Please note, this event is being recorded. I would now like to turn the conference over to Nevan Elam, Chief Executive Officer and Founder. Please go ahead.
Thank you, and good afternoon. Appreciate all of you joining us today for an update on the status of our phase III program for RZ358. I am joined by our Chief Medical Officer, Dr. Brian Roberts, as well as our Vice President of New Product Planning, Jeff Roeseler. Also joining us is Dr. Paul Thornton, a distinguished pediatric endocrinologist and senior author on the Hyperinsulinism Management Guidelines, which will soon be published. Needless to say, Dr. Thornton is a globally recognized expert in the management of patients with congenital HI. Before we go any further, I would like to make a note that during the course of this call and the Q&A period, we may make forward-looking statements regarding future events or future clinical development activities of the company, which involve risks and uncertainties.
Such statements are only predictions, and actual events or results could differ materially from those predictions due to a number of risk factors and uncertainties. I refer you to the documents that we file from time to time with the U.S. SEC, specifically our last filed annual report on Form 10-K, which was filed on September 15th, 2022, and our quarterly report on Form 10-Q, which was filed on May 11th, 2023. These documents contain and identify important factors that could cause actual results to differ materially from those contained in our projections or forward-looking statements. With that, we're pleased to announce that we are poised to start a pivotal phase III study of RZ358 in individuals with congenital HI in the fourth quarter of this year and anticipate having top-line results available in the first half of 2025.
The phase III study, the sunRIZE study, will be initially conducted outside of the U.S., in Europe, the Middle East, Asia, and elsewhere. sunRIZE follows our successful phase IIb RIZE study, which demonstrated that RZ358 was generally safe and well tolerated, as well as effective in improving hypoglycemia in participants who were failing available medical therapies. We have conducted our pre-phase III regulatory and scientific advice meetings with European health authorities and have agreed upon the design of the sunRIZE study, which will include participants three months of age and older. In the U.S., we have had similar interactions with FDA. The agency is maintaining an existing age restriction of 12 years and older on clinical studies for RZ358, and has imposed a dose level restriction based on historical rat toxicology findings.
We believe that the FDA restrictions make it infeasible to include the U.S. in the phase III study at this time, particularly in light of the fact that the pediatric population carries the highest burden of an unmet therapeutic need. Before I ask Dr. Roberts to walk us through some of the highlights of the design of the sunRIZE study, I would like to add some additional background regarding the regulatory history of RZ358 and our regulatory interactions related to sunRIZE in order to provide context surrounding the FDA restrictions. As part of the early RZ358 development program, toxicology studies in rats and monkeys were conducted. In these studies, rats demonstrated a microvascular liver injury at potentially clinically relevant doses and exposures.
Importantly, there were no adverse liver findings in monkeys at dose levels that were more than 10x higher than the doses that were toxic in rats, and more than four times higher than human doses evaluated in clinical studies. Based on the absence of liver toxicity in monkeys and the lack of adverse liver findings in closely monitored human trials, we believe that the toxicity is unique to rats and unlikely relevant to humans. After completing phase I healthy volunteer studies, phase IIa single-dose proof-of-concept studies were conducted in Europe in participants with congenital HI who were 12 years of age and older.
In the U.S., FDA restricted phase IIa enrollment to participants 18 years of age and older, and based on the rat toxicology findings, FDA had a cap on the human drug exposure, equating to approximately 3 mg/kg/week in repeat doses. Subsequently, in the phase IIb RIZE study that began in the fourth quarter of 2019 and was completed last year, regulatory bodies outside the U.S. agreed to reduce the minimum permitted age for eligible study participants from 12 years to two years of age, based on the prospective benefit for children. In that study, the average age was approximately six and a half years of each participant. In the U.S., at the start of the RIZE study, the program remained under the previous 18 years of age restriction, as well as the exposure cap.
However, in the first half of 2020, while the RIZE study was underway, we reached agreement with FDA to effectively remove the exposure cap and dose up to 9 milligrams per kilogram in repeat doses. Further, FDA agreed to lower the minimum permitted age for eligible study participants from 18 to 12 years of age. Each of these developments enabled the harmonization of the global study protocol for RIZE, other than a regional difference in the youngest permissible age to be enrolled, 12 years of age in the U.S. and two years of age in all other geographies. After the completion of the RIZE study, we began our regulatory interactions in the U.S. and Europe, notably with all available clinical and non-clinical information under review, including the historical rat toxicology findings.
