Welcome, Everybody. For those of you who don't know me, My name is Oskar Häfänen. I'm part of the Biotech Equity Research Team at CEPHOL, based out of Sweden in Stockholm. It's my pleasure to host this fireside chat with Niklas Westerholm , CEO of Egetis Therapeutics. Thank you for joining us.
Thank you for having us.
Maybe as a short intro, before we get into the nitty-gritty of what you do, just provide us a quick background of the company and the story behind Emcitate, which is your lead asset.
Sure. It's a privilege being here, everybody. Good afternoon. As Oskar said, my name is Niklas Westerholm. I'm the CEO of Egetis Therapeutics. Egetis Therapeutics is a fairly recently created company. It came about in 2020, back end of 2020, through a merger of two small Swedish biotech companies. Today, we are on a very exciting journey, transitioning from a late-stage development company into a commercial-stage biotech company. Our pipeline is focusing mostly on late-stage development with the ability to commercialize in Europe and the U.S. through an own in-house commercial and medical affairs organization, and for the rest of the world to provide access through partnerships. Our lead candidate and first asset in development is an asset called Emcitate for the treatment of the ultra-Orphan condition MCT8 deficiency.
There, we are very proud and pleased with having the first drug ever approved for this condition in Europe earlier this year on the 12th of February. Subsequently, the first launch took place on the 1st of May in Germany. For the US, they were planning to initiate a rolling new drug application with FDA in December this year, based on the currently available clinical data. As I mentioned, partnerships in the rest of the world will be the key feature for market access. There we have three partnerships already in place, one for Japan with a Japanese company called Fujimoto Pharmaceuticals, one distribution agreement in Turkey with a company called Erkim, and one for the Gulf region with Taiba. From a regulatory standpoint, we have a very key and strong status with all the features that one can think about.
Breakthrough designation that was recently granted by the FDA in July this year, together with Orphan drug designation, fast-track designation, as well as a rare pediatric disease designation, enables us to be eligible for a priority review voucher at the point of approval. That was a longer introduction than I thought.
That is perfect. If we just take a quick step back first, because since it's an ultra-rare indication, many people are not familiar with it, if you could just give us a short overview of the pathology of this indication. Then as a follow-up question, since you started developing Emcitate, how has the general understanding of the disease evolved, its diagnosis, its patient education, etc ?
Sure. No, and I'll start off with MCT8 deficiency. I appreciate that not many people in the room have an understanding of the disease itself. MCT8 stands for monocarboxylate transporter number eight. It's a transporter of thyroid hormone. It's an X-linked disorder, which means that it mainly affects males. With this deficiency, it actually causes system-wide issues, being a thyroid hormone signaling trafficking disorder that results in simultaneously too high and low thyroid hormone levels, causing system-wide issues in different compartments. As you can see here on the slide, tissues that are dependent on MCT8, like the Central Nervous System, the cells, and the neurons, have hypothyroidism, whereas other compartments, like the cardiovascular and peripheral system, experience an abundance of thyroid hormone, i.e., Thyrotoxicosis. This then translates into a very devastating condition with an incredibly high unmet medical need.
Some of the disease characteristics here in the two different clinical phenotypes are a median life expectancy of 35 years. 30% of patients die in early childhood, and the main cause of mortality is sudden cardiac death. It also comes with severe underweight, high level of cardiac arrhythmias in young children, which is very unusual, as well as lack of neurocognitive development that translates into only, for example, 8% of the patients have the ability to sit up independently.
As you said, there are two phenotypes for this disease, both metabolic and neurologic. Could you just walk us through the patient journey? When do patients get diagnosed? By who are they treated? Is it endocrinologists? Is it neurologists?
From that perspective, this is quite fascinating. These devastating children are born seemingly normal. A normal weight, normal head circumference, a normal Apgar. The signs and symptoms are not there, and usually also missed at the heel prick test for newborn screening. The first symptoms start to materialize early in life, around four, five, six months of age, where the initial symptoms are very clearly on the lack of neurocognitive development side or clinical phenotype of the disease. The children doesn't crawl, they doesn't turn around or roll around, et c. The patient journey subsequent to that is that usually they're first seen by a pediatric neurologist. Disease awareness for pediatric neurologists has been very low over the last couple of years, but has improved substantially, I would say, over the last 12-24 months.
It's a mix of pediatric neurologists and pediatric endocrinologists when it comes to diagnosing the patients, as well as treating the patients. It depends from country to country.
Going back to MCT8, how does it correct the issue of MCT8 deficiency? Are there other ways of doing it?
