Thank you very much, operator. Good afternoon and good morning to everyone on the call. A warm welcome to this update by Egetis Therapeutics, with focus on Emcitate and this morning's announcement. Please note that the slides used during today's webcast could also be found at the company's website. Next slide, please. Next slide. We're now on slide number three. For those I haven't had the privilege to meet, I am Nicklas Westerholm, and I'm the CEO of Egetis Therapeutics. With me today, I also have Kristina Sjöblom Nygren, Chief Medical Officer; Yilmaz Mahshid, Chief Financial Officer; Christian Sonesson, VP Product Strategy and Development; Henrik Krook, VP Commercial Operations; and Peder Walberg, Operative Director of the board. Next slide, please. The agenda will be as follows. We will start with providing an overview of Egetis Therapeutics and our lead candidate, Emcitate.
We will then of course focus on the positive announcement this morning, where we have concluded that demonstrating a treatment effect on T3 levels in MCT8 deficiency could provide a basis for market approval for Emcitate in the U.S. We will elaborate on MCT8 deficiency as a disease and focus on the clinical development program. We wrap up at the end to leave ample time for questions and answers. Next slide, please. Egetis Therapeutics, a specialized late-stage orphan drug development company with two assets today in phase III. Emcitate for the treatment of MCT8 deficiency and Aladote for the prevention of acute liver injury caused by paracetamol poisoning.
The orphan drug segment is very attractive to us being a small biotech company with its key features such as shorter lead times, fewer patients required in clinical trials, higher probability of success, coupled with premium pricing. For both our assets, we have a clear path to market in both U.S. and Europe within the coming couple of years. In order to maximize shareholder value, we are planning to launch both our assets through our own in-house commercial organization in Europe and U.S. and focus on partnerships in rest of the world. Very pleased also to say that we have further strengthened our core expertise in late-stage orphan clinical development, registration, as well as commercialization. I wanna express a huge thank you to the team for the great progress the organization has made over the last couple of months. Next slide, please.
We're now on slide six. Emcitate is our lead candidate for addressing MCT8 deficiency. It's a condition with high unmet medical need with no available treatment today approved. We have made very good progress over the last six months and I would like to call out a couple of examples of that. First, the EMC Cohort Study that was published in The Journal of Clinical Endocrinology & Metabolism in October confirms the long-term efficacy and safety of Emcitate to MCT8-deficient patients for up to six years. That enabled us to further engage with the regulatory agencies to discuss the path to marketing application and subsequent approval. Furthermore, we were granted Fast Track Designation by the U.S. FDA in October. We have launched a number of disease awareness activities and initiatives to support diagnosis of MCT8 deficiency.
We had an announcement out which I will come back to in December, where we communicated our intent to submit the marketing authorization application to the EMA based on existing clinical data and of course, today's news when it comes to the U.S. Operator, next slide, please. Today's news then. In summary, in recent positive interactions with the FDA, they acknowledge that treatment effects on T3 levels in MCT8 deficiency could provide a basis for market approval also in the U.S. This comes with a regulatory requirement to conduct a small 30-day placebo-controlled study in 16 treated patients. This is to verify the results on T3 levels seen in previous clinical trials, Triac Trial I, and the publication I was referring to previously and to verify this in the randomized control setting.
That leads us to targeting a new drug application in the U.S. to be submitted in mid-2023 under the Fast Track Designation. This is a major step forward for us towards a marketing authorisation and increases the likelihood of success for Emcitate and of course, subsequently, the probability to receive a U.S. rare pediatric disease priority review voucher. The ongoing Triac Trial II is important. It will continue to further establish the effects on early intervention on the neurocognitive development aspects of the disease as seen in Triac Trial I. Here, let me be very clear. Our confidence in Triac Trial II has not changed. But for a market approval application, both in the U.S. and Europe, we're now not dependent on data from Triac Trial II. Operator, next slide, please. We're now on slide eight.
When it comes to Europe, we communicated on the 13th of December that we have the intention to submit a marketing authorization application for Emcitate to the EMA based on existing clinical data. Of course, having all clinical data required for a regulatory submission at hand significantly reduces the future development risk in Europe as well. Revised EMA submission timelines will be communicated as soon as all parts of the regulatory dossier will be confirmed. What I can say though is that it's safe to assume that a European submission will be made no later than the one in the U.S. With that, I will hand over to Peder, and we move on to slide number 10. Operator, please.
