Diamyd Medical AB (publ)

Good morning everyone, my name is Linus Jönsson and I would like to welcome you to this report presentation which is held by us here at the GV Fund Commission. With us today we have, just like a few times before, Diomid Medical and the company's CEO Ulf Vanilius, who will soon be able to go through the report for the third quarter, for periods 24-25, which came out here this morning. But before Ulf can take over, I just want to mention some quick and practical details. Eventuella frågor tar vi upp efter presentationen och det går tyvärr inte att räcka upp handen utan man får ställa alla sina frågor via chatfunktionen så läser vi upp dem och så kommer Ulf besvara dem efter sen. Med det sagt så lämnar jag över ordet till dig Ulf, varsågod.

Yes, tusen tack och välkomna alla. Jag kommer till en ganska kort, som sagt det här är en kvartalsuppdatering så det blir inte egentligen. Jag förväntar mig att alla vet någonting om bolaget och bakgrunden, så jag kommer hoppa ganska rakt in i själva uppdateringen och så kan vi gå till frågor därefter. Så direkt, och jag tänkte precis som mitt vd-ord också i kvartalsrapporten, så är det fokus på några stycken grejer. Vi har ju både på vår FAST-3-studie, var vi har ett mål att den ska vara fullrekryterad i år, eller i alla fall att vi slutar patientscreeningen. Then, GMP certification is in progress in Umeå, and perhaps the most interesting is the FAS 3 result, i.e. the earlier analysis of the ongoing FAS 3 that will come in a year. And what is extremely important and what we are extremely grateful to our shareholders for is that we have a strong cash flow today of over 300 million kronor, and it is thanks to that Den företrädaren som gjordes och kompletterande riktade emissionen som då gav oss 266 miljoner kronor innan kostnader så var det ju bara 5% eller mindre i kostnader tack vare att vi inte hade några garanter involverade. Så det här har gjort att vi har en mycket stark kassa vilket är extremt viktigt i det här läget just när vi nu sviktar på avlästning med fast trean. Och sen som ni vet så har vi ju teknisk option serie 5 som då can be traded as an extra instrument on the market. And then in April next year, you can then give the opportunity to buy shares for 20 kronor each. And if it goes through, it could give the company up to 330 million kronor before costs and after costs it will be around 300 million kronor or more. So that should of course also be an extremely large value. for the company and for the shareholders as well. But I thought I would focus on these three points a little more in the update. Phase III, as I said, there will be a result within a year, a so-called earlier reading in the ongoing study, and it is done in partnership with Breakthrough T1D, which is the largest patient association in the United States. In Europe and the United States, 60 clinics in total, And as I said before, we have anchored with both the American Medical Society, FDI, and with the European Medical Society, EMA, had enough with one single fast-trigger for a market approval. It is common that you usually have two fast-triggers, but our fast-trigger is one. Partly because we have such a large security database. Previously, we have done 15 clinical studies with medical medicine candidates. And we are looking at a genetic subgroup of type 1 diabetes. So this is, we're almost getting into more now. We have a special status earlier in the USA, but now we're looking at a genetic subgroup of this, so we're almost getting into the rare disease area, where there are a few other, a little easier requirements, you could say, than for normal indications. And as I said, we have the opportunity for an accelerated market application in the USA, based on a previous analysis, where C-peptide, that is, the marker for self-insulin production, is the primary effect measure. And here we are first out in the whole world to be able to get the anchorage from the American FDA. And there is a lot of discussion going on within the field right now about C-peptide. It has actually been going on for a very long time. where the entire field considers that CPEPTID is the marker that should be the primary effect measure, while the authorities have not yet really decided. But here we have then had the opportunity to use CPEPTID as a primary effect measure for a possible accelerated market research. And then we actually have all eyes on us as a company. We also heard that recently when we were down in Chicago at this ADA conference, that Både Big Pharma och Småbolag, alla vet om oss, alla har ögonen på oss, för vi bryter nu mark här och alla hoppas på oss också. För om vi lyckas med det här med C-peptid och den här tidigare avläsningen, så kommer det att öppna upp mycket för hela fältet. Så det är inte bara viktigt för oss, det är viktigt för hela typ 1-diabetesfältet, vad vi håller på med här. When it comes to the randomization, we have now reached 250 randomized patients in the ongoing phase 3 study, so we are on track to be able to complete the screening for new patients this year. We aim to have a little more than 300 patients, so that we have a study with a margin that is powered. had a statistical power in the study of around 288 patients to be able to achieve this final primary effect measure on C-peptide and HbA1c. So we are now on track to have more than 300 patients in if we finish the screening this year, so it goes well with randomization actually here, and there is a great interest in the study, which we can talk a little about here very soon when we talk about the ADA conference as well. What is also interesting and important is that we now see consequently that around 50% of our screening individuals have the right type of HLA, that is, the type of HLA that has shown to be linked to the possible effects of our drug. So it is a consistent 50%, so it just strengthens all previous results from previous studies that this type of HLA is at least 50% in the western world. If we then look at what it looks like in different countries, we see a certain variation between the countries, which is expected. Spain is highest, which we have seen earlier, also in Southern Europe. Spain is at almost 65% of type 1 and has the right HLA type. But then the USA is at 46%. Sweden, 55%, as you can see here. From earlier data, you could see, for example, Finland. I am originally from Finland. It was only around 30%. That is actually what affects this genetic, shall we say, frequency variation on a geographical level, which shows in our previous study that it looked like it worked better in non-Nordic countries. And then we didn't really understand why. But this is the explanation for that. The more common the HLA type is, the further south in Europe it will be. And then in the previous FAST-RE study, when this subgroup analysis was done on non-Nordic countries, it looked like it worked better in non-Nordic countries. And that is the HLA type that is the explanation, nothing else. But in general, it is around 50% of Tibetans who have this. Then we Just as a reminder, also when we think