very strict in terms of use. So we are very pleased to report that none of the patients took any PRN or any calcium supplement of vitamin D during the last week.

And then is it the same definition for the six-month data? And was it also zero contribution to the six-month responder rate?

So, it's a similar thing in the open-label extension. And we are looking in more detail in the results because the patients are seen a little bit less frequently, right? And -- but I can guarantee that what we observed in the Phase II 12-week is will be reproducible and reproduced into the open-label extension.

Right. PRN is not driving our response in this trial.

That's the key message.

Okay. And then just a couple of follow-ups were what does the PD data look like over the dosing interval? I think you took measurements at Cmax as well as trough. And then how does the hypercalcemia rate look over the six-month OLE? Are you seeing less of that as the trial goes on, so sort of like less in the second three months than in the first three months?

Well, it's an ongoing trial, Jess. And as Sam said, we're seeing similar safety in the OLE. And as you would expect, as more patients are normalized, and we provided the calcium -- the serum calcium measures in the slides. And Sam, you're welcome to add.

Yes. No. And the retention rate is pretty good. So also something to confirm that the patients feel good about canvuparatide. So, that's a good sign.

Great. And then just the PD at max trough?

So we didn't see anything that will be a concern. We saw -- in fact, we saw that serum calcium stayed within the normal fluctuation and didn't create any episode of hypercalcemia, et cetera. When we looked at hypocalcemia, there is no pattern in terms of when the hypercalcemia happened during the week. And so it was not particularly a certain day during the week. It was at any point could happen.

And overall, had a low occurrence of hypercalcemia in the trial.

The next question is from the line of Roger Song with Jefferies.

Congrats for the impressive data. Maybe my question relates to the dose response. I think you showed us the 12-week period. So, just curious about the open-label OLE portion, how the dose response look like? And then another question leading to that is the -- what's your current thinking about the dose selection for the Phase III considering this seems higher efficacy at the 800, but also a little bit higher hypercalcemia.

I mean I'm going to start with the dose selection for the Phase III. We are analyzing the results, and it's a dose-finding study. So, the main objective is to find the right dose to start this patient into the Phase III program. We'll be looking not only at efficacy, but also the best tolerability profile and especially when we are decreasing the vitamin D and calcium supplement. So, that's more to come in terms of dose selection and finalizing the dose for Phase III.

Got it. And then how about the dose response for the OLE portion?

So, I'm not sure I understand the question. Because the 79% I referred to the open-label extension dose response.

Yes, that's the pooled patients. So, how about each individual different doses, starting dose?

The patient dose in the open label, it's a wide range of response. I mean, confirming one thing that it's some sort of personalized medicine and every patient will need a different dose level to satisfy their needs. And that's what we will be releasing the data later when we will have the full set of information. But for now, it's top line results.

Our next question is from the line of Jonathan Wolleben with Citizens.

Congrats on the data. Just another one on the Phase III trial design and dose optimization. Wondering if you expect to see kind of an improvement in the hypocalcemia as you perhaps dose slower or start at a lower dose, given the mention that most of these events happen during dose titration? And then I have a follow-up as well.

Well, I think that fundamentally, with our PEP design, we have an excellent PK curve with a peak to trough over a week that's comparable to the competition over a day and a bit of a self-titration built into our molecule. And I think that's reflected in the stable control we've demonstrated and the really strong safety.

Yes. I think -- and the initial PK data that we got from the patient also confirmed that the PK we observed in healthy volunteers is similar to the one we observed in patients with for now a peak-to-trough ratio, which is also in the same order. So which is a really good news in terms of comparing healthy volunteers PK and patients. So very happy with that.

And then with the six-month data today that we were quite expecting, how do you think about additional disclosures from the open-label study? Is it going to be on a set time period of follow-up or when you think there's a fulsome update or an opportunity to present? How should we think about additional disclosures? And how do you think canvu's profile to evolve over time?

We expect to present 52-week follow-up data on the OLE, and we think that our profile is excellent.

Our next question is from the line of Tyler Van Buren with TD Cowen.

Congratulations on the tremendous data update. Can you -- just the zero PRN utilization at week 12, that's clearly very impressive. Can you discuss if that was maintained through the end of the six months in the OLE? And was the dose for canvu set in the last four weeks of the OLE or were patients continue to be titrated? And then second question, just on quality-of-life data, what quality-of-life data are you collecting in the trial, if any, or maybe any anecdotes you've heard from investigators or patients in the trial following treatment with canvu.

Well, the PRN available, data are not available yet. We'll review those when they arrive and plan to present those at an upcoming meeting. The -- so in terms of anecdotes, we've heard very strong interest in our once-weekly drug. I think that's a drug candidate that's reflected in the strong 94% entry into the OLE and the retention as well through the OLE.

Yes. Can I -- in terms of quality of life, I see a good testimony of patients being confident in the product is the rate -- the percentage of patients moving from the double-blind to the open label. 94 patients moved -- 94% of patients moved from the double-blind to the open-label extension. I think it's a good and the retention rate that we observed so far is pretty good. In terms of -- I can tell you that the PRN in the open-label extension is not driving the results, just to be clear. I think you had another question about changing the dose during the -- when moving to the open-label extension. Just I'm going to get back a little bit to the study design. And the study design, by design we had four different groups, 400, 600 and 800 microgram and only the 800 microgram could get to the 1,600 during the eight-week period, you can increase by 200 microgram every other week. So, it's 4x. So, four opportunity to increase the dose. So when the patients switch to the open-label extension and if by any chance, they are not responder at the time of the switch, they can definitely see their dose increased if needed once again. So that's why we -- in the open-label extension, we will see patients taking up to 1,600 microgram. Does it answer your question?

