Egetis Therapeutics AB (publ) (EGTX) Earnings Call Transcript & Summary

A warm welcome to everybody here in the room at Penser Bank for the Capital Markets Day held by Egetis Therapeutics. Also a warm welcome to all of you, 50 plus or so, which I'm very pleased with, that's joining us via the livestream. For those who I haven't had the privilege to meet before, my name is Nicklas Westerholm, and I'm the CEO of Egetis Therapeutics. I have a background in chemistry. And before I joined this company 5 years ago, I had the privilege to spend close to 17 years within AstraZeneca amongst a number of different international business areas such as late-stage development, finance and investor relations, global manufacturing, but also heading up AstraZeneca's business in Japan. We have a very exciting agenda today where we're going to cover, amongst everything, a strategic overview by myself and really illustrate the long-term direction and the ambition we have for Egetis Therapeutics. We're also very pleased to have with us today 2 world-leading clinical key opinion leaders in their respective field. So we have Dr. Edward Visser from the Erasmus Medical Center joining us to talk about our lead candidate, Emcitate, for the treatment of MCT8 deficiency, where we will be elaborated on the disease, the clinical phenotype, the unmet medical need as well as the clinical experience we're seeing year-to-date with Emcitate. We then move on to talk about the development pathway up until the regulatory approval for Emcitate, both in Europe but also in the U.S. We will then break and leave ample time for questions and discussions. We really encourage the audience to ask a lot of questions here to ensuring we have a dialogue. And subsequently moving on, considering the global plans for commercialization in U.S. and Europe, but other parts of the world as well, and focusing in on the commercialization in the European market. We'll have a break subsequent to that, and then we will focus on Aladote for the prevention of acute liver injury caused by paracetamol poisoning. And here again, we have Professor James Dear from the Edinburgh University that's going to walk us through paracetamol overdose, the incidence levels and the clinical manifestations of the same as well as the experience of using Aladote in the treatment of this patient population. We're going to walk -- move towards the development path for Aladote up until regulatory approval in Europe and U.S. and finish off with the commercial opportunity for Aladote. We're then going to move on to the summary of the day and also some closing remarks by our Chairman of the Board, Thomas Lönngren. So starting off with the company then. Most of you know that Egetis Therapeutics is a fairly new and recently created company. The company was actually created in quarter 4 2020 from the merger of the previously listed company called PledPharma and the privately held company called Rare Thyroid Therapeutics. As part of the establishment of this company, we are very clear with our long-term ambition to build a sustainable orphan drug company. The vision for the company is also very clear, it's to bring unique therapies to patients with rare diseases to extend and improve their quality of life. In order to measure our journey towards our vision, we also have stated some very, very clear objectives covering the short term, midterm, but also the long term. And the first one to call out is, of course, to successfully develop Emcitate for the treatment of MCT8 deficiency and Aladote for the development and registration in prevention of acute liver injury caused by paracetamol poisoning. Approvals are expected in 2024 and 2025, '26, respectively, for each candidate. Furthermore, which we'll hone in on, is the commercialization of Aladote and Emcitate through an in-house-focused commercial organization in Europe and in U.S. and also clearly stipulating that we will be looking for partnerships in the rest of the world. An important aspect for a company like ours that have passion for rare diseases is, of course, broaden -- ensuring fast and broad access for these patients suffering from these conditions. Another aspect that we really have as an objective is also looking at additional assets in order to build a sustainable rare disease company. We will continue to work on in identifying further assets in the rare disease space where we can optimize a development pathway up until regulatory approval. And by doing so, we really believe that we are well equipped and set up for the future to create long-term shareholder value. One can also ask ourselves, so when we came together, PledPharma and RTT, creating Egetis Therapeutics, why the orphan segment? Why do we focus on rare diseases? And it's a simple answer to that: we really believe that the attractive features in the orphan space really caters to our setup. We are a small biotech company on our way to internationalize sales ourselves, but we don't have unlimited funds. We truly believe that the features you see here on the slide really caters to us in the sense of shorter development time lines to market approval; fewer patients are required in the clinical trials, which of course then considers a lower cost base; there are generally, which is very important, higher probability of success. And of course, looking at risk/reward from an investor's perspective, probability of success is very important. That, in combination with premium pricing in the orphan drug space or in the rare disease space, is very, very attractive and makes the case, in our humble opinion, as creating our corporate strategy and the optimum way of operating in. One also very important area worthwhile mentioning is the efforts we have made in attract, recruit and retain a very competent team. We have recruited now an organization with global experience and proven track record on designing late-stage clinical studies, execute late-stage clinical studies, analyze them, navigating the complicated regulatory pathways in their different jurisdictions, but also be able to commercialize them. And to pick up some examples, we have Kristina Sjöblom Nygren, our Chief Medical Officer, that joined us last year, who has experience as a Chief Medical Officer in other small biotech companies like Santhera, but also experience from Sobi. Our Head of Development, Christian Sonesson, very experienced in late-stage development from AstraZeneca, being globally leading development programs for large assets, the likes of FORXIGA and BRILINTA, and also being part of leading oral explanations and advisory committee meetings with the FDA. Our recent hire, Sara Melton, who joined us in June this year, brings substantial experience in commercializing orphan drugs in the rare disease space in the U.S. We also have our CFO in Yilmaz Mahshid who is seasoned and experienced in the life science sector with a scientific background, but also been working as an equity analyst in the health care sector as well as an investment manager. We have Henrik Krook, our Head of Commercial, who's actually have a proven track record from Alexion, amongst others, commercializing orphan diseases. So why do I say this? And that -- this is really based on my personal experience being in the life science sector for over 20 years: people will make a difference. So by having a very strong team, a differentiated team, we are very set -- well equipped and set up for the future, making a success for the company. In addition to that, we have a very seasoned and experienced and engaged Board. Our Chairman of the Board, who we'll hear from later, Thomas Lönngren, who amongst others have had a tenure as the Head of the European Medicines Agency for 10 years; Gunilla Osswald, CEO of BioArctic; Elisabeth Svanberg, a very seasoned late-stage development, both from an executive positions, but also operational positions and, amongst others, is also on the Board for LEO Pharma and Galapagos and previous Board member of Sobi. Mats Blom, previous CFO of Zealand, now CFO of NorthSea Therapeutics, bring additional capabilities around the financial market into the organization. Last but not least, you will hear later from Peder Walberg, who's operating also active in the company, who's got a very interesting experience and broad background in the orphan drug space where he, amongst others, was a co-founder of Wilson Therapeutics together with HealthCap, which he was then all, I guess, you know the [ success saga there ]. If you turn our attention then to the pipeline, which will be the focus of today, we have a very well and advanced pipeline. We have our lead candidate, Emcitate, for the treatment of MCT8 deficiency, where we're looking forward to regulatory submissions in Europe first half of next year. When it comes to U.S., we're looking forward to a submission mid-2023, pending a short placebo-controlled randomized study, which Peder will elaborate further on later, that needs to be completed. In addition to that with Emcitate, we also have another opportunity outside MCT8 deficiency in the indication called RTH-beta or resistance to thyroid hormone beta, which is a distinct and separate patient population to MCT8-deficient patients. We also have Aladote, our second candidate for the prevention of acute liver injury caused by paracetamol poisoning. Here, we are planning to start a pivotal study at the beginning of next year, and we'll hear here more about the study design, the incidence levels from the team later on. So with that and no further ado, I will actually hand over to Dr. Edward Visser, and I'm sure Edward will introduce himself properly as well.