about C-peptide as the primary effect model for the previous lecture, we have consequently seen an effect here in previous studies, when we go to the right genetic subgroup. So here are the previous studies, phase III on the left, the previous phase III. on an effect that is close to 40% when you only look at the right unit subgroup, and in this case it is four subcutaneous injections. And then in phase 2, which was done in the USA, i.e. trialnets phase 2, again, where you got two or three, in this case three subcutaneous injections, close to 50% effect. And then our latest phase 2 in Europe with intralymphatic injection, three injections, we were at 55% effect compared to placebo after a 15-month follow-up. And in total, when you put everything together in a meta-analysis, we have close to 50% effect and, of course, a lot of statistical significance. And this is the basis for our entire FAST-3 study, where we only record individuals with a correct genetic background. And the important thing here again, this is C-peptide. And as I said earlier, there is a lot of discussion all the time about C-peptide. And we were invited to a workshop last week, which was organized by the Critical Path Institute, which we are also members of, to share data with them. It is an organization that works with different types of indications to facilitate the development of new drugs for diseases. where they have a lot of interactions with both FDA and EMA. In this case, it is their type 1 diabetes consortium that we are members of. And this was a workshop where you discuss the most about C-peptide as an effect. Where you invited both industry, where we were a participant, Novo Nordisk was with, Sanofi was with. FDA was here from the authorities, and then we have various doctors and patient associations, including Breakthrough T1D. We are one of the biggest examples now where we are closest to having a solution to main C-peptide as a primary effect. And as I said earlier, we will set the example, and I believe that the authorities will look much more closely at our data and how they will set the future for how you can hopefully get approved in type 1 with disease-modified drugs based on C-peptide. So it's exciting that we're really breaking new ground here. And the important thing for us here is that given that we will The first possibility is that, with a C-peptide supplement, we have a large safety database, where we have treated a total of over 1,000 patients with the active drug and around 600 with placebo. We see no difference in the safety profile and our most common side effects, such as irritation. in the injection site. And I think it is important now, when you are first out, that you come up with something that is safe and simple. And that we also have a special status in the USA is important. And we go to a genetic subgroup of this orphan group, because the discussion within unusual diseases is a completely different discussion from the authorities' point of view than when you go to a slightly larger indication. In rare diseases, we usually talk about incremental changes, even small improvements are very welcome and very common with accelerated approval. So that's something that we also really emphasize in our interactions with authorities. You have to remember that we are going to a genetic subgroup in a quite rare disease. Then, GMP certification, we have as a goal now for Umeå, our manufacturing facility, för den aktiva komponenten, det rekommendanta proteinet GAD. Det är då på den här röda byggnaden, den främre delen av den röda byggnaden äger vi som 2400 kvadratmeter. Vi har renrum, labb, kontorsutrymmen och varulager. Nu pågår det förberedelser både interna, en intern inspektion pågår för tillfället just vad vi själva with experts internally, go through our systems in the same way as a company would do. And then after that, to book an external mock inspection, that is, where there will be external consultants who do the same thing, who will see how a company would look at it. And after that, we will invite the Swedish Food and Drug Administration to do an inspection, and then their findings will be presented to us. Beroende på om de inte hittar någonting konstigt så har vi möjligheten att kunna få den GNP-certifierade i år. Så det är målet. Och sen är det ju intressant också här att vårt läkemedel formuleras ju hos APL som i den här vita byggnaden som ni ser mera till vänster på bild. Så det är vår läkemedelsformulerare. Så det är ju också ur ett logistikperspektiv. Mycket bra att ha dem så nära till hands. This is a picture from the AADA conference that I recently came back from, which was held in Chicago this year. There were about 13,000 people on site. We had our own booth, where we mainly talked about the FAST-3 study, because now it is the last half of the year, the last sprint on the patient recruitment side, and where there is still a possibility All clinics should know that now there is still a chance for patients to participate. And then we had some updates to our testers. Several of our testers, especially in the USA, were on site here. But also from Europe, where we gave an update on the study. And just as you have heard here about the screening, how it goes and all that. And then we had a lot of activity around the base. Many are familiar with the study, many are familiar with us now. and we had both influencers on site who talked about us, and at the bottom right of the picture was Mark Atkinson, who is sitting in our board and is also the chairman of our scientific council. He was on site, and he is actually the chairman of the entire ADA conference committee this year and next year, so he is the one who is most responsible for organizing the conference this year and next year as well. So it's great to have such a person in our board. And we also arrange, if you see a picture to the right, we arrange a breakfast panel together with Breakthrough T1D, which also supports our FAST-3 study, where we had invited several key opinion leaders, both from patient associations en patient själv som var där och berättade om sjukdomen och sedan både prövade och som var faktiskt extremt, tog sig emot på ett extremt positivt sätt. Den fick vi höra i efterhand att det var flera som sa att det var det bästa som hände på konferensen. Det här har vi också spelat in så vi hoppas kunna göra den här tillgänglig inom kommande veckor tillsammans med Breakthrough T1 Diesel. even more can take part in everything that was said on that breakfast panel. But there it is discussed about precision medicine, about what needs to be in place if you get approved for a new drug within the new diagnosticated type 1 diabetes, what is important for the patient, what is important for the doctor. But as I said, it was very well received and talked about in the corridors as well. After a while, we heard others walk around and say that we heard that it was an extremely good breakfast that we had ordered. So it's positive to hear such words. And as I said, I think this was my last picture, so we can jump to questions now, I thought.

