Rezolute, Inc. (RZLT) Earnings Call Transcript & Summary

Good morning, and welcome to the sunRIZE Topline Data Conference Call. [Operator Instructions] Please note, this event is being recorded. I would now like to turn the conference over to Nevan. Please go ahead.

Thank you, and good morning, everyone. We appreciate you joining us today to review the study results from our Phase III sunRIZE study for ersodetug in patients with congenital HI. I would like to start by thanking the patients, their families and the investigators for the tremendous effort in participating in the study. We are deeply grateful for the broad participation of the worldwide congenital HI community in working with us to explore the possibility of finally bringing a new therapy to this patient population, where there's a massive unmet need. As you've seen in our press release, the primary and secondary endpoints did not achieve statistical significance. Frankly, we are shocked and dismayed by the outcome of the study. With a drug that we believe has activity, we were unable to demonstrate a significant difference compared to placebo in an outpatient study, where glucose is both the endpoint and the vital sign for patients. Again, both the endpoint and the vital sign for patients. Notwithstanding this result, we believe that our drug works in treating hyperinsulinism, and we believe that the observed study effect in the placebo arm reflects an inherent problem in conducting studies of this type in an ultra-rare pediatric population where knowledge of glucose levels and family vigilance prevent serious hypoglycemic outcomes is critical to patient management. I want to point out that more than 50 children on the sunRIZE study are now on our therapy as part of the open-label extension. And some of those children have now been completely weaned off of other background therapies. They are on ersodetug as a monotherapy. This represents exciting potential for the patient population, but only to the extent we can find a way to responsibly get ersodetug into the hands of other patients and their families by gaining regulatory approval. With all of that as a backdrop, we believe that the negative outcome of the sunRIZE study is definitive proof that the traditional and historical methodology of the "gold standard" of a Phase III randomized placebo-controlled study is simply not suitable for this ultra-rare pediatric indication. Fortunately, FDA has recently demonstrated a willingness to reconsider how we study ultra-rare diseases, and we're encouraged by the statements recently been made by FDA leadership and others regarding the need to streamline clinical development, particularly where there is mechanistic possibility and an indication of real oral benefit. And we know these are not simply just empty words coming from FDA. And here's the case in point. Up until September of this year, FDA wanted us to conduct a Phase III placebo-controlled study for our other indication, tumor HI. However, when we approached FDA to reconsider this study design, the agency recognized our success in treating tumor HI patients under our expanded access program, and they believed that the activity and the totality of evidence warranted a modification. Subsequently, just a few months ago, FDA agreed with us to streamline study design into an open-label fashion and to use glucose infusion rate as a mechanistic endpoint sufficient for registration. We are extremely excited about the tumor HI study and the fact that we have a new paradigm to move forward to treat that patient population, and we will work on that study and complete that study next year. But as we consider congenital HI, we're not giving up. We will be engaging with FDA to hopefully find a sensible path forward for this patient population. Let me be very clear. We are not done. We are committed to the congenital HI community and getting our therapy into the hands of patients and their families. Our commitment is based on doing what is right, doing what is right for patients and their families. And if we're going to do what is right, then it is our duty and our mission to break down all barriers, real and manufactured to achieve the goal that all of us share to improve outcomes for patients that are suffering with severe rare diseases. From a corporate perspective, we're fortunate. We still have the financial wherewithal to pursue our objectives. As of September 30, 2025, we still had $150 million in cash. That said, we have to be conservative, and we are already thoughtfully starting the process of decreasing operating expenses, which includes an unfortunate expected reduction in force. We plan to provide additional details about these updates as appropriate. But importantly, I think we should discuss the study and the results in more detail. And to that end, I would like to now turn the call over to our Chief Medical Officer, Dr. Brian Roberts.

