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

Welcome to Egetis Therapeutics Press Conference. [Operator Instructions] Now I will hand the conference over to CEO, Nicklas Westerholm. Please go ahead.

Hello, and good morning, everyone. This is Nicklas Westerholm speaking, CEO of Egetis Therapeutics. Yesterday evening, we issued a press release announcing the top line results for our Phase II Triac Trial II study for Emcitate. And we will be, during the call, provide you an update on the same. We will also reiterate the [ regulatory ] pathway and timelines for reviews and approvals of the marketing authorization application submitted to the EMA and the forthcoming new drug application to the FDA, which remains unchanged. Next slide, please. With me today are also Kristina Sjoblom Nygren, our Chief Medical Officer; Desiree Luthman, Heading up Regulatory Affairs; Peder Walberg, Operative Director of the Board; Karl Hard, Heading up Investor Relations and Business Development; as well as our CFO, Yilmaz Mahshid. Next slide, please. During the call today, we will cover an overview and a reminder of the ultra-rare disease MCT8 deficiency. We will then focus on reiterating the Triac Trial II objectives and designs, segueing into the top line results for the same and subsequently reiterate the regulatory pathway for Emcitate in MCT8 deficiency and at the end, summarize with key messages. With that, I'll hand over to Peder Walberg to elaborate further on MCT8 deficiency.

Thank you, Nicklas. So I think most of you on the call are familiar with MCT8 deficiency, but a quick reminder then that MCT8 deficiency is caused by a dysfunctional thyroid hormone transporter, which is encoded on the X chromosome. These mutations appear in approximately one in 70,000 boys, which translates then into one in 140,000 of the general population. So thyroid hormone needs to enter the cells in order to have their biological activity. And for this, they need active transporters. Importantly, MCT8 is one of several thyroid hormone transporters in the body. So when you have MCT8 deficiency, we will have an Emcitate-dependent compartment, mostly important, the CNS and parts of the hypothalamus, which regulate the thyroid hormone homeostasis. [ Department ], we will have no or very low thyroid [ hormone ] level. Then, we will have the rest of the body and organs, which will, in turn, suffer from [Technical Difficulty] as a result of disrupted thyroid hormone homeostasis with too high thyroid hormone levels circulating in the system and with intact transporters transporting the same thyroid hormone into these organs. So next slide, please. So what does this mean for the patients? So the chronic peripheral thyrotoxicosis results in failure to thrive, very low body weight, decreased muscle mass, constant stress on the cardiovascular system with hypertension, arrhythmias and also sleep disturbance. On the other side of things, it is well known that the too low thyroid hormone levels in the central nervous system, regardless, of course, is linked to impaired neurocognitive development, which results in severe intellectual and motor disability in these patients. Altogether, this translates into a very severe syndrome with severe and pronounced morbidity across organs and with a significantly reduced median life expectancy of 35 years. So as you can understand, there is a significant unmet medical need. And currently, there is no approved treatment on the market. Next slide. So I hope everyone is well aware of the very strong and consistent clinical benefit we have demonstrated in patients of all ages in previous clinical studies when it comes to reduction in T3 and normalization of the thyrotoxic part of the disease. And this is also the basis for the marketing authorization application, which was submitted to the EMA last October and will likewise be the basis for the submission in the U.S. together with the ongoing Triac Trial. However, as a reminder, in the Triac Trial I, we also had an exploratory endpoint which looked at neurocognitive development, where we saw signs of an effect in the very youngest patients below 4 years of age. You can see that's the left part of the graph here, where you can see that there is a tendency of effect with blue arrows going up from the orange baseline values. So this finding was the basis for designing the Triac Trial II to look specifically at this part of the disease and in this subgroup of the very youngest patients. Coming into the design, 22 patients younger than 30 months of age were included and followed for 96 weeks. Recruitment was completed in spring 2022 and included 5 sites in the Netherlands, Germany, U.S. and the Czech Republic. In order to maximize the thyromimetic stimulation in the MCT8-dependent compartment, these patients were dosed at much higher doses per kilogram per body weight compared to previous studies. The primary endpoint in this trial was a combination of the total score in Gross Motor Function Measurement 88, GMFM-88, and the Gross Motor Skill domain of the Bayley Scales of Infant Development III, BSID-III. It's noteworthy that it's challenging to assess neurocognitive development in infants and very young children and the available scales which have been developed and validated for other conditions such as cerebral palsy, all include a very prominent gross motor function component. So here, when we talk about neurocognitive development, we essentially mean gross motor function. All in all, we can conclude that the trial execution has been good and without concerns. Next slide, please. So coming into the gist of things. Yesterday evening, as Nicklas mentioned, we issued a press release announcing the top line results of the Triac Trial II. As already described, the Triac Trial II was designed to investigate the potential additional benefit on neurocognitive development in young children below 30 months of age with MCT8 deficiency. The trial included 22 patients with MCT8 treated for -- 96 weeks with Emcitate in higher doses per kilogram body weight as compared to the Triac Trial I. Looking at the results, while numerical improvements versus baseline were observed on the primary endpoints of neurocognitive development, again, as assessed by the Gross Motor Function 88 scale and the Bayley Scales of Infant and Toddler Development, the primary endpoint did not show a statistically significant improvement versus historical controls. And with historical controls, here, we mean the data we observed in the Triac Trial I at baseline. On a more positive note, the trial did confirm the finding of previous studies with a significant and durable reduction of endogenous thyroid hormone T3 levels in all patients, which is relevant to alleviate the features of thyrotoxicosis in patients with MCT8 deficiency. Likewise, the trial confirmed the well-tolerated safety profile of Emcitate seen in previous clinical studies despite much higher dosing per kilogram body weight compared to previous trials. At the moment, this is all we can disclose regarding the results, but the data will be presented at forthcoming medical meetings and also submitted to a peer-reviewed medical journal, led by the team of the Principal Investigator, Professor Edward Visser at EMC Medical Center in Rotterdam, the Netherlands. So with that, I hand back to Nicklas.