Thank you very much, Nicklas. So yes, good afternoon, everybody. My name is Edward Visser. I'm an endocrinologist based in Rotterdam, the Netherlands. And I would like to talk about our experiences in MCT8 deficiency. This is my disclosure slide. And I thought it's good to actually kick off with showing a patient because there, it's where it starts and also where it should end. So quite some prominent disease features are seen in this picture. For example, the lack of head control, you see the patient needs support to sit upright. He is underweight, there's dystonia, and there are many other disease features which are not seen in this particular -- actually, in this photograph, but certainly occur in this disease. So what I would like to talk about today is, first, to give some background about thyroid hormone physiology, so basically, a few weeks of first year medical school in a few minutes. And then I will talk about MCT8 deficiency, the mechanisms, the clinical features and the data we have on treatment with Triac, also called tiratricol. So let's start with the physiology. So the pituitary located in the brain produces a number of hormones, amongst others, TSH, and TSH stands for thyroid-stimulating hormone. And it's not a surprise that it does what the name states, it stimulates the thyroid gland to produce hormones, thyroid hormones, mainly T4 and, to a lesser extent, T3. So T4 is a prohormone, which is converted to T3, which is the bioactive form. So that's released in the bloodstream. And for many hormonal systems, there are feedback systems also for the thyroid hormone physiology and that there's a negative feedback loop unto the pituitary. So the hormones, they can be released from the bloodstream and enter many cells and tissues and exert their clinical effects there throughout development, but also throughout entire life. So when the hormone reaches the cells and tissues, there is another kind of intricate regulatory mechanism. So this represents a target cell for thyroid hormone. So this is the plasma membrane. And actually, the hormone binds inside the nucleus to a receptor called the thyroid hormone receptor. And that acts as a switch to induce thyroid hormone-dependent transcriptional programs, thereby ultimately inducing its effects. Inside the cell, there are a set of enzymes called the deiodinases that can either activate or inactivate thyroid hormone. And as these processes occur inside the cell, the hormone needs to be transported across the plasma membrane barrier. And to keep a long story short, transporter proteins and the plasma membrane are required to facilitate this process. It was only in 2003 that our group identified the most specific transporter known to date called MCT8. Right. So let's move to the mechanisms of disease. So what are we talking about? So if MCT8 is defective, there will be a problem downstream. So the first patients were identified back in 2004, basically 1 year after the discovery that MCT8 is an important key player in the cellular regulation of thyroid hormone, both by our group and also by another group. And another year later, it was recognized that the clinical features of this disease described in these 2 papers are very reminiscent of a syndrome already described in 1944 by Allan, Herndon and Dudley. And the MCT8 gene is located on the X chromosome, so mainly males are affected. And basically, this Allan-Herndon-Dudley syndrome was the first X-linked mental retardation syndrome ever described. And it took another 60 years before the genetic defect was identified. So in these slides, I would like to explain the underlying mechanisms of disease. So cells and tissues that are dependent on their cellular -- on their thyroid hormone supply on MCT8, they will be deprived from the thyroid hormone. So that's indicated here. So the level of intracellular hormone is low. And that results in such cells and tissues being hypothyroid, which is the situation in the brain. Why the brain? Because MCT8 is importantly expressed at the blood-brain barrier and also in many neural cells. So that's what we call the neurodevelopmental phenotype, which is one part of the disease. In the blood of these patients, there are very typical abnormalities in terms of thyroid function tests. So T4 levels, the prohormone is low, but the bioactive form T3 is quite elevated. So that means that cells and tissues that are not dependent on MCT8 but on other transporter proteins will be exposed to these toxic T3 concentrations in the blood. And that results in many adverse effects in liver, skeletal and heart tissue. And that brings about the metabolic phenotype. So basically, this disease has 2 parts. There's a neurodevelopmental and a metabolic component, which are indicated with the 2 different colors. So throughout the presentation, if the color turns blue in the title, I talk about neurodevelopmental phenotype. And when it is red, it's about the metabolic phenotype. So let's move to the clinical features of this disease. So how do you study such a rare disease? Well, what we did, we collected data from about 150 individual patients across the world through an international network. And we accrued the data and on different endpoints. So biochemistry, we get a data on neurodevelopmental outcomes, on clinical outcomes and also on mortality. And in the next couple of slides, I will just highlight some disease features. So we were able to define the key presenting symptoms in this disorder, and it's mainly developmental delay and hypotonia that ultimately results in referral to physicians. So this slide illustrates well the severity of the neurodevelopmental phenotype, and I'll try to guide you through. So this is the Gross Motor Function Measure, GMFM, in which 100% represents the normal motor capacities of a healthy 4-year-old child. And as you can see, all these patients, they score very low irrespective of their biological age. So they have a very poor development. So what can we measure in the blood of these patients? So when we -- when it comes to measuring the thyroid function tests, you can measure TSH, which is mostly normal in these patients. Free T4 concentrations can be normal but are mostly low-ish. But when you measure T3, then actually, irrespective of the age, it is nearly always elevated. And it's certainly the ratio between the low T4 and the discordant high T3, which is a very, yes, nearly diagnostic feature for this disease. So it's very important that physicians should measure T3 in, well, in a diagnostic process. And actually, for most common thyroid disease, the TSH and the FT4, they do the job. So it's important for this particular disease that this one is added. So this is about body weight in these patients. So what is plotted here is the body weight corrected for age because all -- well, children, they gain body weight anyway. So this is expressed as Z-scores or standard deviations. So normal growing children, they should be between plus and minus 2 standard deviations of their growth chart. And what we plotted here, all the individual blue circles are of untreated patients with MCT8 deficiency. So what you can get from this picture is that they are born at a normal body weight, then they deteriorate in the early phase of life, then they stabilize and then again during puberty, they again start to deviate from their, well, from their expected weight gain. And the same holds true also for body height and also sexual maturation is delayed, although ultimately normal. A couple of data -- some data on cardiovascular outcomes. So due to the high circulating T3 concentrations, patients have an elevated heart rate. Also when we quantify the number of patients with tachycardia or so-called premature atrial complexes or premature ventricular complexes, they're occurring frequently in this population. And also other disease features like conduction abnormalities and systolic hypertension occur in this disease. So when analyzing all these data from these 150 individuals, we were able to conclude something about mortality. And as you can see is that around 30%, 40% of individuals die during childhood. So what are the causes of death in these patients? So from the patients, we do know the cause of death. It's either aspiration pneumonia or pulmonary infections. Also certain death is occurring quite frequently. So what we did, we stratified the mortality for 2 basically -- possibly representing the 2 main components of the disease. So first, we stratified between patients who are able to keep their head upright versus those who could not. And as you can see, the patients who cannot keep their head upright in early life have a much worse survival than those who can do. And as you can see, it's the majority of patients who cannot keep their head upright. And perhaps as a proxy of the metabolic phenotype, we took underweight. And again, a similar picture seems to emerge. So patients who were underweight at a young age have a much worse survival than those who do not. So what about diagnosis? So there seems to be quite a difference between the age of symptoms appearing versus the diagnosis. So this is a graph, and please note this is a logarithmic scale on the age, that symptoms start to occur after a few months of age. Well, the diagnosis was, yes, beyond 2 years of age for patients born before 2017. We did the same analysis for patients born after 2017. And what you do see is that the diagnosis -- the age of diagnosis has been reduced. And