Earnings Call Transcript - MBX 2025-09-22

Operator

Ladies and gentlemen, greetings and welcome to MBX Biosciences Conference Call. Today's call is being recorded and all lines have been placed on mute and all participants are in listen-only mode. The question and answer session will follow the formal presentation. As a reminder, this conference is being recorded. It is now my pleasure to turn the call over to MBX Biosciences Senior Director of Vesta Relations and Communications, Jim DeNike.

Jim DeNike, Head of Investor Relations

Thanks, Rob. Good morning, and thank you for joining us this morning to review the exciting top line results from our Vail Phase 2 clinical trial. I'm very pleased to report that earlier this morning, we issued a press release announcing positive results from our Phase 2 trial of once-weekly can-bu-paratide in patients with hypoparathyroidism, as well as six-month 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 Parlick, 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 Ken. Thank you, Jim. Good morning and welcome.

P. Kent Hawryluk, CEO

Today, we are thrilled to share positive top-line results from our available FASU trial. The results exceeded our expectations and reinforced the potential of once-weekly Tandu Paratide 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 wanted 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 Kambu Paratide's clinical profile and provide a strong foundation as we plan for phase three and ultimately registration. I know you're eager for the data, so let's begin with the top-line results shown on slide four. 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 Candu Paratide 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 Cambu Paratide as doses are optimized over time. At week 12, urine calcium excretion was reduced in Cambu Paratide-treated patients with elevated baseline values, highlighting the therapy's ability to help restore calcium balance. We also saw increases in bone biomarkers in Kambu Paratide-treated patients at week 12, with continued improvement at six months, which is consistent with reestablishing normal bone physiology. Once-weekly, Kambu Paratide was well-tolerated in a 12-week trial, with no treatment-related serious adverse events or discontinuations. Together, we believe these results underscore the potential of once-weekly Kambu Paratide to establish a new standard of care for adults with hypoparathyroidism and strongly support advancement and defaced redevelopment. 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, Kanbu Paratide 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 Kanbu Paratype 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.