Thank you, Nevan. Let me continue by repeating the obvious. We are extremely disappointed and surprised by the results, which showed that the sunRIZE study did not meet the primary or secondary glucose endpoint. While we have not yet evaluated all secondary endpoints as part of this top line analysis, it's our view that the main outcomes are clear. And for that, I'd like to thank our clinical development and operations team, as well as our clinical supply team for executing a high-demand study at a very high quality. Of the 63 enrolled participants between the open-label arm and the initial 8 infant participants and the remaining participants enrolled into the randomized controlled arms of the study, only 4 patients early terminated the study, which were due to adverse events that I'll discuss later. 59 participants who completed the study universally elected to enter the open-label extension, as Nevan has indicated, and an overwhelming majority of these remain on the OLE or open-label extension to date, with some approaching 18 months now of total treatment duration. This is a very high retention rate in the study and into the OLE in the setting of needing to visit study centers every 2 to 4 weeks for a 30-minute IV fusion is no less than remarkable considering these circumstances and is a testament to the efforts families, study sites and our Rezolute employees made and continue to make on behalf of ersodetug in the sunRIZE study. As I lead up to a more detailed discussion of the efficacy results during the pivotal treatment phase of the study, I'd like to first emphasize the final study demographics and baseline characteristics confirm our preliminary reporting at the Annual Congress of the Endocrine Society this past July. The short conclusion here is that we enrolled the right patients and they were well matched across the treatment arms. Amongst a total of 55 enrolled participants randomized fairly equally across the double-blind treatment arms, the average age was about 3.5 years, and the majority of patients were using one, if not more standard of care therapies for hypoglycemia management, including about 40% on diazoxide, almost 70% on somatostatin analogs and almost 40% who were using regular tube feeding regimen. Notably, and in spite of these background therapies, baseline hypoglycemia rates were high, including an average of almost 13 hypoglycemia events per week by self-monitored blood glucose or glucometer across the treatment arms and almost 20% time in hypoglycemia by continuous glucose monitoring. Importantly, the 3 treatment groups of placebo and 5 and 10 milligram per kilogram of ersodetug were generally very well matched across these characteristics. As we indicated in the press release earlier this morning, ersodetug target drug concentrations were safely achieved across all age groups studied. There were 2 benchmarks we used when designing the study and selecting the dose regimen. One was a model of efficacious concentration based on an EC50 derived from both in vitro and early phase clinical studies. And the other was the observed concentrations from the open-label Phase II RIZE study where reductions in hypoglycemia from baseline of up to 75% were observed with administration of 6 or 9 milligrams per kilogram of ersodetug every other week for 8 weeks. This threshold range was reached at the sunRIZE study dose regimens of 5 and 10 milligram per kilogram administered every other week initially, followed by every 4 weeks over the remainder of the 24-week treatment duration. As with the patient population enrolled, we believe the dose regimen also set the trial up for potential success. Safety observations from the study were generally favorable and in our opinion, support safe use of ersodetug in pediatric and adult patients. Two participants from the study experienced serious hypersensitivity reactions, which led to early discontinuation of study drug. The incidence of serious allergic reactions across the program is quite low compared to biologic or monoclonal antibody treatments at about 2% or less overall. As I mentioned earlier, 4 patients discontinued early overall. And the other 2 -- as I mentioned earlier, 4 patients discontinued overall, so 2 being the serious allergic reactions I mentioned and the other 2 were also due to adverse events. One was for hypertrichosis and one a more mild infusion reaction. Hypertrichosis was the most commonly reported study adverse event associated with the study drug, and this occurred in 14 ersodetug treated patients and in 1 placebo patient. But this is generally mild and self-limiting and reported to be much less significant than the typical diazoxide experience. And there were no other ersodetug-related safety findings in the study. Unfortunately, although ersodetug target concentrations were largely safely achieved in this enrolled patient population with demonstrated baseline hypoglycemia, this did not translate into the ability to show statistically significant reductions in measured hypoglycemia in the pivotal study portion. For the primary endpoint, which was the percent change in the average weekly number of hypoglycemia events by self-monitored blood glucose or fingerstick glucometer, the observed reductions from baseline at the week-24 end of treatment visit were 33%, 45% and 40% at the 5, 10 and placebo treatment arms, respectively, which were not significantly different. As you can conclude, there was a significant study effect with measured events and the effect size in the ersodetug arms was not meaningfully more than this for this endpoint. The highest priority secondary endpoint in the multiplicity and fixed sequence testing strategy was the percent change in the average daily percent time in hypoglycemia by continuous glucose monitoring, which may be somewhat less prone to measurement bias because of its consistent nature. Although a 7% increase in hypoglycemia time from baseline to week-24 in the placebo group indicated that no study effect was observed, the observed reductions from baseline and hypoglycemia time of 17% and 25% in the 5- and 10-milligram ersodetug groups, respectively, did not reach statistical significance. We'll continue to evaluate the impact on other secondary endpoints and report those at an appropriate future time and setting, but it should be noted that those would not be controlled for type 1 error in light of the failed primary and key secondary endpoints and therefore, would need to be interpreted with caution. Again, this is an extremely disappointing and frankly, surprising result for all involved, considering that it doesn't reconcile with past and present reports in clinical trials and expanded access in our open-label patients. On the one hand, the explanation could be as simple as this being a controlled clinical trial. On the other hand, past experiences in congenital HI patients as well as aspects from the present trial, including learnings from the ongoing open-label extension portion of the study do merit additional investigation. As would be expected, we are conducting a thorough evaluation to gain a better understanding of the study outcomes, and we intend to meet with the FDA under our breakthrough designation to consider next steps for the program. In spite of the setback with our congenital indication, we remain committed in our efforts to bring a better therapy to patients and families suffering with the consequences of hypoglycemia caused by congenital as well as other forms of hyperinsulinism. And with that, I'd like to open the call up for questions.