we attribute that to a couple of factors, amongst others, disease awareness and perhaps also improved diagnostics. But certainly, there is some way to go there. Perhaps for the future, neonatal screening might potentially be employed. So in the Netherlands and in some other countries as well, we have a T4-based neonatal screening for congenital hypothyroidism, which is designed to pick up problems with the thyroid gland itself. But we were able to retrieve data from, in a retrospective manner, from these patients. And it seemed that they were all, yes, below the threshold. And then according to the current flow diagram, they were kind of booked, let's say, it was concluded. They did not have a thyroid disease, so there was no follow-up. But one can imagine that, for example, adding T3 or adding another marker might have potential to diagnose these patients already at birth. Right. So let's move to the last part of my presentation, which is about the treatment with Triac. So when you have in mind the mechanisms of disease, so hypothyroid tissues and hyperthyroid tissues, we had a, back in the day, we had a very simplistic rationale. So one should increase the T3 action in the hypothyroid tissues and one should reduce the T3 action in the thyroid toxic issues. So one of the ways -- well, possibly, at the time we were hypothesizing, that T3 analogs could do the job. And the hypothesis was as follows: so this is a cell in a MCT8-deficient patient. So T3 and T4 are unable to enter via the normal route. But one can imagine, if there is a mimic of thyroid hormone that can enter the cell via another transporter, that might hold potential, certainly, if this T3 analog binds the receptor like the endogenous T3 would do and is also degraded. So we tested this hypothesis by using Triac. And Triac is, as you can see from these structures, is very much similar to the T3 molecule. It's only this -- the alanine side chain, which is replaced by acetic acid, but it's very similar to T3. Actually, the Triac was already synthesized back in the '50s by Dr. Pitt-Rivers, the person who also discovered that T3 was the main bioactive form. So ever since, this molecule has been kind of searching for its application, and it seems that, well, that might be the case for MCT8 deficiency. So we first -- and I have only one slide with preclinical data, but we had years of preclinical data where we try to tackle each of these requirements in the lab. And so this shows the data in animals. So this is a normal, a control, a wild-type animal. So these are Purkinje cells in the brain. So this is what a normal brain development look like. This is what happens to a mouse model mimicking MCT8 deficiency. So it's clearly disturbed. And if you start treating these mice immediately after birth, it completely restores the brain development. And there are also data that they functionally come back to normal control mice. So this was done in collaboration with [ Haikohoier ] in Germany. So when having all these preclinical data available, we reasoned how might this work in human patients. And yes, it might work as follows. So this is the normal situation. So if T3 is administered, it would fire the negative feedback loop. It would reduce TSH, thereby leading to a reduction in the stimulus of the thyroid gland. So the endogenous hormones decrease. And actually, in the bloodstream, the Triac is able to exert the T3-like effects in all the tissues, whether MCT8 is defective or not. So this was the hypothesis before moving to a trial. So we started a trial called the Triac Trial I. And the primary outcome -- so actually, the main idea was to see whether we could alleviate the metabolic component of this disease. So the primary outcome was a reduction in the elevated T3 concentrations. At secondary outcomes, we had measures like body weight, heart rate, blood pressure and also a number of biochemical markers. Then we had a number of exploratory markers and safety outcomes, so as said, mainly the metabolic phenotype. And we had a number of tests that -- in which we scored the neurodevelopmental phenotype. Again, the trial was not designed for it, but we thought it was a unique opportunity, so we just took it along. So the trial run in 9 different countries with the idea having extensive baseline visits, treating them for a year and then extensive and study visits. So we enrolled 46 patients, of whom 40 completed the trial. And then in the next slide, I would like to discuss the main findings in this trial. So this is the primary outcome. So these are the T3 concentrations plotted for the individual patients with the red balls being the baseline condition and the arrows representing the reduction over time after a year of treatment. And as you can see, actually, in all patients, it's reduced and actually bringing back in the normal range as expected. And we also noted that TSH and free T4 concentrations were also reduced, very much compatible with the mechanism of action of Triac. So this is one of the secondary outcomes, the body weight, again, plotted as Z-scores. So as you can see, patients were far off their expected normal body weight. And what you do see is that there is an improvement in the majority of patients. And it's important to -- because it's not very perhaps intuitive, these Z-scores, but this can translate to many kilograms in individual patients, dependent, obviously, on the age. Also, heart rate elevated in the majority of patients, improved in particular in those who had an elevated heart rate at the beginning. And also, premature atrial contractions, which are very unusual in children, were present to a very high extent, but subsided in the far majority of the patients and were reduced in the others. Then one slide on some biochemical markets, reflecting the activity of thyroid hormone in different tissues, SHBG and cholesterol for liver and CK for muscle. And again, you do see a similar pattern, so an improvement of the thyroid state in these tissues. So this is one slide on the -- one of the exploratory outcomes. So this is, again, this GMFM score, this motor score, with 100% being a 4-year-old healthy kid. And as you can see, they -- all the patients scored very low. On the group as a whole, there is no change. But we noted that those individuals that seem to respond were all at the younger -- in the younger age range. So we are very cautious how to interpret this. This was exploratory. The study was not designed for it. But at least for us, it was reason, together with this preclinical data in animals, to proceed with a second trial to see whether this other part of the disease, the neurodevelopmental phenotype, can be alleviated as well. Then I'd like to finalize this presentation by showing some real-world data. So currently, we are guiding like 70, 80 individual patients across the world. So what happens is that physicians are mostly caring for 1 or maximum 2 individual patients. So they're sending information and blood to us. We measure the bloods and send the advice back to these patients on Triac dose. So we were able to collect data via this way. So this is not a trial, this is real-world evidence. So this is the age distribution in the trial, and this is the age distribution in the real-world cohort, having many more patients of a younger age included. And together, this is also results in a very long follow-up, up to 6 years of age in quite a few patients. So -- and I would like to show you the main outcomes, the primary, secondary as also in the trial. So again, the T3 concentrations were reduced and back to normal in all, basically, all individuals, so actually mimicking the effects we saw in the official trial. Again, here, we have this complicated body weight graph. I guide you -- tried to guide you through. So this is what normal healthy children should be. The gray dots are the individual patients untreated. So -- and then the dashed red lines indicate the confidence intervals. And the blue lines are the individual patients that are treated with Triac over a varying duration. And what you do see is that most of the patients, they deviate from the natural course of the disease. So they are either stabilized or improved compared to the untreated patients. And the same holds true for heart rate, which also improves in the far majority of patients. And to me, actually, as a physician, I think this real-world data, it's much less controlled. But I think the very fact that we do see actually exactly the same as in a very controlled situation speaks to me, yes, very much. So one slide on safety. It seems that Triac is a very safe drug. We have had only transient signs of some thyrotoxic symptoms like agitation or perspiration that subsides after a couple of days. There are no clinical signs of hypothyroidism, and we haven't seen any drug-related adverse events. So to conclude my talk, I think it's important to realize that this disease has 2 components: there's a neurodevelopmental and metabolic component. For now, I think we can conclude that Triac is able to alleviate the metabolic part of this disease, and it seems that Triac can also be administered in a safe way to individual patients. And I would like to highlight the main individuals behind the work I've shown you, Stefan Groeneweg and Ferdy van Geest of my team. And I feel very pleased and humbled to collaborate with a very large international network of very dedicated doctors who seek the best for their patients. So thank you.