Regulatory authorities in Europe agreed with a further downward age progression for the sunRIZE study, such that participants three months of age and older will be permitted to be enrolled. The observed benefit in the RIZE study, coupled with the entirety of the clinical and non-clinical history of the program, justify the lowering of the age down to infants for phase III. Following the RIZE study, we also sought to reach agreement with FDA to further liberalize the minimum age to achieve alignment with the other geographies. In our interactions with FDA, the agency revisited prior concerns regarding the historical rat toxicology findings, and despite the absence of no new non-clinical or clinical data other than the favorable RIZE data, the agency decided to maintain the age restriction of 12 years and above, and to reimpose the previous exposure cap, which had been removed during the RIZE study.
Rezolute interacted with the agency in an effort to resolve these restrictions, particularly in light of the fact that the program was advancing in other regions of the world, all of which culminated in a meeting with the agency last month on May 24th, where these restrictions were affirmed. Together with FDA, we have discussed potential solutions that could enable removal of these restrictions, and as a result, we are evaluating non-clinical studies to address FDA's concerns. Concurrently, we will proceed with the initiation and advancement of the sunRIZE study in multiple centers and countries outside the U.S. Now, I'd like to turn the call over to Dr. Roberts.
Thanks, Nevin. Good afternoon, everyone. We are excited to advance into the registrational sunRIZE study, which will be conducted in a total of approximately 56 participants who are as young as three months old in multiple countries outside of the U.S. The study is a randomized, double-blind, placebo-controlled, parallel arm study of RZ358, with an adaptive interim analysis for sample size re-estimation as applicable, as well as a smaller open-label arm for initial enrollment of the youngest infant participants. The target study population will include participants with congenital HI, who have not achieved adequate glycemic control on available or standard of care medical therapies, based on a careful characterization of hypoglycemia events and time during screening. In this way, the enrolled population will be very similar to the RIZE study.
Approximately 48 eligible participants, one year of age and older, will be randomized equally to receive either 5 or 10 milligrams per kilogram of RZ358 or placebo as add-on to their pre-existing standard of care, with 16 participants per treatment arm. An additional open label arm will accommodate the first approximately 8 eligible participants within the youngest age category of three months to one year of age, who will receive RZ358 as a starting dose level of 5 milligrams per kilogram, which may be increased to 10 milligrams per kilogram as needed. All participants will receive RZ358 as a 30-minute IV infusion. The first three doses will be administered every other week during an initial six-week loading phase, followed by four doses that will be administered every four weeks during a maintenance phase, for a total treatment duration during the pivotal treatment period of six months.
This reduced administration frequency is supported by exposure-normalized modeling and our ongoing observations with monthly dosing from our expanded access program, while also serving to optimize the target product profile for RZ358 delivery. After completion of the pivotal treatment phase, eligible participants across all treatment arms will be able to receive RZ358 in an open-label extension phase to support the unmet need in this patient population and to provide longer term post-approval efficacy and safety data. Weaning or stopping of background standard of care therapies will be permitted during the open-label extension. Blood glucose will be monitored throughout the study by self-monitored blood glucose using a point-of-care glucometer and by continuous glucose monitoring systems.
The primary efficacy endpoint for the study will be the change in weekly hypoglycemia events, defined as less than 70 milligrams per deciliter by SMBG, or self-monitored blood glucose, at six months of treatment. The key secondary efficacy endpoint for the study will be the change in percent time in hypoglycemia by CGM or continuous glucose monitor. These endpoints were previously and successfully assessed in the RIZE study. Additional secondary and tertiary endpoints will evaluate hypoglycemia and its related outcomes across several other additional metrics, many of which were also previously assessed in the RIZE study. These will also include patient-reported quality of life outcomes, hypoglycemia-related hospitalizations, and symptomatic hypoglycemia.
In addition to carefully accounting for registrational and reimbursement factors coming out of discussions with key regulatory bodies and payers respectively, the study design that I've just described also reflects our successful experience coming out of the RIZE study, as well as the culmination of significant discussions with and input from global patient advocacy organizations and physician experts in congenital HI, with whom we are closely partnered. The Rezolute team held a successful investigator meeting last month to kick off the sunRIZE study, which was attended by more than 15 participating countries globally, as well as our other partners in patient advocacy. We continue to build excitement and momentum for the program.
