This month webinar series with Nicklas Westerholm, the CEO of Egetis. Thank you so much for your time today.
Well, thank you. I'm delighted to be here.
Yeah, so this is, a really interesting company that I think is flying under the radar, but a couple of people have flagged it to me, so I wanted to spend the time to talk to you and also learn a little bit more about the company. But maybe to start, do you mind just introducing yourself first for us?
Yeah. Happy to. I'm Nick Westerholm, CEO of Egetis Therapeutics out of Stockholm, Sweden. Small biotech company focusing on rare disease development, with the ability to commercialize ourselves in the U.S. and Europe. I've been the CEO of this company for the last seven years. Before I joined this company, I spent close to 20 years within AstraZeneca. Being a chemist by trade, I started off my career in development, late-stage development, where I spent close to 10 years across a number of different therapeutic areas. I then had the privilege to work in global supply chain and manufacturing for two years. Subsequent to that, moved into finance and investor relations, where I had the privilege to work at AstraZeneca's headquarters in London. Subsequent to that, moving to Japan, leading AstraZeneca's business there.
Came back to Sweden in 2015, back into R&D within AstraZeneca, focusing on late-stage development in the cardiovascular metabolic disease area, I joined this company seven years ago.
Well, on a side note, I'll definitely have to reach out to you next time I have some travel plans for recommendations. Starting with your lead program, it's for a rare disease called MCT8 deficiency, also known as Allan-Herndon-Dudley syndrome. Maybe to start, can you help us understand the key role that MCT8 plays as a thyroid hormone transporter? What's its key role in the brain's development as well?
Sure, and I appreciate that, or I guess that most of the audience have never heard about MCT8 deficiency as a condition. Maybe a few words around that, Kristin, before we move into your actual question. MCT8 deficiency is an X-linked disorder, and hence it affects males mainly. We generalize it and call it a male disease, even though we know a handful of female cases. The hallmark of the disease is highly elevated T3 levels, i.e., T3 is the active form of thyroid hormone. MCT8 deficiency really results in dysfunctional thyroid hormone trafficking, as you rightly said, Kristin. In 2003, MCT8, which stands for monocarboxylate transporter number eight, was identified as the first thyroid hormone transporter. Previously, thyroid hormone was incorrectly believed to be able to pass...
To passively, sorry, cross cellular membranes without the need for a specific transporter. However, since then, several additional transporter has been identified with different preferential distribution across different tissues, types, and cells. Coming back to your question on the role of MCT8 deficiency in the brain development, MCT8 is actually the only thyroid hormone transporter in the cells of the blood-brain barrier and neurons. Hence, as I'm sure the audience appreciate, that in order to develop the brain is somewhat, of course, high or somewhat highly dependent on thyroid hormone for normal development. That's the background of the disease and how it actually impacts the lack of neurocognitive development in MCT8-deficient patients.
For maybe another point, and furthermore, is that also the thyroid hormone homeostasis is also dependent on MCT8 as a transporter, which means that it doesn't sense thyroid hormone, so it signals to the thyroid gland to increase production and release, which then means that tissues that are not dependent on transport, other than MCT8, suffers from elevated or too high levels of serum T3, like kidney, heart, muscle, et cetera. Sorry for the long answer to your very simple question, Kristin.
No, it's definitely needed, and I think you're right, most people are probably learning about this for the first time. How can you talk a little bit more about how this specifically triggers excess T3 thyroid hormone, and why are the consequences to this so detrimental?
Yeah, as I mentioned, the thyroid hormone homeostasis is dependent on MCT8 as a transporter to sense T3. Obviously, without sensing it signals to the thyroid gland to increase production and release of T3, which means that the tissues not dependent on MCT8 as a transporter will suffer too high levels of thyroid hormone or active T3, and those are, excuse me, tissues like the heart, the muscle, the kidney, as I mentioned. What this actually translates into is pronounced clinical phenotype of thyrotoxicosis. That then drives increased blood pressure, heart rate. Severe underweight is a clear symptom or phenotype of thyrotoxicosis. 76% of the younger patients suffers from cardiac arrhythmia or PACs, which is very unusual in younger children.