Thank you, Edward.

Yes, hi. So I'm Peder Walberg. As Nicklas mentioned, I was the founder of Rare Thyroid Therapeutics, which merged with PledPharma and brought in the asset, Emcitate. I'm now on the Board of the company, and I'm also the major shareholder. My background, I'm a physician by training. I spent a couple of years in big pharma and then spent 15 to 20 years within orphan drugs, searching for and identifying products and then bringing them to market for rare conditions. And in companies such as Swedish Orphan, also cofounded Wilson Therapeutics, Medical Need, which is now called Immedica; and then now Rare Thyroid Therapeutics, which is now Egetis. So I'm going to talk a bit on how to bring this product to the patients, to the market, and starting off with some of the key regulatory features we have with the product. So I mean the orphan drug legislation, we've been through a bit. I mean just -- it's a framework for making sure that it's worthwhile to investigate and commercialize products, which are aimed for a very small population. So this is the legislation which you have in both Europe and the U.S. And of course, Emcitate is designated as an orphan drug in both jurisdictions, and this gives a couple of benefits, closer dialogue with the authorities and so forth. But I mean, most importantly, it also gives us market exclusivity. So we will have a market exclusivity in Europe of 10 years and in the U.S. of 7 years from approval. For the U.S., we also have Fast-Track Designation, which is a system they have for therapies where they address unmet medical needs and show promising results. So this makes us eligible for a faster-than-usual approval process. So we will, provided everything goes as it should, I mean, enjoy a process of 6 months review time in the U.S. We also got what's called the Rare Pediatric Disease Designation, which is another way of stimulating research into rare pediatric diseases. And what this does is, upon approval, we are eligible to receive what's called a Priority Review Voucher. This voucher can then be used for a different product, another product to accelerate the time line for approval for that product. So that voucher can either be used by the company itself or it can be sold. And for a company like ours, I think it's fair to assume that we can sell this. We plan to sell this voucher. And recent trades are in the area of USD 100 million to USD 110 million, which then would be an income for us some time, I mean, shortly after approval in the U.S. So looking at the actual approval, so we have all clinical data at hand in Europe. So we are targeting an MAA during the first half of next year. I'll come back to this. And for the U.S., we are performing a small controlled study. I'll give you more details on that as well. So we are targeting a submission during mid next year. But with the review times, both of these lead to a potential launch in beginning of 2024. On top of this, we also have an Orphan Drug Designation for the distinct condition, which is called resistance to thyroid hormone beta. So this is not linked to a transporter of thyroid hormone. This is linked to the actual receptor for the thyroid hormone. And the beta receptor being mutated, which causes a set of problems, which is not too different from MCT8 deficiency, but it's a distinct disease, so there is no overlap between those populations. So we have Orphan Drug Designation for that also in the U.S. and in Europe. So looking at the different components then, I mean we saw Edward talk about the Triac I trial, which is the controlled trial in 46 patients, which was concluded in 2018 and published in 2019, which will be an important part of the submission package. We have the EMC cohort study, which Edward also described, with treatment periods for up to 6 years, also involving a completely new cohort apart from the Triac I trial, which gives us additional comfort to strengthening the scientific evidence. And we also have the natural history cohort, which, of course, is important. I mean both the trials are not controlled, so we need something to compare it to. So natural history is really important to understand how would these patients look and feel without therapy. So for Europe, these 3 components are what will be included in the clinical package. We've discussed that with the EMA, and they agree. So we have all the clinical data necessary at hand. For the U.S., we need this small controlled study, which will be started any week now. And we have 16 patients, and I will come back to the design of that trial. On top of this, we have the Triac II trial, which is running where we recruited 22 patients. We fully recruited sometime during Q2 this year. So it's running for up to 2 years, 96 weeks. So we expect the data to be available sometime around H1, H2 in 2024. So that will actually be post approval provided everything goes according to plan. So looking at the dossier, you may wonder why don't we file in Europe right away if we have all the clinical data available. So as you may know, this is a schematic of what's called the eCTD document, which is the basis for all approvals for a drug. It's essentially the same in the U.S., in Europe and in other jurisdictions, but it might be structured slightly different, but the components are there. So that's composed of nonclinical data. You have some general overviews. You have the clinical data, but then you have also the manufacturing control and chemistry parts, the CMC. And for that component, we are not yet ready. We are waiting for stability data for our drug to mature. So we need to wait for a sufficient time to pass before we can actually add that data and include it in the dossier. And unfortunately, in Europe, you're not able to submit an incomplete dossier. In the U.S., they give you an option of a rolling submission, but that doesn't exist in Europe, so we will have to wait. So coming into the small randomized controlled trial we are performing in the U.S. So we had a lot of discussions with the FDA. They -- according to the legislation, I mean, you should have some controlled data. We thought that this -- we have really compelling data and that having a placebo-controlled trial at this stage in the clinical development for a very severe disease where we also know that we have some very statistically significant and clinically relevant outcomes is complicated. So we had a lot of discussion back and forth. How will it be possible for us to, at this stage in the product's development, conduct a placebo-controlled trial. And I think we ended up in something which is quite okay. We just published this on ClinicalTrials, the design. So we will actually have patients who are part of our -- primarily part of our named patient or early access program who are on stable therapy with our product. So basically, this means that the patients are already identified. We have a pool of patients who could be eligible for participation in this trial. So we will have a running period to make sure they are stable, and then we will randomize to either stay on therapy or get placebo. So what we expect is that the patients who are switched to placebo will very rapidly, actually, perhaps within weeks, reach -- their T3 levels will bounce back to their native T3 levels, and they will then reach the upper limit of normal. And once the patient reaches the upper limit of normal, we will break the trial for that patient and put them back on the active product. And that's also the -- the primary endpoint here is the proportion of patients that reaches the upper limit of normal. So we have data on this. We know, for patients who have been on drug holiday for various reasons, we know that they quite quickly when you take away the therapy, they will bounce back to high T3 levels. So perhaps from a scientific standpoint, this is perhaps not the most exciting trial. But what it does, it adds placebo-controlled data in a good way, which the FDA has requested and agreed to. So -- and we believe that it's a quick trial. It's a 30-day trial for 16 patients from a population of -- we have 160 patients on a name patient program already. So we believe it's a trial that we can conduct fairly quickly at a low cost and with fairly low risk. Moving then to the Triac II trial. This slide, you already saw, perhaps formated a bit different in Edward's slides, but really showing that we saw interesting dynamic in the younger patients who were treated when we look at the neurocognitive phenotype. So we have this trial, which is running at 10 sites in the EU and U.S. where we look at very early intervention, so looking at patients below 30 months of age, early intervention with our therapy, and following them for a neurocognitive developmental standpoint. So we are looking at various established scales, the GMFM, which was the scale we just saw, the BSID scale and we're also looking at some motor milestones and the development of that. 22 children included, and the recruitment was completed in April, 96 weeks of follow-up. So this trial will continue to run, and we will have the data, but the data will come post the approvals, and we will then add the data into the approval through a variation. So looking again at the time lines, we are running the trial starting within the coming weeks. And that will hopefully conclude then in the beginning of next year and then finalize and file for EU in the first half of next year and for the U.S. in mid next year, paving the way for approvals in 2024 in both jurisdictions. Thank you.