[Operator Instructions] Our first question today will come from Debjit Chattopadhyay with Guggenheim Partners.

I have a couple. Could you walk us through the interim analysis and what could have been done differently at the interim? And then given that sunRIZE was supposed to be the pivotal for the upLIFT study, what does this mean for the tumor indication going forward? Can you file based on the outcome of the upLIFT, would you need a second study? Not entirely clear at this point.

Sure. Thanks, Debjit. Both obviously key questions. There was nothing we could have done differently at the interim analysis. It was executed exactly as planned. Please recall, we were blinded, and we reran the interim analysis. The study conclusion is one of our evaluations on the same 24 patients who finished, and we produced a result that was consistent with the decision to continue the sample size as is. Unfortunately, we were in a tiny sliver area where we were not in the [fetal] zone, but also not in what was called the promising zone that would have led to a study sample size increase. And in a blinded fashion, I think based on, again, past results, past outcomes across the program, observations, empiric anecdotes, we hear all of it. We were optimistic, but we were blinded and we didn't know the outcome. We've confirmed that with our own analysis. We've confirmed that that's, in fact, what the DMC saw. So there was nothing we unfortunately could have done differently, and it's a disappointing outcome. As far as carryover and what it means for the tumor program, it doesn't. As far as we can understand, this is a separate IND. The FDA and our discussions with them clearly indicated it had to be a separate IND. It's the same division. They wanted the primary supporting study in the tumor indication to be the tumor study. And so we believe that the planned study there, which is a different endpoint glucose infusion rate, an endpoint that reflects severe continued consistent hypoglycemia in a hospital setting and can't be confounded whatsoever has a high likelihood of success based on what we've seen thus far in the program.

And to further add to -- sorry, go ahead, Dejit.

Finish your thought, Nevan.

Yes. And just to add to Brian's thoughts there as well. We know that the tumor indication from a financial perspective is a much larger indication. And there's a lot of interest and excitement around that. And given what we've seen to date and the real-world use of our drug in the really dramatic change we've seen in hypoglycemia and getting patients out of the hospital and substantially changing their lives has been really impactful. And so that remains the same. And so some could say we should be still delighted that we have a larger indication that is well intact, and we're moving forward with that. But we are really disappointed by this study result because this is about children, it's about families, the most impactful patient population you can ever imagine. And we have to do what is necessary to get this drug into the hands of children and their families. And so you can hear from the tone of our call and our thoughts that we're really dismayed by these study results because notwithstanding the fact that this is a smaller indication relative to tumor, this is extremely important.

So just a follow-up, if I may. Do you think the CGM data, if it was unmasked to caregivers and patients could have impacted the placebo response kind of what was observed in the [indiscernible] glucagon study?

Debjit, I think patterns are potentially consistent with that. If I can talk about a spectrum, for example, just to add to that of assessments with point-of-care self-monitored blood glucose is only a fraction of the day. It's influenced by when a patient checks. We certainly control for that as best as we can. As we discussed before results with a variety of people, we required a minimum of 4 times a day. We have patients check whenever there's a source of information that suggests a possible event. But ultimately, they're influenced by what they see when they choose to check. And I think on the spectrum of endpoints, that's probably the most difficult. And that pattern has persisted here. And I've heard that feedback from key opinion leaders already that that's extremely challenging. They believe in this patient population and outpatients where these are the endpoints that the FDA has required to date. On that spectrum, I would say, CGM then is less prone to that. And then as you move along that spectrum, unfortunately, it's a patient population you can't study as outpatients are those that are on a glucose infusion rate. So again, as I indicated, that is an endpoint that is pretty hard, clear and mechanistically driven. And I think that's what we see in the tumor patients, it's quite clear in our expanded access program. That is the primary endpoint in that study. And as we look for possible directions on the congenital program and have discussions with FDA, we'll certainly look at how we can implement that into a potentially additional small study, whether that's our planned neonatal study or in another form to be focused on that endpoint in a very concise fashion and see where that can go. We have to have those conversations with FDA. There's still work to be done to get there.