Of course, with having chronic thyrotoxicosis over a longer period of time, this actually leads to a median life expectancy of 35 years of age, where 30% of the patients die in early childhood, mainly driven by sudden cardiac death. Again, a very severe clinical phenotype as such, driven by the excess levels of T3 in the serum.
Okay, how do patients and their caregivers go from suspecting that something is wrong to formally receiving a diagnosis? Are there any telltale symptoms, and is there anything that's specific to MCT8 versus perhaps misdiagnosing it for other neurodevelopmental conditions?
Well, yeah, yes and no, and the MCT8 deficiency is quite interesting from that perspective. Patients actually appear normal at birth. What I mean with that is that normal weight, normal head circumference, normal APGAR. The children are born seemingly normal. However, the first signs and symptoms starts in a couple of month of life, and the first symptom is really failure to thrive, which then builds on to lack of development, so they can't turn their head, they can't sit up independently, et cetera. This, of course, then puts a bit of a challenge in diagnosing the patients, and the diagnostic journey is quite cumbersome today since the disease awareness is low.
Since we started to work with the disease back in 2020, the median time to diagnosis was 20 month plus, and now it's down to 10. I think we're making progress there. The whole community is making progress there. Again, since these children are born seemingly normal, it's not evident how and what to diagnose them with.
That's great that it's dropped that much in such a short time, and great strides to be making there. When we think about treatment goals that patients and their caregivers are looking for, what's top of mind for folks?
Well, I think it comes back to the two different clinical phenotypes. As I mentioned, one of the clinical phenotypes is chronic thyrotoxicosis, driven by excess levels of T3 in the peripheral system, and then it's lack of cognitive development due to more or less no thyroid hormone stimulating across the blood-brain barrier into the cells and the neurons. I think it's two components to it. One is, of course, looking at the median life expectancy. That is an important factor. Of course, as I mentioned, when I speak to mothers, they are, of course, having a full-time job to, as an example, 24-hour care, looking after these children, of course, also very afraid of sudden cardiac death or premature death for their children, right?
Reducing the stress on the cardiovascular system by normalizing T3 levels, that translates into reduced risk of mortality, is an important factor, for sure. The other aspect which comes back to the lack of neurocognitive development is, of course, from a parent's perspective, they want their children, of course, to be more receptive to communication. One of the biggest issues the parents are facing is actually that the children doesn't sleep through the night, so they wake up every second or third hour. Again, sleep patterns are very important, and then the agitation. Those are the aspects we're looking at when it comes to clinical relevance in this disease.
How many patients are known to have a diagnosis in the U.S. and Europe today, and how do we know this? Is it through claims data? Maybe what's kind of the suspected number of patients that have a diagnosis that are out there?
What we know, when I say we, it's Egetis, we actually know of slightly more than 140 patients diagnosed with a confirmed mutation in the U.S. alone, 140. In Europe, it's slightly more than 200 patients today. What that tells you, 'cause I got to come to incidence levels, is that as for many rare diseases, this condition is severely underdiagnosed or misdiagnosed. Come back to the incidence level. Quite a few, there are quite a few papers out there in the literature coming back to an incidence level of one in 70,000 males. One in 70,000 males are born with this condition, which then translates into roughly one in 140,000 in the general population.
Of course, you need to account today, without treatment, for a median life expectancy of 35 years of age. If you do the math, you'll end up at around 1,000 to 1,500 patients, theoretically, in the U.S., and slightly more in Europe. I think, again, comes back to the level of underdiagnosing or misdiagnosis is very much there. Disease awareness, as for, again, for many rare diseases, has been incredibly low. Just to calibrate that for you, again, when we started as a company to work with this disease back in 2020, and without any people on the ground in the U.S., we knew about 28 patients diagnosed. With very few people, actually, we had to have had three people employed in the U.S. up until October last year, we found 140 patients.