We and our partners are working diligently at putting all the pieces in place to launch the study and are anticipating initiation of the study in Q4 of this year and top line results in the first half of 2025. With that, I'd like to take this moment to thank our patient and physician partners for their tireless dedication in working towards finding better treatments for patients with congenital HI, and for their ongoing collaboration with us on the RZ358 program. Now I'd like to turn the call over to Dr. Paul Thornton for further comments.
Thank you, Brian. I cannot overemphasize our need for new therapies in congenital hyperinsulinism. This is a truly devastating disease, with approximately 50% of affected children having neurological dysfunction. It's for this reason that my colleagues and I spoke with the FDA so that they could appreciate the severity of the disease when they evaluate the risk to benefit equation of whether a therapy should be studied and eventually approved. As you may know, I treat children with congenital hyperinsulinism. In fact, it's a cornerstone of what I do. I also interact with their parents and loved ones of the children who have congenital hyperinsulinism, and believe me, it's an extremely taxing and difficult journey for everyone.
Many of you have seen the data that show that patients on the current standard of care have far too many episodes of hypoglycemia, or have required invasive near-total pancreatectomies and are at risk of developing the lifelong complications of diabetes and all of its problems. I was an investigator in the RIZE study, as well as a member of the committee that reviewed safety data as part of the dose escalation in RIZE. The RIZE data that you have all now seen and reviewed speaks for itself. I do hope that Rezolute is able to satisfy FDA's non-clinical concerns. Simply put, I believe that RZ358 should be studied in the U.S. as part of the global phase III program. We are all hopeful that sunRIZE will continue to demonstrate that RZ358 is safe and effective in correcting hypoglycemia.
If that is the case, many of us who treat these children and their parents will want to have this therapy approved worldwide, including for patients here in the U.S. I was at the recent sunRIZE investigator meeting that Brian just referred to, and I had the opportunity to interact with colleagues from all over the world. I can report to you that there is genuine excitement about RZ358, because there is now the possibility that we are closer to having a therapy approved that can make a significant difference in the lives of patients and families. Thank you, and I'll hand you back over to Nevin.
Thank you, Paul. really appreciate your thoughts and your perspective as a treating physician, and in particular, helping those of us who are not on the front lines of the disease to better understand the congenital hyperinsulinism patient journey. Like many rare diseases, there's a lot of work to be done to not only define optimal treatment guidelines, but also to better characterize the population that suffers with the disease. Along those lines, given that our therapy is in late stage development, and we need to be thinking about potential launch of the therapy, we have undertaken the initiative to better define the prevalence and incidence of congenital HI.
To that end, Jeff Roeseler joined us last year as our head of new product planning, and with his many years of experience working in rare diseases and successfully bringing therapies to market, he and his team and others have made significant progress characterizing the epidemiological aspects of the congenital HI population. I thought it'd be appropriate to have Jeff give us a brief update on some of that work.
Thanks, Nevin. I'm excited to share some of the work that we've done to better understand the incidence and prevalence of congenital HI. Based on my experience, I can confidently say that congenital HI has some very unique characteristics that I believe will contribute to the successful commercialization of RZ358, should the therapy continue to demonstrate safety and efficacy in the phase III trial and be eligible for approval. Congenital HI is a highly concentrated market. Over 80% of patients diagnosed are managed through a select number of centers of excellence. This dynamic is consistent across markets throughout the world, and we believe that this factor may enable rapid adoption of an effective therapy, especially given that there has been no new treatments approved to treat congenital HI for over 50 years.
Historically, the literature for congenital HI has quoted a wide incidence range between 1 in 50,000 to 1 in 25,000 births. To understand the true congenital HI population, we engaged third parties who conducted claims-based market assessments to quantify the number of individuals who are living with congenital HI. We now believe that the disease occurs in 1 in 28,000 births. This work was also validated by a third-party epidemiological analysis, as well as engagements with KOLs and international advocacy organizations. In primary geographies where we would expect to commercialize RZ358, this equates to over 10,000 individuals living with congenital HI. In the U.S. and Europe, each market has roughly 3,500 individuals, and we believe that more than half of these individuals lack adequate treatment options to control their hypoglycemia.