Thank you, Peder. Let me now summarize the regulatory pathway for Emcitate in Europe and the United States. We submitted the marketing authorization application, or the MAA, to the EMA on the 9th of October last year. It consists of our clinical data from 3 studies. In the first one, Triac Trial I, conducted in 46 patients, the effect of 12 months of [ MCT8 ] treatment on thyroid hormone T3 concentrations and clinical endpoints related to peripheral thyrotoxicosis were established. The Erasmus Medical Center, or EMC, cohort study confirmed these treatment effects in a real-life setting in 67 patients with treatment up to 6 years. The third study included in the MAA was an extensive natural history study of an untreated MCT8 deficiency population, which enabled an indirect [ compensation ] to the essence the clinical relevance of the treatment effects seen with [ Emcitate ]. For the U.S., our regulatory strategy is somewhat different. In consultation with the FDA regarding a new drug application, the FDA has requested a placebo-controlled withdrawal study to verify the effects seen on T3 in the single-arm studies, Triac Trial I and the EMC cohort study. This is what we refer to as the ReTRIACt Trial. Finally, the Triac Trial II, as mentioned before, is complementary to both the MAA and the forthcoming NDA. Next slide, please. This slide is a reminder about the regulatory status for Emcitate in Europe. As I mentioned, we submitted the MAA in October, and the application was validated by the EMA on the 26th of October. At the moment, we're compiling answers to the so-called 120-day list of questions, which we received from the EMA in February this year. The results from Triac Trial II will be included in the response to these 120-day questions, with focus on safety in younger children, which we plan to submit to the EMA in August this year. Next slide, please. Finally, let me summarize the key take-home messages from today. For Triac Trial II, the numerical improvement from baseline observed on the primary endpoints of neurocognitive development did not show a statistically significant improvement versus historical controls. However, the trial confirmed the significant and durable reductions of thyroid hormone T3 levels in all patients, which is relevant to alleviate features of thyrotoxicosis in patients with MCT8 deficiency. Importantly and very reassuring is that the trial also confirmed the well-tolerated safety profile of Emcitate seen in previous clinical studies. As mentioned, the Triac Trial II is complementary to the data already submitted and validated in the MAA for Emcitate for the treatment of MCT8 deficiency, based on the benefits of normalization of thyrotoxicosis, which has been demonstrated in patients of all ages and agreed with EMA. As mentioned also, the results from Triac Trial II will be included in the response to the MAA 120-day list of questions in August. In the U.S., the forthcoming NDA will also be based on already observed treatment effects on T3 concentrations and the manifestations of chronic thyrotoxicosis together with the results from the ongoing pivotal ReTRIACt trial, as acknowledged by the FDA. I would like to emphasize that the timelines for regulatory review and approval in EU remains unchanged. For the U.S., as previously communicated, we will update the market with regards to timelines for the NDA submission as soon as 16 evaluable patients have completed the randomized phase in the ongoing ReTRIACt trial. We don't consider the approvability of the product to be affected by the Triac Trial II results, and Emcitate has the potential to become the first treatment for MCT8 deficiency, an ultra-rare disease with high unmet medical needs. With this, I would like to open the lines for any questions you may have. Please go ahead.

