Welcome to Egetis Webcast. During the Q&A session, participants are able to ask questions by dialing #5 on their telephone keypad. If you are listening to the presentation via webcast, you can ask written questions using the form below. Now, I will hand the conference over to CEO Nicklas Westerholm. Please go ahead.
Good morning, everyone, and welcome to Egetis Therapeutics Webcast. My name is Nicklas Westerholm, CEO of Egetis Therapeutics, and with me today I also have Kristina Sjöblom Nygren, Chief Medical Officer, Kristian Sonesson, Vice President, Product Strategy and Development, Karl Hård, Head of Investor Relations, and Yilmaz Mahshid, Chief Financial Officer. This morning we issued a press release announcing positive top-line results from the ReTRIACt study of MCT8 in MCT8 deficiency. We are, of course, incredibly pleased with this positive study outcome. The positive top-line results demonstrate a statistically significant difference in the rate of change in serum T3 in patients randomized to placebo versus patients continuing on tiratricol, with a p-value of 0.034.
The ReTRIACt study is the last clinical study to be reported for Emcitate in MCT8 deficiency and complements the EMC survival study data and other clinical data for the upcoming new drug application, as discussed with the FDA in our October 2025 pre-NDA meeting. Subsequently, we'll plan to start a rolling NDA submission in December this year, targeting a complete NDA submission in early 2026, with an anticipated completion of the FDA review process in the third quarter of 2026. Let's now turn our attention to the design of the ReTRIACt study. The ReTRIACt study is a double-blind, placebo-controlled, randomized withdrawal study. Patients included in the trial could be either already on tiratricol treatment or be treatment naive. During the run-in period, patients were titrated to achieve stable serum T3 levels within the normal range.
Once patients had a stable T3 level, they were randomized to either continue tiratricol treatment or to receive placebo. When patients are randomized to placebo, it's reasonable to expect a reversal of the tiratricol treatment effect and hence increased T3 levels. As a result of the pre-NDA meeting we held with the FDA in October 2025, the NDA for Emcitate will be based on currently available clinical data, where data from the ReTRIACt study will complement the already robust and existing dataset we have from the likes of the EMC survival study and other clinical studies with tiratricol. Based on comments from the FDA, the statistical analysis plan of the ReTRIACt study was revised, and the study was closed.
A Primary Endpoint 1, evaluating the rate of change in serum T3 during the randomized treatment period, was added to the previously described Primary Endpoint based on T3 rescue criteria, from here on referred to as primary endpoint 2. Type 1 error is controlled via alpha recycling, testing Primary Endpoint 1 first, and if Primary Endpoint 1 is met, Primary Endpoint 2 will then be tested. The revised statistical analysis plan was submitted to the FDA before database lock and the unblinding of the ReTRIACt study. Now, let's turn to the results in the study. What you see depicted to the left is the ranking of patients according to their change in T3 during the 30-day randomized treatment period. Displayed with a dashed line is the line of no change from baseline.
Hence, the patients with the largest increase of T3 during the randomized treatment period are in the top of the figure, and the patients with the largest decrease are at the bottom of the figure. What we have observed is exactly what we expected. When withdrawing Emcitate, the T3 levels in all placebo patients increase between 0.49-2.08 nanomole per liter. In the Emcitate Group, not much happens when they continue the Emcitate treatment, with the change in T3 ranging between negative 0.24-0.40 nanomole per liter. In fact, there is a complete separation of the two groups, with all eight patients randomized to placebo having a larger increase in serum T3 during the randomized treatment period than all seven patients randomized to continue Emcitate. What does this mean for the results of the primary endpoint?
On the right-hand side, the upper table shows the results for primary endpoint 1: the rate of change in serum T3 during the randomized treatment period. For the placebo group, the rate of change was 1.590. This means once Emcitate is withdrawn, there is a 59% increase in T3 over 30 days, whereas there was essentially no change for the Emcitate group over the 30 days. Comparing the two groups, as per the definition of the Primary Endpoint 1 in the statistical analysis plan, there was a statistically significant difference between placebo and Emcitate, expressed here as the ratio of the T3 rate of change, which was 1.494, with a p-value equal to 0.034. On the right-hand side, in the lower table, you can see the results for Primary Endpoint 2. Four patients randomized to placebo met the rescue criteria. No patients randomized to Emcitate met the T3 rescue criteria.
One patient randomized to tiratricol discontinued during the randomized treatment period. This discontinuation was not drug-related. The patient is marked with D in the left-hand figure, as you can see. Also experienced essentially no change in T3 during the randomized treatment period. However, per the statistical analysis plan, this tiratricol patient was still imputed as a rescue for the analysis of Primary Endpoint 2, leading to a 4 versus 1 comparison for Primary Endpoint 2, which is not statistically significant. However, the sensitivity analysis below only considered the observed cases of rescue, leads to a comparison of four patients meeting the rescue criterion on placebo versus zero patients randomized to Tiratricol, with a p-value of 0.070. Furthermore, after the randomized treatment period was completed, patients randomized to placebo reinitiated tiratricol treatment, and they all showed, as expected, a decrease in serum T3 levels in the so-called follow-up period.
