SANTHERA PHARMACEUTICALS HOLDING AG (CHF.IMC) — Analyst Meeting

0:01 Good afternoon, and welcome to the SANTHERA full year results presentation. Throughout this recorded meeting, analysts will be in listen only mode. Questions are encouraged, they can be submitted at any time by the q and a tab situated in the right corner of your screen. Just simply type in your questions and press send. The company may not be in a position to answer every question received in the meeting itself. However, the company can view all the questions submitted today and publish responses where it's appropriate to do so. I'd now like to hand you over to Dario Oakland, CEO. Good afternoon to you, sir.

0:27 Thank you, Alessandro. Welcome to the full year results of the year ending 12/31/2024. Given giving the presentation today will be myself, Daria Eklund. I'm the CEO, as well as our CFO, Katherine Eastead. Our chief medical officer, doctor Shabir Hasham, will also be joining us for the q and a at the end. I'd encourage you to type in your questions, as just mentioned, the q and a box as we go along, so we'll try to answer those questions at the end of this, this call. Should we not be able to answer all those questions that you may have, we will definitely get back to you later after the call. I'd like you to draw your attention to the disclaimer. This is that we will be making forward looking statements.

1:13 I invite you to please feel free to read this at your leisure. And with that, I'd like to switch our focus now to the overview of SANTHERA PHARMACEUTICALS in general. While we appreciate that this is a results call, we thought it's worth maybe spending a bit of time going through what who is SANTHERA, what we do, especially as some of you were unable to attend our Capital Markets Day recently. So we will be covering off some of the key slides we presented at the Capital Markets Day today as well. I'll start with this snapshot that you're looking at right now. We are a small, nimble company. We're based in Pratil near Basel. We're today around a 110 employees. We intend to remain small. So even with the full commercial team hired, we're expecting to be less than a 150 people, globally.

2:02 Our lead commercial product is a GammaRi, a differentiated product for Duchenne muscular dystrophy, a dissociative steroid which has similar efficacy to existing steroids but with a much more benign safety profile. We are already in the commercial stages with a global rollout, which started last year. We received over a period of little of more than twelve months approvals in US, Europe, UK, China, and Hong Kong, and we have now launched in our first markets in Europe, in Germany, and in Austria. And after one year, we had converted around thirty percent of existing steroid patients to our product, the GAMRI. In parallel, our partner in The US, CATALYST Pharmaceuticals, also launched in March 2024 and has made some very nice inroads there as well.

2:51 On the financing side, just to mention that we had a financing last year in August '24 with a gross funding of up to 69,000,000. This gives us a cash runway to take us to breakeven in mid twenty twenty six, and we currently or I should say, at the end of twenty twenty four, we were holding 40,900,000 Swiss francs of cash. Moving to Duchenne muscular dystrophy and, just a brief introduction to the disease. This is a disease that is genetic. It's about one boy in three thousand five hundred. It affects only boys. The disease is inherited from the mother's side. It is caused by a missing protein called dystrophin that is produced by the largest gene in the human body.

3:38 What this dystrophin protein does is it functions as shock absorber, when muscles expand and contract. And and miss if this protein is missing, the muscles get chronically inflamed, and you have scarring, fibrotic tissue buildup, and fat tissue buildup, and over time, the muscle, becomes weak and ineffective. These boys are, typically diagnosed between the ages of three and five. The parents notice that the boy does not get off the floor as fast as he should. He doesn't run as fast as his peers, and they take him to a doctor who then refers the patient to or the boy to a pediatric neurologist, but then eventually diagnosis Duchenne. They typically have the disease starting with the muscular the mus the muscles of the skeleton, so legs and then later arms.

4:35 But, eventually, they they they they'd also, have a deteriorating heart and lung muscle capacity, and they die in their late twenties and early thirties. Typically, they lose ambulation, which means that they end up in a wheelchair in their early teenage years, and they start having a respiratory decline, where they need nighttime ventilation around the age of 16. Now what was how are steroids used in this disease? Steroids are standard of care now for a decade or two because what they do is they reduce the inflammation of the muscle. Ideally, the boy should be prescribed a steroid as soon as he's diagnosed and stay on steroids for the duration of the disease to slow down the disease progression.

5:24 The steroids are very potent anti inflammatory drugs, but they're also very toxic. And as a result of them being so toxic, parents or when they're told that their that their son needs to be on these steroids and they hear about the side effects that will come and the toxicities that will come with the chronic use of these steroids, they typically try to delay the start of the steroids until a little bit later when the boy is clearly and visibly in decline. So today, the typical boy started on steroids around the age of seven or eight when, in fact, they're diagnosed already at the ages of three and five. So they start too late. Over time, because of the toxicities, these boys also have their steroid doses reduced to reduce the side effects, but reducing the dose of steroids also means that you're dabbling in a nonevidence based dosing range where you don't know for sure if you're doing any good, but you know for sure that you're not causing all the toxicities that come with a full dose of steroids.