Our next question today will come from Maury Raycroft of Jefferies.

I'm sorry to hear the news. Maybe to start off with the upLIFT study, wondering if you're going to advance the program if FDA recommends that you switch back to your original plan for a randomized controlled study. Maybe just talk about what are the most likely scenarios there? And how could this impact your time lines to approval?

We don't anticipate that, Maury. We are in the middle of the upLIFT study. We're enrolling, and we don't expect any changes to that.

Got it. Okay. And just for the Phase III results, do you have perspective on just -- or can you comment on just the lower-than-expected reduction in hypoglycemia events in the 10 mg per kg arm versus what you observed in your Phase II?

Certainly. So I think -- I wish I had an answer for you. I covered a couple of things that obviously, everyone would want to think about in terms of explanations, including baseline demographics. We've done some subgroup analyses already. We'll continue to do that. Nothing has emerged thus far as an explanation with regards to factors that could influence results. Dosing, I talked about that we had very good exposures in the study. I've also taken a portion of the dosing period in the sunRIZE study, the first 8 weeks, which reflects biweekly dosing over the same duration in RIZE, frankly, at a 10% higher dose level, 10 milligram per kilogram versus 9. When you look at that time point, we don't see any differences compared to the end of treatment time point on every 4-week dosing. So the explanation is not -- does not appear to be in the dose or dose regimen. So Maury, I don't know the answer. I wish I did. One possibility is that RIZE was 15 patients between the 2 treatment arms that did show that type of effect, and this was 18 participants per arm in sunRIZE in the active arms. We still think as we had indicated in RIZE that especially in this patient population on standard of care failing all therapies, a reduction of that magnitude is meaningful. Of course, the confounder here is what was observed also in the placebo arm.

Got it. Okay. And maybe last question, and I'll hop back in the queue. Just wondering if you guys looked at antidrug antibodies. And is there anything more you could say about the 2 patients who discontinued due to the serious hypersensitivity reactions? Were those due to the positive ADAs?

Those 2 patients did not have positive ADAs. I'll get back to the ADA as a whole, but the circumstances for those, one occurred at the fourth dose with some mild indications, a rash at the third dose, worsen rash and some early evidence of a systemic allergic reaction with the fourth dose. The medication was stopped and it resolved quickly on its own without further intervention. The second patient occurred with the first dose within about 10 minutes of the infusion, similar experience and it also resolved without further intervention. But both patients were not reexposed at that point. As far as ADA, we collect those in batch and we analyze them in batch. So we don't have the full study results yet. But the batches we've run so far, we do not appear to have any meaningful antidrug antibody levels.

Our next question today will come from Peter Stavropoulos from Cantor Fitzgerald.

Nevan and Brian, sorry for these outcomes. Can you help us understand the response over time on the weekly -- average weekly hypoglycemia events? Was there a treatment effect initially that waned over time? Or was the response consistent, say, from the first dose through the end of the study?

Pete, thank you. The response was fairly consistent, not necessarily right after the first dose, but pretty early in the treatment phase and relatively consistent over the course of the study. I would say that for the CGM endpoint where, if anything, the placebo arm sort of bounced around and was generally worse, meaning an increase in time in hypoglycemia to a magnitude more than the end of treatment endpoint, which was a 6% increase, whereas the active groups, there was a pretty consistent and reduction in time in hypoglycemia over the endpoint. So the net effect at end was a little bit smaller actually than the net delta than at earlier time points in the study just because of what placebo did.

I know that you touched on it, but again, can you just sort of try to help us understand the placebo response and reduction in hypoglycemia events? What sort of drove that higher-than-expected response? And how did you actually calculate the expected placebo response?

