Welcome everyone to our fireside chat with Egetis Therapeutics. I'm Joe Schwartz from the biopharma equity research team at Leerink Partners, and it's my pleasure to be joined by Nicklas Westerholm. He's the CEO of the company. Thanks so much for joining us.
Thank you for having us.
Why don't you get us started by telling us a little bit about what you're working on and any recent progress to note and maybe the upcoming catalysts we can look forward to?
Sure. For those who are not familiar with the company, Egetis Therapeutics is a small biotech company out of Sweden. Very, very simple strategy, solely focusing on late-stage development for treatments for rare diseases with the ability to commercialize ourselves in Europe and the U.S. Our most advanced candidate is a drug called Emcitate for the treatment of the ultra-orphan condition, MCT8 deficiency. Translating that into the progress over the last year, which we are very proud of, 2025 was a year of strong execution. We actually got Emcitate approved in the European Union as the first and only approved therapy for the treatment of MCT8 deficiency. That, too, aside, when it comes to the U.S., we were granted a breakthrough designation by the FDA on the fourteenth of July last year. This was solely based on our own analysis of mortality data.
Mortality data has evolved over time, where we now see a reduction of mortality stronger than 3 times lower risk of mortality in patients treated with our drug versus untreated patients. That led us then to engage with the agency at the pre-NDA meeting in October, which was very constructive, very positive, with 3 outcomes I would like to call out. 1, their support to move ahead to, and submit the NDA with currently available data. 2, we were granted a rolling submission. And 3, to prematurely close the ReTRIACt study, our previously deemed pivotal study in the US, which we did in November with positive outcome, top-line results, which led us to an initiation of a rolling submission in December last year.
Great. All right. Can you remind us what the changes were to the statistical analysis plan for the ReTRIACt study that you reported back in November?
Sure. The ReTRIACt study, just a couple of steps back, was originally signed back in 2021. It was deemed to be pivotal in the U.S. for registration. The study was designed to be randomized and placebo-controlled, a 30-day randomized treatment period, where the primary endpoint was rescue, which means that the patients on placebo going over upper limit of normal for T3. That was the original design. Obviously in light of the data that has evolved over time, including the mortality data I was just referring to, where the breakthrough designation was granted, we decided together with FDA to prematurely close the ReTRIACt study.
Subsequently, with fewer patients in the study to maintain the statistical power, we looked at better endpoints together with the original endpoint, which we kept, but to better endpoints utilizing the data we generated during the randomized treatment period, and hence the change in the statistical analysis plan.
Okay. You agreed upon those with the FDA, and is that right?
Yeah, we had some really good dialogues.
Yeah.
With the agency around this. Then again, I think in light of the data we have generated over the course of the years since the initial discussion, we of course kept the original design primary endpoint as well, but added a new primary endpoint to the statistical analysis plan to utilize all the data generated over the randomized treatment period where we saw a 59% increase in the rate of change for T3 in the patients on placebo with a P value of 0.034.
Okay. Can you put that T3 rate of change that you saw into perspective, clinical perspective for us? How does that compare to the rescue rate?
I think it's important to recognize that this randomized treatment period is only 30 days. Translating that into clinical benefits are difficult. This is something we've been very, very open with, that this request for this study was driven by the agency's view to have something that was randomized and placebo-controlled, and a triangulation between our drug and the lowering of active T3. That is what the study is showing when it comes to clinical benefits and evidence there. We have, as I'm sure you appreciate, Joe, unusually large data set generated in an ultra-orphan condition where we can pull on sources like Triac Trial I, Triac Trial II, the EMC Cohort Study, the survival study, and ReTRIACt.
The totality of evidence there illustrates lowering of T3, clinical effects on organs with peripheral thyrotoxicosis like the heart, the muscle, the kidney, then also now translates into a survival benefit.
Right. Okay. What are the top two or three topics you expect the FDA to focus on in your or in their NDA review for Emcitate?
Well, it's difficult to speculate, right? In the midst of the acceptance for filing period. Just to make it clear to the audience that, as I mentioned before, we initiated the rolling submission on the 19th of December last year, which included the non-clinical and the CMC parts of the dossier. Then we completed the submission on the 28th of January this year. We are in the validation period or acceptance for filing period with FDA. We expect to hear back from them on the 29th of March. Based on the very constructive and positive dialogues we had at the pre-NDA meeting, of course, it's reasonable to assume that they will further ask questions and focus on the data on mortality benefits.