If we start with our treatment and Emcitate, or with active substance, Tiratricol, that's a thyroid hormone analog, an analog for active T3 or thyromimetic. The difference between our drug and the active T3, which is the hallmark of the disease, is that it can pass into the cells without being transported by MCT8 deficiency as the transporter. What it does is really restoring the signals in the system, i.e., normalizing the thyroid hormone levels in both the hypothyroid compartments as well as the thyrotoxic compartment. What we have seen in our clinical data is substantial improvements in the peripheral system through the normalization of T3 levels of the peripheral Thyrotoxicosis, such as improved heart rate, blood pressure, the increase of weight, that now also most recently being illustrated by what I refer to as our survival data, also have a mortality benefit.
When it comes to treatment in general and treatment paradigms going forward, there's no other drug today in clinical development that we are aware of. Having said that, though, we know that there are some preclinical activities at some of the universities, both in Germany and also in the US, looking at gene therapy for potential treatment or cure of the neurocognitive phenotype.
Going to the data set that you've generated so far, which is pretty robust for an ultra-Orphan indication, could you just walk us through the key findings of some of your studies? I'm thinking of track one, the natural history study, the survival study.
Of course. I have a slide just to illustrate it. Otherwise, it might become a bit too complicated for parts of the audience. I must say we have a very robust data set for being an ultra-Orphan condition. I mentioned the prevalence, one in 70,000 males that translates into one in 140,000 in the general population. We have a number of both prospective clinical studies as well as real-world evidence studies that have been gathered over the last six years. One should know that this is a fairly new disease in the life science setting. MCT8, as a transporter, was only discovered in 2004, and the first publications actually materialized around the disease in 2010 and onwards. What you see here is a summary of the studies and the clinical data generated either from prospective clinical studies or retrospective real-world evidence trials.
Starting from the left, you have what we call the Track trial one that was completed in 2018, and the results were published in Lancet in 2019. Forty-six patients, nine countries, focusing on normalizing T3 levels in patients. The results were stunning, I must say. We were able to normalize all the patients. That also then translated into clinical benefits on the cardiovascular parameters, such as heart rate, blood pressure, improved weight. This was a one-year study. The second study that was published was a real-world evidence study that we refer to as the EMC cohort study. Sixty-seven patients, a different patient cohort, followed up to six years. What we saw there was exactly the same thing as in Track trial one.
We were quickly able to normalize T3 levels within a couple of months and now durable up to six years, with the same effects and continued effects on the clinical parameters around heart rate, blood pressure, and weight. I will not mention it too much, but we also have data from the US Expanded Access Program. We had the second prospective clinical trial, Track Trial Two, in younger children of the age of 30 months and below, where we saw also normalization of T3 levels across the board that translated into improvements in clinical parameters. Having said that, though, the primary endpoint of this study was improvement in Neurocognitive development, where we saw positive trends, but it was not statistically significant. Most important in this study I really want to call out here is what is abbreviated as the survival study here on the slide.
This is a retrospective study carried out by the Erasmus Medical Center in Rotterdam, including 607 patients, which is by far the largest data set ever generated in this patient population. One third of the patients in this data set are patients that have been on treatment or are on treatment, and two thirds of patients not on treatment. Unfortunately, the manuscript has not yet been published. It was an abstract out ahead of the European Thyroid Association in September last year, illustrating a three times lower risk of mortality. Bear in mind, the median life expectancy for these patients is 35 years. This was, of course, very, very important for us, and it also served as the basis for the breakthrough designation that Egetis Therapeutics submitted in May this year, and it was granted by the FDA in July.
Last but not least, we have also the Retrack study, US-specific focus study that has been closed as of last week.
On the survival study, because obviously it's a very important piece of the puzzle, that package, and we've only seen an abstract on it, how did you perform the statistical analysis? Did you case match patients based on certain variables like time of diagnosis, age, et c ?
It's a really good question. Yes, we got full access to the data set in February. The key task for our stats team was really to torture the data, looking at all the different covariates, introducing time bias together with case matching, with propensity scoring, etc . Our own analysis of the data and the outcome was verifying what you saw in the abstract, a substantial mortality benefit for sure. This obviously served the basis for the breakthrough designation that was submitted to the FDA. The FDA has reviewed all the data and obviously granted the breakthrough designation and subsequently put some value into the data itself.
You've obviously had several interactions with the FDA in the last couple of months. How instrumental has the survival data been in your interaction with them? How did it impact in the end the granting of the Rolling NDA submission?
It has served a vital part because I think, as I mentioned, the survival data actually formed the basis of the breakthrough designation. The breakthrough designation was granted by the FDA, which opened up for an interaction as a pre-NDA meeting with the agency. We had a very productive pre-NDA meeting with the FDA face to face here in Washington on the 21st of October in a very, I must say, commend the agency collaborative spirit, where we discussed the clinical contents and structure of the upcoming dossier. The FDA acknowledged the relevance of the survival data and subsequently has enabled us to move forward. That has led to an agreement to start a rolling NDA in December this year.