Sam Azoulay, Other

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 EVEL trial was a randomized 12-week double-blind placebo-controlled phase 2 study designed to establish the optimal dosing range and titration strategy for phase 3, while also assessing the efficacy and safety of once-weekly conduit paratide. 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 pre-specified minimum threshold levels. After an optimization period, a total of 64 patients were randomized and equally distributed into one or four treatment arms. One sweetly country paratide starting at 400, 600, or 800 micrograms, or placebo. The 12-week blinded treatment period consisted of a four-week, six-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 to maintain normal serocultium by following a pre-specified 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 convuparatide 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 convuparatide as patients continue treatment beyond the initial 12-week study. Turning now to slide nine, 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 groups. 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 post-surgical setting, which was one of the two stratification factors, while the reminder had HP from other causes, including idiopathic, 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 micrograms. These numbers illustrate the high treatment burden patients were carrying at baseline. The mean baseline serum albumin adjusted calcium was 9.2 mg per deciliter in all patients and mean serum PTH level ranged from 9.2 to 12.1 mg per liter across treatment arms with slightly higher levels noted in the placebo group. The slow PTH levels were consistent with the disease. The other stratification factor was patients with 24-hour urine calcium or below, above or below 250 milligrams per day, and fewer than half of patients in the trial at baseline urine calcium excretion above 250 milligrams 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 chandriparatide. Here, on slide 12, are the results of the pre-specified primary composite endpoint. At week 12, 63% of patients across all starting dose of once-weekly chandriparatide achieved the primary composite endpoint compared with 31% of patients on placebo. This was a statistically significant difference. Patients met this endpoint in the full country paratide 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 COMPOSIS criteria at week 12, all three showed a statistically significant difference between country paratide treatment, treated patients, and placebo. These results provide strong evidence of once-weekly countryparatide'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 the pre-specified secondary endpoint designed to explore the dose response. As shown in the table, 50 percent of patients in the 400-microgram arm achieved responder status at week 12, compared with 69 percent of patients in the 600 and 800-microgram arms, with the 800-microgram arm achieving statistical significance. In addition, the 800-microgram dose was the median dose of responder at week 12. Overall, this data demonstrates that responder rates were generally higher at the 600 and 800 micrograms starting dose compared with the lowest 400 micrograms starting dose. This data not only demonstrates once-weekly country-paratized dose response and wide therapeutic range across multiple dose levels, but also helps inform dose selection for phase three 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 country paratide consistently maintained serum calcium within the normal range at every visit. Placebo patients trended downward initially, but then leveled out through continued use of conventional therapy. We'll take a closer look at supplement use later in the presentation. We believe this result supports the profile of a once-weekly therapy providing stable control. Now, let's turn to slide 15, which shows the effect of once-weekly counterparatine 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 with conviparatide, 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 milligrams in the conviparatide group versus 117 milligrams in placebo. This reduction in the conduit paratide group occurred while maintaining serum calcium in the normal range with less reliance on conventional therapy compared to placebo. In summary, the 12-week result shows that once-weekly conduit paratide achieves a primary endpoint and helps restore the key features of PTH physiology. Now we are going to turn to the results from the ongoing open-label expansion study. At six months in the open-label expansion, 79 percent achieved responder status, an increase from 63 percent observed at week 12 in the blinded portion of the study, which is a terrific result. Patients who had already been receiving country paratide 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 followed 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 than what we observed at week 12, providing highly encouraging evidence of the potential durability of once weekly convuparotide over time. On slide 18, you can see changes in serum calcium levels from the start of the AVEN study through month six in the open-label extension. Calcium levels were in the normal range in both the convuparotide and placebo groups before treatment. As we have already shown, convuparotide-treated patients maintain 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 confuparitide beyond the initial treatment period. In the placebo group, calcium levels declined early and remained low through week 12, despite ongoing use of active vitamin D and calcium suplemer. However, after switching to country paratide in the open label extension, shown in light blue, serum calcium level in this patient increased to well within the normal range, demonstrating a direct effect of once-weekly country paratide in restoring physiological calcium control. This occurred while active vitamin D and calcium supplements were gradually decreased or discontinued, which we'll 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 2 study through six months in the open-label extension. On the left, in the country paratide 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-level extension at the starting dose of 400 micrograms of candiparatide, those patients were able to decrease active vitamin D and ultimately discontinue. On the right, you see a similar pattern for calcium supplements with patients on candiparatide paratide, reducing their daily intake, while placebo patients required higher dose until they transition into the extension. Overall, this result demonstrates the durability of effect of canviparatide 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 contiparatide on bone health in patients with HP. As a reminder, in the absence of PTH, the skeleton cannot properly release calcium and This leads to abnormally low bone turnover. Here, we are showing three markers of bone turnover and formation over the 12-week double line period and through six months into the upper label extension. CTX is a marker of bone resorption and overall turnover, while BSP, BSP, and P1NP are bone formation markers. The blue line represents patients treated with once-weekly conviparatide 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 chanduparotide-treated patients in comparison to placebo. This upward trend continued through the six months. We are very encouraged by these findings. They show that once-weekly chanduparotide is restoring normal bone remodeling activity, both formation and resorption, which is a hallmark of reestablished PTH physiology and contribute, in fact, to long-term bone health. Now let's turn to the safety. On slide 22, we demonstrate that once weekly, convupyriotides were generally well-tolerated. As you can see in the top row, 73% of convupyriotide-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 those interruptions. Approximately half of patients in the pooled country paratide group and approximately 40% of placebo patients experienced adverse events that investigators considered related to this 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 canviparactite treated patients were headaches, 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% of 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 hypocalcemia events occurred within the first weeks of the titration period, again, while patients were still titrating down from congenital therapy. 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-level 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 these data strongly supports the potential of once-weekly to become a new standard of care for patients with HP. And with that, I will hand it back to Ken.