6:26 And in practice today, many of these boys and young men at this stage will be taken off steroids altogether by the time they lose ambulation, although they should continue on steroids for much longer, mainly to provide them with strength of upper limbs, arms, to be able to feed themselves, to brush their teeth, but also to play games, to use the keyboard because these boys are often socially isolated. Staying on steroids longer is also beneficial for supporting the heart muscles and the lung muscles and delaying endpoints. But, unfortunately, when they lose ambulation, very often, it's seen that the benefit risk just doesn't justify these toxic drugs anymore.

7:11 So in summary, they start too late, they dose too little, and they stop taking these steroids too soon. Now when we look at what are these side effects that we're speaking about, this graph that I'm showing here really, really illustrates well how the cumulative toxicities are starting to kick in in these boys. Early on, you you'll see immediately see stunted growth. You see mood and behavioral disorders and aggression, and you see weight gain. But over time, you start seeing a lot of other long term toxicities kick in. We are running a study currently called the Guardian study, which will have its first readout in q four of this year, where we are studying boys who have been on steroids, versus boys who have been on a gammarie for up to eight years.

7:58 Many of these boys, have been on long term a gammarie because they continued taking a gammarie after the phase 2a studies and phase 2b pivotal studies, as part of our long term extension program. So we're gonna be mining this data and hopefully be able to show some of the longer term benefits of, using a gamma ray versus prednisone or deflazacort, are the two other steroids in use for Duchenne. One point I want to mention on this slide also is that steroids are used, added, or steroids are a foundational therapy, and other Duchenne drugs such as exon skippers, gene therapy, or the recently approved givinostat are used additively to steroids.

8:45 Steroids are given foundationally, and all of these other new modalities are coming on top of steroids. The clinical trials were run with steroids as an inclusion criteria. So they are not competition. They are synergistic to a GAMRI. Now a few words about a GAMRI. It is an oral suspension, as you can see in this picture. And in the pivotal study that we ran for approval, in the it was a one year study. And in that study, we already showed three very clear benefit benefits. We showed that these boys, they grow at a rate that is similar to their healthy peers. We showed that they had normal bone turnover, which over time will likely translate into less fractures and osteoporosis, and we showed that they had less severe and less frequent mood and behavioral disorders.

9:38 What we have also since then uncovered is that we have a differential mechanism of action from compared to prednisone, for instance, by being a mineralocorticoid receptor antagonist, and being in this category means that you're potentially cardioprotective. Prednisone is a mineralocorticoid agonist, which are these are compounds that are known to potentially be damaging to the heart. So over time, we will hopefully also be able to see cardioprotective properties with the drug. But most importantly, because of this benign side effect profile, boys should be able to start on steroids or on a Gambri as soon as they are diagnosed because of the more benign side effect profile.

10:29 They should be able to stay on an evidence based dose because our dosing range is from two milligrams per kilo up to six milligrams per kilo, where the recommendation is to start on six milligrams per kilo and only down titrate if cumulative side effects start to be seen also with the gamma ray. So they have an evidence based dose that they can a 3x range dose that they can use, still know that they are getting an efficacious reduction in re inflammation in the muscle, and they can probably stay on dose longer because they tolerate the drug better. So as a consequence, by taking a GAMRI, you can start on time, you can remain on dose, and you can remain on treatment longer. Now switching to the Duchenne market for a moment.

11:20 This is a market, in the rare and orphan disease space that is somewhat unique. With rare and orphan diseases, you often have a challenge because they are rare and orphan diseases that they are not frequently diagnosed, and there is nobody who is a specialist in these rare and orphan diseases that sees these patients early. So the challenge that many rare and orphan disease compounds or companies selling compounds have is how do you educate the population of specialists to actually diagnose the disease in the first place? Once you've done that, that you've created awareness around the diagnosis and recognition of the disease, the next challenge you then have is to establish and coordinate the multidisciplinary care for this disease. And finally, you typically have the challenge of ensuring a smooth change in the treatment algorithm where clinics and clinicians and healthcare practitioners have to change their treatment algorithms in the practice to accommodate a new drug that is being introduced in this rare orphan disease.

12:20 When it comes to Duchenne, none of these challenges apply. I don't want to belittle the commercial challenges, but in reality, all of the patients, at least in North America and in Europe, are diagnosed. Not only are they diagnosed, but they're treated in centers of excellence by neuropediatric clinicians, and these neuropediatric clinicians are already using steroids today, have been using steroids for, in some cases, decades, and know how to use them, how to down titrate and up titrate these steroids. So bringing in that more benign form of steroid in a disease that is well recognized and and where the treatment centers are are all all well known is a commercial benefit, obviously, when you're launching a product like this.