Thank you. A short recap on MCT8 deficiency. As you may be aware, MCT8 deficiency is a genetic inborn error caused by a dysfunctional transporter of thyroid hormone. It's an X-linked disease, meaning that it affects males only, and it occurs in a prevalence of about 1 in 140,000 individuals. Absence of a functional MCT8 thyroid hormone transporter leads to an inability of thyroid hormone to pass into the central nervous system, and it also causes the body's sensory mechanism for thyroid hormone to be off, which causes a very high levels of circulating thyroid hormone which affects other organs which are not dependent on MCT8.
We have a situation with too much thyroid hormone in large parts of the body and too little or no thyroid hormone in the central nervous system. The consequences of this disease are detrimental. We have a significantly reduced life expectancy of 35 years and we have a significant morbidity with patients presenting with severe intellectual disability and their cognitive development severely delayed. And also a wide range of symptoms from chronic thyrotoxicosis which leads to significant morbidity. Currently there is no available therapy to address the root cause of this disorder and the standard therapeutic approaches for other thyroid hormone dysfunctions are not effective or suitable. This is a significant unmet medical need. Moving on to the next slide.
We have already completed the Triac Trial I, which was published in 2019, looking at the effects on chronic thyrotoxicosis from treatment with Emcitate for up to one year. We included 46 patients in nine countries and we can move directly to the next slide, where we see the primary endpoint being plotted out with the orange dots being the T3 values when the patients entered into the trial, and the blue arrows being the values at 12 months. Perhaps already here I can point out that the blue corridor you see here is the normal range for T3 values and the upper dotted line there is what we call the upper limit of normal, which will be important when we come to a description of the clinical trial we are now about to conduct.
Coming back to the data from the Triac Trial I, it's a couple of observations. We see that all patients have high to extremely high T3 values at baseline, and we are able to bring them all down into or below the normal range of T3, and we do this with a very strong significance. We also know what's not visible on this graph, that this effect is rapid. Within weeks, we are able to bring the patients down into the normal range. Importantly, when we look at the table below describing some of the secondary endpoints. We can see that this also translates into an amelioration of the chronic thyrotoxicosis leading to improvement in clinical symptoms which are clinically relevant to the patients and where we also have significance on some important parameters.
We can move to the next slide 13, which describes the EMC Cohort Study. This was a cohort study looking at patients who have been treated with Emcitate. These are 67 patients, and we can perhaps move directly to the next slide where we see where these patients come from. Part of these patients have been patients who were part of the Triac Trial I and have now been followed long term for up to six years. Then we have a completely new cohort of patients who have been recruited from the Named Patient Program or Early Access Program and have been followed for as long as data was available.
On the graph in the middle, you can see that this makes a nice age distribution to our program and really complements the data we had in the Triac Trial I. Going to the next slide, we can then see the same scatter plot basically of T3 in these patients. Again, we see the same pattern. We see that patients at baseline have very high values and that on therapy, regardless of how long, basically this is up to six years, we can see that we are able to bring them down into and maintain them in the normal T3 corridor there below upper limit of normal. This is also highly significant. You can see on the right there that there is no sign that this effect is fading away over time.
Moving to the next slide 16, we see that this data then confirms the results from the Triac Trial I. We can say that we normalize the T3 values in patients with MCT8 deficiency and that this normalization then translates into an improvement of the thyroid hormone status in the end target tissues. We know that this effect is rapid, and we can also now say that it's durable for up to six years. We see a very consistent pattern here across all the parameters we have studied. Coming then into slide 17, which is relating to today's announcement. We have been in discussions with the FDA during the past year and have now reached an agreement with the FDA to perform a controlled study.
We have also reached their acknowledgement that effects on T3 levels in MCT8 deficiency translating into the beneficial effects on chronic thyrotoxicosis we have already shown can be a basis for marketing approval in the U.S. What we will do is we will perform a small 30-day placebo-controlled study in 16 patients to, in a randomized controlled setting, verify the strong correlation we have seen in the previous trials with MCT8 therapy leading to normalization of T3 values in a randomized controlled setting. This study design has been agreed with the FDA and the primary source for patients will be through our existing Named Patient and Early Access Programs. Important to note, it is well established that the T3 levels in untreated MCT8 patients are significantly elevated.