Yes.

Our next question is from the line of Annabel Samimy with Stifel.

Congratulations on the data. Just on the prior question regarding the titration during the OLE, you mentioned that patients who had -- were at the 800 milligram were the only ones to reach the 1,600 milligram. To what extent did the other patients have to titrate up? Like do you have the various percentages of patients who had to continue titrating up? In other words, do you feel that patients had, for the most part, reached a steady state at 12 weeks, and it was just a little bit of tinkering in the doses going forward. And then I guess, secondly, during the OLE period, the secondary biomarker data were great. I was just wondering if you had any additional biomarker data, the urinary calcium biomarker data and the bone biomarker data all the way through the six-month period? And if you don't, do you have any sense of whether it remains going in the right direction?

So, just a good -- back to the design and the results. Well, in terms of responder, 63% at the end of the double-blind period were responder, right? And this number increased up to 79% at the end of the open-label extension. I think it's done also to continuing to titrate up the patients who needed to be titrated up. And I hope that this answers your question. About bone biomarkers. Bone biomarkers on the slide, in fact, you see the results that at 12 weeks, but also at six months. including the patients who were initially on placebo and switched to treatment. And you see that still continue to improve in terms of all the bone markers, CTx, P1NP and on the very good right direction and maintenance of the positive effect that we saw at 12 weeks.

Okay. Did you have the same for urinary calcium as well at six month?

At this stage, we don't have the results. As I said, we have to make some choices in terms of top line results. We got that quite a week ago, and we had to really analyze the data as much as possible.

Okay. Got it. And just one other question. you mentioned that -- I mean, you had the sensitivity analysis regarding the stratification of patients with baseline PTH level. And are you planning on doing that stratification in Phase III? And did Yorvipath do that stratification to get the placebo responses lower, I guess. Just trying to understand if it's going to be similar design as to what Yorvipath in Phase III.

So, what we are going to do is really to analyze in depth our Phase II data and look at what could influence furthermore even from the sensitivity could influence the placebo response and adapt it include this modification -- potential modification into the Phase III. As I said, the PTH is a good marker, and it would make sense to stratify. So, it's likely that we will be doing it.

And in general, we'll be looking to the precedent of Phase III studies in this disease, not really full thought reinventing the wheel.

Our next question is from the line of Trevor Allred with Oppenheimer.

My congrats on the data as well. I got a few questions. First, is there anything you can share about the active dose levels where we saw AEs? Since we're titrating here, were these presentations seen above 800 micrograms? And then also, can you give us any detail on what the placebo response rate might be if there was no PRN use there? And can you also clarify PRN criteria was only for the last week?

So, PRN criteria was for the last week of the evaluation because patients could be titrated up to the week 10. And so we did -- we thought that it was appropriate to look at PRN in the last week of -- at the period -- at the time of the evaluation, if you want. The placebo, they were not -- I mean, they were not responders for most of them, 70% of them. So, the PRN use was not interesting as an information. We looked also at the five patients with placebo, but I don't remember if I had the PRN news or not. We looked mainly into our active treatment.

Got it. And can you also -- is there anything you can share about the active dose levels where we saw some of those AEs? Were they seen above 800 micrograms?

Yes. So the AEs happened mostly during the titration period, mostly because -- and that's why you see it at 800 microgram because when you start decreasing the supplement, calcium supplement and vitamin D, it may not be fast enough when you start a higher dose. And that's the reason why we observed this hypocalcemia at the time of the titration and with the 800 microgram. That's the rationale behind.

Our next question is from the line of Uy Ear with Mizuho Securities.

Congrats on the data. I guess one question that we've gotten is maybe could you sort of help us clarify the proportions of patients that may be titrated up and those that titrated down in the study? And the second question that we have is, I guess you expect to meet with the FDA. Maybe just sort of help us understand the time line to that meeting.

I don't have the proportion of responder exactly -- the exact proportion of responder, but I can tell you already that most of them were titrated up. But you can see during -- in the table, you can see that the extent of the dose in the 600 and 800 micrograms, if I remember correctly, the dose could go down to 400 microgram. That's an option the patient -- the investigator has to not only go one direction, but if needed, go the other direction. But clearly, the goal and what we observed is, in most cases, was titrating up.

So, we're really thrilled with our positive top line results and our clear clinical proof of concept for best-in-class. So we are eager to request an end of Phase II meeting, and the team is just very energized to go pursue our global Phase III registration studies with a sense of urgency.

At this time, we've reached the end of our question-and-answer session. I'll hand the call back to Ken for closing remarks.

I'd like to thank everyone again for joining us today to discuss the compelling top line results from our Avail Phase II trial. We cannot be more thrilled with the results and look forward to sharing further progress as we continue to advance canvuparatide's development with the goal of bringing a best-in-class once-weekly treatment option to patients in need.

Thank you. This concludes today's conference. You may disconnect your lines at this time. We thank you for your participation. Have a wonderful day.