Okay. I guess when we think about the breadth of data that you included in the NDA submission, you pulled results from multiple sources and multiple trials, which is pretty impressive given the very rare nature of the disease. How comfortable are you that this kind of an approach is acceptable to the FDA?
Well, again, it's difficult to speculate on what FDA will focus on during the review, right? We, as a company, believe that we have a very strong position going into the NDA. We have a clear view of the benefit-risk of the product, for sure. As you mentioned yourself, yeah, we have a numerous amount of clinical data generated from 6 different sources, which is somewhat unusual being ultra-orphan disease. We have the first clinical trial, the Triac Trial I, 46 patients, 1 year. We have the EMC Cohort Study, 67 patients with treatment up to 6 years. You have the ReTRIACt study that we referred to. We have Triac Trial II, and then we also have the mortality study or the mortality data, which includes more than 600 patients in that data set.
I think overall and all in all, we have a very good view on, from a company perspective, of the benefit risk of the product and of course, subsequently, strong belief in approval.
Great. What is the association between serum T3 levels and clinically meaningful outcomes in the disease?
This is something that the agency also asked for sure, and this is something we have provided in the new drug application, the NDA, that was submitted most recently. There we are able to illustrate a clear link actually between elevated T3 and mortality, and also treatment of elevated T3 reduces mortality. I think we can all agree that the ultimate clinical outcome in this, in a condition like this is mortality benefit.
Right. I realize these are difficult questions heading into these events.
Not at all. Please fire away.
Thank you. What is your current most likely scenario for the U.S. label in terms of age range and claim language? Are there any likely constraints that you're planning around?
Well, how we see this and again, as I mentioned, the product is approved in Europe already, and there we don't have any age restrictions. We have clinical data generated actually from the age of 6 months up until 67 years of age, right? We have quite a broad span of clinical data being generated. In contrast to the approval in Europe, we now have also the mortality data. Obviously a key component of the dossier that was submitted is the mortality data from the so-called mortality study. We have, as a company, positioned that as the adequate and well-controlled study with the ReTRIACt study amongst others to serve as additional confirmatory evidence.
Our assumption there or how we went in with NDA is to ensure that or ask for having reduction of mortality in the label and/or in Section 14 claims truly reflecting the benefit-risk profile of the product.
Yeah.
Of course, it's up to the agency to review and put their.
Understood.
Thinking in it.
Yep. No, that's very helpful. What have you learned from the ex-U.S. launch over the last 12 months? Anything you can apply to the U.S. market?
Well, yeah, for sure. A couple of things and one of the most intriguing things, which maybe not that was a surprise to us, was that we launched in Germany. Germany is the only country where we have pricing today. I'm sure you're familiar and the audience are familiar with the somewhat challenging and timely, time-consuming pricing and reimbursement processes that are different across the 26 member states in Europe and takes everything from 1 to 4 years. What we have learned from the launch in Germany, where we have launched a commercial product on the first of May, is that the number of patients subsequent to the launch and a commercial product on, in the market, has increased exponentially.
When we launched in Germany, we were aware of roughly 15-18 patients diagnosed with MCT8 deficiency. Post the launch in Germany, we have identified further 20 patients.
Wow.
Only within nine months with MCT8 deficiency. That is one of the learnings, of course, for sure. Coming back to, not surprising again, disease awareness have been and continue to be somewhat low.
Yeah. What's driving that? Are these patients misdiagnosed or overlooked for any other reasons?
For sure, I think here we need to take a step backwards. MCT8 deficiency, the actual transporter of thyroid hormone for vital compartments, was discovered only in 2003 as the first transporter of thyroid hormone. Previously, it was assumed that it was passively transported across the cells and into the neurons. One, it's a relatively new disease from that perspective, for sure. Then in combination with not having any treatment available, it's been very much underdiagnosed. Of course, the patients we have identified that are in the older ages are misdiagnosed. As an example there, we actually identified 2 patients here in the United States, in Texas, just during the autumn, that was diagnosed with cerebral palsy.
Wow.
Wrongly diagnosed then, of course.
Sure. Amazing. That's great work. Are there any practical considerations to monitoring T3 levels that's important to consider for management of these patients in the real world now that the drug's available commercially?