[Operator Instructions] The next question comes from Mattias Haggblom from Handelsbanken.

I have 2 questions, please. So firstly, can you help us understand the doses used in this trial compared to previous trials? Because you stated in the release that doses per kilo body weight were much higher, but we don't know the magnitude of the difference. And then secondly, you would use the data from the Triac II Trial to respond to EMA's 120-days questions in August. To what extent, if at all, would your ability to respond to the outstanding questions have changed in a scenario where Triac II hit its primary endpoint?

So perhaps I can respond to the dosing. This is Peder. So the objective here, I mean, was to see if we could maximize the thyromimetic effect in the CNS basically. So with that in mind, we dosed these patients very much higher in terms of body weight, so more than double actually compared to what we did in the Triac Trial I and -- as repeated several times already. But again, I mean, despite such an increase in dose, we did not see any signs of -- that we reached the dose which was not tolerable, rather the contrary.

Thank you, Peder. And to your second question, Mattias, and good morning, by the way; which was around the ability to answer to the 120-day list of questions from the EMA, we don't see any change in our ability at all to be able to answer that. On the contrary, actually, this helps us and as planned to be able to answer those questions. The focus from the EMA has been on safety in younger children. And of course, the data set from Triac Trial II, which has robust data from 22 patients below 30 months of age with a very well-tolerated safety profile enables us to answer in a very swift and credible fashion. Thank you, Mattias. I hope that answered your question.

A quick follow-up, please, if I could. So I understand it's early stage, but could you elaborate on the potential risks of having a more narrow label instead of treatment of [ MCT8 ] group or possibly treatment of thyrotoxicosis of MCT8 deficiency?

Thank you, Mattias, and that's a really good question. And as I think we have mentioned in previous calls and presentations and as I'm sure the audience will recognize, we have already submitted the MAA in October last year to the European Medicines Agency, and they've suggested a broad-label treatment of MCT8 deficiency, full stop, regardless of ages. This was, of course, in light of the results that will be further discussed with the agency, but I think it's very important to recognize, and Peder touched upon this, that essentially all patients with MCT8 deficiency have both neurocognitive development delays and peripheral thyrotoxicosis. There is no patient that only has one or the other. And obviously, we have a very good and robust data set for the treatment of peripheral thyrotoxicosis through normalization of T3 levels regardless of age. Peder, I don't know if you have any comment.

Yes. Perhaps, I mean, you mentioned potential restriction in age. I think with this data, rather, we have strengthened the data package in that regard. We have now more patients treated in the very youngest age groups. So when it comes to an age restriction, I mean, this rather work to the other direction. I think we have very, very good data that we are able to improve the peripheral thyrotoxicosis and the normalized T3 levels in all age groups now, including the very, very youngest.

The next question comes from Chien-Hsun Lee from Pareto Securities.

So 2 questions from me. Just trying to understand, so why do you think the reduction in hormone -- I mean, you show a sustained T3 level decrease. How -- what's the reason that you think it cannot be translated to the neurocognitive endpoint? And the second question is that do you plan to do additional study or what's your strategy to address the neurocognitive endpoint? Because I guess this will have impact on the reimbursement decision and pricing.

So if I understand correctly, the first question was -- to summarize it, I mean, why do you think you didn't see an effect? Was that -- so early days here, we don't know. I mean, we -- as we said, the study was well executed. We had the patients we wanted to recruit. And it's hard to say. We will, of course, look further into this, including potential mutation analysis and so forth to try and see why we were unable to see what we hoped for. But I think that's all we can say today.