P. Kent Hawryluk, CEO

Since our IPO one year ago, we set out to deliver on the promise of once-weekly Kanbu Paratide, so it is particularly gratifying to share data that bring that vision to life. These results are very encouraging and reinforce our conviction that Kanbu Paratide is poised to be best in class. The strong Phase II avail data unequivocally demonstrate that once-weekly Kanbu Paratide can generate high responder rates in treated patients. Data from our open-label extension study show the potential of even higher responses on Cambu Paratide as patients are titrated to their appropriate doses. Our results are already competitive to historical studies of an FDA-approved once-daily injection. Significant unmet medical need. We estimate the U.S. and the EU represent a multibillion-dollar market opportunity, and once-weekly Cambu Paratide is well-poised with a best-in-class profile. The belief that once-weekly Kanbu Paratype 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 the disease every day, let alone inject themselves daily. Once-weekly Kanbu Paratype can provide freedom by relieving patients from the significant burden of current standard of care and daily injections. I was going all in on this program and 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'll be presenting full Phase II data at a major medical conference and end 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 3 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.

Operator

Now we'll turn the call back to the operator to open up the line for questions.

Operator

Thank you. We'll now be conducting a question and answer session. If you'd like to ask a question at this time, you may press star 1 from your telephone keypad, and the confirmation tone will indicate your line is in the question queue. You may press star 2 if you'd like to withdraw your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment, please, while we poll for questions. And our first question today comes from the line of Seamus Fernandez with Guggenheim Partners. Please proceed with your question.

Seamus Fernandez, Analyst — Guggenheim Partners

Hey, thanks, guys, and congratulations on the data. So, you know, a couple things to just clarify. We've got a lot of questions on the placebo response here. you know, 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, you know, I think the, you know, dose response that you see with the 600 and 800 microgram, you know, clearly suggests a very wide margin between placebo on your endpoint. But, you know, maybe you can just help us understand how you're looking at the data from a comparison perspective, you know, versus the Yorva Path phase two data that we, that we have. Um, really appreciate, uh, those data. And again, congratulations, um, appreciate the OLE data as well. Um, you know, I think it's, uh, important to look at the, you know, characterization of the response, um, you know, uh, uh, 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 three? 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, you know, phase three design? Is it identical to this phase two 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. Thanks.

Operator

Thank you, Seamus.

P. Kent Hawryluk, CEO

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 has increased further at six months, we believe, confirms the potency of can-do 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 injectables showed a placebo response of 27% in Phase 2, which reduced to 5% in Phase 3. And we would expect that trend in our Phase 3 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.

Sam Azoulay, Other

Yeah. Thank you, Kent. We also checked our results with four experts and author of the hypoparaparadism guidelines. After looking at the baseline characteristic and the responder rate across the different arm, we decided to perform a sensitivity analysis, including patients with PTH less than 20 picograms per ml before treatment. Patients with low PTH are usually considered as more severe than patients with inappropriately normal PTH. A PTH above 20 gigograms 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 this patient from both groups, the placebo response declined to 15%. As a country-paratide 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 confirms our conviction in our results. But it's also learning for phase three in which where these patients will be stratified between treatment and placebo to ensure equal distribution. That was one of the learnings already from the phase three.

Seamus Fernandez, Analyst — Guggenheim Partners

And just on that phase three, the phase three, the possibility is, you know, is it, you know, do you see any changes in phase three 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.

P. Kent Hawryluk, CEO

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 phase three study design following the anticipated end of phase three meeting with the agency. I'd also like to point out the very high responder rate we got from the placebos 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 So we, again, are really encouraged by these results.

Sam Azoulay, Other

Shemesh, it's a dose-finding study. Shemesh, it's a dose-finding study this phase two. So we'll be looking at every detail and apply the learning to the phase three program just to make sure that here we are delivering the top-line results that we'll be looking at all in order to optimize the patient program great thanks so much and congratulations the sensitivity on the placebo was also super helpful appreciate that and great the next question comes from the line of jessica fai with jp morgan please proceed with your question hey guys good morning thanks for taking our questions i had a few here first can you please clarify the definition of PRN calcium used in the trial?