13:09 Moving to the market size of agamry in Duchenne. The slide we're looking at here shows the various sources revenue that we expect to see over the coming years. The first one on top is our own markets. Our commercial strategy is to launch a gamma ray in the 17 markets of Western Europe ourselves through our own commercial team where we retain 100% of the net sales. This market represents about 13,000 patients, and as we've said in the past, about eight thousand of those are currently on steroids. And by 2030, we plan to have five thousand or more of those patients converted to a GAMRI. The next two boxes you see are our licensing partners. Licensing partnerships typically are a sale of the rights of the drug to those territories where you have a licensing partner.

14:02 There's an upfront. There are revenue milestone payments, and there's royalty income. But the partner now owns the asset in the territory, and they also have typically rights to develop additional indications as well as, establishing local manufacturing for the drug in their territory. The last two boxes, which is rest of Europe and rest of the world, are territories where we plan to have a distribution partnership. These, have different structures. Distribution partnerships, you don't typically get an upfront. You don't get large milestones, and you don't get royalties, but you get a percentage of the net sales in those markets. And in our case, we target to have net sales from our commercial distribution partnerships north of 60% of the net sales, and that represents the the part of the circle that you can see on the bottom there.

14:57 As I've said before, the €150,000,000 of revenue from our own territories in 2030 is still our guidance.

15:10 Moving on to the operational highlights for the year 2024. As I've already mentioned, we had a successful launch in Austria, Germany, where we, gained 30% market share in the steroid market. In other European markets, we are, working to get market access, and pricing. In The UK, we had a nice, positive recommendation in that actually, the recommendation was in December. It was finalized in January 2025. And just a few weeks ago on April 16, just before Easter, we had our UK full launch, including England, with agamarin. So it's too early, right now to give you any guidance on how things are progressing in The UK since it's only been less than two weeks, there was an Easter in between.

15:59 But we look forward to updating you on that soon. As it pertains to The US, Catalyst successfully launched, as I said, in March. They surpassed their initial guidance and their revised guidance throughout the year and landed the year with $46,000,000 of revenue. For this year, 2025, they have guided to a 100 to 110,000,000 of revenue in The US. Should they exceed the 100,000,000 revenue in The US during the calendar year 2025, This would trigger a $12,500,000 milestone to be paid to us in early twenty twenty six. In China, the Spirigenics relationship is on very strong footing. We are working very closely with them to prepare their rollout in a soft launch in '25, second half of twenty five, and hope to have a fully reimbursed launch in '26, but I'll speak more about that in a second.

16:57 In other territories, we are continuing to look at distribution partnerships. We have already signed up a partner in Israel and in Qatar. We're expecting to see first revenues from those two markets also in the second half of this year. And finally, the manufacturing expansion that we also mentioned at the Capital Markets Day is progressing well. We are setting up a second contract manufacturing organization in Switzerland for ourselves, for SANTHERA, in addition to the existing contract manufacturer, which we have in Belgium. And CATALYST themselves are also in parallel setting up a contract manufacturer in The US. These two are gonna have both of them have EMA and FDA approvals, which means that we'll have redundancies in case we need additional capacity between the two sites or the three sites, I should say.

17:50 Moving on to the specifics in the markets and going back to the GermanyAustria launch. I've mentioned before that between Germany and Austria, there are about 2,300 patients who have DMD. Both Germany and Austria are markets where there's a relative low level of usage of steroids. Steroids are used in those markets. Between fifty percent and fifty five percent of the patients are on steroids at any given time. There are other markets that are similar. France, for instance, is a low steroid use market, whereas countries like Italy, US, and UK have a much more aggressive use of steroids where there's seventy percent plus penetration of steroids in the patient population. The 30% market share that we have after one year in Germany is particularly, impressive in my view because we did not have any clinical trial sites during the pivotal trial in Germany.

18:43 So by the time we launched the product in Germany, there was nobody who had any previous experience with the drug. And yet in the first year, we are we're able to switch thirty percent of the patients. Now I wanna manage expectations here that we're not gonna be switching another 30% of the patients during 2025. Our peak sales forecast in Germany is about 60% market share by 2030. So the the growth in Germany is going to become more linear in nature, rather than the, the bolus jump that you see in the first year because of high unmet medical need where many of the patients had been waiting for the drug and were switched quickly in that first year. Looking closer at Germany, this map that you're looking at here, on the left hand side, you see all the top clinical trial or top clinical centers for Duchenne in Germany, whereas on the right, you see all the treating centers, centers that treat Duchenne patients in Germany.

19:40 This is a very unusual picture. Nature of the Duchenne treatment market is typically very centralized, as I mentioned earlier, centers of excellence, and Germany actually has a lot more sites to visit than most markets do. In comparison, in The US, there are about ninety, nine zero, centers that treat more than ninety percent of the patients. And as you can see on the map here in Germany, they have roughly the same number of centers for a much smaller population.