As we have just seen, we also have shown in both the Triac Trial I and the EMC Cohort Study that MCT8 is able to rapidly and durably normalize these levels. We also have data available for patients who for various reasons have been on a drug holiday, so they for various reasons for a period of time not taken the medication. We know that the T3 values will rapidly rebound to pretreatment levels in these patients, again within days to weeks, returning back to normal once treatment is reinstated. This leads us to a more description of the design. Going to slide 18, we have an initial run-in period to make sure that the patients are on stable therapy with MCT8 and we have stable T3 levels.
We will then randomize the patients to receive either continued treatment with MCT8 or placebo. This randomized period will be up to 30 days. Important to note, we have a strict rescue criteria. Once a patient's T3 levels reaches the upper limit of normal, again the top dotted line of the corridor we saw in the previous graphs, the patient will be rescued, and Tiratricol or MCT8 treatment will be reinstated. The efficacy parameter here, the primary endpoint will be the proportion of patients in the MCT8 and placebo groups reaching this T3 value above or at the upper limit of normal within the randomization treatment period.
After the 30 days have passed or that the patient has met the rescue criteria, they will all receive Tiratricol treatment and will be followed up. Going to the next slide, touching a bit on the Triac Trial II Nicklas already mentioned. Just a reminder of what we saw in the Triac Trial I. The effects on neurocognition, as we have discussed previously, we believe is reserved for patients who are below four to five years of age. You can see again on this slide, this is now a score of neurocognitive development, the GMFM score. You can see that the patients are performing very poorly at baseline and really no correlation with age.
On therapy with the blue arrows, we can see some nice dynamic in the lower age groups which are not present in the older age groups. This is exactly what the Triac Trial II is there to verify. Going to the next slide, again confirming what Nicklas said. We remain very confident in the Triac Trial II, and that data will be important. It will not be critical or time critical for the marketing approval, given that we now have a clear path forward with the existing data and, for the U.S., with adding the trial we just discussed. The first patient was included in December 2020 and the last patient is expected to be included in this quarter.
Given that we now have a market approval possibility without Triac Trial II data, we have also removed the interim analysis which we previously had at 48 weeks to facilitate. It was there to facilitate a marketing approval earlier and being able to get access for the patients to this important therapy earlier than otherwise was possible. Now when we can access the market earlier, we have discussed with regulatory authorities and draw the conclusion that we do not need this, that we can wait for the full effect at 96 weeks. And of course, this is a parameter neurocognitive development where we would expect the development to increase over time, obviously.
We believe that the data at 96 week will be more robust. The data at 96 week, important to note, will still be available about the time of approval so available for the HTA health economic negotiations we expect for pricing of this product. This will remain important and perhaps just important to state as well is that when we made this decision and introduced this change of the interim, no patient had reached the 48 week data point collection. Just to state that. Thank you. Handing back to Nicklas.
Thank you, Peder. We will go to the next slide on the subsequent slide. We're now on slide 22. To summarize, we have now an aligned regulatory strategy for market approval, both in Europe and in the U.S. based on treatment effects on T3 and chronic thyrotoxicosis, which in essence increase the likelihood of success for Emcitate. Hence, this is a substantial opportunity for Egetis Therapeutics, as well as the patients suffering from MCT8 deficiency. Focusing on the marketing authorisation application in Europe, as we mentioned before, here we already have the clinical data available for a marketing authorisation application. For the U.S., we will verify the already strong data we have on T3 and chronic thyrotoxicosis from the Triac Trial I and the EMC Cohort Study in the randomized control setting.
That will lead us then to submission in the U.S. targeted mid-2023. With that, I'll hand over to the operator to start the question and answer session. Operator, please.
Thank you. If you do wish to ask a question, please press zero one on your telephone keypad. If you wish to withdraw your question, you may do so by pressing zero two to cancel. There will be a brief pause while questions are being registered. Our first question comes from Joseph Hedden with Rx Securities. Please go ahead.