Jessica Fai, Analyst — JP Morgan

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.

Sam Azoulay, Other

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 milligrams a day. However, we went one step further and we looked 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 it's really 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 So it's a similar thing in the open-level extension and we are looking in more detail in the results. So the patients are seen a little bit less frequently, right? But we can guarantee that what we observed in the phase two, 12-week is reproducible and reproduced into the open-label extension.

P. Kent Hawryluk, CEO

Right. PRN is not driving our response in this trial. That's the key message. Thank you.

Jessica Fai, Analyst — JP Morgan

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 TROS. 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?

P. Kent Hawryluk, CEO

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've provided, you know, that calcium, the serum calcium measures in the slides. And Sam, you're welcome.

Sam Azoulay, Other

Yeah, no, and the retention rate is pretty good. So also something to confirm that the patient feels good about the convuparotide.

Operator

So that's a good sign.

Jessica Fai, Analyst — JP Morgan

The PD at max and drop?

Sam Azoulay, Other

So we didn't see anything that will be of concern. 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 hypercalcemia, there was 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.

P. Kent Hawryluk, CEO

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

Operator

Great. Thank you.

Operator

The next question is from the line of Roger Song with Jeffries. Please just use your question.

Roger Song, Analyst — Jefferies

Great. Congrats for the impressive data. Yeah, thank you for taking the question. Maybe my question related to the dose response, I think you showed us the 12-week period. So just curious about the open-label OLE portion, how did those response look like? And then another question leading to that is, what's your current thinking about the dose selection for the phase three, considering this, you know, since a higher efficacy at 800, but also a little bit higher hypercalcemia. Thank you.

Sam Azoulay, Other

I'm going to start with the dose selection for the phase 3. 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 3 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 the calcium supplement. So that's more to come in terms of dose selection and finalizing the dose for patients.

Roger Song, Analyst — Jefferies

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

Sam Azoulay, Other

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

Roger Song, Analyst — Jefferies

Yeah, that's the cold patient. So how about each individual, different doses, starting dose?

Sam Azoulay, Other

Oh, as a patient, dose in the open level, 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. That's, for now, the stop-line results.

Operator

Got it. Thank you.

Operator

Our next question is from the line of Jonathan Rollin-Bendwood Citizens. Please just hear your question.

Jonathan Rollin-Bendwood, Analyst — Citizens

Hey, congrats on the data, and thanks for taking the questions. Just another one on the phase three trial design and dose optimization. Wondering if you expect to see kind of an improvement in the hyper-hypercalcemia 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 have a follow-up as well.

P. Kent Hawryluk, CEO

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.

Sam Azoulay, Other

Yeah, I think 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-trap 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, we're very happy with that.

Jonathan Rollin-Bendwood, Analyst — Citizens

And then with the six-month data today that we weren't 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 CanBoo's profile to evolve over time?

Operator

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

Operator

Our next question is from the line of Tyler Van Buren with TD Cowan. Please proceed with your question.

Tyler Van Buren, Analyst — TD Cowen

Hey, guys. Good morning, and 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 Kanbu set in the last four weeks of the OLE, or were patients continued 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 CAMBU?

Operator

Well, the PRO available, the data are not available yet.

P. Kent Hawryluk, CEO

We'll review those when they arrive and plan to present those in an upcoming meeting. In terms of anecdotes, we've heard very strong interest in our West Weekly drug. I think that's a drug candidate that's reflected in the strong 94 percent entry into the OLE and the retention as well through the OLE.

Sam Azoulay, Other

In terms of quality of life, I see a good testimony of patients being confident in the product is the rate of the percentage of patients moving from the double blind to the open label. But 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 have 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 when moving to the open-label extension. 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 micrograms. And only the 800 micrograms could get to the 1,600. During the eight-week period, you can increase by 200 micrograms every other week. So it's four times, four opportunities 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 increase if needed once again. So that's why in the open-label extension, we will see a patient taking up to 1,600 micrograms. Does it answer your question?