When you started interacting with the FDA, it was first with the Department of Rare Disease. Now you are interacting with the Department of Endocrinology. Did the dynamic change based on this change of interlocutor? Did this play a role, in your opinion, in the NDA submission strategy?
I think it's difficult to comment because obviously data has matured over time. We have new survival data that was, as I mentioned, just recently floated past the agency through the breakthrough designation request. I think what I'm seeing, though, based again on my own participation at the pre-NDA meeting with the agency a couple of weeks ago, is it was in a very appreciated tone, very collaborative spirit. They fully recognized the ultra rarity of the disease and have an appreciation, of course, now being within the chronology division of thyroid hormone signaling disorders. It's difficult to comment how much of a role has that played or not.
Yeah. One outcome of this pre-NDA meeting was the fact that the Retrack study will not be pivotal. The question we often get is, what will happen after the readouts? Will it impact in any shape or form the NDA submission?
No. And yes. The discussion we had with the FDA was that we will be able to submit with currently available data. That then means that we are now closing and actually have closed the Retrack study as of last week with the patients we had enrolled at that point in time. The Retrack study will be seen as additional confirmatory evidence to the already, again, as you see here on the slide, robust data package we have, the survival study and other clinical components from the studies in the upcoming NDA. Data accrued today will, of course, be included in the upcoming submission.
Okay. Got it. Now the plan is, I mean, it's a rolling NDA submission, which will start by year-end and hopefully finish up early 2026. How confident are you that you will eventually get priority review?
Very.
Very?
Simple answer. The rationale behind that is, of course, if you look at all the regulatory features we have, right? We have breakthrough designation. We have fast-track designation, et cetera. It would be surprising, I would say, to me if we did not get the priority review granted.
Which is good to hear. Obviously, being an Orphan drug nation, there's always this question around pricing. Based on historical benchmarks and your analysis, what do you think would be your base case scenarios of pricing for this drug in the US?
Let me be clear. I'm not giving any guidance. We have that as a policy as a company on pricing or pricing assumptions. What I can allude to more is analogs, I would say. If you look at the work we had performed up until spring this year, we had, of course, done a lot of market research and analysis engaging with payers and bringing forward what we believed at that point in time was relevant analogs. Those that have the same characteristics, it's an ultra-Orphan condition with similar prevalence, it's a pediatric patient population, it's chronic treatment, and the same disease severity as ours. You end up from those analogs in a price range between $500,000 and $750,000 per patient. Having said that, though, that was before the survival data had materialized.
Of course, we're redoing our analog review and our market research. It's not unreasonable to think, recognizing that the FDA have recognized some value of the survival data through the breakthrough designation, that one may end up with having either mortality benefit as part of the indication statement or as part of Section 14 in the USPI claims. That then provides an upside to a potential US price.
You also set up, I mean, not only in the US, but also in Europe and other parts of the world, an early access program. How many patients are currently in that program, and how many are in the US? Because obviously, it's an important factor to factor in when you think about market size, patient implication, and diagnosis.
Up until the approval, just to clarify, I think where you're coming from, up until the approval of Emcitate as the first and only approved treatment for MCT8 deficiency, we have had a, I would say, unprecedented managed access program around the world, covering 28 countries and providing drug to 230 patients. The majority of the patients were based in Europe, but also some patients in the US. In the back end of 2023, the US FDA actually requested us to open an Expanded Access Program to facilitate, of course, the access pre-approval to treatment of these patients. What we're seeing today is that we have been driving disease awareness very focused, both in Europe, of course, but also in the US.
When we started to work on the disease in the US with people on the ground, which was in 2022, we were aware of around 30 patients diagnosed in the US. At this point in time, we are aware of 140 patients diagnosed in the US. I think we're making great strides in educating physicians through medical conferences, scientific conferences, advisory boards, and other means to further enhance the identification and diagnosis of patients. Today, 140, and I think that will further accelerate going forward in light of that we are increasing our investments in the US commercial and medical affairs infrastructure.
When your product gets approved in the US, your toolbox of abilities to raise awareness will change as a consequence.
For sure.
What are your strategies going into the approval in order to increase disease awareness, drive up the diagnosis rates? I mean, just be curious to hear your view on this topic.