20:13 The colors on the side on the right side of this map, the blue ones are sites that have started prescribing a GAMRI to their patients, whereas the brown sites are sites that have not yet started prescribing a GAMRI to their patients. This shows a typical picture of early launch, uptake, an adoption ladder, uptake. You have the, early adopters and the lead users. These are typically the clinical trial sites or clinical trial clinical centers, sorry, you see on the left. They are very quickly to

20:45 adopt new technologies. Then you have the early majority, the late majority, and eventually the laggards that will start adopting a new drug. So we can see here on the right that we still have plenty of room to grow in Germany with sites that have not yet initiated GAMRI prescriptions.

21:05 Moving to the future launch plans in Europe. As I mentioned, The UK, is added now to Germany and Austria in terms of a country that has a price negotiated and a launch with reimbursement. The next countries we expect to have on that list are Spain, Italy, Nordics, and Benelux, probably in the sequence of Spain, Italy, and Nordics. In Spain, we are hopeful that we could get an agreement on reimbursement before the August holidays in Spain, but it may be that it drags out and it we only get that reimbursement decision in four time frame. In Italy, we are hopeful that we might get something by the end of the year agreed, but we are, guiding towards early twenty six, probably first quarter of twenty six.

21:54 Nordics, the first countries will probably have reimbursement before Christmas, potentially all of them, but one or two of them might fall into the Q1 of 'twenty six timeframe. In France, which is worth mentioning, we've had discussions with the CFES, in France, recently. And given that we have an ASMR five, they are, reluctant to give us the price that we expect to get in our markets, and we have agreed that we will wait for the long term data from the GUARDIAT study to resubmit that data to France to

22:30 hopefully then get an ASMR4 and get agreement on price. I want to mention that France is not in our guidance. We have no revenue in the next couple of years in our guidance coming from France, so we take a very conservative position there. But we're pretty confident that we will have a reimbursed price in the launch in France during the year of 2026.

22:52 Now a few words about The US. In The US, they have roughly the similar number of Duchenne patients as we have in Western Europe, so somewhere between eleven thousand and thirteen thousand, depending on which source you look at. They have, as I mentioned, a very aggressive use of steroids, they're north of seventy percent of patients are on steroids at any given time. And guidance from Catalyst, as I mentioned earlier, is 100,000,000 to $110,000,000 of revenue in 2025. I believe they will announce their first quarter results in the next week or so.

23:30 Moving to China. I've mentioned before that we had an early access program on the island of Hainan. This was before we were approved in China. In that early access program, we have about 100 patients or slightly above 100 patients already on drug in China.

23:46 Since then, we have been approved in China, and the negotiations for reimbursement are ongoing. Our partner in China, Spiragenyx, are planning to have a soft launch, so a self pay launch in the second half of this year, and a full launch with a reimbursed price in China is expected in the first half of twenty twenty six. I wanna mention here that DMD was included in China's first national list of rare diseases, which was published in 2018 by the National Health Commission and other authorities. The list comprises of 121 rare diseases and serves as a foundational reference for policy development, clinical guidelines, and regulatory prioritization in China. So we're hoping that this very prominent display of Duchenne being a priority should help in the reimbursement negotiations there.

24:40 Finally, before we move to the financial highlights, just a few words about our manufacturing expansion. As I mentioned, we are setting up our own contract manufacturing organization in Switzerland. That facility should be up and running by late twenty twenty five this year with supplies going to first markets in early twenty twenty six. We will wait with a submission to places like Latin America and Brazil specifically until this facility is up and running and we can include the CMC data, the chemistry manufacturing and controls data from this facility in our Brazilian submission. Having this second manufacturing site for ourselves and a third one in The U. S. Allows our ambitious plans to be to be materialized with security of supply and managing risk, but it also allows for larger batches to be produced, which will over time reduce our cost of goods.

25:42 With that, I'll hand over to Catherine who will speak about our financial highlights of the year. Thank you, Dario. So moving to the financial highlights. As we previously highlighted in our trading update, about a month or so ago, our total revenues for the year were 39,100,000. This was driven by the strong sales growth we had in Germany and Austria. Comparing it, however, to the previous year when we had a 103,400,000 of sales, it was obviously lower. However, the 2023 number had significant milestones as we out licensed the program our product to both China and The US in that year.

26:28 Looking at product sales, they were 14,800,000, in the year. As previously mentioned, this is due to the successful launch of a GammaRay in Germany and Austria. Milestones for the year were 19,300,000. Again, these were lower than than the prior year, but that was due again to the Catalyst and Spiragenyx out licensing. Revenue from supplier product and services, so this is mainly to our US partners at present, although this will include, our sales of product to Spiragenyx in the future, was 5,000,000, so nearly double that of 2023. Looking at the operating expenses for the year, these were 57,000,000.

27:17 The 2023 number, which was lower, however, was impacted by a net gain of 70,000,000. This was on the sale of, ibetanone, when we disposed of that business. However, if you exclude this gain, 2024 operating expenses were 15% higher. This was driven by increased development and, as you'd expect, increased marketing and sales expenses, but offset by lower g and a. We had a share based payment also included in that that figure of 3,900,000.