Thank you very much, Peder. And thank you very much, Edward. I think what you have gathered so far is focused on MCT8 deficiency, the unmet medical need, the mechanism of action of the disease, but also the mechanism of action for Triac or Emcitate as we use the terminology, also the clinical manifestations and the severity of the disease. That, in combination with the regulatory pathway Peder has just illustrated, it's about time for question and answers. So can I invite up Edward and Kristina as well for Q&A. And the floor is yours. We like that, many questions, that's good.

Johan Unnerus, Redeye. Yes, Edward, the most interesting question, it was interesting also to see that a large proportion of the children were diagnosed, I believe, as early as 10 months. What was the median...

I don't know by heart, but I think that will be around 12 months of age in that -- I mean in the group analyzed between 2017 and now. Yes.

Yes. And you alluded too that there might be some biomarkers exploratory at this stage, I suppose. Any signs that any countries are sort of screening or intending to...

Yes. Yes, it's difficult -- I think it's, I think, disease awareness that -- but also, I think the tendency in many countries to now have a genetic testing for using panels, next-generation sequencing. So we do see also quite a number of patients who have a developmental delay. They're screened for a series of genes and then MCT8 is identified.

Maybe to chip in there, Johan, because I think it's a very valid question, and I think you'll hear more about that in the next session. Because obviously, a key activity within our company, together with the key opinion leaders around the world, is how do we, in a constructive way, drive patient identification, diagnosis and confirmation. So we'll elaborate further a bit around the initiatives we have in that space later on.

Yes. And presumably, it's the mother who carries by natural reasons. Is there a sort of mapping on the base of identified kids, sort of going back in families and to see who could be at risk?

Yes. Yes, obviously. So once -- I think that's current practice in actually all countries I'm aware of. So once a child is identified, then let's say, through the female line, it's investigated where the mother is a carrier and then the whole family, yes, can be screened.

And finally, if I may. It's great news that the kids are so young when they are diagnosed. But the big challenge here is, of course, that there is a great majority that is not diagnosed, and that's a big challenge and a big opportunity, I suppose. But maybe the -- yes.

Yes, what can I say to this? I completely agree with you. The only thing I see is that, in general, the number of patients also relatively is increasing. But I think there's, I think, many -- I wouldn't be surprised that many patients are not diagnosed as yet. Yes.

I have 2 questions for Dr. Visser also. First one is in something we have talked before in the past, it's in the study on T4/T3 ratio in the Netherlands, evaluating this ratio as a potential marker for MCT8 deficiency. And could you give us a high-level time line on this study? And what does it have to show to be considered successful in order to incorporate this measure into neonatal screening? And would it be like a few years? 5 years? 2 years?

Yes. Yes, okay. So actually, we have been trying this with, let's say, varying intensities over the last years. We were not successful ourselves. But actually this year -- or last year, a paper from Japan emerged where they were able to measure T4, but also T3 and reverse T3 in the blood spot. So we are currently collaborating with another group in the Netherlands to try and copy their method. And if they're able to do that in, let's say, controls, then we have a small series of neonatal cards from patients. And if we are able to distinguish with this ratio of, well, whatever combination, then we will go back certainly to the Dutch neonatal screening program. And actually, I've already talked with them 5 years ago. And they mentioned, well, if you're able to show a difference between patients and non-affected individuals, we would be very happy to consider to implement this starting with as a research program and perhaps later on as normal, yes. So they're very open to it.

Perhaps I can add my experience. I mean the neonatal screening, I mean, that's one criteria that you need to be able to discriminate, but it's also quite often so that it needs also to change for the patient, right? So typically, it's harder before you have an approved therapy. So my experience is that you kind of unfortunately first need to have the therapy approved, which is hopefully soon then. But I mean, that will help with the implementation of neonatal screening. That said, I think the time frame for implementing neonatal screening today compared to 10 years ago is much shorter because there's simply a lot more therapies around for rare diseases, so it's become more of a standardized procedure compared to what it was 20 years ago. Yes.

Yes. And if I can add, I mean, I can only talk for the Dutch situation. But that -- actually, I was discussing this argument, should you first have a therapy, but we should diagnose them first. So they understood that and they were very open to it and say, okay, this is a realistic story. So they -- yes.

Okay. And I have a second question. About a month ago, a paper was published in Frontiers describing the potential role of thyroid hormone and analogs such as Triac for the treatment of multiple sclerosis because it has been shown that these molecules can promote the migration of oligodendrocyte progenitor cells to areas in the brain where there is demineralization happening and promote remineralization there. What is your view on this? Do you think it's a good approach to target neuroinflammation in multiple sclerosis?

Well, this is -- well, this is certainly beyond my area of expertise, so I should be very cautious. Actually, I've been kind of hitting this area, I mean, because of similar questions. I think oligodendrocytes are -- so actually, thyroid hormone is one of the key regulators of oligodendrocytes. So multiple efforts have been in place to mimic that action. If you're hinting whether Triac could be, let's say, have another application, I don't know. Yes.

Ulrik Trattner from Carnegie. Perhaps first question for you, Dr. Visser, and we have seen the data thus far on Emcitate and the data on the metabolic effects that are quite compelling. And you also talk about this neurocognitive effects, but these are for now purely exploratory. Could you just walk us through your impression on the importance of each of these 2 aspects? And would this be beneficial if we were only to show metabolic positive effects because that would essentially prolong the life of the patient, but with neurocognitive dysfunctions over time?

Yes. So the reason why I also was emphasizing that the disease has 2 basically components is that we shouldn't focus only on the neurodevelopmental part. So I think that there is room to improve the quality of life if you alleviate the metabolic phenotype, basically, what you do in every common hyperthyroidism in the general population. So there you're, let's say, also only restoring the metabolic phenotype, but there's no doubt that any doctor would not treat it. So from that point of view, I think irrespective of the age in general, there is room with Triac to improve that part.

