Right. Thank you all for being here. I'm James Machin from the Morgan Stanley team. Delighted to have Nicklas from Egetis Therapeutics here today. We'll walk through a few of the ins and outs around the business over the next 30 minutes. I think starting point, maybe for the benefit of those that haven't come across the company before, maybe a short intro to yourself and Egetis and the difference you're looking to make for patients.
Thank you very much, James, and a privilege to be here. For those I haven't met before, my name is Nicklas Westerholm. I'm the CEO of Egetis Therapeutics and have been so since the formation of the company. Short background, chemist by trade. Started off my career in AstraZeneca, where I spent close to 20 years of my professional career across a number of different business areas, mainly internationally, but late-stage development for 10 years, global supply chain and manufacturing for a couple of years. Privileged to work in Finance and Investor Relations as well at AstraZeneca's headquarters in London. Responsible for AstraZeneca's business in Japan, and the last role I had within AZ was late-stage development responsible globally in the cardiovascular metabolic disease area.
Shortly about the company, rightly so, James, as you mentioned, Egetis Therapeutics is probably a company, especially here in the U.S., that's been somewhat flying under the radar, driven by a number of things. One, it's actually recently created, as I mentioned before. The company came about only back- end of 2020, so we've been in our current shape and form for close to six years. The purpose of the company has been very clear from the outset. It's focusing on rare diseases only. Late-stage development is our sweet spot. With the ambition and ability to commercialize ourselves in Europe and U.S. and provide broader access in the rest of the world through partnerships. So that's Egetis in a nutshell.
Okay, great. Let's maybe turn to the lead asset within the business. Clearly some news flow coming over the coming weeks, which we'll get to. The asset's for an indication called MCT8 deficiency. Let's start there. So what's the disease? What's the unmet need, and how does this present within patients?
Sure. Again, for the audience, I appreciate that MCT8 deficiency for many is unheard of, and that's not a surprise. It's an ultra-orphan condition where the gene was only discovered back in 2004, so it's actually relatively within the context of life science, a new disease. MCT8 deficiency is a mutation in a thyroid hormone transporter. This is a thyroid hormone signaling disorder. MCT8 actually stands for monocarboxylate transporter number eight. It's an X-linked disorder, which means that it affects mainly males. Incidence levels are estimated to be around 1 in 70,000. It's a really severe and debilitating condition, and the manifestations translates into two severe clinical phenotypes in actually one patient. In different compartments in the body have either too high or too low thyroid hormone levels. In the peripheral system, you have too high thyroid hormone levels, i.e., thyrotoxicosis.
That translates into severe stress on the cardiac system. In the central nervous system, you get more or less null or very limiting exposure to the thyroid hormone, which leads to lack of neurocognitive development. You have a very intriguing patient phenotype divided into two specific phenotypes in one patient. As I mentioned before, this is an ultra-orphan condition with 1 in 70,000 males being affected by this. Up until now, no treatment has ever been approved for this condition. Our product, Emcitate, or the active substance, tiratricol, was the first and only approved treatment in the European Union last year on February 12. Here in the U.S., we are of course very excited about our upcoming PDUFA date on September 28 this year, so only 12 days away.
Indeed. I guess therapy has Priority Review, has Breakthrough, has Fast Track, has Orphan Designation, so clearly well supported by the agencies to date. Focus will be on the PDUFA, the approval over the coming weeks. Can you provide a short overview of the data that supported that approval and the work that you've done to date to get to this point?
Yes, and to put this into context as well, the severe thyrotoxicosis for these patients leads to a median life expectancy of 35 years, as well as 30% of the patients die in early childhood. I think that's important to put it in context with the clinical data we have generated. We have, in my humble opinion, an unusually large and robust set of data generated over a number of years being an ultra-orphan condition. We have actually three prospective clinical trials, and we also have three real-world evidence studies that have formed a part of the NDA, the New Drug Application here in the U.S. What we have seen across the board, the hallmark of this disease is elevated T3 levels.
What we have seen across the board, the prospective as well as the real-world evidence studies, has been our ability to normalize T3 levels in the peripheral system. That then translates into clinical benefits on the cardiovascular system, such as blood pressure, heart rate, et cetera. Why is that important? I will mention median life expectancy of 35 years. The main cause of mortality in this population is cardiovascularly driven by sudden cardiac death. So we see substantial improvement in all these clinical parameters I referred to. Most lately, even though it is not fully published, it has been an abstract out in 2024, which we could refer to as the survival study, which is by far the largest patient cohort ever gathered information around for this condition.
It included 612 patients in total, where it illustrates also the ability for a substantial survival benefit in patients treated with our drug versus untreated patients. So I think all in all, we have a very robust clinical data package. It has been recognized by the agency from a Breakthrough Therapy designation perspective, Fast Track Priority Review, et cetera. We, of course, very much, again, looking forward to the PDUFA date in the coming weeks.