Great, thank you very much, Olof. I can just remind you before we jump into the Q&A session that if you have any questions, it's great to send them in via chat, so we'll raise them directly. It is not possible to raise your hand. But we have already brought in a lot of questions during the presentation, so I think we'll jump right down into the pool and start with a question here. Can we look forward to a normal start in the coming year when it comes to insulin-based antigens, and are there any other antigens that can be relevant to develop?

That's a good question. As I said, we want to continue with the insulin track now, that is, to broaden our platform. What we have now, GAD, as you can see, is about 50% that are on the right type of genetics to be able to belong to the group that has shown to respond in previous studies on our treatment. And then insulin, the other big antigen that is linked to another important HLA group, that covers about 40-50% more. So together with both, we should be able to cover up to 90% of type 1 diabetes, at least in the western world. Here, of course, preparations take place internally. A lot is about being able to set exactly what type of insulin antenna we want to develop, and in what way, the manufacturing method, and then how we should... Our goal is actually to to have it as ready as we did in the previous lecture. If it is positive, we want to be able to go as fast as possible and be able to take the next program into the clinic. We do not want to spend too much time in the pre-clinic because it has not been done as much with insulin in the pre-clinic. We know that it works, you can buy a mouse, but it's nothing strange. It was necessary to be able to take it quickly into the clinic, learn quickly in phase 1, to then be able to go into a pivotal study as quickly as possible. So hopefully we will be able to update on that front as well. Then there are some other companies in the world that have insulin-like projects going on. We are mostly in the pre-clinical, early clinical phase, when we know all of them, they know all of us too. And we have some patents that are primarily about this JLA type and aim to choose the alternative. So there are opportunities for such possible collaborations with other companies that already have different types of insulin-based treatments on the go. Then when it comes to other antibodies, there are absolutely other ones. We usually talk about four or five antibodies. or autoantibodies in type 1. So there is a possibility to add more, the question is how much added value it gives, I don't know. You usually talk about GAD and insulin as the two most important from an anti-antibody perspective, but there could be a possibility to add In the future, we might be able to improve or reach some patients who do not respond to the other two antibodies. So it's up to us to see how we should work on that. Then we can also say that the vision is to be able to, if this works with antibody-specific immunotherapy that we are working on now, then we should be able to broaden this to other autoimmune diseases as well, with the same concept, to choose either one that is specific for other autoimmune diseases, in the same way to focus on the right HLA group there. But now there is full focus on GAD and then to be able to prepare the insulin track and hopefully we will be able to update on that front as well.

When we still talk a little about Bredning and so on, what are the possibilities of being able to treat stage 1, 2, 3 and LADA then given that there will be positive results in March 26?