Great. And just sort of a follow-up question on sort of disease awareness. And I know it's quite an uncommon disease. But your impression, how have disease awareness changed since the Triac I trial was published? It was published in The Lancet. Have you seen any change in disease awareness since this data was sort of developed or taken forward given that previously, there was this disease that was quite unknown as well as there wasn't really any treatment for it? So I'm guessing that the disease awareness should be rather low.

Yes. So I don't know whether I can -- actually, I've never looked from that point of view to the -- so I get kind of numerous e-mails every week, every month on new patients across the world. I don't know whether that's linked to this, particularly to this publication. My feeling is it has been a kind of a gradual increase over time. What I do see that nowadays, if they send me an e-mail, they are referring to the publication and say, hey, we found this data and might this help for this -- for my patient.

From a corporate perspective then, I mean, we see a clear increase in the requests for treating on a named patient basis. I mean that's increasing over time. So we see a clear trend -- increasing trend in requests. And I guess on some level, that's kind of a secondary effect of increasing disease awareness.

Yes. And then as you know, Ulrik, we talked about this before that, and Henrik will show it in his slides later, that the substantial increase in requests of using Emcitate under the managed access umbrella has substantially increased, has increased by more than 50% over the last 12 months. So we're now at more than 160 patients being treated. I think that's a token on the disease awareness increasing gradually. Henrik will like also give some examples in his presentation around disease awareness and the activities we do there. And the feedback we're actually getting from prescribing from physicians, pediatric endocrinologists or pediatric neurologists starts from a low base, but it's gradually improving.

Great. And just final question, and that would be for you and Nicklas and Peder. What type of label are you looking at? Are we talking about any age restrictions when starting treatment? Or will this be for the sort of entire patient population of MCT8 deficiency?

Do you want to take the start or...

Yes. No -- I mean, yes, so we base the submission on the available data, and both the Triac I trial and the cohort study, I mean, treated all-comers. So we do not see a restriction in age. We think that the benefits we see are of benefit for all ages, and we have quite a good age distribution when we pull these 2 data sets together. I mean we have a very nice age distribution in all the pediatric groups and also in adults. So we don't expect to have a limitation in age. We are also not expecting any other kind of limitation in terms of what we actually do. So I mean what we are aiming for is a treatment of MCT8 deficiency, full stop, right? So not going any regardless of that, yes.

I have one more question, if I may, and that would be for you guys as well. I might have missed this in the randomized U.S. trial. The patients that are to be included in the trial, are these patients that are newly recruited? Or are these patients that are currently on the named patient use program?

Yes. So we are open for both. So we have -- I mean, obviously, we have a large pool of patients who are in the named patient program and which we know and we are -- I mean the physicians know them and are able to contact them. So we believe that, that will probably be the majority. But it is possible for a patient to enter into the run-in period and become stabilized and then enter into the randomized controlled fashion, but we believe that, that will be a minority of cases. So really -- and that's also one of -- why we see that we are able to do this quickly. We do not need to wait for a patient to be newly diagnosed, put on therapy. We can actually use the patients we already know, which, of course, is much quicker for us. And perhaps I didn't say that, but we have sites in both Europe and the U.S. for this trial as well. So we are hoping to be able to recruit this very quickly.

I had one question on the neurocognitive scales. So you mentioned it's quite established, but also you're looking for other scales as well. Can you maybe discuss that? How well do they capture the disease? And what's your thinking on that?

Shall I take that?

Yes, yes, whatever you want.

Just a clarification, [ Fredrik ], are you talking about the GMFM-88 scale and BSID-III? Are those -- yes.

So the BSID-III is perhaps a broader scale than the GMFM. I mean it has several domains. However, I mean, these children, the gross motor function is not functioning well. So the BSID scale, just to give you an example, is something like, well, if I take this doll away, can you follow it with your eyes? And perhaps if you -- you might hear what you say, you might want to comply, but I mean if you can't turn your neck, it's impossible to comply with the scale. So that's why the gross motor function becomes very dominant in these children. So having those kind of more advanced evaluations will not become meaningful. So the GMFM scale -- I mean the BSID scale and the GMFM scale have both been used for drug approvals. The GMFM scale lately in the SMA setting, spinal muscular atrophy, they have used a modified version of gross motor function scale and also motor milestones. So that's something we have discussed a lot with the FDA to try and see what they did and have a look at that. So both of those scales are very highly correlated with each other, of course, because they measure basically the same thing. I don't know if that was answering your question, but yes.

And maybe to build on that, coming back to what Peder said during his presentation that, of course, this trial is utterly important from a medical standpoint, from a scientific standpoint. But we also need to be clear that market approval is not dependent on the results from Triac Trial II. I'm sorry, we have a question here in the front of the room. [ Joe ], you've been raising your hand for a while now. I'll hand over to you.

Just for Dr. Visser, I was just wondering how many identified mutations of MCT8 are there? And is there any -- is there a good correlation between the levels of inactivation of the transporter and the degree of both neurological and impairment on the hyperthyroidism?

Yes. Thanks for the question. So that's actually where we are currently working on. So this is all unpublished data. So there are tens of different mutations. And we have -- well, we are currently investigating, in a set of like 350 individual patients, a correlation on actually 30 different disease features. And there is a clear correlation between the impact of the, let's say, the defect of the transporter in vitro in the lab. So there are different levels of defectiveness, and that correlates with different clinical features. Yes. So basically, we categorized patients as having a mild, moderate and severe impact. Yes.

So do you have any idea at the moment where the patients in the phase -- in the Triac I trial with the very young ones where you've shown they're creeping into the wellness of -- they've reached a milestone and they've gone from the 10% to the 20%? Do you have any idea what mutations those patients have? And would you expect that they might naturally improve as they got older? Or is that just impossibility for the...

Yes, good question. Yes, so actually, all these mutations were severe mutations. And yes, I don't know whether we -- can you go back to your slide?

Yes, I think we have the asterisk if that's what...

Yes, that's the asterisk. Now going back to the...

That's the one, yes.

Yes. Okay. So we had the -- actually by chance, we had 3 unrelated patients all carrying the same severe mutations, those 3. And as you can see, these -- those 2 were older, did not respond at all. And this patient -- I think it's this one, actually, had an increase. Again, I mean, we -- I mean, as a doctor and also scientist, I'm very cautious to interpret this. But I mean these are the data. And for us -- so we are not kind of overstating or over-interpreting, but it was, let's say, reason enough to proceed with the second trial.

And then maybe for Nick and Peder. So you got Fast Track. What about PRIME in Europe? Is there a route there to shorten the time -- review time?

I mean PRIME -- I mean, typically, it's designed for something which is much earlier. I mean now we are, I mean, months or half a year away from filing. I mean that's -- I mean it's not really -- I don't think it adds value right now.

No. And to chip in on that, I think that's a valid question thinking about where we are in the development game, so to say. If we were in Phase I or potentially starting a Phase II study, of course, one would consider that more in detail. We need to put in perspective also that we are a small, nimble organization. We need to focus our efforts in the right aspects and then we've been focusing on a potential submission based on the data we have with EMA. And we've been successful in those discussions. So we believe that where we stand today, it's too late in the game to do that. It won't add too much to where we stand. You should ask our Chairman on the Board that later, by the way, in his closing remarks as a preview. Thank you.