Yes. I mean, I can only speculate. It's now the second occurrence in a controlled clinical trial where this magnitude of placebo response was observed. And I think I touched on this a little bit, Pete, but to reiterate, patients only capture events when they measure events, number one. There -- we certainly control for standard of care therapies that there was very good stability in standing or scheduled doses of therapies like diazoxide, somatostatin analogs, tube feeds, all of that. We can't control for small -- everything patients do. And I think I hope you picked up on Nevan's comments at the beginning are critical. Glucose here is both the endpoint and the vital sign for patients. And these families, this is a serious illness where hypoglycemia has tremendous consequences. And so if there's any indication on any source of information, they do tend to react. And that means -- that doesn't mean at a level where they suddenly increase the diazoxide, but it could mean that they're intervening around the margin with smaller interventions or acute interventions, and/or feeling that they don't need to intervene and then not checking as much. We didn't see a decrement in measurement frequency over time, which is good or a difference between treatment arms, which is good. So yes, Pete, I think it's intrinsic to studies in congenital HI, I believe, at this point and I think that KOLs I've spoken to also believe that as well.

Okay. Just one last question. Was there any changes in therapy during the treatment period, especially in placebo?

No.

No. Okay.

And Pete, maybe just to address the second part of your first question. I think in spite of being surprised by the magnitude of the placebo effect and in spite of Zealand having seen that previously in a controlled trial, I didn't think we would see that to the same degree we did. Nevertheless, we modeled for a placebo effect of this size. So that was built into our assumptions and our powering. So we -- I didn't think we'd see this it was reproduced. And now I think it's pretty clear in these types of studies. This is what happens when patients get on a study and you're measuring an endpoint that's very discrete and patient dependent.

Our next question today will come from Catherine Novack of Jones Research.

Just want to express my condolences to you and the patients for this outcome. I wanted to ask, was the drug lot between Phase II and -- Phase IIb and III the same? Were there any changes in the manufacturing process that might have impacted the results?

Thanks, Catherine. I appreciate that. No, there were no changes. And to our knowledge, there's nothing different in the manufacturing lots or in drug supply that would explain anything that happened in the study.

Okay. And then thinking about the standard error and the 10 mg per kg, how did that look? Do you think there would have been any different outcomes if this study were run, let's say, in a 2:1 randomization of just looking at 10 mg per kg versus placebo?

The standard deviation was actually within the model deviation for the powering as well, Catherine, so -- and 5 milligram and 10 milligram were not all that different. So certainly for the primary endpoint, the modeled placebo effect, the modeled standard deviation, we were in the ballpark with those. I think with CGM, the study was not powered for the key secondary endpoint. We were statistically significant at a couple of time points at 10 milligram and close -- in fact, also close, if not reached significance at 5 milligram per kilogram in time in hypoglycemia at a couple of time points. But there's more variability with the CGM. So that's where we lost on the CGM endpoint is the variability in CGM. The error was greater than 35% there, which is that was not our endpoint that was powered for.

Got it. Yes. And on CGM, can you just confirm when you say that missed significance, was it nominally significant? Or was multiplicity control plan allowed for this to be significant even if the primary endpoint failed?

The p-value was 0.3 at 10 milligram per kilogram at the week-24 treatment endpoint.

And our next question today will come from Julian Harrison of BTIG.

Sorry about this outcome. On upLIFT, has the FDA communicated an expectation in regards to response rate on the primary endpoint? Also, are you able to comment on or indicate the target number of enrollment sites for that study? And how much cash runway you're expecting after top line data next year?

Julian, the endpoint is the number of patients who achieved a 50% reduction in glucose infusion rate. And so just based on exceeding the lower bound of 30% on the confidence interval, the math is that out of 16 potential patients, you'd have to achieve that in 9. So that's how that endpoint works. So just to put that in some perspective, patients we've treated in the expanded access program in the past to be clear, are not part of the study. We feel like we need to reenroll with -- under clear protocol treatment guidelines and clear data collection. But had they been those patients, we would have already met that because patients often come off of glucose treatment completely. And I'm going to have Brian address the other question.

Yes. Thanks, Julian. So we have sufficient capital. Again, we're in a good position to get through the tumor study, and we will do so. And with our cash position just as of end of September, north of $150 million, that allows us to get through all of 2026, well into 2027 and through 2027. And that's why we're taking conservative measures now to make sure we reduce our spend, to make sure that independently without taking any action externally, we can actually hit our endpoint and be in a strong position with cash to actually then move forward. So the tumor program is not impacted by our current cash position or where we sit today.