27:53 The operating loss for the year was 33,200,000. This is versus 68.8, profits in the prior year. Another key event during the course of 2024 was the financing. As Dario highlighted at the the very start of this presentation, we secured 39,000,000. This was broken up between two components. 69. 69,000,000. This was broken between two components, a new term loan of 35,000,000, Swiss francs, and a royalty monetization agreement of $30,000,000. We ended the year with cash and cash equivalents of 40,900,000, and as we have highlighted, this extends the, cash runway through to mid twenty twenty six when we expect the company to be breakeven.

28:48 So moving on now to the financial guidance, not only for this current year, but moving forward. We expect revenues for the year 2025 of 65 to 70,000,000 Swiss francs. If we move to 2028, we have a revenue guidance of a €150,000,000. This is related to our direct and partner markets as well as our royalty income from North America and China. We've excluded, milestone payments from that figure. So really what that 150,000,000 is showing is the underlying business without the the lumpiness of milestones. If you then go to 2030, we've given a guidance of in excess of a €150,000,000 euros, but this is on our own direct sales.

29:42 So this excludes our distributor and license markets, as well as the milestone payments. Looking at operating expenses, so s g and a and r and d, for 2025 and going forward on a constant currency or constant portfolio basis, we expect this to be 50 to 55,000,000 Swiss francs, and it note that this excludes non cash share compensation. I'll now hand back to Dario to discuss the strategic outlook and priorities for 2025 and beyond. Thanks, Catherine. So our revenue generation comes over the next five years from four different sources. The first and the most obvious one is our go direct strategy in Europe, where, as I mentioned, we plan to commercialize ourselves in the 17 countries of Western Europe.

30:36 In addition to that, we're very busy with our geographical expansion. We have negotiations ongoing currently in Turkey, the GCC or the Gulf countries in The Middle East, Brazil slash Latin America, and and a few other markets. And these negotiations obviously take time because you have to do conduct the mutual due diligence. You have to make sure that the quality systems are up to date, that the pharmacovigilance reporting systems are up to date, and you have to negotiate the agreement itself. So there's a certain bandwidth issue where we have to prioritize markets, and we can't really expand to all of the world right away. But you'll hear more about that soon and throughout '25 and '26.

31:22 We've also announced that we are, very actively looking to acquire, additional assets in addition to a GAMRI, either through a license agreement or a distribution arrangement or potentially even through an M and A transaction. The target compounds that we're looking at are compounds that are rare and orphan. So that's the space that we're in. I know we're that we that is our core competence. They need to be late stage assets that have completed their pivotal clinical program, so we are not willing to take clinical risk. However, we are very happy to take regulatory risk if during due diligence of such an asset, we are our competent regulatory and medical clinical teams feel that they can get this approved in Europe. Our therapeutic area, focus is neurology.

32:12 Having said that, we are also agnostic. If an asset looks very interesting in the rare and orphan disease space, has solid clinical data, we would be happy to also bring in an asset that would be in the space of nephrology or rheumatology, for instance. Now the question I often get is how do you how do you compete with other much bigger boys in Europe when it comes to such such asset licenses from, for instance, US companies that have decided to launch their own rare orphan disease asset in The US but are looking at Europe as a potential expansion territory. And my answer to that is that if if you're looking at an asset that has 500,000,000 or more of potential revenue in Europe, they're gonna be much bigger boys than are gonna be wanting to to license in such an asset.

33:02 If it's an asset that is 200 to 500,000,000 in Europe, there are midsized European companies such as Recordati, Kiesi, Lundbeck, Sobe, and so on who would be very strong partners for such an asset and where we can't compete currently. However, there's a niche of assets that have that are in the rare orphan disease space and have 50 to 200,000,000, say, revenue potential in Europe. And there are not too many European companies that have the full capabilities across the entire value chain of regulatory, quality, pharmacovigilance, supply chain, marketing, medical, sales in Europe that would be interested in an asset that is of the size the size of 50 to 200,000,000 of peak sales.

33:48 But that would be exactly what we're looking for. That's the kind of perfect fit for us, and we believe that there's less competition in that space. So we have engaged multiple parties already. It's still very early stage. It will take through '25 before we identify an asset and have negotiated it, and and so don't expect there to be an announcement this year. But I would be very disappointed if in 2026, we wouldn't be able to announce at least one, if not two, late stage deals like this to strengthen our our portfolio. And then finally, additional indications for a gamma ray. We've mentioned this in past calls. A gamma ray, obviously, with the profile you have now and the safety that has been shown in pediatrics, has potential in additional indications, additional therapeutic areas.

34:38 But here, we have decided that short term, we're gonna be spending our our money on, bringing in additional assets as well as maximizing the the Duchenne opportunity and investing in in both the commercial expansion in Duchenne as well as additional data generation in Duchenne, and we will leverage the work for indication expansion that our partners, CATALYST in The US or North America as well as Spiragenics in China, are going to be undertaking. So by the time they have completed their programs and done the clinical work for indication expansion, we would then have an option to leverage that data and get the rights in Europe in our own territories. So to summarize, we have a differentiated product with worldwide rights. We have a unique selling point, that is very well understood in the market.