Indeed. You mentioned no other therapeutic options. Is there anything else emerging for the indication? How do you think Emcitate will really differentiate and make that difference for patients?
Yeah. No, and I think this is an important point. So today, there are no other active drugs, sponsored drugs, in clinical development. So I think that is important to recognize. Nothing is out there in clinical development by a sponsor. We know there are a few investigator-initiated studies locally in certain countries, but nothing in the context of potential competition in the mid- to long-term distance is something we see in the future. So I think from a caregiver, from a patient perspective, obviously just bringing a treatment to provide some hope for this devastated patients, but also the families and the caregivers, is very much appreciated.
We have had, up until the approval in the European Union, but also now here in the U.S., have had a very comprehensive managed access program, or EAP program, with several hundreds of patients treated globally, worldwide, with our drug even before approval. I think all in all, it's good. There's very little competition out there, and there's no other treatment available, with the exception of course, in general, if you have some symptomatic treatment for if you have a seizure, you get an antiepileptic treatment, et cetera.
Great. Makes sense. We'll go through, hopefully, the approval. Focus will turn then to the commercial launch. Can you frame a little bit around how prepared you are for that? How quickly can we expect the product being brought to patients, and what's the footprint that you've put in place in the U.S. so far?
Sure. I think with, of course, the progress on the regulatory front in the U.S., being a small Swedish biotech company, not having unlimited means, we have been very careful until we have clarity on the regulatory milestones and potential PDUFA date. Obviously, with the visibility we gained towards the back- end of last year, based on a very successful pre-NDA meeting, we started to invest exponentially, I would say, in the U.S. commercial and medical affairs infrastructure. Today we have 23 employees in place in the United States alone, only focusing on commercial and medical affairs. Key focus is really in two buckets.
One is the medical affairs side of things, together with the key account managers, to make sure that we launch readiness, educate the physicians, make sure that we have patient support programs in place to ensure a smooth transition from EAP to commercial product. The other bucket, of course, is access and pricing. Those are the key areas we've been investing in. Today, as an example, we have four key account managers up and running in the different territories. We have four regional medical affairs directors in their respective territories to be out and about and really preparing for launch. I think in essence, last week or two weeks ago in Boston, we had with the whole team a dry run launch readiness meeting where we went through everything from patient flow, diagnostic journey, product flow, et cetera. In my humble opinion, we're in good shape.
Okay, great. Clearly field force is ready. Clearly you have the patients that are on the EAP already. Clearly also a number of other patients that you are aware of. Any commentary on how we can expect that uptake over time and also any learnings from Europe as to how that has translated to more patients starting to be identified post-launch?
No, thank you, James, and that is a really good and important question. I am sure everybody appreciates that short- term, and when I refer to short- term is zero to six months after launch. The key focus there would be to have the 60 patients, 60 patients we today have on an EAP program to facilitate a smooth transition and continuity of care to commercial product. These 60 patients are spread across 17 EAP sites, so obviously it is a decent site to be managed with a small team like we have. So the key focus short- term is really to facilitate that transition to commercial product with the caveat, of course, that the product got approved. That, of course, then will realize short-term revenues.
The expectation, without giving any guidance, if you look at other companies out there that has gone through the same journey in the ultra rare disease space, one would envisage that within roughly six months, all these patients, the 60 patients, have been transitioned over to commercial products. That to a side, we have another 50 + patients also identified in the United States, but are treatment naive today, so not on the EAP program. That of course also have priority to now cater, go broader than the 17 EAP sites to cater to their needs as well, and ensure that they initiate treatment once the product is approved. Then last but not least, is to further work on, as we have done in Europe, driving further disease awareness and facilitate further patient identification.
Because coming back to the incidence numbers, one in 70,000 males are born with this condition. You need to account for median life expectancy of 35 years. That gives you ballpark theoretical figure on the number of patients in the U.S. That amounts to roughly 1,000 patients. Then it's all about finding these patients.
Okay, great. Final part on the U.S. I believe, and correct me if I'm wrong, eligible for a Rare Pediatric Disease Designation, sorry. How does that play into your plans and clearly there's been some good value in those recently given the recent sale transactions that we've seen.
For sure. That's a very important part of our future financing plans. Of course, we just recently, a couple of weeks ago, reported our quarter two results, and we reported roughly $40 million cash at hand. Of course, then with us being granted a Rare Pediatric Disease Designation, that makes us eligible for a priority review voucher. It's not unreasonable, James, as you said, that a company like ours will most likely monetize that as soon as possible. Worthwhile noting is that 50% of the net proceeds of a monetization of a priority review voucher for our company goes to the founders of the company, so 50% to Egetis as an entity.