I think the patients are there, but unfortunately underdiagnosed and somewhat misdiagnosed. We found two patients in Texas, actually, during the autumn last year, who was misdiagnosed with cerebral palsy, as an example.
It does sound like things are at least moving in the right direction again. Now that we have a good understanding about this disease background, let's turn to some of the work that you're doing. Again, we know the issue here is these MCT8 cells are deficient, thus, the thyroid hormone signaling becomes problematic. How does your lead asset, Emcitate, work to bypass this?
Our lead asset then with an active substance called tiratricol, brand name in Europe, only region where the drug is approved, just to be very clear as of now, is Emcitate. Tiratricol actually is a small molecule. It's a T3 agonist with a very similar structure and affinity as active T3. Unlike T3, though, tiratricol can actually cross cellular membranes without a functioning MCT8 transporter, and by doing that, it will actually restore the thyroid hormone signaling and the levels in the respective cells, regardless of the cell being dependent or not on MCT8 as a transporter. It's a very, from a mechanistic perspective, sorry, it's from a mechanism action perspective, it's very mechanic in how the drug works, but it actually restores the signaling pattern.
Okay, how can we measure in cells that the thyroid hormone signaling becomes active again, and do you have a general understanding of how much is required to aim in brain development?
This is interesting, and it's, of course, a very highly educated scientific question. To take a couple of steps back, there are very developed transgenic mouse model, where you're actually able to measure tiratricol and how it passes the blood-brain barrier, which it does. It's actually published some in the literature, in a paper called Chen et al., from 2021, there it illustrates that when you dose mice, this is mice, of course, at day zero, you can fully resolve the clinical phenotypes, and you can't distinguish them with wild-type mice. However, measuring this in humans today is unfortunately not possible.
Considering where we are, and I think this is important, considering where we are, this is more of a translation and science question. What we see, of course, is in a number of studies, that we are able to lower endogenous T3 into the normal range. We are far beyond this translational science model from that perspective, and we generate then clinical, strong clinical evidence in organs, where we're able to, by normalizing the endogenous T3 levels, improve organs like the heart, muscles, kidney, et cetera, by reduced heart rate, blood pressure, improve weight gain for these patients. That ultimately translates into survival benefit, and that's the strongest data set we have. It's actually survival data, where we illustrate that treated patients with tiratricol or Emcitate has versus untreated patients, has a four times lower risk of mortality.
Okay, Emcitate has been approved in Europe for one year now. What data were really the basis of the package? Anything else beyond what you just told us? Where are you today in terms of country-by-country launching and the whole reimbursement process?
This is something, of course, I'm sure you appreciate, Kristin, that we're very pleased with. Emcitate was approved as the first and only treatment in the European Union on the 12th of February last year. It was based on a very much smaller data package, actually, compared to what we have now submitted to the FDA, and I'm sure we'll come back to the FDA and the interactions with the FDA. It really consisted of data from only two studies. One was a single-arm study, 12-month, focusing on normalization of T3 levels, which translated into clinical benefits in organs, like I mentioned, heart, kidney, muscle, et cetera, 46 patients. We had an additional data set that formed a part of the EMA submission was- which was what we call the EMC Cohort Study, which was a different, a slightly different patient cohort, 67 patients, that was now treated up to six years.
Here, we saw exactly the same thing as we saw in the first clinical trial, Trial One, as I mentioned earlier, where we normalized very quickly, within two to three months, T3 levels that translated into clinical benefits across the organs I was referring to, and it was also durable up to six years. That was the clinical data package from efficacy perspective that was submitted to the EMA, and subsequently, got approved last year.