Additionally, we conducted primary research with KOLs to understand the average treatment duration on therapy. The output of this research estimates that congenital HI patients are on therapy an average of 25 years. This is specifically the case for those individuals that are non-responsive to diazoxide. Across all the research we conducted, one thing has clearly resonated: there is a serious unmet need, and everyone is looking for new options. In addition, many of the clinicians that we've spoken to highlighted not only the shortcomings in efficacy, but also the unacceptable side effects of current treatments. There's a significant opportunity to educate and raise awareness around congenital HI, and we look forward to partnering with KOLs and advocacy organizations over the coming years. I'll turn it back to you, Nevin.
Thanks, Jeff. And before we open up the call to questions, I would like to make a closing comment about our therapy, RZ358. We believe that based on the clinical data generated to date, RZ358 is highly effective at safely correcting hypoglycemia, and this belief was recently reinforced in a completely different setting. As you may have seen, last week, we announced that Dr. Mary-Elizabeth Patti, Director of the Hypoglycemia Clinic at the Joslin Diabetes Center at Harvard, presented at the Annual Endocrine Society meeting held just a couple of weeks ago in Chicago. Specifically, she reviewed a case study involving her administration of RZ358 to a 55-year-old male patient with refractory hypoglycemia due to malignant insulinoma with liver metastases. Following receipt of the requisite FDA and IRB approvals for compassionate use, Dr.
Patti's patient began receiving RZ358 in the fourth quarter of last year and has remained on our therapy since that time. At the conference, Dr. Patti reviewed the patient's refractory treatment history and after receiving RZ358, the substantial improvement in hypoglycemia, which led to the patient being discharged from the hospital. The patient has now been on RZ358 for more than six months, and the ongoing outcomes further validate the pharmacology of RZ358 and its potential to safely and effectively treat hypoglycemia associated with congenital and other forms of hyperinsulinism. We are pleased that we could provide RZ358 to this patient with cancer-related hyperinsulinism as part of our RZ358 expanded access program. All of this gives us further confidence and emboldens us to move forward with the goal of making RZ358 available to all patients in need. Let's open up the call for questions.
Thank you very much. We will now begin the question and answer session. To ask a question, you may press star, then one on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw from the question queue, please press star, then two. At this time, we will pause momentarily to assemble our roster. The first question today comes from Jason Butler with JMP Securities. Please go ahead.
Hi, thanks for taking the questions, and congrats on all the progress. Nevan, could I just ask you to start with maybe giving us some more color on why FDA is taking a different view here, including the reversing the dose restriction? I guess more importantly, what preclinical data could enable expansion of the trial to the U.S. and how those timelines fit into the enrollment timelines you've set out today? Then I have a follow-up. Thanks.
Sure, absolutely. You know, dealing with regulatory bodies worldwide, it's definitely difficult to predict and understand how decisions are arrived at in every circumstance. In this particular case, given the progress that we made in the RIZE study by having the age lowered down to 12 and the removal of the exposure cap, we were definitely a bit surprised to learn of the agency's new position. I can't really comment on to exactly the inner workings of the FDA, and how they arrived at that conclusion. Other than, you know, we are where we are, we believe we have a path forward, and particularly in our conversations with the agency.
In terms of what types of things can we do, you know, these are, you know, really relatively potential short-term type analyses, whether it's in vitro, looking at different studies we may do, to be able to provide some comfort that, in fact, the rat specific findings are indeed species specific. We've already engaged, you know, relevant experts in the field and look to have, you know, hopefully more to say on that in the near future.
Okay, great. It's probably too early to speculate on the potential to explore a label in the U.S. for patients just over 12, but can you maybe just give us some color on what you learned from the RIZE phase IIb trial in terms of efficacy in different age groups under and over 12? Lastly, can you clarify what drove the dose selection for 5 and 10 milligrams versus the 6 and 9 you used in RIZE? Thanks.
Sure. I'll ask Brian to comment on the dose selection specifically. One thing I will say that across the RIZE study, what was really fascinating is we did dose down to two years of age. Again, average age of the study participant was six and a half years. The effect was profound, really, across the entire age spectrum in the study. This just underscores, I would say, the robust nature of the antibody and how it actually can correct hypoglycemia. That's further underscored, again, by now having seen a 55-year-old patient with, in a different setting, with an insulinoma-related tumor that's creating hypoglycemia, also having a pretty profound response to the antibody. We actually think that it's effective across all ages.