Well, not really. I think this is something that is very positive for both diagnosing patients, but also initiating treatment with Emcitate, is that to diagnose these patients, it's a simple blood test serum T3. You can analyze it in any lab, either through immunoassay or LC-MS, and it's quite cheap. It's not anything that are invasive as such. What we know is that we will make sure, as we have done in Europe, that when the product is on the market, we will recommend to analyze with LC-MS rather than immunoassay to ensure that one can avoid potential interference between our drug, Emcitate, or an active substance, tiratricol, and active T3.
All in all, very simple, actually.
Do the additional data from the ReTRIACt study help bolster your narrative any more in Europe?
No, I wouldn't say that much. What will help us bolster the narrative in Europe is, again, the survival study. Here one should recognize that in Europe, the drug was approved with very much more limited data compared to what has now been submitted as part of the NDA. What will bolster, I would say, the narrative in Europe going forward is the survival data, where we are now planning to submit the so-called Type II variation in Europe. For a label enhancement to also include the survival data in the European label. That will bolster.
Yeah.
The narrative rather than the ReTRIACt study.
Okay, that makes sense. I think you have 30 patients in an EAP program here in the United States.
Well, it has evolved a lot since we last spoke.
Okay.
It's now 45.
G reat. Okay, what do these patients represent in terms of like, all the diagnosed patients that you know about?
Here in the United States, we are aware of roughly 145 diagnosed patients today. As I said, that's quite intriguing bearing in mind that the disease awareness is still very low. We haven't worked actively here in the United States with feet on the ground since last year was the initiation of that. When we started to work on this disease back end of 2021, we were aware of 28 patients in the United States diagnosed with this condition. Today, we are aware of roughly 145, as I said, and we know that it's again a patient pool that is severely underdiagnosed.
If you look at numerous sources, when it comes to incidence levels, that points you in the direction in 1 in 70,000 males.
The mutation is an X-linked disorder here, so we call it generally a male disease. If you then translate that into the general population, it's one in 140,000, accounting for untreated patients having a median life expectancy of 35 years. If you do the math, you end up with roughly around 1,000-1,500 patients in the United States.
Wow. What are you doing currently on the ground in order to educate about the disease?
Yeah, no, I think this is one of the key levers we're driving as the pre-launch activities. One is that, of course, based on the success we had back end of last year with the breakthrough designation, positive outcome of the pre-NDA meeting, and then the NDA submission, we have substantially increased our investments in the United States. Up until October, we had actually three people employed in the U.S. only.
Amazing.
Which is not a lot, right? We still found 140 patients, right? Now we have an infrastructure of 10 people today. We have four regional medical affairs directors, very important out there driving disease awareness, interacting with physicians, data mining through claims data, participating actively at conferences, et cetera. We see that as a huge opportunity, and I think we should calibrate that with finding roughly 140 patients with very limited activities where we now increase the investments exponentially, and we expect to be 25 people here in the U.S. at the point of launch.
Very interesting. Can you talk a little bit about your manufacturing strategy?
Yeah, sure. It's a very simple manufacturing strategy in the sense that this is an oral tablet. It's a small molecule. We had the supply chain set up already five years ago, and of course, we have now launched through that supply chain in Europe. The API is produced in Switzerland, and then the drug product is produced in France. We have actually most recently contracted a 3PL here in the U.S. together with a specialty pharma that also includes patient support services, ensuring that we have an adequate, robust supply chain. We haven't had any disruptions in it through the European launch.
Okay. Interesting. How are you thinking about pricing in the United States? It seems like there's some pretty dramatic benefits, and you could attach some nice pharmacoeconomic value to that.
Yes. I think we can, right? Here, of course, as a company, we tend not to disclose our pricing strategy nor our pricing assumptions together with peak year sales, right? In order to calibrate that for you, I think all in all, it depends, and sorry for the diplomatic answer, depending on the label. If we look at a label with reduction of mortality together with having that in Section 14, claims to clinical data, there to point you in a direction, you have some very interesting analogs. We have done a thorough analog review together with payer research as well. With those assumptions, you have some interesting comparators or analogs out there. Similar type of disease characteristics, pediatric, chronic treatment, et cetera.
I will point you in the direction of VYKAT, for example, from Soleno Therapeutics. You have SKYCLARYS. You're looking at, based on the analog's prevalence and the disease severity together with the treatment benefits I was alluding to, a price point in the region of $1 million per patient per annum.