Good afternoon and thanks for taking my questions. I've got a few so maybe I'll go one at a time. First of all, congrats. Is this following the accelerated approval pathway and is that the understanding that you've reached with the FDA?
You're referring to the regulatory pathway in the U.S. now, Joe, as I understood it.
Yeah. [crosstalk] Sorry.
Good afternoon, by the way. Sorry, we're breaking up a bit. Yeah. Yeah. This is in the accelerated scenario, accelerated pathway, and we envisage to have 6-month of regulatory review timelines. Please note that we're seeking a full approval. It's not a conditional approval we're seeking here based on the data. It's a full approval.
This is a full approval based upon the data already generated and the 16-patient trial?
Correct.
We're not waiting for the results, so it's not accelerated, and then there's a confirmatory step which would be fulfilled by the ongoing phase IIb, phase III trial.
No, that's correct. Yes. It's a full approval we're seeking.
Okay
Under the Fast Track Designation.
Okay. Okay. Excellent. So the next one, you're guiding towards an NDA in mid-2023, and this trial is a 30-day treatment period. I'm just wondering how, you know, what other things you need to do because it's almost a year and a half, as you appreciate from now until that potential NDA filing. I'm just wondering how that small study might take that amount of time or are there other elements that you need to get in place before filing that NDA?
No, thank you, Joe, and that's a very good question. Obviously, when it comes to study preparation, there's a number of aspects need to consider everything from having placebo available to ensuring that the protocol and synopsis are available, CTA application as well as agreements with sites and so on and so forth. It's also worthwhile mentioning is the IRB reviews in the U.S. It will take some time to start getting into a position to start recruitment. Having said that, though, as Peder mentioned, when we are at that position to start the recruitment, we believe that the recruitment period will be close to minimal.
We will use our Named Patient Program as a main vehicle to identify patients going forward, and we will expect subsequently also the treatment period, as you've seen, will be very short. It's study preparation, of course, that's to a certain extent our rate-limiting, Joe, and hence why we're guiding towards a marketing NDA submission towards mid-year next year.
Okay. Thanks, Nick. Just on the upper limit of normal range, that's the primary endpoint for the trial. Is that particular level the same as what you defined in the phase IIb trial that we saw the results where, you know, you treat and you see patients T3 falling into that range. Is that relatively the same level as agreed with the FDA what that is?
Yes. I mean, the treatment goal here is, of course, to bring the patients d own into the normal range, which is, I mean, the upper normal limit is the top range of that limit. The reason for this is, of course, that we have an effective therapy which adds, I mean, value and clinical benefit to the patients. We don't want to withdraw that therapy more than absolutely necessary to show what the FDA needs us to show in the randomized controlled setting. Really by reinstating the therapy when the patients need to meet this upper limit of normal, we are able to demonstrate the correlation without causing harm to the patient. It's the same level you saw as the top of the blue corridor in the slides. Yes, it's agreed with the FDA.
Okay, thanks, Pede. Thanks, Peder. Just picking up from that, is there any experience from the previous trials where perhaps treatment was interrupted for whatever reason? How long did it take for patients to kind of see their T3 levels start to go up and perhaps hit that top of the range? Is that? Have you seen that before?
Yes. I think I mentioned we have seen we have data from a number of patients who have for various reasons have had interruptions in their therapy. We know that the T3 values they return up to the naive levels very quickly, I mean, days to weeks. That's of course what we expect in this trial. Hence the short duration as well, I mean, up to 30 days, but of course, no longer than needed to reach the upper limit of normal.
Worthwhile commenting there, Joe, I think Peder mentioned it before as well, but of course, when Tiratricol or Emcitate was reinstated, they also fairly rapidly returned into the normal range.
Yes.
Worthwhile recognizing.
Okay, great. Thank you very much.
Yep. I mean, yeah, just to add, I mean, this is the regulatory value, I mean, from a scientific standpoint, I think we have a good idea of what will happen. I think this is something we need to do more from a regulatory perspective.
Thank you, Joe.
Okay, great. Thank you.
Our next question comes from Adam Karlsson with ABG. Please go ahead.