You had a question on how does the launch progress, and I think I, and I hope the audience are very familiar with the somewhat complex and lengthy pricing and reimbursement processes in Europe. 26 member states that has 26 very different pricing and reimbursement processes, both on expectations on the dossier, but also length of time. We launched in the first country, Germany, on the May 1st and Germany is the odd one out in Europe, where you can set a price, keep that price during the pricing and reimbursement process and the price negotiations that last for 12 months. We established a price in Germany on the May 1st , and we subsequently launched there.
The price point is public. I can share that to the audience as well. Annual treatment cost per patient is slightly north of EUR 200,000 per patient per annum during the pricing and reimbursement process. There, we have managed to convert all the patients that we have previously had on the WEP in quite a generous managed access program. We also identified over 20 new patients, actually, during last year, where a few of them are already converted to or being initiated on treatment. When it comes to the other countries, we have initiated pricing and reimbursement processes in France. We are on the verge of initiating it in Italy and Spain as well. We do it on a country-by-country basis.
We're focusing on initially on EU four markets, and then subsequent to that, we're going to go for the rest of Europe. However, with a caveat, Kristin, that there are some countries like Austria, Poland, and Switzerland, where we have been successful to identify and realize what we call alternative funding pathways, which means that you, s ince this is an ultra-orphan condition, if you are in that space, you have an opportunity to generate revenue, so, through so-called name Patient Sales Mechanisms, where it's either reimbursed through the region or a local hospital or an insurance company, and then you export it from Germany to that price. There, we've been successful already last year to realize that in Austria, Switzerland, and Poland. I hope that gave you a bit of a flavor on the somewhat lengthy launch process that actually takes place in Europe.
The good news is we, think about the U.S., it's only one area you're dealing with.
Exactly.
Let's talk about what's been going on there. You recently completed your rolling NDA. What's been the latest dialogue you could share with us around discussions with the agency and your confidence in the filing strategy here?
I think we are starting off with the last part of the questions. We are very confident in the filing strategy, there are a number of reasons behind that. As I'm sure both you and the audience appreciate that during a drug development journey, you have multiple interactions with the agency on the development program. However, I will call out two of those interactions that took place last year, which was very important for us in order to move forward to the NDA and being able to complete the submission in January this year. The first interaction I would like to call out was the Breakthrough designation that was granted by the FDA on the July 14th last year.
This is something we are in particular, very proud of, the Breakthrough Designation was granted by our own analysis, so Egetis analysis of the survival data that has been generated, which, as I said before, demonstrates significant and substantial improvements in survival in tiratricol treated versus untreated patients. We're particularly proud with being granted a Breakthrough Designation towards the end of phase III. As I'm sure you appreciate, that is quite unusual. That really opened up quite a few doors when it comes to interaction with the agency. On the back of that, the FDA actually granted us a pre-NDA meeting that took place in October, where, in my humble opinion, was very successful.
Where the FDA really, of course, we discussed a lot of things, but we focused the discussion on the clinical content of the upcoming submission. One, they confirmed that the upcoming NDA could be based or will be based, or is now based on currently available data. That was something that was really important to us. We have, without going through all the studies, six different patient sources of clinical data that we have generated, including this survival study I was referring to. That was a very important point, a very constructive dialogue, where they agreed to for us to submit with currently available data.
Why that is important is that we, at that point in time, had a phase III, deemed phase III, before the pre-NDA meeting, a phase III study called the ReTRIACt Study, up and running in the U.S. In light of the positive dialogues we had with the agency at the pre-NDA meeting. We agreed with the FDA that the ReTRIACt study will actually complement the existing data that I have been referring to, i.e., the survival data and other clinical components. Therefore, we actually closed down prematurely the ReTRIACt study in November last year, and the data accrued today was included in the, or at that point in time, sorry to say, was included in the NDA more as additional confirmatory evidence rather than being pivotal. That was the second very important aspect of the pre-NDA meeting.