So there it is, We know that, at least in the USA, before you have been formally approved, depending on the type of treatment you have, in the USA, you can say, strangely enough, up to 50% or more of all medical treatment is done off-label, that is, done outside the formally approved indication. So you can see, we don't know, it remains to be seen, that if we get approved for stage 3 type 1 diabetes, there could be a whole lot of treatments, both in older age groups and younger age groups, and also possibly in the earlier stages. Of course, we have already collected insurance data from both individuals up to the age of 70, and we have a smaller study in progress with intralymphatic injections in stage 1 and stage 2, and have gone with subcutaneous injections down to 4-year-olds in children with stage 1 type 1 diabetes. To be able to get formal approval, we have to see what is required to do that. For example, with LADA, we have said that it is now beginning to be classified as type 1 diabetes, that it is not a separate indication. And there could be opportunities to get approval, if we get approval for stage 3 type 1 diabetes after Diagnosis 3, that it would include older individuals. And then the entire LADA population is included in that as well. I do not think today, given the discussions we have had, that one would need to do a separate large study in LADA, since it is the same disease as type 1 diabetes. But we should still have those discussions with the authorities to understand a little better what is required. And then it comes to the earlier stages, as I said, we have a study going on there, we have done the study there earlier. The question is what is required to get approved formally again. You don't want to do a 10-year study, like following up patients for 10 years until they get the diagnosis and then get approved. Neither we nor I think any shareholder wants to follow up for 10 years and wait for 10 years for that. It is of great interest, especially for us, given our safety database and that you are not admitted to the hospital when you do our treatment. There is a lot of talk about step 2 and step 1. There is even talk about step 0, that is, when you have one single autoantibody and then you should treat to see if you can reduce the time to the other autoantibody when you get step 1. And we have the right type of treatment se på alla så kallad preventiv behandling. Men exakt vad som krävs ännu, det kan jag inte säga, utan vi vill ju se till att vi inte behöver göra en stor, jättelång och dyr studie. Så det får vi också återkomma med. Men just nu är det ju fullt fokus på fas 3 som pågår.

Jag tänker nu när du ändå tog upp just med Säkerhets- och Säkerhetskommittéen, ni hade ju den femte och näst sista säkerhetsgranskningen här under kvartalet för fas 3. So there was one more before the interim solution in March of 26. Do you see any risk that it can be a negative result of that assessment or how do you see that risk?

Given that we have done 15 clinical studies so far and we have aldrig sett några allvarliga bieffekter som kopplar till läkemedel, så ser jag att det är en minimal risk. En risk finns ju alltid, den är ju aldrig noll någonsin med någonting man gör i det här. Men i stort sett så ser jag det mer som en positiv milstolpe innan läkemedel, alltså att vi har ute att Säkerhetskommittén samlas och ser att det inga liksom, högst troligen, fortsätter det ser lika bra ut som hittills. So I see it more as a positive milestone before the reading that will come. And today we have, as I said, 250 patients in the study. As far as I know, there are two who have finished the study, but it does not connect at all to the medication, but it is only one patient who, according to the doctor, simply could not continue due to other problems. did not want the patient to continue the study. And another patient who simply after a few years did not want to take part anymore, I thought it was a teenager or something like that, who simply did not dare to take part. But it's less than 1% dropout when the industry standard usually lies at 10%. So it's some kind of indication of how easy and also an indication of security in our healthcare. So that future security surveys would be something strange to say as highly unlikely. And as I said earlier, also in our security database, one of the most important things now before the previous reading, it is important to have something that is simple and safe when you as the first company hopefully will be able to go towards a approval with a new benchmark.

I think we go a little bit into the manufacturing process in Umeå, so there have been some questions here about the fact that large-scale technical versions of GALT65 have been manufactured there. On that basis, do you see the upcoming studies or the upcoming studies, perhaps one might even say, being sold commercially?

Not those bachelors, they are so-called technical bachelors. They are on a large scale made, but it is not yet done under a, shall we say, under a GNP certificate, but those that can be sold, that is, both used in studies and sold commercially, will then be done before this market survey, so to speak. There are PPQ batches, i.e. process, i.e. under a validated and qualified process, you should do three, usually you do three batches on a large scale when you have locked the whole process and it is a validated process and everything is controlled. And they should partly be available as a subject for market research, but they can also be used i studier och kommersiellt liksom. Men just de här tekniska batcherna kan inte användas. De kan ju användas såklart för annat. Det använder vi för andra kvalitetskontroller och skulle kunna användas för preklinik och liknande grejer.

And you have also talked a bit about the fact that the facility has a national role of preparedness and the like. What kind of drugs do you see that could be manufactured in the EU and the facility to ensure access to it in Sweden, for example, if it were to be a form of crisis in the form of war or something like that?

We have our The existing platform is based on how we do GAD, which is insect cells that are infected with a baculovirus that contains the sequence of the protein you want to produce. And this is, among other things, where you can make a vaccine, a little depending on which vaccine, but this would be a recommended vaccine, that is, what you develop that part of. of the virus that you want to have an immune response to. And other biological substances for other types of drugs that require recommended proteins, for example, it could be used for. And our platform has some advantages, a little depending on what you want, what the purpose is, so our platform is still When they are produced in these cells, it is done quite little so-called post-translational modifications, that is, the cells do not throw a lot of strange sugar molecules on the protein that perhaps the human body would react to. So it's a pretty grateful platform in that way that you get pretty clean proteins. But it is mainly for upcoming pandemics where you would quickly need to take, a little depending on again what type of vaccine that is needed or other small-scale and quickly get something in place, small-scale, there could be opportunities for that. And we have an interest in being part of this preparation as well, because it gives the company the opportunity to get some kind of support, like base support, to have it in place. And then it is also important to emphasize that when we build up the entire manufacturing expertise in the company, quality systems, routines, everything, it is extremely much easier to expand the business than to start from scratch. Because one of the big investments is primarily to build up a complete quality system around GMP processing. Once you have it in place, you can reuse the whole quality system. If you want, for example, to expand the existing facility or build up a new facility or something, you will not need to build up a new quality system, but it is already in place.