What we really want to do, and what's really important, and why we're very encouraged by where we are in other geographies in the world, is that we're dosing down to three months of age. This is a congenital disease. We need to be in the youngest possible patients and have even been pushed to think about, you know, the neonatal phase as well. And so we'll have more to say on that in the near future as well. You know, clearly, you know, we want to get down as young as possible and give the therapy to the youngest children that really are in need.
As far as the dose selection, the rationale there is, as I stated in the comments, the decrease to a maintenance, you know, approximate monthly dosing frequency, definitely is an advantage in terms of the administration of this, you know, the IV administration of this antibody therapy, and the, you know, the frequency of visits to the site, both during the study setting as well as we think past the study. It's clear what would drive that.
In terms of the supportive data that justifies doing so, Jason, it's really looking at exposures at the 5 and 10 milligram proposed doses of the proposed regimen, and showing that they match very well the exposures that were achieved with the 6 and 9 milligram per kilogram biweekly dosing in the RIZE study. Furthermore, you know, just to elaborate on what I said, we have patients on monthly dosing now, you know, patients on our expanded access program that came off the RIZE study, as well as the patient that was mentioned, who received RZ358 from insulinoma. So we have this, a real-time validation of our exposure modeling, as well.
Just to follow up Nevin's comments on the subset analysis, we've done those formal analyses to support the regulatory interactions in the U.S. and the ex-U.S. Patients in all age categories, namely less than 12 as one group, had identical, if not somewhat better efficacy, as well as excellent safety with receipt of RZ358.
Okay, really helpful. Thanks for taking the questions, and again, congrats on the progress.
Thanks, Jason.
The next question comes from Maury Raycroft with Jefferies. Please go ahead.
Hi, thanks for taking my questions. You said after the May 24th meeting, you discussed additional studies to potentially address FDA's concerns. Can you clarify if there was any alignment with FDA on what the additional studies would be? You said there would be short-term studies. Are there any more specifics on how long you think the studies could take, and maybe bookend timing for when you could expand the phase III to the U.S.?
Yeah, thanks for your question, Maury. This is Brian. The studies were under discussion on what. They did provide some general guidance. We did not discuss the specifics, and the FDA, you know, typically wouldn't suggest a specific study. They did provide guidance in terms of studies that might allow them to liberalize the age of the dosing. They really focus around helping to characterize the mechanism of action of this injury to the liver microvasculature in rats, and then in turn, whether that might be relevant to humans. That would, as you might imagine, could be done in cell-based type studies.
We are also looking at the possibility, for example, of conducting other in vivo non-clinical studies that could help, perhaps explain the mechanism of action or characterize a safe dose that would permit, you know, dosing in younger ages. All of that is on the table. It's, you know, the FDA didn't specify which of those they would want. We are evaluating that closely, and we also have, of course, you know, an advanced, late-stage clinical program progressing outside the U.S., who, you know, those regulators are fully informed of all information. Whatever we do, you know, has to have a clinical context and weighting applied to it, and that affects the decision of the studies we might choose to do, as well as the timing.
In theory, these studies could be done, over a relatively, over a timeframe that might support the U.S. being involved in the Phase 3 program, if we chose to do that.
Maybe just to add a thought there as well, to give you a little more color from the interaction with the agency. The agency has said that they wanna be helpful. They recognize that they have actually changed positions here, and that can happen. They also recognize that we are not interested in doing exploratory biological studies that could go on for years. They assured us, "No, no, we're not talking about that." That's, I think it's important that I think everyone should understand we're looking at something potentially very focused to be able to address their concerns.
Got it. That's helpful. Maybe one other follow-up question. Was it discussed with FDA on potentially getting some clinical data from the ex-U.S. study on a blinded basis, or maybe even something specific that FDA wanted to see, and bringing that clinical data back to FDA to discuss that with them?
You know, no, it really wasn't, Maury. That was not specifically discussed. You know, they were looking at the clinical benefit, and they've acknowledged what we've all seen in the RIZE study. This is the same division that approved the compassionate use for the patient, at Harvard, that's receiving our therapy right now. They're very well aware of what's happening. This is purely a non-clinical theoretical concern, which is what this is, a theoretical concern, in one species. We, you know, they're not really focused on additional efficacy data that could come from the U.S.
I think it goes without saying, the more robust of a data set we have, dosing children for longer periods of time, continuing to see a solid safety record as we've seen to date, in all of the studies that we've conducted, should be encouraging as well, though.