And then just on the stability data, I mean, when did you start that work? And how long has it been going? And when can you -- when do you expect it? I mean...

Yes. No, it's a valid question. It comes back to, I guess, to what Peder said that we are in a privileged situation for the submission in Europe first half of next year. And obviously, in an ideal world, we would have submitted already now since we have all the clinical data at hand. What we have also done in parallel with the clinical development plan is, of course, upgrading the manufacturing process since data needs to meet this current standards and guidelines from all the different regulatory bodies. So there, we are in the final process actually of completing the validation batches that is now put on stability. And hence, why we are guiding for a submission first half of next year, we'll be ready then. I think we have time for one more question. It's very exciting that we have a few. And I think we'll hand over to Suzanna. Sorry, Johan, you had your opportunity. We'll get back to you.

Suzanna Queckbörner, Handelsbanken. My first question is on Triac II. So if I follow the time line correctly, that's after your actual submission to the EMA as well as the FDA. Can you sort of expand on how you think this will contribute in terms of possibly reimbursement, but also could it just be a safety net? How should we think about Triac II?

Yes, I can start. So Triac II was initiated and then we received the cohort data, and I think that's changed things because we went to the authorities and we presented this -- I mean it made the situation very different because we suddenly had a lot more information. We had a whole new cohort. We saw the same thing. So now we had 2 trials already. So that's when we engage the authorities and discussed the possibility of submitting already on that data. And that outcome was positive. So that's what we're pursuing. The trial is still running. And I mean, in fact, that will report sometime after, not only after submission, but after the approvals. So it will come after, but it will probably, I mean, come sometime in H1, late H1 in 2024. So with approvals in earlier that year, I mean, we do not think it will delay the approvals, but it will be available for pricing reimbursement discussions in certain markets in Europe, for example. So timing-wise, it's actually quite -- we believe that's quite good. So we will have -- not have to wait for it for the regulatory approvals, but we will still be able to leverage the data for pricing and reimbursement discussions. I don't know if you want to add something.

No. And I think we apologize, Johan, we are running out of time. I'm a hard taskmaster today, so we need to continue. I would like to thank Edward, Peder and Kristina for responding to the questions. We'll have more time for questions later on, so hold that thought. And with that, I will hand over to Henrik to talk about our plans for commercialization of Emcitate with focus on Europe and U.S., but also focus on the key aspects that was brought up in the room today, which was around diagnosis and disease awareness. Henrik?

Thank you. So very happy to be here today. I'm Henrik Krook. I've worked for Egetis now for 2 years. Before that, I've been roughly 20 years in the pharma and biotech sector. And most of those years I've spent at larger international companies. So Roche, Novartis and Alexion, for example, where I have been a part of both planning and executed several launches of pharmaceutical drugs, also including several orphan drugs. And today, I will give you the update on where we are right now with the commercialization preparations for Emcitate. First of all, I think it's really encouraging to see that we already now, before marketing authorization, are able to supply Emcitate to more than 160 patients in over 25 countries. And that's something that we can do, thanks to this named patient use program that was discussed in the Q&A session here. And it's also very interesting that we are frequently getting more requests and that patients stay on treatment, and we really see that also as a confirmation that it's clear that physicians think that we are addressing an unmet medical need with Emcitate. And if we look at the bar chart here, actually from the beginning of last year, we have been able to increase the number of patients in this NPU program with 50%, and it's continuously increasing. And this will also be important at the time of marketing authorization because then, these patients will be transferred to commercial drug. So that means that we already, the first months after marketing authorization, will get a number of patients on commercial drug. There are some very favorable conditions with Emcitate and the setting here that I would like to stress before going more into how we plan to execute on this launch. So first of all, and I think that was also clear from Edward's presentation that Emcitate is addressing an unmet medical need. It's also interesting in this kind of ultra-rare diseases that the treatment normally is centralized to a relatively few number of hospitals per country and that treatment decisions also are protocol driven. And that means that we do not have -- need to have huge sales organizations to be able to communicate information about Emcitate at the time of launch. We can do that through a relatively limited number of caregivers. Also lastly, we are the only company having an active clinical development program in Emcitate -- sorry, in MCT8 deficiency. So based on these conditions, we have now started the stepwise establishment of a small in-house commercial organization and really preparing for the launches in U.S. and Europe 2024. And at the time of launch, we plan to be in the range of 40 to 50 people in the commercial organization, including medical affairs. And based on the prevalence numbers, there should be roughly 2,400 patients in U.S. and 5,400 patients in Europe. Not all of these are diagnosed as of today, and that's why we are focusing a lot on disease awareness and educational effort for the health care so that patients that are living with MCT8 deficiency, but the parents or the physicians haven't understood that this is the actual disease, that they become diagnosed as soon as possible. We will, as mentioned, take care of North America and Europe ourselves with our own commercial organization and are planning to commercialize in the rest of the world through partners. And there is quite a lot of interest from potential partner companies who clearly also have seen the opportunity with Emcitate just as we had. So we have initiated this stepwise commercial organization buildup during the spring this year, and I'm really happy that we have been able to attract actually some of the best people in the industry to this team. And all of us have done and worked for quite some time in the big pharma setting, but then also have worked in smaller settings with less resources and managed to also use what we learned in big pharma in a smaller setting to execute good launches, also with less resources. And to really make sure that we get the launch success here and we'll be able to improve the lives of both patients and also improve the life of their caregivers, we now really have laser focus on 2 key -- or areas, which is identifying patients and driving and ensuring access to treatment as soon as possible after marketing authorization. If we start with ensuring access then. So there, we really aim for a broad access to Emcitate to the patients as soon as possible after marketing authorization. And as you are aware, in this kind of orphan diseases, payers are used to reimburse prices that have somewhat a higher price tag compared to traditional pharmaceutical drugs. And this is even more so if the setting is a very severe disease and ultra-rare indication. And Emcitate fulfills this criteria. So it is very unique in this area. And to be able to navigate the pricing and reimbursement landscape in the best possible way, we have kicked off now several key initiatives to be able to do this in the best possible way to get an optimal reimbursed price. And some of the key activities that we are running there is a Vignette study that we have done by involving physicians that are used to treat these patients so that they have been grading the different health states in MCT8 deficiency, and we have also started the Caregiver study where we collect information about costs and quality of life for parents. As already has been discussed, we are also focusing a lot on this disease awareness and education. And we're not alone in this process. There is also a lot of activities going on from patient advocacy groups and support by key opinion leaders. We are having exhibitions at scientific congresses within pediatric endocrinology and pediatric neurology. And a couple of weeks back, I was myself at the European Society for Paediatric Endocrinology, and there, I had a lot of interactions and discussions with physicians, and they were all extremely interested in this disease. And we received, related to this, 50 requests or more information about MCT8 deficiency. And we were in discussions about 14 different patients that were diagnosed but not yet had treatment and 15 patients that are, based on their new learnings, understood that yes, maybe these patients have MCT8 deficiency without -- that the physician was aware of it, and they would now go home and test these patients. So it's clear that these activities helps to identify patients, and we will continue to be present at different congresses. We also have our more digital platform where we have our mct8deficiency.com website and the social media platforms, Instagram, Facebook, LinkedIn where we post information about the disease. And publications, as already mentioned, is, of course, also an important part here. So this was more of a flavor of some of the activities that we are doing in the pre-commercialization preparations from a global perspective. So -- and all in all, I think we're really on a good track here. And we have now also initiated preparations in the major markets. And to give you a little bit more information about what we are doing in U.S., which obviously is one of the key markets, our President, North America, Sara Melton, will update you a little bit further on that.