And then, if we talk a little more generally about the pharmaceutical market, then FDI released a new type of priority review vouchers to be able to shorten the review time to about one to two months. Is that something that the company is looking for?

Yes, I have read a little about it. You don't really know, we'll see where it will end up. A little depending on how you interpret it, some interpret it as if you are based in the USA, so then it's a little premieres American companies. Others say that it is above all to promote American interests, that is, if it is a hospital that is highly prioritized for the USA, then it is important. But it is something we are looking at, and it is above all the review time that is short to one to two months. We will most likely get a priority review, that is, we will get a six-month review. period, but this would shorten it even further. So it's of course something we're looking at, but it's a bit difficult to say. It's so new that we have to see where it ends up and how other companies will look at it as well, because there's still a while before it becomes relevant to us.

We have gone through this and you have mentioned it at some earlier times as well, but I think you brought it up a little short in today's presentation, but can you just say a few words about the market potential for the drug, just with the phase three that occurs and if it leads to a approval?

We usually update that in our presentations. We have calculated and done market analysis in the USA, and there we see for the launch indication, which is this stage 3, step 3, type 1 diabetes, that the market potential, and then you assume a 30-40% market penetration, that is, not that you achieve 100%, but that In a relatively conservative way, the peak sales potential is around $2 billion per year. Then we take into account the pricing of around $150,000. We also have the possibility to increase it to more than $200,000, but then we count on $150,000. Some rebates, up to 20% rebates, which you usually see in rebates in the USA, and we assume a fairly high coverage for type 1 diabetes, i.e. paid coverage. Type 1 diabetes is almost 100% covered in the USA as a disease. But that comes with a number of patients that are to be treated when they get closer or around or even over two million dollars, only that. And then we see the LADA population, which is actually type 1 diabetes, has at least as much potential. And then we have this previous stage, step one and step two, where the requirement is to have a large market, that there are these screening programs in place. Which is worked with a lot, and today it is even harder, we have heard that. Among other things Sanofi, which has the only approved drug there. One of the big challenges is to find these actually healthy individuals who do not go to the doctor today and test if they have type 1 diabetes. But on the day it is in place, it is a huge market. There are perhaps ten times as many who have the risk of getting sick with type 1 than those who get sick. And there we see that our largest market in the future will be there in the earlier stages, type 1.

I think now that we are still talking about screening and a little more detail, there has also been a question here about Sanofi and their treatment site and that they, according to the report, have had a little trouble finding patients. Do they have a similar system as this Mail.ai, which you are a bit involved in, both as owners and in the form of projects, but do you also think that Breakthrough T1D could help you with a larger production study in the USA, for example?

Yes, the USA is just, it's public figures, you can see how many free sellers there are at the moment in the USA, and it has been slow, and the difficult thing is that you need these sprinting programs. It may happen that screening programmes will first come into place in Europe, where there is a different type of healthcare system, a little more tax-paying healthcare system, than in the USA, where it is insurance companies that should pay for such things, which makes it perhaps a little more difficult to get that in place, even if the USA is the largest market. But there is a lot of work to be done with this, so it will probably be easier and easier every year to find these individuals. So it's good for us, we should say, that we don't have to do that rough job, but that someone else does it. When it comes to what we work with in ASET, we are absolutely involved in Sanofi in the same way, and they have also been at a conference that we have organized together with Sanofi. Här i Sverige kring awareness, typ 1 diabetes screening och liknande. Och det är många som jobbar med sådana här typer av AI-modeller också för att bättre kunna hitta individer som har riskat insjukna. Och det finns ju ett intresse kring det som har gjorts inom Asset också, bland annat från Sonofi och andra spelare också. Alla säger ju vad vi också håller på med, men det är många andra som håller på med samma saker. Och alla har ju samma intresse i slutändan. Det är ju det här som brukar kallas pre-competitive. project, that is, that everyone has an interest in this becoming better and better, to be able to find stage 1 and stage 2 type 1, because if we get good at it, then everyone will benefit from it. So it's much more altruistic, altruistic cooperation that takes place on that front. Was there something I forgot in your question?