To conclude, we are very, very pleased with the positive outcome of the ReTRIACt study. We now plan to submit an NDA for MCT8 with the current clinically available data. We have a very robust dataset for such an ultra-rare genetic disorder, including data from trial 1 with 46 patients, trial 2 with 22 patients, now the ReTRIACt study with 15 patients, the EMC cohort study with 67 patients, also the EMC survival study with over 600 patients, by far the largest dataset ever generated in this disease condition, together with the US Expanded Access Program with around 30 patients today. Our plan, as previously mentioned, is to commence a rolling submission in December 2025, targeting a complete NDA submission in early 2026 and anticipated completion of the FDA review process in 2026, quarter three. With that, I would like to open up for questions.
Operator, please go ahead.
The next question comes from Oscar Haff en Lamm from Stifel. Please go ahead.
Hi, Nicklas and team. Thanks for taking my question. How do you expect the FDA to weight the Primary Endpoint 1 versus the Primary Endpoint 2 of the study when they look at the data package as a whole?
Thank you, Oscar, and thank you for the question. I think here we need to take a couple of steps back. I'm sure you appreciate that we received a granting of a breakthrough therapy designation during the summer, where the agency recognized the substantial mortality benefit seen in the survival data. Subsequently, we, of course, interacted with the FDA through a pre-NDA meeting in October to discuss the clinical content in the upcoming NDA and to get their view, actually, on the ReTRIACt study, given this new situation, and them acknowledging the value of the survival data. As a result of that interaction, it was agreed to stop the ReTRIACt study immediately. Subsequently, we modified the statistical analysis plan because the ReTRIACt study is now seen as complementary additional evidence to the other clinical data generated. All in all, positive.
Okay, got it. Thank you very much.
The next question comes from Chiara Montironi from Van Lanschot Kempen. Please go ahead.
Hello, team. Thanks for taking my question, and congratulations again on the update. I was wondering, do you already have a sales force in place in the US? If not, how much do you think this will wait for spending?
No, thank you very much, Chiara. It is a valid question. Thank you for congratulating us. I am sure you appreciate that. Both myself and the whole team in Egetis are very proud of today's announcement. When it comes to the commercial and medical affairs infrastructure build-up in the U.S, that is something we have started to initiate already a year and a half ago. Having said that, though, we have been very cautious in gating investments based on milestones. Of course, we have achieved two very important and substantial milestones within the company over the last month. One is the successful outcome of the pre-NDA meeting in October, and, of course, subsequently, the announcement today of the positive top-line results. We are now continuously building up the commercial and medical affairs infrastructure. We actually have two employees joining us this week to further strengthen the organization.
At the point of launch, we expect to be around 25 FTEs in the U.S. around quarter three next year. It is a stepwise build-up with focus really on two aspects. One is, of course, further identification and diagnosis of patients, and of course, market access together with pricing and reimbursement. I hope that answered your question, Chiara.
Yes, it does. Thank you so much.
Thank you.
The next question comes from Qian Li from Pareto. Please go ahead.
Hi, good morning, and thanks for taking my question. Just wondering if you can provide some more granularity on the data, like how many patients are treatment naive and how many are already on treatment, and do you see any difference in the effect between these two groups? Thank you.
Sorry, you were breaking up there a bit. No, thank you, Qian, for the question. You too, as I'm sure you appreciate, the full dataset will be available at the upcoming scientific conference. At this point in time, we can't share anything else than what we have shared today. What we can say is, as I mentioned in my introductory remarks, is that we see exactly what we expected to see when we designed the study. We also see that after the randomized treatment period was completed, patients randomized to placebo reinitiated tiratricol treatment, and they all showed an expected decrease in T3 levels in the follow-up period. Unfortunately, we can't share any more data today, more than what we have already referred to.
Okay. Yeah, perfect. Thank you.
Thank you.
There are no more questions from the telco at this time. I hand the conference back to the speakers for written questions and closing comments.
Thank you very much, Operator. With that, I really want to take an opportunity to also thank the whole Egetis team that has been instrumental in the journey over the last couple of years. We have seen the first and only approved therapy for MCT8 deficiency in Europe on the 12th of February this year. We are now getting closer to a U.S. submission and subsequent approval, which we are, of course, very proud of, both from an internal perspective, but also, of course, making sure that we can provide access to this very much in need treatment for patients suffering with a devastating condition of MCT8 deficiency. The organization now will be laser-focused on the upcoming NDA submission and subsequent approval. With that, thank you all, and I wish you all a great day. Thank you.