Last but not least, they also granted us to submit a rolling NDA that we started in December last year with the non-clinical and CMC sections, and we completed the NDA with the clinical section now in January this year. Sorry, a long answer to your fairly simple question, Kristin, but I think it's important that the audience get the full context of the really good progress we had in the U.S. last year.
Well, it was arguably one of the most important questions I had for you today, so fair enough for the response. Assuming you do get good news, and you get an approval later this year, are you planning to commercialize this yourselves? How big of a sales force is required for this rare disease?
Yeah, no, and as I said before, you know, we're very confident in filing, especially based on the outcome of the pre-NDA meeting, where we have aligned expectations both on content and structure of the NDA. We are confident in the filing strategy for sure. When it comes to the corporate strategy around commercialization, as I mentioned in the beginning, that we will commercialize ourselves in Europe and U.S., and then we will be commercializing in the rest of the world through partnership. When it comes to the U.S. then, we are now accelerating based on the good progress on the regulatory side, with the NDA submission now completed. We are now accelerating our investments in a number of fronts, of course, the infrastructure, the commercial and medical affairs infrastructure.
Today, we have eight employees in the U.S., and we will be around 25 at the point of launch. In addition to, of course, strengthening the capability as well as the capacity, we're also driving quite a lot of initiatives in the disease awareness space, the market access space, and also establishing the 3PL specialty pharma patient support setup.
What do you ultimately imagine the peak sales opportunity could look like for this worldwide, and are there any regions to think about ex U.S. and Europe?
Well, I think as for many companies, and especially in the rare disease space, the U.S. is by far our most important market. Unfortunately, I won't be able to answer your question with a straight answer, as we don't disclose peak year sales estimate from a corporate perspective. Just to triangulate it for you, focusing on Europe and U.S., as I said, theoretically, there is around 1,000-1,500 patients in the U.S. Today, we know 140. In Europe, theoretically, it's around slightly north of that, so between 1,500 and 2,000 patients. Of course, one need to be realistic. Will we ever find all of these patients? For sure not. The reasonable assumption there could be around 50% of the patients being identified at the peak.
That, in combination, and now focusing on the U.S., where I've done some thorough reviews from an analog perspective, where we see analogues recently launched, same disease characteristics, same type of clinical benefits and label, we assume a price point of then one can assume a price point of somewhere in the region between $700,000 to slightly north of $1 million per patient per annum. I think the opportunity is there for sure. It's a large opportunity, and based on what I just referred to, we believe we'll be profitable within 12 months after the launch in the U.S.
Okay. As an under-the-radar company not based in the U.S., are there any other rare disease companies or drug launches that investors should look at as comps?
Well, it's always difficult, especially in the ultra-rare disease space, to compare apples with apples, right? The ones, I'm just thinking off the top of my head, that maybe resonates to a certain extent, is probably VYKAT XR for treatment of Prader-Willi syndrome by Soleno. Mirum is another good example, of LIVMARLI in the liver space, also a rare disease product. As I said, based on some of the assumptions I gave you, coming back to the Egetis perspective, is that we'll be profitable within 12 months after launch. That's based on, of course, one, the price point is higher compared to Europe. The access, the pricing reimbursement processes are a lot swifter. It's between zero and six months, depending on state-by-state level.
I think the uptake in the U.S. will be more prominent than Europe, driven by processes.
Okay. Yeah, fair enough. I know it's there's no perfect comparisons here.
Mm-hmm.
Why should U.S. investors and our broad audience today take a look at Egetis today? What is the market missing based on your current valuation?
Well, no, I think that that's a reasonable question for sure, Kristin, I tend not to comment on share price. I'll stay away from that because I don't think it's appropriate. What I will say is that what you called out, that we have been flying under the radar. Egetis is a fairly newly created company. It came about only in back end of 2020. Again, in the life science world, it's a fairly newly created company. Of course, we made huge strides from the formation of the company to now actually have a product in the market in only five years. What I would refer to is that despite flying under the radar, we still see some quite a lot of interest from U.S. specialist investors.