Yes. I think you said it well, Peder, to build on that. Of course, this is early days. We have really reviewed and had a hard look at primary endpoints, of course, and held subsequently the communication yesterday evening. We will further analyze, of course, secondary and exploratory endpoints to see if we see any opportunities there. But I think it's worthwhile reiterating that we didn't see statistically significance on the primary endpoint here. When it comes to further studies, if I understood your question today, this is something in together analyzing, of course, the data from this study in collaboration with the Erasmus Medical Center and Professor Visser, we'll look at opportunities. It's premature to comment on additional studies if when, how, I think, is something, of course, we will assess going forward when we scrutinize the results further in detail.

The next question comes from Arvid Necander from Carnegie.

So when we judge the pricing potential here, we have very little to go on in terms of health economic analysis. So if you were forced to speculate what could a label without any neurocognitive claims means for pricing, how important would this be in your cost benefit calculations?

Thank you, Arvid, for a very good question and a very good try. I'm usually hesitant, as you know, to speculate with regards to pricing impact and label. But I think in general, and as we said many, many times before, we don't give price guidance for Emcitate. And more importantly, in this situation, it's very, very difficult to speculate and comment before we know the outcome of the label. I think it's important to recognize that the pricing work and preparations when it comes to health technology analysis, caregiver studies, vignette studies; has been based on the data at hand, i.e., before Triac Trial II. That is something, of course, in light of the results of Triac Trial II. We now will revisit. But I think it's also important to note that Triac Trial II was designated, as Peder mentioned, to investigate a potential additional benefit on neurocognitive development in young children below 30 months of age. One should recognize that the main pool of [ Emcitate ] patients was always going to be older and beyond what was perceived as the window of opportunity for neurocognitive development. So I think in essence, I apologize, I can't speculate and I won't speculate on this matter, but -- since it's premature, until we have a good view on the label.

Just a quick follow-up, if I may. So without assuming that these claims cannot be done, would the ultra-orphan sort of drugs you've suggested as good pricing analogs still be fair references? Or do you see any reason to revise these?

No, no. I think it's going to be also orphan pricing regardless, right? And I think it's important, it comes back to some of the -- I'm sure the analysts and investors on the call have looked that, when it comes to ultra-orphan segment, there are [ premium ] pricing. We don't see that, that will change regardless of label, it will be within that range. But where in that range, it's difficult to speculate.

The next question comes from Fredrik Thor from Redeye.

I was wondering, can you remind us a bit about the power, the statistical power in the trial related to the primary endpoints?

Yes. Thank you, Fredrik, and let me start. And Peder, you can elaborate. So the question was around how was the study designed and powered. I think it was designed in relation to historical controls, as Peder mentioned, from the baseline values in the youngest patients in Triac Trial I, a cutoff level was determined based on these data, such as that if we could show to be better than the cutoff in Triac Trial II after 96 weeks, we could conclude them to be better than historical controls. The study had more than 90% power to be successful. Peder, I don't know if you want to further elaborate on that.

No.

Thank you, Fredrik.

And a follow-up question, if I may, about the possibilities for screening programs in Europe or U.S., for example. They have an impact, this outcome on the potential, for example, early screening or [ screening ] overall of [ treating ].

I wouldn't think so. I mean we still have shown that there is value in treating this disease in all ages. I mean finding them as early as possible is better. We know that thyrotoxicosis -- the consequences of thyrotoxicosis aggravate and worsen over time. So I still think that the hypothesis that early initiation of therapy is better, still holds true.

And maybe to build on that, and I'm sure you are aware, Fredrik, we have a couple of [ pilot ] screening programs ongoing in the Netherlands, in Portland in the U.S., but also most recently in the U.K., right? So that is some pilots ongoing, which we're very pleased with to be part of. We also will conduct own screening programs going forward through our investments, further investments in our medical affairs organization. I think, as Peder mentioned, this is an ultra-orphan condition. It's a devastating condition, no treatment exists. With the treatment effects we've already shown, we see really good reasons to continue, of course, and no change with regards to screening programs. Thank you, Fredrik.

The next question comes from Patrik Ling from DNB Markets.

Just one question here. I mean, even if you didn't reach the primary endpoint on the neurocognitive side, could you say anything about the [ encosis ] since you're -- I mean, you bolster impact or a deeper impact? Or do you see anything that you can elaborate on?