I don't know. Was there anything? No, I think you got everything, actually. It was a long question, but it was a good question. Sen har det kommit lite mer frågor här om just insulinspåret som du var inne på tidigare och om bolaget kan genomföra kombinationsstudier med både GAD och insulin parallellt eller om det måste ses sekvensiellt och om bolaget kommer använda insulin, proinsulin eller preproinsulin?

På den första frågan är ju viktigast att man ska kunna komma in i klinik så att man har godkännande att börja göra klinisk utveckling. And there are absolutely opportunities to make combinations. And I think that it is in our interest to be able to come up with a plan. What is the fastest, most possible way to get... We learn as much as possible in the early clinical phase and move on as well. And now we have the garden in place and done, and there are then opportunities to be able to potentially do a study. It's always a question of cost, how big it will be and how many different treatment arms. But to be able to do a study where you would have insulin alone in a few different doses and take injections and also a combination arm with GAD. In this case, it would be rational to primarily have combinations for the individuals who are so-called heterozygote, who have both HLA types, DR3 and DR4. i.e. those that are linked to GAD autoimmunity and insulin autoimmunity, and then they should be treated with the combination. So there are absolutely possibilities and a rationale to do that. Then when it comes to exactly what type of insulin molecule, it is something that we will have to come back to before we see anything in public. So far we can see that it is an insulin-like molecule that we will have to develop, Just as it is insulin or pro-insulin or pre-pro-insulin, a variant of an inactivated insulin molecule, a little dependent on, or some other variations. We get a little look at that. It is important to take into account both what we think will give the best possible effect, how to manufacture it in the best possible way, and how to protect it in the best possible way. So you have to take into account everything when you start developing someone new. En ny sådan nytt samtal till.

Ja, och så har det kommit en fråga här om att vi menar att det sagt att marknadsexklusiviteten från Orphan Drug i särläkemedelsstatus då trumpar patenttiden. Gäller den särläkemedelsstatusen ni har även steg 1 och 2, den eventuella dag det är aktuellt att gå till marknadeprevention, eller hur ser marknadsexklusiviteten ut för just steg 1 och 2?

Precisely, we have Orphan for stage 3, and then we also have, sorry, in the USA, 12-year market exclusivity. Orphan gets 7-year market exclusivity from the day you get approved, and then when you have a biological drug, you get 12-year market exclusivity from the day you get approved. So that will be the biggest exclusivity, this Biologics, in 12 years, and in 10 years in Europe. When it comes to step one and step two, there are of course many more individuals, and the question is if they are so many that I would think that they are broken, that there will be more than what Orphan covers, so it's not Orphan for that, but we have Orphan for stage three, which is the launch indication, and the others will not be under Orphan, but we'll have to look at that. In the end, we believe that it will be the same genetic subgroup that counts on that prevalence. Then it can happen that we get approved for stage 2 or stage 1. It's not stage 1 and stage 2. Depending on this, you have to go back and hear about the discussions with the authorities, if there is a possibility for Orphan on that side, but so far it is stage 3 we have Orphan for.

You were talking about Sanofi and Epidro, how is it going? This is always a question that everyone has on their lips, but do you feel now that you have a little better financing and that it is moving forward with agreement negotiations with Big Pharma and could Sanofi be a part of that?

They are absolutely one of our potential partners. All of us who are active in diabetes are potential partners for us or companies that are active in Immunology, autoimmunity, inflammation, even in cardiovascular diseases, given that when we treat type 1 diabetes early, it is one of the major stora framtida målen att kunna drastiskt minska risken för hjärt- och kärlsjukdomar. Det finns många olika bolag med olika kompetens- och fokusområden som är potentiella partners för oss. Givet en stark kassa är det såklart extremt viktigt i förhandlingar att kunna sitta hela tiden med den starkaste möjliga kassan. Det bästa caset egentligen för partnering är att ha en stark kassa and to have a standalone strategy all the way to the market, that we know how we are going to commercialize this. Because if you can show and you know that we know how much we would feel about commercializing ourselves, when there is an order on the table, we can take that into account and see how it pays off and be able to say to Vidfarma that we are doing this better ourselves. And of course, the longer we come, the more and more we look at such opportunities as well. As I said earlier, we should never be dependent on a potential partner, because they also know that. If they know that we are dependent on them, they will easily just sit in the boat and wait. And we get desperate. But here we are in an extremely attractive case. And type 1 diabetes is not a giant indication, so there is no need for a giant or an organization to sell this. But absolutely, it is a great, great strength to be able to sit on this, what is it called, our cash position, and it is something that we also update our partners with when they get the update, to tell how well it has gone in our financing. De gratulerar oss också till våra finansieringar. De ser det ju också så mycket positivt. Nu har vi ju ögonen på oss. Det som jag redan påminner om, det är ju faktiskt roligt att höra att... Ursäkta, även till exempel Breakthrough T1, det är ju som också träffar oftast många olika farmabolag ur sitt perspektiv. berättar till oss så att alla vet om oss. Alla följer oss för de vet att vi är först ute nu. Så vi har ögonen på oss och det är spännande.