Operator

Yep. Thanks so much. Thank you.

Operator

Our next question is from the line of Annabelle Simimi with Stiefel. Please proceed with your question.

Annabelle Samimi, Analyst — Stifel

Excuse me. Thanks for taking my question, and congratulations on the data. Just on the prior question regarding the titration during the OLE, you mentioned that patients who were at the 800 milligram were the only ones to reach the 1600 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 remained going in the right direction? Thank you.

Sam Azoulay, Other

So, just a good – back to the design and the results. Well, in terms of responders, 63% at the end of the double-blind period were responders, And this number increased up to 79% at the end of the label extension. I think it's done also to continuing to titrate up the patient 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 at 12 weeks, but also at six months, including the patients who were initially on placebo and switched to treatment. And you see that that still continues to improve in terms of all the bone biomarkers, CTX, PA1NP, and on the right direction and maintenance of the positive effect that we saw at 12 weeks.

Annabelle Samimi, Analyst — Stifel

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

Sam Azoulay, Other

At this stage, we don't have these results. As I said, we had 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.

Annabelle Samimi, Analyst — Stifel

Okay. And just one other question. You mentioned that, I mean, you had the sensitivity analysis regarding the stratification of patients based on PTH level. And are you planning on doing that stratification in phase three? And did your Vipath 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 your Vipath did in phase three.

Sam Azoulay, Other

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

P. Kent Hawryluk, CEO

And in general, we'll be looking to the precedent of phase three studies in this disease, not really whole cloth reinventing the wheel.

Annabelle Samimi, Analyst — Stifel

Got it. Thanks a lot.

Operator

Our next question is from the line of Trevor Allred with Oppenheimer. Please just see you with your questions.

Trevor Allred, Analyst — Oppenheimer

Hey, everybody. My congrats on the data as well. 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?

Sam Azoulay, Other

So PRN criteria was for the last week of the evaluation because patients where it could be titrated up to the week 10, and so we thought that it was appropriate to look at PRN the last week at the time of the evaluation, if you want. The placebo, there 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 use or not.

Operator

We looked mainly into our active treatment.

Trevor Allred, Analyst — Oppenheimer

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?

Sam Azoulay, Other

Yeah, so the AEs happened mostly during the titration period. mostly because that's why you see it at 800 micrograms because when you start decreasing the supplements, calcium supplements and vitamin D, it may not be fast enough when you start a higher dose. And that's the reason why you observe this hypercalcemia at the time of the titration and with the 800 micrograms. That's a rationale behind it.

Trevor Allred, Analyst — Oppenheimer

Got it. Okay. Thanks for taking my questions and congrats again on the data. Thank you.

Operator

Thank you, Dollar.

Operator

Our next question is from the line of URI with Mizzou Ho Securities. Pleased to see you with your question.

Uri Landau, Analyst — Mizuho Securities

Hey, guys. Yeah, thanks. Congrats on the data, and thanks for taking our question. I guess one question that we've gotten is maybe could you sort of help us clarify the proportions of patients that maybe titrated up and those that titrated down in the study? And the second question that we have is, you know, I guess you expect to meet with the FDA, maybe to sort of help us understand the timeline to that meeting.

Sam Azoulay, Other

I don't have the proportion of responder, the exact proportion of responder, but I can tell you already that most of them were titrated up. But you can see 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 micrograms. That's an option the investigator has to not only go one direction, but if needed, go the other direction.

P. Kent Hawryluk, CEO

But clearly, the goal and what we observe is in most cases was titrating up. with our positive top-line results and our clear clinical proof-of-concept for investing class. So we are eager to request an end-of-phase-two meeting, and the team is just very energized to go pursue our global phase three registration studies with a sense of urgency.

Operator

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

P. Kent Hawryluk, CEO

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

Operator

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