Hi, guys. Thanks for taking my questions. Just the first one, just to clarify perhaps, are you expecting the Triac Trial II data in Q1 2024, I think it was said, will that inform HTAs in the EU as well as the U.S. or was that only for the U.S. that you expect that data to be informing HTA discussions?
Thank you. Yes, you're absolutely correct in the sense that the data from the Triac Trial II after 96 weeks will be available as it looks now in Q1 2024, and hence available for the HTA discussions in the U.S. Pending of course, when it comes to Europe since we do not have confirmed the exact timelines of submission yet, due to that we're working on other components of the dossier. It's somewhat difficult to comment but one would assume that it will be available for HTA discussions in Europe as well. In terms of neurocognitive data, we will of course include the data from the Triac Trial I, both in the submission but also in the HTA discussions.
In that scenario that would imply kind of pricing and reimbursement in 2024 in the EU as well, irrespective of when potential approval would be granted in the EU.
Yeah. You're breaking up a bit, Adam. We have a bit of a difficulty to hearing you actually. Apologize.
Okay. No, but I think that answered my question. I'll move on to another one, if you can hear me. That question is on recruiting for the U.S. study. Just to understand kind of the incentive for patients to participate in that trial and go from the Named Patient Program to the study and then potentially risk receiving placebo for months as opposed to just carrying on with their Emcitate treatment, just as it relates to kind of the feasibility of recruiting patients from that Named Patient Program. What is kind of the incentive for patients to participate in the trial?
It's a couple of things. Maybe I'll start off and I hand over to either Peder or Kristina. I think it's worthwhile noticing that if you think about our Named Patient Program that is a vehicle for identifying new patients as well as, of course, treating existing patients under the program. As you probably have been aware that we have a continuous influx of new patients into the study. Of course, if we have this controlled study being set up, of course, any new patients should have been eligible for treatment under the Named Patient Program will of course then be funneled into actually this controlled study. I think that is one important aspect to note. Peder, I'm sure you can further elaborate on this as well.
Yes. Just, I mean, that's also why it was so important for us to include the rescue criteria. I mean, it's important of course that the patients are safe. In order to get patients to participate in the trial, it's important that they will be able to stop the placebo phase as soon as their T3 values exceed what is the treatment goal here. We will also exclude patients who are below five years of age. This will be for the older patient group. We have also tried to facilitate with things like home nursing and making it easier for patients to participate. It's a short trial, but you're absolutely right. We need to make the barriers to participate as low as possible.
Okay. No, that makes sense. It would primarily be by the sounds of it then new patients identified or entering the main patient program as opposed to kind of established patients.
Yeah
[crosstalk] receiving Emcitate transitioning
Yeah
[crosstalk] into the study.
It will be a combination of both, Adam. Yeah.
Okay. All righty. Just a question on power and statistical significance. It's a small study, obviously. Our kind of back-of-the-envelope estimations assuming no MCT8 patients breach the upper limit of normal during that 30-day period would suggest you'd need five or so patients in the placebo group reaching that upper limit of normal to show a statistical difference between the two groups. Is that a strict requirement from your discussions with the FDA? Is that estimation somewhat accurate or do you have a different view?
Based on our power calculations, we have a power well above 90% and that's based on the assumption of 85% in the placebo arm reaching the rescue criteria and vice versa.
That's [crosstalk]
Vice versa.
Yeah.
No. In the placebo arm reaching rescue criteria and 5% in the Emcitate arm.
Okay
Power above 90%.
Okay, great. No, that was all my questions. Thank you very much.
Thank you very much, Adam.
As a reminder, if you do wish to ask a question, please press zero one on your telephone keypad. Our next question comes from Dan Akschuti with Pareto Securities. Please go ahead.
Hi everyone and thanks for taking my questions and congratulations for revealing this path forward with the FDA. One question here is that, of course, that is now clearer. At the same time we won't get the interim readouts end of this year. How will this affect the pricing discussions if one would assume you wouldn't be able to show good effects on the neurocognitive motor function and skills Bayley Scales that you have there in the trial. If you would, how are you [crosstalk]
Yeah
considering that?