Vad är det som ni känner att i de diskussioner som ni har, det kanske är svårt att gå in på detalj, men vilken del eller delar är det som det har varit mest utmanande eller mest diskussioner kring att nå samsyn kring, är det frontbetalningar, royalties eller mytstolpar som ni ska uppnå? Vad är det som liksom har varit den största diskussionspunkten?

Jag tror det, alltså igen man vet ju Big Pharma, de har absolut inte ont om pengar så det är nästan, jag skulle inte säga en bisag för dem liksom utan det viktigaste för dem, de är ju extremt konservativa, vill absolut inte ta risker och då är det ju mer det här liksom att just kring C-peptide and approve it. Today, there is no approved treatment just for stage 3 diabetes, so we will potentially just put it out there. So that's what it is, that they want to feel comfortable with it. But there we are on very good data, very good security, and everyone realizes that with FastTrack, Orphan Indication and all that, so we have the best possible case, I could say, that you can just have now, before a reading and then discussions with the FDA. But there's a lot more about that. And then, as we've already talked about, commercial potential is important for them. How big can it be? How do the indications develop towards step two and step one? How big can this become? How much money can you make from it? And long-term? And all that. So, those are the two big things. Then, when it comes to the milestone payments and royalties and such, Man ska inte säga att det inte är viktigt för dem, men pengar har de. Det är väl mera det här när de en gång satsar på ett nytt läkemedel. Det är alla resurser, mera personalresurser och allt sådant som man binder till det som de kanske som är då resurser bort från annat som de skulle kunna satsa på. Det är mera sådant som de tittar på. But the more activity within type 1 that these companies have, the more they start to link resources to the area, and then it is easier for them to take in new programs within the same area that they have invested in. So it's a bit more of that type of discussion, if I may say so. It's a lot, of course, the eyes on us now, CPAP time of reading and all that, what it means. And then it's a bit dependent on Is it possible to do something before the pharma partner? Or do you do it afterwards when you know more about the results? For us as a company, the most important thing is to focus on all preparations. And of course, as I said, it is also very important, especially in negotiation positions. But also for us as a company, if we want to grow, it is also important to be able to have a standalone strategy. och det har vi ju rengjort marknadsundersökningar i USA och vi vill ju fortsätta på rätt sätt att förbereda på det så att vi aldrig bara blir stående och väntande och hoppas att någon Big Pharma-bolag ska komma in för att de kommer ju att veta om vi behöver dem eller inte behöver dem.

Och lite kapat är det också, du berättade ju lite om de milstolparna som man kan förvänta sig i närmsta året, men är det ändå satt på in egentligen närmsta tiden att man kommer fokusera på att egentligen to run this standalone and then if it becomes a partnership, then it is, but that you still work from a standalone perspective.

Exactly, it seems like a study question, a strategic question, but I see it now that we have already started it to a certain extent and I think we should continue it too, it is important. And as I said, if you do it right, you can make a lot more money by doing it yourself, and then you can build up a commercial company and in a completely different way start broadening the portfolio and and sell in the USA and in Europe as well. So you should have that strategy, given how far we have come. And there is an opportunity to hire. You don't have to build up your own sales organization. You can hire the sales organization. The important thing is that you are on the strategy and the right type of, let's say, high-level competent people who know how this should be done on a strategic level. Then the rough work, sales and such, they don't have to be experts, but you have to be an expert on how it's going to be launched. And key opinion leaders in the USA, above all, we have good contact with them. We have the largest, most important clinics in our study. John Hopkins, for example, in Baltimore, which is a really big hospital that covers a large area, and Jocelyn in Boston and other extremely important clinics that will be our predecessors when we go to the market, will be the ones who will first start writing out the medication as well. But more important, of course, is the standard and strategy. But you have to do that, you shouldn't take too much risk too early, but take it in the right step. And at the same time, of course, we run both discussions with partners as well. We see that there is a great interest there as well, but we should never be dependent on them. Because then it can happen that we make mistakes as well, types of mistakes, way too low upfronts or milestones and things like that, if we become dependent on them.

Yes, it sounds like a clever way to go. Just with a few last questions here, we're starting to run a little short on time, but as a conclusion here, will FDI be based on market satisfaction only on Diagnostics 3 or will they also include the earlier results from Diagnostics 2 and meta-analysis as well?

De kommer att titta på allting. Vi har ju redan förankrat med dem vad som krävs för en säkerhetsdatabas. De baserar från tidigare studier plus pågående fast trea. Sedan kommer effektdatabasen med att titta på helhetssatsen. Det blir ju att de tittar på allt. Fast trean blir ju viktig. and the safety and effect of fast training becomes important, but they take into account everything, that is, the accumulated knowledge about the entire drug in their decisions, so they will do that.

What can happen then, as a small pre-question on that, we talked a little about dropout and how it is very, very low, Is there any statistics on those who have left the study, if they have been on placebo or if they have been on active medication?