But as you said, if you have sales values of, let's say $180 million or $200 million, half of that to us, that will fund the reminder of the launch with even further investments during 2027 in the organization in the U.S., and takes us to profitability.
Okay, great. Let's transition from U.S. to outside the U.S. You cited the German launch previously. Any updates on where you stand now with that launch and what really should we be focused on as we think about other markets across Europe over the coming months?
Sure. Here we need to be very clear because we have to navigate this carefully, of course, when it comes to U.S. and Europe and launch timelines in relation to pricing without saying too much. The only country today we have launched and established a price in the whole of the European Union is Germany. There we launched 1st of May last year. We saw the initial conversion of patients in Germany as a country being on the managed access program there converting very swiftly into commercial product. Since then, we have managed to identify further patients that has been enrolled to treatment.
What is a side note to this, which is important, and in my humble opinion, most likely transferable to the U.S. market as well, obviously recognizing that the U.S. is and will be our most important market in the short- to long- term perspective, is that as for many other rare disease, the ultra-rare diseases, when you have a product available, the number of patients being identified tends to increase drastically. Because then you're not just having a disease, but you also have a treatment option. Without providing exact numbers, the numbers of patients being identified in Germany at launch, and now 15 months into the launch, has actually doubled. This is an increase by 100%. Hopefully, that's transferable into the U.S. as well. But coming back to your point, excuse me.
Germany is the only country we have launched in, and that's where we generate the majority of our revenue today. We have submitted our pricing and reimbursement dossier in Spain as well, and we'll be submitting in Italy and France in the not too distant future. On top of that, we are also carefully navigating other countries in Europe. Most likely, we will never seek national pricing and reimbursement in all European countries. There are countries where you can utilize the German reference price and navigate and generate revenue via a so-called named patient sales route that is already been established with the German price in countries like Switzerland, Austria, Poland, et cetera. All in all, I think we're making good inroads in the European market, but deliberately somewhat phased based on what I just mentioned.
On top of that then, to provide broader access, we have also signed partnerships because access is a very important perspective in our company vision. We have signed partnerships with Er-Kim for Central, Eastern Europe and Turkey. Then again, this is through named patient sales. We also recognize already now revenues from Turkey through that partnership. We have signed a partnership for the Gulf region. Same philosophy there, named patient sales. No regulatory approval needed or a pricing and reimbursement dossier needed, and also starting to recognize revenue there. Most lately, we signed a supply agreement for Australia and New Zealand as well, only a couple of months ago.
Last but not least, which is the one that I think something is somewhat flying under the radar, is the development and commercialization agreement we have in place in Japan with the Japanese specialty pharma company called Fujimoto . There we are progressing towards a submission of the MAA, so a Marketing Authorisation Application, the dossier, in early next year. Japan is important for us because there more than 60 patients has already been identified, all of them treatment-naïve, because it's no such thing as a managed access program that exists there. That's also an opportunity we're very much looking forward to.
Okay, great. How do you think about then further regions? Will there then be partnerships in other regions and countries globally?
Yeah, most likely. As I mentioned, of course, we're going to build this out stage- by- stage basis. Again, we're still a very small organization. Egetis Therapeutics only employs 60 people today. What we have achieved is something I'm really proud of with a very limited footprint. I think, again, as I mentioned, we've done Turkey, we've done Australia, New Zealand, the Gulf region, Japan. Of course, we have further prospects that we're working with from a partnership perspective more than anything else.
Okay, great. Let's turn to the longer-term potential. You obviously have orphan exclusivity. The other piece, you had your first U.S. composition patent announced of being granted over the summer. Can you characterize the exclusivity runway for the product?
Sure. I will characterize it in different levels because I.
Yeah.
Or layers is probably the right expression I am, excuse me, looking for. Of course, as a base, we have orphan drug exclusivity that provides exclusivity in 10 years in Europe and seven years in the U.S., respectively. On top of that, as you alluded to, James, we had our first patent granted by the U.S. Patent and Trademark Office now during spring. It is a patent which includes a number of different claims. So the composition of the tablet, including excipients. It is the dosing regime, but more importantly, also method of use, so treatment of MCT8 deficiency. This patent is Orange Book listable and brings exclusivity out to 2045. Of course, as I am sure you appreciate, we have other aspects to consider from an IP strategy as well moving forward.
Okay, makes sense. Next step beyond MCT8. You have talked around RTHβ as a next indication. Given the expected life you were just talking about, there are clearly other areas you can take it into. RTHβ, similar question to earlier, what is the indication? Can you frame it, maybe compare and contrast the prevalence a bit versus MCT8 deficiency, and how you see the potential there?