Our next question today will come from Douglas Tsao of H.C. Wainwright.

I guess, Brian, I'm just trying to understand in terms of the placebo response rate, did you see -- it sounds like there were not changes within the study in terms of background medications, diazoxide or somatostatin analogs. But I'm just curious, were there changes relative to the prior Phase II study and sort of changes significant or noticeable changes in terms of sort of standard of care as you went to a broader set of institutions, sites for the study?

Yes. No, Doug, there weren't. The disease is managed similarly worldwide. There's no regional differences that we observed in the baseline characteristics in management, no regional differences in how they manage the background therapies on study, very stable overall. Even we've looked at sub-analyses of per protocol population. It mostly reflects the -- what used to be called the ICT, is now called the FAST population, the full analysis set that we just -- we don't see any differences. What we don't know and never know is what smaller incremental things patients do, but it's not just about what they might -- how they might intervene, it's also how they might choose to check. So it's both factors. And I know everyone wants to always understand, well, what therapies are patients changing. We are all over ensuring stability of standing scheduled medications, and we are all over defined rescue criteria. When a rescue happens, it has to meet a certain glucose threshold and it necessarily means that it's associated with the event capture, so it doesn't confound the endpoint and a short-term rescue being short-acting doesn't affect future events or time and hypoglycemia input. So those are not things that we can necessarily control, watch, capture or even understand or quantify completely other than what we say in a protocol. And we don't know how patients engage with their reporting of these smaller measures or whether they even check an event when there might be hypoglycemia. Those are things that are just frankly inherent to outpatient studies where to date, at least the FDA has required self-monitored blood glucose events or discrete events to be their primary endpoint.

And I guess, Brian, as a follow-up, and I know it's early, so there's like an element of sort of just a challenge, trying not to overreact or jump too many quick conclusions. But when you think about the endpoint, I think you indicated that there was more variability with the continuous glucose monitoring. But do you think that, that is ultimately a better measure of drug performance and perhaps even if there's more greater variability that you just need to revisit study size sort of in planning and powering assumptions?

Perhaps, Doug. I mean this study, arguably other studies have now shown that possibly. But I think that there are even some limitations with CGM and the FDA has not wanted CGM to be a primary endpoint. So I think that the best endpoint is mechanistic. Frankly, it's GIR or even controlled mechanistic studies or perhaps we intend to do this to very much look at our OLE extension, real-world data. We'll see what we can do with those data and the ongoing OLE because, again, I think Nevan reiterated this, it's our belief based on what we've heard, what patients are doing in the OLE that they seem to be receiving some benefit anecdotally. They're on the drug. They're continuing to come for IV infusions. Some of them have stopped background therapy. So there's ways I think we're going to have to look at to show this benefit that we believe is there.

And Brian, just as a quick follow-up along those lines, when will you get your first cut or first meaningful cut of that OLE data?

We haven't determined that yet, Doug. We've been so focused on the pivotal. We don't -- and I should be clear, we -- the results we released were entirely on the pivotal portion of the study. That's the data that's been quantified -- quantitative, cleaned, programmed, validated, et cetera. I don't have...

Yes. No, but just understood, but I think it is, to your point, powerful that patients are remaining in the study and if they were not seeing a benefit, right, both either the families themselves or the clinicians would presumably sort of take them off the study because these studies are not -- it's not easy to participate, they're a hassle and obviously, these patients have sort of -- these impacts their lives already.

Yes. And then just to add, as soon as feasible, I mean, we're coming into the holiday period. There's still a few things to learn here on our end. But as soon as feasible, we'll be meeting with the advocacy group, we'll be meeting with KOLs, and we will seek a meeting with the FDA as soon as it makes sense to do that to look at these various things.

Our next question today will come from Albert Lowe of Craig-Hallum.

I was wondering for the hypertrichosis, that was noted that like an unexpected effect of ersodetug or could that perhaps be reflective of maybe some of these changes on background diazoxide where [indiscernible] comment?