Okay. I would imagine you would get orphan drug exclusivity. You probably have the designation already.
Yes. For sure.
Is there any other IP strategy that you're working on?
Yeah, yeah. That's something we're very active on, actually. I don't know if you picked that up, Joe, but we actually had a press release out Monday this week where we have just now received a notice of allowance from the U.S. Patent and Trademark Office on a formulation patent, including the composition and purity of the tablet together with excipients in combination with method of use. That patent, we need to go through the bureaucracy process in order to get it fully granted, of course. The notice of allowance was very positive. There we have an additional coverage of 20 years from the filing of the patent, which was 2025. On top of that, we're looking at a different type of more pediatric-friendly formulations, and that we have started to.
It's not unreasonable to think that we will have a potential patent around that as well.
Okay. How is Emcitate dosed currently?
It's an oral solid. It's a tablet. The patients takes roughly 2-3 tablets per day. Yeah.
Great. Is this a program that could be PRV eligible?
Yes, for sure. That's something we're also considering milestones this year, I think. I didn't answer that question 'cause you had that in the beginning. I apologize for that, Joe. Obviously, 2026 will be very exciting for us. As I said, we concluded or completed NDA submission back end of January. We expect acceptance of filing from the agency here back end of March together with a priority review and a PDUFA date. Considering a priority review is being granted, we expect a PDUFA date towards the back end of September. Again, a very exciting milestone there. That in combination with us being granted already back in 2020 a Rare Pediatric Disease Designation, we are eligible for a Priority Review Voucher.
Okay.
Which most likely will be monetized as, I'm sure.
Yeah.
One would appreciate.
That makes sense. Great. How does this program tie into the company's overall business model and vision for the future?
The vision for the future and the mandate I have as a CEO is to build a sustainable rare disease company. Obviously, this is the first step in that journey where we have the product approved in Europe for the treatment of MCT8 deficiency, and hopefully, within this year, also get the approval in the U.S. What we are working on in parallel is, in order to be sustainable and not being a one-trick pony, really indication expansion. We have a really interesting opportunity with this molecule in a totally different patient population called Resistance to Thyroid Hormone Beta , also an old orphan condition, where we have orphan drug designation as well. We already have a Managed Access Program in place treating over 40 patients.
With our drug in this condition, there was a publication out there in November last year illustrating clinical benefits in using our product in the treatment of RTH-β as well. It's not unreasonable to think that we will embark on this indication expansion opportunity in the not too distant future. In parallel with that, we are also very active on the BD front, identifying further assets in late-stage development that we can use our what I call sweet spot from a capability and capacity perspective design one clever pivotal trial to get the product approved in Europe and U.S.
Okay, interesting. Just a few words on RTH-β and that treatment setting. How does that disease compare to MCT8 deficiency?
It's not as severe, but the median life expectancy are reduced, compared to the general population. It's a disease that doesn't have any approved treatments today either. It's somewhat more prevalent, so it's four times more prevalent than MCT8 deficiency. Here we are looking at 1 in 20,000 or to 1 in 40,000 is the prevalence estimated to be. It's also a very heterogeneous population and also affects both males and females. Here we have an opportunity again, as I mentioned, to design a clinical study with the ambition of having only one clinical study that could be considered pivotal in the eyes of the EMA and the FDA and get it registered.
Interesting. What do you know about the activity of MCT8 in RTH beta, and what questions do you need to answer still?
Well, as I said, this is quite intriguing, and it's a very heterogeneous patient population. If you look at the younger population here, so below teenagers, et cetera, it's very much the symptoms are centered around ADHD, hyperactivity, etc. Whereas when they further evolve into their adult ages, you see the same cardiovascular problems as you see for MCT8 deficiency, i.e. effect implications on the cardiovascular systems such as heart, like blood pressure.
We need to be very careful when we design a clinical study for this patient population and maximize the opportunity there.
Super interesting. Anything we didn't touch on?
No. It's I think to summarize, it's gonna be an exciting year for us. The submission has been completed. We expect an acceptance to file and if granted, also a priority review for sure, and a PDUFA date towards the back end of September with a subsequent launch in the US.
Very exciting. Well, thank you so much for the update, Niklas, and best wishes.
Thank you very much, and thank you for having us.