35:35 We have a very clear growth strategy for Duchenne with the GammaRay. We have a market that has been clearly segmented into three segments. The naive segments, I I e, the patients that have been recently diagnosed, the switch segment, the patients who have been on other steroids for a while and, are not tolerating them well and want to switch to a more benign product like a GAMRI. And over time, we will also penetrate the segment of older patients, patients who have lost ambulation, who have potentially stopped taking steroids altogether or have never started taking steroids, but would still benefit from a steroid for the slowing down the progression of the disease and to give them upper limb strength.

36:24 We have a strong and growing partner network. You will hear more about that throughout the year. We have a small and nimble organization. We're able to keep our costs under control. Basel is at and Zurich and Zug, the triangle of space that we are operating in has a lot of talent. We have been able to recruit some very experienced senior people and are able to keep the organization small and nimble with all that experience. And finally, and maybe most importantly, to shareholders, we're funded to project break projected breakeven, in around mid twenty twenty six and don't expect to have any, further fundraising or share price shareholder dilution under the current structure and circumstances.

37:12 So with that, I'd like to hand over to Catherine who will moderate our Q and A session. And I wanna remind everybody that our chief medical officer, Doctor. Shabir Hasham, is also in the room with us. So feel free to ask any questions that you may have, and we hope to be able to answer them all before the end of the call. Catherine? Thank you, Dario. So, got a number of questions here. We're trying to get through, these during the time, available. If not, we will be publishing all of the answers, including the ones that we don't get to, on the website, the investor meets website. So to start with, first question, initial UK sales were expected for q two twenty five. Understanding it's still very early days, how would you rate the uptake in The UK in the first month? Now I know, Dara, you you commented a bit on that in your presentation, but I don't know if you had any further comments there. It's not it's not really even the first month. As I mentioned, we we received the the blue tech code for England, which really is the majority of the market in The UK only on April 16, just days before Easter.

38:21 And then you had the Easter holidays, and it's been two weeks since then. So it's way too early to to give any any commentary on The UK for the time being. Thank you. The second question is around the Guardian study. So data from the Guardian study is still expected this year. Can you comment on the progress of the study? And in terms of the data, what would be the best case scenario for you and how could it impact the uptake of a gamma ray in the market? It then goes on to say, do you see also see any potential risks, I e, that some of the benefits observed in the pivotal trial are not confirmed? So I'll hand that over to Shabir, I think. Thank you. So just to remind you that the Guardian study is aimed at a long term follow-up of patients who've been on the mulleride for quite some time, somewhere between five to eight years.

39:14 So we know who the patients are. We know where they are. So we started enrolling towards the end of last year about December. We're about fifty percent enrolled, so we'll just need to see how progress is the next few months, but we we still believe that's on track. The objective of the study is to determine long term effectiveness. So one of the key variables we want to look at is the durability of treatment with vimmarone. And then to explore further long term safety now, in particular, we have a focus on bone health. We know from all of our studies that vimmarone shows a very consistent benefit in terms of the bone biomarkers. We've had some early, analyses of bone fractures, so this really just aims to strengthen that as a clinically hard endpoint.

40:01 In addition to that, we are collecting information on, eye health, so cataracts, glaucoma. We're looking at puberty, although these boys will be just entering the age when we would see any any hint of a normal puberty. You may know that steroids cause delayed puberty. The other important thing to remember about The Guardian is that there is a three year follow-up. Okay? So at the moment, they're rolling into the study. The data we're anticipating in quarter four is the first readout. We will have further readouts annually for the next three years, so it's not a one stop shop. This is continuous news flow. For me, the best case scenario is that we are able to to show a robust durability in terms of treatment effect. We are able to show progress in terms of the robustness of data with bone health.

40:52 We know that height is not affected. We also know that the results in the in terms of bone biomarkers are very consistent. We have those data already. And any other additional data, safety data would be just a bonus on top of that. How do I expect this to how do I expect this to be used in the market or at least in top of mind for physicians? We know already that if the effect is durable, we can show robust bone health data, I. Reduction of clinical fractures, that will already significantly impact the use of the molybdenum. We know already that the average dose is about eighty percent of the recommended, so that's already a significant advantage over current standards of care. So, really, it's just tying up the story and and presenting a really nice long term overview of the moraine my aim really to do.

41:46 Okay. Yep. Okay. Thank you, Shabir. Right. Moving on to the next question. So can you please comment on your exposure to US tariffs if imposed on the pharmaceutical products? I think I'll probably take that one. So in terms of our sales over to CATALYST, in the end you've got to remember that they're actually buying the product. So in terms of any tariffs that we actually wouldn't be impacted, so we're not impacted at all. However, you could say if there were very large tariffs, you know, would that increase the price and therefore would there be less sales? In terms of the cost to catalyst, if you look at our product sales, that was only 5,000,000 for the year. So Catalyst are making a in excess of 90% margin. So the cost of this product is very small.