Sure. Coming back to your point, RTHβ, resistance to thyroid hormone beta. Here we are referring to a mutation in the receptor rather than a transporter. This is a totally different and distinct patient population. The prevalence is somewhat broader. It is still rare, but it is not ultra-rare. It is somewhat broader. Its prevalence is estimated to be in the region of 1 in 20,000 to 1 in 40,000 affected by this condition. Both genders, though, in contrast to MCT8 deficiency, which is an X-linked disorder. What we see here is that over the last couple of years, there has been several natural history publications out there triangulating this back to also here reduced life expectancy, driven by the cardiovascular factors in this disease as well, i.e., higher increase of heart failure, MACE, overall morbidity and mortality are substantially higher.
What we see is that this disease is a very heterogeneous disease. You also have actually here patients that are asymptomatic. The symptoms in early life is more ADHD type of symptoms. When it materializes over a number of years, you are actually somewhat referring back to MCT8 deficiency in the peripheral thyrotoxicosis in the system. This disease, in contrast to MCT8 deficiency, that is the hallmark with high elevated T3 levels, is high elevated T4 levels or free T4 levels. That then subsequently over a period of time drive longer-term thyrotoxicosis. Here we are really intrigued by this, we have orphan drug designation granted as well. In 2024, the European Thyroid Association issued guidelines, this was before the approval of Emcitate, for MCT8 deficiency in Europe.
In those guidelines, it stipulates that both patients with MCT8 deficiency as patients with RTHβ is recommended to be treated with tiratricol or our drug. That's actually quite intriguing before approved in a certain indication. On top of that, we have more than 50 patients being treated with our drug with a condition of RTHβ around Europe. There was a publication out in November last year illustrating treatment benefits in a cohort of eight patients after this, where we saw the ability here to normalize free T4 levels in all patients that translated into improved benefits and some of the clinical parameters in the cardiovascular space. This is an opportunity we're very excited about. We see that without giving any guidance from a commercial standpoint, on par with the one in MCT8 deficiency.
We are at the final stages of concluding a clinical development plan, which involves one pivotal clinical study, that we will, of course, interact with both EMA and FDA towards the back end of this year or next year to align on endpoint, et cetera, with ambition to start that study next year.
Okay, great. Any sense of how long that could take? Any sense of when you could have that towards market?
Well, it's a bit premature. We will update the market later on this year. This is an orphan condition, so one would assume around 60 patients, one-year study, placebo controlled, most likely.
Okay, great. Let's pull it back big picture again, and you mentioned at the beginning around ambition of a rare disease platform company. Beyond MCT8 and the various indications, can you maybe characterize anything else either within the business that you have aspirations to bring forward? Or equally, how do you think about that opportunity outside of the business?
Yeah.
And longer-term ambitions, clearly once you get through the approval of Emcitate.
No, this is also a very important question, and it comes back to my remit as a CEO, I would guess, which is to build a sustainable rare disease company. We have seen that journey being stepwise. The first step and the foundation of that journey is, of course, Emcitate approved both in the U.S. and the European Union for MCT8 deficiency as a stepping stone. The second part of that journey is the indication expansion into RTHβ, as we just discussed. The next stepping stone in that is, of course, in licensing or potentially acquiring additional assets in the rare disease space to take that further through our sweet spot, late-stage development, and then commercialization in Europe and U.S.
Okay, great. I guess last couple of minutes, let's maybe bring it together of focus on the 28th of September, but really remind us all of what are those catalysts that you have over the next 12 months, and what are those expectations?
Yeah, sure. For those who are not familiar with the story, the NDA was submitted to FDA in January this year. It was accepted by the agency end of March with a priority review, so the six-month stipulated timeline. We have a PDUFA date on the 28th of September, 12 days away. I can't comment on an ongoing NDA review and the granularity, but it's reasonable to assume, considering where we're at in time, that we have concluded a mid-cycle review meeting, we have concluded a late-cycle review meeting. As many of you know, 30 days ahead of the PDUFA date, label negotiations have started. All in all, my reflection of the process has been a very collaborative process with the agency, and we look forward to the PDUFA date on the 28th.
Post that, of course, we're looking forward to the actual launch of the product. As many appreciate that the product will be available between 8 to 12 weeks after the PDUFA date, and that's driven by secondary packaging, printing of the USPI, et cetera. I think the short-term triggers obviously are the PDUFA date, no doubt about that. Commercial product available in the U.S. market, and then focus on the transition for patients and conversion for patients from EAP to commercial product.
Great. Okay. I think with that, I think rather fulsome coverage and an exciting couple of weeks. We look forward to hopefully seeing the approval.
Thank you, James.
Brilliant. Thank you very much.
Pleasure being here. Thank you.