Our largest shareholder is Frazier Life Sciences, out of Menlo Park. We also have Woodline, Petrichor, Invus on our share register, that has actually materialized only over the last two and a half years. Being a publicly listed Swedish company originating out of Sweden, our shareholder base back only four years ago, was solely dominant by either Swedish institutional investors or private investors. We've seen a shift, and we've seen that even though we're flying under the radar, maybe not as much as before, there are some investors that really have recognized the opportunity here.
Okay, great answer. Beyond a successful launch for Emcitate, what are some of the mid to longer term goals of the company? If you're granted a potential PRV sale, will you use the funds to further fuel the rare disease R&D engine?
I probably should have mentioned this at the beginning. Egetis, as a company, and me as a CEO, have a very clear mandate, that is to build a sustainable rare disease company. Emcitate is not the only asset we need to work on other dimensions, on making this company sustainable, for sure. As you mentioned, rightly so, Kristin, that we have a rare pediatric disease designation, which makes us eligible for a priority review voucher at the point of approval. I'm sure you, amongst others, are following the PRV market closely and realize that there's been a couple of PRVs sold this year already. Jazz is one, around $200 million. Fortress Bio, most recently, I think it was $205 million.
Of course, that is a very, very important piece of our future investment thesis in building. Re- monetize that and realize that value in building a sustainable rare disease company. More shortly, we have a very, very exciting opportunity with Emcitate as a next indication, so an indication expansion into a totally different patient population called resistance to thyroid hormone beta. Also orphan condition, where we have orphan drug designation. No treatment exists in that condition either today, there's been quite a lot of work by academia over the last couple of years, illustrating the characteristics of the disease. We reduced also in this condition, median life expectancy. Actually, in November this year, there was a scientific article published describing actually significant clinical benefits of treatment with Emcitate in this patient population.
We have a fairly generous managed access program that generates data for us in RTHβ as well. Close to 50 patients are being treated with Emcitate for RTHβ. That is where we see most definitely the next short-term opportunity, where we are now in the process of considering a clinical development plan, of course, and one pivotal study for Emcitate, the treatment of RTHβ. Needs to be aligned with the FDA and EMA, but that is a very imminent, I would say, short-term opportunity.
Okay, Nicklas, would like to turn the floor to you. Anything that I should have asked you and I didn't, or any other key takeaways you'd like our audience to have today?
Well, I think it's more of a summary. I think you picked up most of the aspects, Kristin, but I think when I reflect back at the year in passing, it's been featured by a very strong execution with. A number of very important milestones, not just for the company, but also for the patient. We had the European approval on the February 12th and subsequent launch in Germany. We're rolling it out broader in Germany, through the pricing reimbursement processes, with the caveat that takes time in Europe. We got granted a Breakthrough Designation by the FDA in phase III based on mortality data, that is very strong.
I think that's the Holy Grail when it comes to clinical benefits, especially in this disease, to show mortality data. That translated into a very, very positive and constructive pre-NDA meeting with the agency, that subsequently led us to the initiation of the rolling NDA in December, which was completed in January. Then, of course, we now have the agency reviewing the file for 60 days, so we expect a response back at some point towards the back end of March, i.e., acceptance of file. Obviously, we have the regulatory features of both Breakthrough designation and Fast Track designation. We have requested a priority review, which then leads us to a potential PDUFA date towards the back end of quarter three, and a subsequent launch subject to approval in quarter four.
Reflecting back on 2025, that was historical from a company perspective with the milestones I'm referring to, but it will be equally exciting this year with a potential U.S. approval and launch in the not-too-distant future.
Well, we're wishing you all the best, Nicklas. Thank you so much for your time today and for telling us more about the story. Thanks to our audience for tuning in, and hope everybody has a good day. Thank you.
Thank you.