42:43 So even if they did have a tariff on it, it would be very small in comparison to the sales price. So it would only be for them to decide whether or not that would impact their sales price, but all we can say is that it would be very minimal. And from our side, there will be no implications. I think in addition to that, we can we can also confirm that since they're starting to manufacture themselves in The US towards the end of the year or early next year, the tariffs will not have any impact at all. So if if if at all, it's minimal and only for a few months. Okay. Alright. Move on to the the next question. Can you provide an update on your plans for Brazil?

43:30 Yeah. So Brazil is a is a relatively large market with 200, people in it. We are in, discussing with a shortlist, you know, a very shortlist of, potential partners in Brazil. But what we have decided because of volumes, potentially, being high in Brazil, that we want to be able to submit our new contract manufacturer in Switzerland to the Brazilian authorities, which means that we will only be able to submit a file in Brazil in early twenty twenty six when the contract manufacturer is up and running. So there's a there's a clear plan to go to Brazil. Brazil is an attractive market, but it's not something that we are in are going to be announcing as a as an approval or as a launch in the 2526 time frame. Brazil, with a submission in early twenty six, will be approved towards the end of twenty six or early twenty seven.

44:28 And and stay tuned for partner news later in the year. Thank you, Dario. The next question is, you mentioned about in licensing a product. What what can you say about criteria? What are your preferred areas that you are looking at? I think that we've actually fully answered that in the in the presentation, so maybe I think we'll move on from that one. The next question is around Catalyst. Assuming Catalyst will reach a 100,000,000 of sales this year, will you get that milestone in 2025? And is that included in your guidance for revenues for of 65 to 70,000,000 this year?

45:16 So basically, it's an annualized 100,000,000 of sales, so a calendar year. So in terms of actually when we would receive payment, assuming that they did reach that, that would be during 2026 in terms of the cash payment. However, as it refers to the year 2025, the milestone in the p and l itself will be booked in 2025. I hope that answers, that question. Moving on to the next one. How long do you expect to supply a GAMRI product for CATALYST and Spirigenics? So let's start with CATALYST. They're they're setting up their own manufacturing partner in The US.

46:02 As far as we know, that one should be ready to provide product end of this year or early twenty twenty six. How long we will be supplying them with finished product from our current manufacturing site depends a little bit on their inventory level. We don't know exactly what their inventory level looks like, but I would expect that we will be continuing to supply them into q three of this year plus minus. And after that, they would they would manufacture themselves in The US. Thank you. The Oh, sorry. Spiragenyx was the other part. Yes. Spiragenics has a a timeline where they want to have a local manufacturing set up by the latest by the end of twenty twenty eight.

46:50 So we we will continue to supply them with product from our existing site and potentially from the new site as well for the foreseeable two to three years. Thanks. The next question is around Spiragenyx. When do you expect the first sales from China, and does this trigger a milestone payment from Spiragenyx? So we we are expecting this as I mentioned in the presentation, we are expecting the first soft launch sales. So these are self pay sales coming in the second half of this year, so after the summer, probably q three, and then a full reimbursed launch in the first half of twenty six. The first commercial sale of a reimbursed product in China does trigger a milestone, but it's a tiny tiny milestone relative to to to the the overall deal size. That that particular event does not trigger a large milestone.

47:52 And, in the foreseeable future, there will be two other, trigger points for milestones with Spiragenyx. The first one will be when, they reach 10,000,000, US dollars in revenue, in China, and the second one is when they reach 30,000,000 of revenue in China. Both of those milestones will trigger payments to us from both Spiragenyx and the financing partner that we have for the royalty financing, which is CBC. K. Thank you. Moving on to the next question. When do you expect CATALYST to announce new rare disease indications for a gamma ray?

48:39 Well, I can't or we can't speak for CATALYST, really. They it it's up to them to decide when they want to initiate additional indication work. But what they have told us is that they wanna spend 2025 still analyzing the various opportunities further and see the results from their ongoing multiple ascending dose study in Duchenne patients or sorry, in volunteers in order to see whether a gamma ray has immunosuppressive properties at higher doses. They're conducting this study in order to know when, how, and if a gamma ray could be used in conjunction with the gene therapies from Sarepta that have been launched in The US.

49:27 Just to remind everybody that when you're dosing a patient with a gene therapy in Duchenne, for instance, there's a period of several months after a few days before and several months after the dosing of the gene therapy where these patients are given much higher doses, sometimes two to threefold, doses of steroids, to prevent an immune rejection from the, foreign virus that is the delivery vehicle for the gene therapy. So there's an opportunity there to introduce a gamma ray in that context, and they want to run that study during 2025. It's currently ongoing. It will read out towards the end of the year. And based on the results from that study, they will then evaluate which indications could be of interest.