We don't know. It's totally blind. We have no idea. The only thing we know is that if you find adverse events and things like that, then it's some kind of of the Security Committee, they are sometimes a bit blind to that, because they have to be able to make a decision, is this something connected to the drug or not, so that they can say that this is probably not connected at all to the drug, but we as a company have no idea about that, and we should not know that either, because we have to show that we are blind all the time.

And as a final question, you also mentioned a bit about off-label treatment. Have you mentioned that doctors can give larger doses or more doses to their patients to increase the effect?

How exactly, it depends, but what I know is that off-label is often not so that doctors can do exactly what they want, but they have to If you have approved medication, you have your medical advisors at the company, who often call and ask. If you have a patient like that, it would be okay, for example, who is younger than your label, it would be safe to be able to give the medication to them. beslut om det, okej, men vi har ju gjort studier i den åldern, det borde inte vara någon risk hit och dit, och sen kan man liksom ge någon typ av rekommendationer, det skulle vara okej att göra det, men att de kan liksom börja använda helt andra doser och sådant här, det har jag svårt att säga. Visst, i USA är ju en lite annorlunda typ av marknad, det har ju varit mycket på tapeten det här kring de här nya GP1-agonisterna, alltså de här type 2 diabetes medication, which is now for obesity, there are such compounding pharmacies, actually pharmacies that mix the same active ingredients in new doses at the request of doctors. And that has become a bit of a problem, we can say commercially for Nordic countries and others, what they have, now I think they have succeeded in stopping it. But it's a slightly different type of market dynamics, but I don't know There are more drugs that go towards really large, broad groups, but now we have an orphan drug, a specialist drug. I don't think that will happen, but off-label. Possibly that extra injections could be used, because we have also done a study, Diagnosed B, where a fourth or fifth dose has been evaluated, and there is a certain certainty about that. Possibly that could happen, but again, it should happen at the company's knowledge and in discussion with the company, so that it is not done completely uncontrolled.

Ja, jag tänkte vi har ändå någon minut till här. Det kom in en liten avslutande fråga så tänker de få sin chans också. Men vi pratar ju väldigt mycket om USA och att det känns som det är väl förberett där ni har Fast Track och Orphan Drug och annat som vi har diskuterat. Men vad händer i Europa? Och sen så egentligen en liten avslutning där man får väl hoppas på positivt svar men det är om du själv tror att ni kommer komma ut på marknaden de närmaste året.

First, regarding Europe, as I said, the important thing is that EMA has also approved that it is a single pivotal trial, one FAST-3 is enough, and of course with good results from it. And there we expect that, if nothing else, it is the end result from FAST-3 that will be the basis for it. There may be a possibility for a similar one, as in the USA, if there are good news about this early readout next year. that one could have a discussion with the EU about a potential permit approval. Then it becomes more of a question of resources for the company to be able to start launching in the USA and in Europe. Europe is a little different, many countries in Europe, you get a central approval, then you are going to sell in each country separately. In most countries you should first get reimbursement, i.e. payment, to make sure that this reimbursement comes into place before you can start selling. Germany is a country where you can start selling directly after approval. So it's a bit more like the US. But it's also a matter of resources for us. The US is the most important. The biggest money is there. But there is also a possibility for Europe to be able to, if they want, give conditions for approval. But we'll have to see that after we've done the review and how it looks and all that, so that we don't lose too much at once. But otherwise, it is Europe that we will also send into the second market. And then, what was the last question?

Was it more likely that we would... What do you think? Will you come out on the market?

Yes, I think and I hope that we will come out on the market. And we have good results so far on CPEP since earlier, so I think and hope also on this early readout that it will be positive and then there will be a discussion with FDI where they will look at all the data and make the decision. As I said, I don't think you can find a better case than us right now, given the orphan designation, genetic subgroup, large safety database, many, many clinical studies, most of which are placebo controlled, given that there is also a new leadership now at the FDA. som är både kritiska till att kanske tidigare ledning på FDA har varit lite välfrikostiga med vissa genterapier och cellterapier och accelererat godkännande inom onkologi, men samtidigt är de mycket måna om då att du har bra säkerhet, placebo-kontrollerade studier, särläkemedel, rare diseases, absolute incremental changes, jätteviktigt. Så jag tror inte man kan hitta ett bättre case än just nu för oss. Sen i slutena handlar ju om effekten av biologin, hur det visar sig, men vi har gjort allt vi kan inför det här så vi tror och hoppas på att det här kommer att gå bra.

Ja, det låter som en perfekt positiv avslutning på den här presentationen och frågestunden så tack så jättemycket Ulf för en fantastiskt fin presentation och tack även alla ni som har lyssnat. Precis när sommaren drar igång så får vi önska alla en trevlig dag och en fin fortsatt sommar.

Tusen tack och trevlig sommar alla!