Thank you, Henrik. Good afternoon. My name is Sara Melton. I'm the President of Egetis North America. Since this is the first time I'm seeing most of you, I'll give you a little bit of a background about myself. Been in the pharmaceutical industry for 25 years, working for both large pharmaceutical companies like Astellas and Bristol Myers Squibb as well as small biotechs like Egetis, launching rare disease products in the United States. So we are well on our way to building a presence in the United States, and Egetis Therapeutics US Inc. has a new home in Naples, Florida. Our business entity was established in Delaware, and we are looking at approximately 20 to 25 full-time employees at the time of launch. And we're going to have medical affairs, market access, sales and a fully functioning commercial organization once we launch the product. We've already begun recruitment. And I'm happy to announce that Kate Sulham, Vice President of Market Access and Pricing, has just joined the organization. Kate comes to us with a wealth of experience in health economics, market research, market access, and she worked for companies like The Medicines Company and Spero Therapeutics. We are going to also be recruiting and almost very close to hiring for our vice president of medical affairs who will be recruiting a whole team of regional medical affairs directors that will be focused on hospital center of excellence strategies. So we are going to be going into about 25 centers of excellence across the United States and working with the multidisciplinary teams within them that treat MCT8 deficiency like pediatric neurology, pediatric endocrinology, genetics, physical therapy, occupational therapy. As we engage with clinicians who will participate also in U.S. advisory boards and functions and they treat these patients, we have confirmed that there is a high unmet medical need for MCT8 deficiency patients. There is no approved therapy, and they're looking for something that can treat this peripheral thyrotoxicosis. They're looking for something that will help to improve the clinical manifestations like poor weight gain, disturbances in bowel function, rapid heart rate. And these clinical manifestations are very concerning to caregivers. Mortality is high, and causes of death, as Dr. Visser described, are lung infections and arrhythmias. And we hear that they're looking for these novel treatments to treat MCT8 deficiency, and this one shows promise. And they're looking to treat the underlying cause of this severe metabolic disease. At Children's Hospital of Philadelphia, Dr. Bauer has now got 29 MCT8 deficiency patients that he either treats or consults on. And he thinks that, that's just scratching the surface. And we think that this is severely underdiagnosed. So 2 very important initiatives that we're going to be focused on in North America are disease awareness, as Henrik mentioned, and patient identification. So awareness of MCT8 deficiency in the United States, even amongst pediatric neurology and endocrinology, is relatively low. So when caregivers first identify something is off with their child, they're looking for a clinical manifestation like hypotonia. What we want doctors to think is, okay, I need to do additional thyroid testing. And so we're aiming to educate and advocate to add T3 testing to the standard thyroid function panel so that we can start to uncover these MCT8 patients. In addition, we're looking to obtain a specific ICD-10 code in the United States. This will help for us to be able to code correctly -- doctors to be able to code correctly and also get reimbursed for the drug correctly once we're launched, and we intend to submit for that to CMS by the end of the year. And in addition, we would like to roll out a sponsored genetic testing program where when a physician or a patient is identified or there's a suspected MCT8 genetic malfunction, so we want to provide the sponsored genetic testing. We're pleased to report that the FDA has requested to move to an expanded access program versus the high demand for single patient INDs or investigational new drugs. This new program will not only provide a simpler process for patients and clinicians to get early access to Emcitate, but patients who want to continue Emcitate after the re-Triac study will easily go into this program and be able to access Emcitate through expanded access program. When we hear from caregivers of these patients, they are concerned about easily getting their children, once they're diagnosed, into this expanded access program. They're also concerned about early diagnosis. But what really is concerning is the inappropriate utilization of drugs that can worsen the symptoms and cause further brain damage. So we're really focused as an organization on patient advocacy efforts. And we want to educate stakeholders like the FDA on the patient voice so that they can understand some of the unmet need from the patient and caregiver perspective. And so we'll be moving forward with initiatives to be able to do that. This quote is from a mother of an MCT8 patient whose child was prescribed an inappropriate drug, which severely impacted their development and resulted in further brain damage. And this mom often wonders if she had a diagnosis at birth and were given an appropriate drug right away, where her child would be. The pricing and reimbursement of ultra-orphan drugs is relatively straightforward in the United States. We select analogs based on similar value drivers. In this case, epidemiology, pediatric patient population, no FDA-approved treatment options and chronic treatment and the severity of the disease. And we then conducted payer research with commercial and Medicaid payers, our 2 top payers that we anticipate for Emcitate. And we confirm with them that they agreed with our value drivers. And so we've aligned on U.S. analogs ranging in price from $500,000 a year to $750,000 a year for this particular research. A proven solution for rare disease product access and reimbursement is through an exclusive distribution model. A single specialty pharmacy will act as a hub for the clinician, the patient and the payer and the company. So when a prescription is written of Emcitate, it will go directly to the specialty pharmacy that we partner with, and they will navigate the approval process with the payer. They'll work directly with the physicians and the caregivers to make sure from an outcome standpoint that we're providing a white-glove experience to any physician and any patient who wants access to Emcitate. We'll also be working with the specialty pharmacy to implement our patient assistance and co-pay support, and it's our aim, our goal as an organization that no family will pay out of pocket for Emcitate. So in summary, significant progress has been made to establish Egetis Therapeutics US and build out the infrastructure to support the North American effort. There is a high unmet medical need that's been confirmed by the conversations that we've had with doctors in the U.S. We're going to be rolling out a sponsored genetic testing program that will support patient identification. We'll be continuing efforts working with the patient advocacy groups and the patient foundations to include the patient voice as the FDA considers our application for Emcitate. We have confirmed the fact that there is a significant market opportunity, and the value drivers for Emcitate will -- have basically been confirmed and that there will be broad access and reimbursement through payers in the United States for Emcitate. Thank you. I'm going to turn it back over to Nicklas.

Thank you, Sara. And thank you, Henrik, and I'll invite Peder up to the panel as well. So it's now time for your Q&A, and you can ask any questions, of course. We have around 15 minutes for this, and then we'll take a break. And Ulrik, you were quick at grabbing the microphone. So the floor is yours.

And I was just wondering regarding the prevalence of the disease, 1 in 70,000 males. What are you basing these assumptions on? Are there any sort of country-based evidence that this should be the prevalence? Anything in the literature? Could this be half? Or what are you currently basing this on?

Do you want to go first, Peder? Or we might invite Edward to give your view as well.