Got it. Understood. Thanks for taking my questions.
The next question comes from Pete Stavropoulos with Cantor Fitzgerald. Please go ahead.
Hi, Nevan and Brian. Thank you for the update, and I look forward to the study start. I'm just continuing on, I guess, the rodent finding. You know, taking into consideration, you know, the mechanism of action of three-five-eight, you know, is there any mechanistic rationale that can actually explain the tox finding in rodents? Or do you believe it's an off-target effect, you know, sort of restricted to rats?
Yeah. We believe it's very likely an on-target effect that's unique to rats because rats, of course, are not humans. They depend heavily on the liver for metabolism, and there may be, you know, exaggerated pharmacology in rats that we see mediated not only in the toxicity, but in the way rats behave from a glucose perspective to RZ358. That separates them very strongly from what happens when we dose RZ358 at substantially higher doses in monkeys. Pete, we do think that it's likely to be mediated through primary pharmacology and is not off target. We don't know that for certain. Those are the types of things that, you know, we may have to explore further based on FDA's comments.
Right. All right. Just moving on to the phase III summary study. You know, are you gonna focus on patients who have, you know, known genetic mutations, or are gonna go more broadly? Will there be any restrictions of patients based on genetics or any phenotypic characteristics?
The short answer to that question is no. We are evaluating patients broadly. We'll assess the genetic subtypes at baseline so that we're able to characterize the response in, you know, in analyses after the study is done, but we are not using genetics to determine eligibility. The population that we'll be enrolling will be very similar to the RIZE study. It's genetics agnostic, it's all comers, as long as they are having persistent hypoglycemia in spite of available standard of care therapies.
Okay. Thank you. If you don't mind, one question for Dr. Thornton. You know, Dr. Thornton, you know, seeing the effects of three-five-eight, as an investigator in the RIZE study, you know, can you just sort of.
I'm sorry, could you repeat the very last part of your question there?
You know, seeing the effect of 358 as an investigator on the RIZE study, you know, can you discuss what also improves, you know, besides hypoglycemia, any other type of clinical benefit? You know, I recall seeing a poster discussing the seizure frequency.
Yeah. The key thing with RZ358 is that it blocks the action of insulin. This is why when you you know, when you ask a genetic question, we believe it'll work for all forms of hyperinsulinemia. What we saw in the studies was basically a very significant reduction in hypoglycemic events and a big increase in time within range and a decrease in time below range on CGM. This has a you know, a dramatic effect for the families, because every time you have a hypoglycemic event, it causes an intervention and then time checked to follow up. We saw although we didn't measure specifically, we could tell from the families in the studies that their quality of life was better and that their fear of hypoglycemia was less.
Of course, the less hypoglycemia you have, the less risk you have of seizures, and other consequences. Really, the dramatic effect was on the frequency of hypoglycemia, and then the knock-on effects were really those related to having to do less interventions, less emergency feeds to bring the blood sugar up, and those sort of patterns changed.
Okay. Thank you very much. Evan and Brian, thank you for taking my questions.
Thanks, Pete.
The next question comes from Jorge King with H.C. Wainwright. Please go ahead.
Hello, this is Jorge King on behalf of Douglas Tsao, and for taking my question. I'm just curious, I think this was briefly mentioned during the call, but because this indication is also present in the neonatal population, I'm just curious if you're if you want to avoid this antibody in patients that are younger than three months old? Thank you.
Hi, Jorge, this is Brian. I can take that question. We definitely have a plan that we've proposed in our regulatory interactions as far as neonates, and that would be to evaluate neonates as a supplemental study. That patient population is very different in terms of the diagnostic journey that they're going through, the implementation of therapies for the first time, the management, with, for example, infusion of dextrose as opposed to chronic therapies, and the endpoints in a study. Those are two patient populations that we'd want to, you know, separate in terms of how we investigate them. Our approach, you know, we think is very efficient.
We seem to, we're still working on gaining alignment on this. It will essentially be to initiate a neonatal study in a deferred manner, as a supplemental type study, a smaller study where we're really more focused on the short-term PK and PD and the use of modeling to extrapolate doses in neonates and into a potential label in neonates. We're looking to kind of minimize the actual study of neonates because it is a more challenging study to do.
This concludes our question and answer session, as well as today's conference. Thank you for your participation. You may now disconnect your lines and have a nice day.