Yeah. Sure. As I said, really, from a US perspective, from a commercial and medical affairs part of the organization, we focus on two things. Simple as that, It is further drive identification and diagnosis of patients, and then market access, i.e., pricing reimbursement. You wanted to focus on the patient identification and diagnosis. I think it is a number of vehicles. Obviously, the drug is not approved in the US today, so we are only allowed to talk about the disease. We cannot do any promotion, of course. That is the difference between Europe. Now we are actually able to promote and be participating in conferences with Emcitate as the brand name. Here, it is a number of vehicles we are using. The ones that have been most beneficial so far with the limited means we have had investing in the US have been scientific conferences.
Having a booth at a medical or a scientific conference, we have participated in more than eight conferences this year in the US alone. Speaking about the disease, the signs and symptoms, if you have a child with these types of symptoms, think about T3, measure T3, confirm it with a gene panel, and the SLC16A2 gene. I think scientific and medical conferences is one. The second piece is advisory boards. There we have had, and it is two types of advisory boards. It is advisory boards with caregivers to raise the awareness in the community, and then advisory boards with key opinion leaders. Those so far have been the two key vehicles for us to drive disease awareness.
Zooming out of the US and zooming into Europe, where your product is already approved and it's launched in Germany since May. Obviously, in Europe, there's always kind of a struggle to get price and reimbursement settled in a short period of time, which this is why you launched in Germany first, because you have this free pricing system for the first year. How confident are you that the reimbursed price will come in line with your expectations in various countries in Europe?
I think taking a step back, of course, we are incredibly pleased with the European approval on the 12th of February this year. That is a Pan-European approval, which is great. I think the audience fully appreciates that when it comes to pricing and reimbursement, you need to do that on a national level across the 27 member states. Each member state has its different process. It is quite complex, and it is costly, and it takes time. I think on average, it is between one to two years, at least in EU4, for having a formal price in place. In other countries, it could take up to four years. Excuse me. I think when it comes to that, it takes time. I think that is an important aspect.
Obviously, we have launched in Germany with a price point that's the only publicly available price that we will use as a reference going forward. Then it's up to the different pricing and reimbursement processes at the national level. It's very difficult to predict where we're going to end up. I'm sure many of you know that you can have huge price differences between country A and country B in Europe, despite you have the same reference price. I can't give any more color to that. I know where you're coming from, Oskar, but I can't give you any more color than that since we're in the middle of the process.
No, I understand that. We talked a bit before about the managed access program. One advantage of it is that it's quite easy to then switch a patient from the early access program to a commercial setting. Based on your early experience in Germany, how has this transition happened? Have there been any delays? Is it an easy fix?
No, I think that's something we're very pleased with, and we haven't announced our quarter three results yet, so I can't shed too much light on it. Actually, it took us three months to convert, if I use that word, to convert the patients that have been under the umbrella of managed access into commercial packs, which is good. I think that's very positive. It hasn't been any hesitation from any prescribing physicians. The team has been very diligent in identifying new patients in Germany as well. We have identified a handful of patients. I think all in all, the KPIs I can share so far have been very positive. What I would like to call out as well is a potential of alternative pathways in some countries in Europe. As I mentioned, each country has their own pricing reimbursement process.
Recognizing that this is an ultra-Orphan condition with not too many patients out there, in some countries, there is an opportunity to actually not formally apply for a pricing at the national level, but rather have direct engagement either with regions or hospitals or insurance companies and facilitate that through export from Germany with the German price as a reference price. There we have made some good progress in some of the countries like Poland, Austria, and Switzerland.
Good. I'll stop here because we're running a bit out of time, just to see if there's any questions from the audience that you would like to ask Niklas. If not, I still have a few, so that's good. Maybe just the last one as an open question. One other indication that you're contemplating is RTH beta. Is this an indication which is kind of similar to Emcitate? Are there any studies that tend to show that tiratricol does work in this indication? I mean, I guess my question is, what's next for Emcitate?
No, no, no. I think this is an incredibly relevant question, right? With the ambition of building a sustainable rare disease company, the key question, obviously, is what's next subsequent to US approval of Emcitate for the treatment of MCT8 deficiency. We have an interesting indication expansion program that will materialize going forward. This is for a totally different patient population called resistance to thyroid hormone beta, where you have a mutation in the receptor rather than the transporter. It's an Orphan condition. The prevalence is slightly higher than MCT8 deficiency. Here, one is estimating between 1 in 20,000-1 in 40,000, affecting both genders, so slightly more prevalent. We are holding Orphan drug designation for that indication as well. We have been providing drug to a couple of patients under a managed access umbrella there as well.
There was a publication out a couple of weeks ago illustrating some initial clinical benefits with using Emcitate as a treatment for this condition as well. This is something definitely we will consider going forward and further Elaborate on at an appropriate time.
Good. Thank you so much for this fireside chat. It's been a pleasure, and I hope to see some good news on the.