Yes, Albert, based on the numbers that I reported, 14 events in treated patients and 1 in placebo, there's no imbalance between treatment arms and diazoxide use. These are treatment-emergent adverse events. They exclude patients, and there are many on diazoxide who had extensive hypertrichosis noted at baseline. So the study data tells us that these are study drug related. It also tells us, though, that they're mostly mild, the distribution of hair growth, the pattern is less extensive based on what we've heard and less concerning than diazoxide, but it does seem to be something associated with the drug, whether -- the term hypertrichosis is very familiar to the -- this indication and those that treated in patients. So it may be excess hair growth more broadly could have different causes. And if I can comment a little bit, could be when under a different term hirsutism, an indication of some attenuation of insulin and actually an indication of activity. So it seems to be active at the hair follicle without a significant safety consequence. And so -- and I think it's clear we believe it should be active at the liver, muscle and fat for glucose as well.

Okay. And maybe just to clarify something that you were saying before, for these patients that did have scheduled tube feeding for any changes there, is that data that was collected in the study?

Yes, we collected that. We followed that carefully, and there were no changes in tube feeds. So as I -- as we presented at the endo meetings, I didn't go through that in detail here. About 40% of patients were on scheduled tube feeds. Most of those were on continuous. So either 24-hour continuous or overnight continuous. Those were not changed in any material manner. And a couple of patients that had a de-escalation or a decrease in standing tube feeds, we have modified analysis to adjust for that and account for that. Those didn't seem to have any impact at all. And it's -- again, it's a fraction of the overall patient population, extremely small. So I just -- I want to emphasize again, things that are scheduled standing, routine doses that affect not just the current single point estimate of glucose, but future glucose values were very stable over the course of the study as a whole.

Our next question today will come from Yun Zhong of Wedbush Securities.

Very sorry to hear the negative outcomes. The first question, a follow-up question on upLIFT, and apologies if you already commented on this, if I missed it, but would you consider adding some type of interim analysis into the study to, well, kind of increase the likelihood of success? And were there any discussions when you reached that alignment with the FDA back in September that you will need to do certain steps or potentially could do certain steps in the case of sunRIZE fails to confirm the efficacy of the treatment, please?

Thanks for the question on upLIFT. No, first off, the latter part of your question, there is nothing that we heard from FDA or that's related from FDA related to the congenital study. To be clear, again, these are 2 separate INDs in very different patient populations, and the FDA has been clear with us along the last couple of years through our interaction that we should view it that way. And to that end, this study now and the clarity we have on the upLIFT study stands independently. So from an interim basis, there's nothing we really need to do, and here's why. This is an open-label study. So this is a completely different study, and this is back to my earlier point about responsible and thoughtful drug development in an ultra-rare disease where there's a massive unmet need as there is in the tumor study. These are patients that are often otherwise on the cusp of dying, and we're able to put our therapy into use and to make a huge difference. So given that it's open label, it's a small number of patients, we don't feel the need or desire to do an interim analysis as you would do typically as we did do in a Phase III randomized placebo-controlled study. So that study, the upLIFT study is very clear, very clear pathway, and we'll be marching along that.

Okay. And just to confirm because I believe you have breakthrough therapy designation for both indications. So when you seek a meeting with the FDA to talk about congenital HI, are you going to also confirm the FDA's approach or attitude towards the tumor HI indication? Or will that be strictly limited to discussion about the congenital HI indication?

Yes. No, thank you. And discussion will be all about the congenital. We are now squarely focused as we are dealing with this unfortunate outcome of this study, engaging with FDA and again, finding the responsible and a better path forward that will be clear and direct to be able to treat children. So that's what our discussion will be about is we will be completely focused on the congenital indication.

At this time, we will conclude our question-and-answer session. I'd like to turn the conference back over to Nevan for any closing remarks.

Thank you. And again, thank you all for joining us on the call today as we review the results from the sunRIZE study and understand initially the top line results and the implications as we move forward. I just want to reiterate that we remain very committed to the congenital HI community. We have, as we've discussed, more than 50 patients still on our open-label extension study. And again, some who have been weaned off of background therapies, which is very, very significant. And we've had children now on our therapy and who remain on our therapy for a number of years, and that's very encouraging. So we know we have a drug that has activity. We believe in our drug, and we will work with regulatory bodies across the world to make sure that we find a way to thoughtfully get this drug into the hands of patients and families, not in a clinical setting, but in the commercial setting. That's our duty, that's our obligation, and that's exactly what we're going to do. There's a reason why we've named this company Rezolute. We have to resolve, and we will do what our mission is. Thank you all for joining us, and thank you for believing in us, and stay tuned.

The conference has now concluded. We thank you for attending today's presentation, and you may now disconnect your lines.