50:17 If the if a GAMRI has immunosuppressive properties, it would obviously open up a door for a lot of autoimmune diseases, which we had not considered before. But as I mentioned on previous calls, we had a short list of indications, pediatric indications, where we thought a GABRII could be very interesting. CATALYST is aware of that in those indications. We've had extensive discussions with them about it, but, but they want to evaluate the immunosuppressive properties first before making a final decision. So it's a long way of saying that the earliest we could probably hear from them is, end of this year or early twenty twenty six. The next question will be for Shabir. It's a follow on question around the Guardian, trial. So again, with results expected in q four, how can these long term efficacy and safety observations be included in the label, and how long would that take?

51:15 So just bear in mind that currently steroids are used off label within Duchenne. We have in our label the European label is actually very well differentiated. So we have the basis and language for many of the the endpoints we're looking for in the Guardian study. Our focus really for the Guardian study is to use it as an educational tool. Physicians and it's a it's such a small community and very tightly knit community that we believe that the educational component will be sufficient for us to be able to achieve our objectives. So at the moment, pending actually looking at the data, the focus really is is on communicating the data at congresses and publications. Thank you. So on to the next question. I think it's also for you, Shabir. On the on positive POC data results from from lost lost the question.

52:14 Becker's muscular dystrophy. Is that expected to report in q four twenty five? How long would it take to include BMD patients in the label? What kind of peak sales do you project for this indication? I'll leave the peak sales, Daria, but just in terms of the BECCA's now, it's a pilot study. And so, really, what we want to do is to see the data and then make a determination of the next steps. And there is a possibility that it could be a biomarker led strategy moving forward, but I'd need to see that confirmed first before we make a comment. And with regards to peak sales, as as Shabir mentioned, we we don't know what the label looks like yet. We don't know what the data looks like yet and if if it even is going to be successful or not. So it's a little bit too early to to speculate on peak sales.

53:09 But just to give a bit of an order of magnitude maybe about this market. So the the the number of patients in Becker's is roughly one third of the number of patients you have in Duchenne. So it's onethree of the Duchenne market. However, in this study, they are using a higher dose than than they are using in Duchenne patients, and Becker's patients also live longer. So, typically, these patients are heavier than our Duchenne patients. So while the number of patients is lower than in Duchenne, the dose would be higher if successful. And so you can then extrapolate what the market size could potentially be if you if you just look at the average dose in that study and the number of patients being about onethree of Duchenne. But as I said, it's a pilot study at this point. If successful, it will still require a pivotal study, a formal pivotal study, in order to get it into into the label for for Becker's muscular dystrophy. We're still a few years away.

54:12 The next question, when do you expect to announce late stage pipeline and distribution agreements to leverage your EU sales infrastructure and expand your pipeline in rare diseases? So and, again, I know we talked about that a bit earlier. I don't know if you want add anything more. Yeah. I mean, I I spoke about it already. I mean, we have a we have an infrastructure which is which is fully fledged. Basically, all functions as if we were a large pharmaceutical company, but we have that all for just one product at the moment. Even with that one product, we're gonna become profitable in 2026, cash flow positive and profitable in 2026 and beyond. So you can imagine that if you could add a second product and potentially a third product to that infrastructure and leverage that infrastructure with very limited incremental costs, that would obviously be a very attractive proposition.

55:07 So we're working hard to to make that happen. And I as I said, one or two announcements in 2026. Thank you, Dario. Just moving on to sort of one more question. So so some of this has already been asked around, talking about the milestone timing from Spirigenics, and then it talks about how might this counterbalance any milestone obligations in 2025, 2026. So just to remind you, we do have milestone obligations to our originator companies, and we do pay that through the the cost of goods line. We haven't actually disclosed the exact agreements that we've got with them. However, what we can say is roughly overall that the the milestones that we have to pay out of cost of goods will all balance out with the the milestones that we receive in.

56:06 I think that is pretty much all the questions that I've got there. And actually, we are now up for time. I don't know if you wanted yeah? Well, that that's perfect. So Dario, Catherine, Shabir, thank you very much for answering those question. And as mentioned previously by Catherine, the company can review all the questions submitted today and publish the response on the investor meet company platform. But just before redirecting analysts provide you with their feedback, Dario, could I just ask you for a few closing comments? Yes. Of course. Thanks, Alessandra. So I I I thank you for the the hour you spent with us today. I hope you're as excited as we are about the future prospects of SANTHERA. We're in really good shape now. It's been a rough couple of years, but we're really not only out of the tunnel. We're running or driving fast out of a tunnel, and I have a lot of lot of exciting things going on. So stay tuned for more news from us. And should we not have answered some of your questions today, feel free to email us, and we'll get back to you as soon as we can.

57:14 And thanks again, everyone, and bye until next time. That's great, Darian. Thank you once again for your presentation. I please ask analysts not to close the session as you now be redirected to provide your feedback in order that the management team can better understand your views? On behalf of the management team of SANTHERA, we'd like to thank you for attending today's presentation, and good afternoon to you all.