No. Thank you for your good question, Dan. Taking a step back, of course, giving the possibility to proceed with regulatory submission, both in U.S. and Europe prior to data from Triac Trial II, I, we're not dependent on that. Of course, based that on the submissions on T3 treatment effects on T3 and chronic thyrotoxicosis, of course, substantially reduces the risk. That's one aspect of the thing. Based on that, since we're no longer dependent on it in discussions with agencies, we have agreed to no longer conduct the interim analysis based on 48-week data. We'll perform the statistical analysis on the complete data set after the full 96 weeks of treatment, making the data more robust than of course, and subsequently letting it mature.
Coming back to how will it affect HTA interactions or payer and reimbursement discussions, I think we mentioned that before, but let me reiterate that. Based on U.S. as an example where we envisage a submission mid-2023 and under the Fast Track designation, we are looking for full approval. We're looking at roughly six month of a review timelines. There of course considering that we will have data available in quarter one 2024, that will be part of the HTA discussions in the U.S. But of course, as you said, when it comes to data on neurocognitive development, of course having strong data on that will inform us for a better price.
Okay, thank you. Maybe just a follow up here. Would you still expect to be able to get the six-digit price tag per patient per year if you don't show strong data on the neurocognitive parameters?
Yeah. No, again, Dan, it's a very good question, Dan, and I think it's worthwhile recognizing this awareness of this disease. Peder elaborated on the two clinical manifestations. You see the chronic thyrotoxicosis side of the disease that's caused by elevated levels of T3 in the peripheral system that leads to chronic thyrotoxicosis and subsequently have a substantial impact on the median life expectancy of 35 years, mainly caused by sudden death or cardiac failure in the cardiac system. Given the rarity and severity of the disease, we can still justify a significant price only on the data from chronic treatment of chronic thyrotoxicosis and normalization of T3 levels.
Perhaps worthwhile just adding, I mean, again, as Nicklas mentioned, we are seeking a full approval. We are seeking an approval for the treatment of MCT8 deficiency. Of course, we will include the data on neurocognitive data we have from Triac Trial I. We do not expect the label to be restricted in any way. We believe that the label we are or the label we are
Seeking
are seeking is treatment of MCT8 deficiency, the entire entity. That will not change.
Okay. Thank you. Very good answers. Regarding the EMA submission, you would be ready more or less now, maybe mid-year. As understood now is that you're timing it more or less to be in line with the FDA submission. Why is that? Is that because you're also waiting for that 96-week readout now versus the previously communicated 48-week interim readout?
No. No. Thank you for the question, Dan. No, it's not. The key reason for why I can't give you a more granular timeline for a European submission is what I mentioned before, that we have work ongoing to confirm the content of other components of the regulatory dossier. As soon as this work is completed, we will communicate a more detailed timeline for the submission in Europe. What I said before, it's safe to assume of course that this won't be later than the submission in the US.
Okay. Thank you very much. One last question. Are there any development on the Aladote side?
The development on Aladote, it's very unfortunate, and it seems like, apologies for the misused of word, never-ending story. Considering the challenges we see around the world, and especially in the countries where we're planning to execute the clinical trial, we're not in a position to start the study as of now. This comes back to, as we all know, Aladote for the prevention of acute liver injury caused by paracetamol poisoning. These patients are treated in the intensive care units or the acute setting. Again, when we are engaging with the sites, it's more or less impossible to release resources to start up a new study in that setting. Unfortunately, we're not in a position to start it now, but hopefully, as time progress, we can start it sooner rather than later.
Very difficult to give you guidance on when. I think it's important, though, to recognize that from an internal perspective, when it comes to regulatory interactions, study design, protocol, et cetera, everything is completed from an internal perspective, so we're ready to go. It is the external circumstances that is challenging today.
Okay. Thank you. Just one last one that just came up. You say Q1 2024, so that's, I would assume that you're expecting now for sure that the enrollment for Triac Trial II will complete this quarter or before March?
That's our target to complete it. The recruitment in Triac Trial II, we'll have a few patients remaining to recruit, and our target is to complete that within this quarter. You're correct, Dan. Thank you.
Okay. Thank you very much.
Thank you, Dan.
There are no further questions. I hand back over to our speakers.
Thank you very much, operator. I would like to take the opportunity to thank all the participants for listening in to the call and for asking the very good questions. With that, a huge thank you from the Egetis team as well, and we wish you all a good rest of the afternoon or the day. Thank you.