Yes. Perhaps I can start. Again, we are not able to disclose details of the data. So what we can say is that we see what we have seen in the previous studies when it comes to the relationship between treatment and the possibility to suppress and normalize T3 levels. And yes, I don't know if you can say more details.

No. I think I apologize that we can't be granular, obviously. What we're sharing today has been an agreement with the Erasmus Medical Center, which, of course, are planning a peer-reviewed publication on the data presentations. We need to be a bit careful on how much we disclose. But as Peder said, the trial really confirmed the significant and durable reduction of endogenous serum T3 levels in all patients, very important. Despite we're not giving granularity on the secondary endpoints around thyrotoxicosis, we all know that this is -- the reduction of T3 levels is relevant to alleviate features on thyrotoxicosis in patients with MCT8 deficiency.

Great. Can I just have a quick follow-up? Do you have any sense on when this data will be presented? I suppose they will first start with a scientific meeting somewhere. Is it during the autumn?

This is Karl. No, we can't say anything at the moment. We're in very early stages of analyzing together with the Erasmus team. So we will come back on that when they submit something to summer conference, but it will definitely be published.

The next question comes from Joseph Hedden from Rx Securities.

Just to pick up on Fredrik's first point, and I appreciate that you can't say anything granular about the secondary endpoints, and we know that lowering T3 is linked to alleviating these features of thyrotoxicosis. But I mean, from a regulatory perspective, presumably, the -- that they want to see this link demonstrated is appropriate in other disease areas, too, when you have these kind of [ markers ]. Maybe approaching it from a different angle, are you happy with what you've seen on the secondary endpoints that this isn't going to raise any concern among FDA and EMA that there's a divergence between T3 and endpoints such as heart rate, blood pressure and in the [ markers ] of kidney and liver function that were all positive in the first study? Is everything consistent? Could you broadly say anything there?

Yes. The simple answer, Joseph, is yes, it is consistent. And as I'm sure you're aware, of course, we have the first study Triac Trial I, 46 patients where we saw the effects of 12-month treatment of [ Emcitate ] on thyroid hormone levels T3 as well as clinical endpoints related to thyrotoxicosis that was verified by the EMC [ CORD ] study, 67 patients with treatment up to 6 years. What we're seeing in this study, Triac Trial II, is nothing that contradicts that. And I apologize, we -- it's more reassuring, actually, and I apologize that we can't give that granularity, based on what Karl and Peder just said around upcoming presentations, et cetera. But it's reassuring, is a simple answer.

Okay. That's very helpful. And then just on the financial side. On the BlackRock second loan tranche, appreciate there were some conditions linked to ReTRIACt. I just wanted to confirm that does this result affected your ability in any way to draw down that tranche?

Joe, thank you for the question, Yilmaz Mahshid speaking. I hope you hear me. No, it does not. As we have mentioned before, it's more -- the debt drawdown from BlackRock is more dependent on the top line results from the ReTRIACt study. I hope that clarify to you.

Please, if I could -- yes, third one. Just on pricing again. I just wondered in those analogs that you presented in the past and -- are there any where we've seen a similar situation to this where there are perhaps 2, 3 core elements of the disease and the drug is hitting one of those elements, and it's really doing good, but it doesn't have an effect on perhaps another significant area of the disease? If there's anything like that, that you could point to us, that would be really helpful.

Thanks for the question. I don't have anything off the top of my head at this point in time. But I hope if you don't mind, we'll come back to you offline with an answer to that question.

There are no more questions at this time. So I hand the conference back to the speakers for any closing comments.

Thank you very much, operator, and that brings us to the concluding remarks. I would like to thank all the participants and the individuals asking all the enlightening questions. To summarize and concluding remarks, we want to reiterate that the timelines and probability for regulatory approval remains unchanged. And we have a clear pathway in Europe. The marketing authorization application has been submitted, and we are in the process to respond to the 120-day questions. For the U.S., as previously communicated, when it comes to the timelines for the new drug application to the FDA, we will update the market as soon as 16 evaluable patients has completed the randomized treatment period in the ongoing ReTRIACt study. And subsequently, we don't consider that the probability of the product to be affected by the Triac Trial II results. And Emcitate has the potential to become the first treatment for MCT8 deficiency. Thank you.