Who we are. We are all about treating inflammatory diseases with a totally new concept, which we very much believe in that can be broadly applied for quite a lot of different indications. I also understand today that this is the first biotech company in the Avanza Börsdag, right? It's quite complicated. My task today is really to give you a flavor of what we do in a more general sense and not from a specialist point of view. As I said, very much about inflammatory diseases, totally new concept. As also what was said, we are on the Stockholm main list on the mid-cap section, as you said, SEK 2.3 billion in market cap. We have more than 14,000 shareholders, and we're very proud of that.
All of them being extremely important for us and quite a few of those has been with us since we listed at the at the smaller stock exchange in Stockholm or at the Aktietorget. Last year, we went up to the main market directly in order to capture more investors and in order to be more prepared for what to come. As you can see, in terms of the milestones in 2022, there was quite some important milestones beside the up listing to the main market. It was also approval from the FDA that we could do development in the U.S.
This is quite important for a drug development company because the U.S. is the biggest market, and it is a sample of quality if we can get a U.S. IND as we got. Well done from the R&D department there. We also have initiated 2 phase 2 studies. These are the studies that I will talk more about today because these studies will read out in the end of or the second half of this year, which will be quite important. I'll also show you some of the data that is behind our lead compound, AP1189, and what that compound really does in inflammation. The real value in the company is the pipeline.
As you can see here, for those of you that are not familiar in reading pipeline slides from biotech companies, the preclinical is when the compound is in animals, and we are preparing to get into human beings. The Phase 1 is when we are testing it on volunteers that do not have any disease. If that is still okay, then we can get into patients. This is exactly where we are today with AP1189 in several Phase 2 development programs, both in rheumatoid arthritis, which is a very big indication. I will get back to that and why we choose that one, but also in some nephrotic syndrome disease, which is more narrow and more often indication, seldom diseases.
In addition to that, we have proved the concept of AP1189 also in COVID-19 inflammation in the lung, and that is quite important. We got results showing that we could get COVID-19 patients more quickly out of the hospital. That was important. They required less oxygen treatment. That was also quite important. We acquired TXP Pharma. That acquisition went through in the beginning of this year, and that broadens out the pipeline all within the melanocortin receptor field. I'll explain to you why is that field so important for us. First, what is inflammation? When we get something that we don't want into our body, that could result into inflammation.
When you get an inflamed tissue, for example, a hand, I normally say that if you get something in your hand, you get an inflammation. You get recruitment of immuno cells. That can be so-called white cells, and that can also be the so-called trash cells, the macrophages, which is cleaning up after the inflammation. If it's an acute inflammation, then you can get rid of all the debris and this factor that came into your, for example, your skin, or if it was bacterial, you get rid of the bacterial, and you recover. There are diseases that results in a more chronic inflammation, and that is, for example, rheumatoid arthritis, where the inflammation does go on and on and on.
It's much more difficult to get that inflammation down to normal levels and you get rid of the symptoms. The normal drug that everybody knows in inflammatory diseases like this is corticosteroids, Cortisone. Cortisone dampens the whole inflammation, but it's also linked to a lot of side effects. Which is unbearable for quite a few patients. For example, in rheumatoid arthritis, quite a few patients in the beginning do get steroids in order to get the inflammation down. It's really linked to severe side effects. What we do and is to rebalance the immune system. Instead of totally shutting off the immune system, we make the immune system in a better shape to conquer the inflammatory response.
We get a dampening of the immune cells, we reduce the immunostimulatory cells, and we stimulate the macrophages, the so-called trash cells, that are quite important, very important in this inflammation in order to clear off the debris in the inflammation. This is a very, very unique way of acting. We believe, in fact, that this is something that can be applied for quite a few different inflammatory diseases, not only RA. Quite unique there. Why RA? Why rheumatoid arthritis? It affects 1% of the global population. About 70%-80% females. It's devastating. You get more and more symptoms. You get more and more handicapped through those symptoms. The treatment today, we have quite a few different treatments. However, importantly, the treatment doesn't do the trick. It's often a combination treatment.
You start with what we call methotrexate, which is kind of cell poison, with a lot of side effects. If you stop having benefit on methotrexate, you add on treatments up to antibodies where you inject into the body, which dampers one of the, one of these mediators in the inflammatory response. At the end, you can have really a lot of different options. However, more than 50%, up to 70% of these patients do not get symptom relief. It's a big medical need in order to find something that could add on and not have a lot of side effects, as the existing drugs do have. This is our aim.
Our aim is to develop a safe and efficacious treatment, a per oral efficacious treatment that can be added on and be important in the treatment of rheumatoid arthritis and other inflammatory diseases. We finalized the BEGIN study. The BEGIN study is the first study, right? Where we looked at severe newly diagnosed patients with a high symptom score to see if 1189 could help dampening the symptoms and maybe get totally into what we call remission. When you do clinical studies in RA, there are different endpoints that you need to follow. These endpoints are all linked to different symptoms in the disease, like, you know, redness, like the joints being swollen and the pain, but also some biomarkers.
The acute phase proteins, the CRP is quite important as well for when you get more into the disease. When we looked at the four-week study, and four week is rather short period in a chronic disease. However, when we looked at that, and you can look at the left side here, this is so-called C line. C line is one of these composition of symptoms that is so important for these patients. There are a couple of things that you need to look at here. One is the dose response. We went in with 50 mgs, and we went in with 100 mgs, and then the placebo was methotrexate that I just talked about. That is the base treatment for newly diagnosed patients. They can only get so much efficacy.
We added on to see if we could get even more efficacious readouts with AP1189. As you can see here, when you look at the dark blue one, that is the 100 mgs per day, you can see a significant effect of AP1189 being added to methotrexate. This is importantly a clinically meaningful efficacy already after four weeks, already after four weeks. The same we could see with what we say is ACR20, 50, and 70. This is the fraction of patients that do have effect: 20%, 50%, and 70%. Also in the 100 mgs per day, we could see a significant effect on the 100 mgs patient on ACR20.
This is the readout for the American FDA, the authorities that do either dismiss or approve new drugs coming to the market. This was an important readout, but it's also a compositional of different symptoms as C-C-line. Importantly, we saw significant effect on two different parameters here, both being extremely important in the development of new drugs for rheumatoid arthritis. If we look at the so-called DAS28, this is also a comparison of swollen joints, pain, and so on and so forth, in addition to CRP, which is this acute phase protein, which some of the newly diagnosed patients do get. Here we also saw a quite a decrease in disease activity, and this is important, a decrease in disease activity.
Another point on the right side is the fatigue score. These patient, and you might know some patients with RA, they can be extremely tired. The fatigue is a major problem for these patients, and it's difficult to treat. Here we could see, although not significant, but we could see a clear trend towards a much better relief of the fatigue. All these parameters was quite important for us, and that led us then to look at the safety profile. One thing is the efficacy, we could tick that off after 4 weeks in the BEGIN study. However, we also wanted to look at the safety profile, because if eleven eighty-nine should be a important add-on in the treatment of rheumatoid arthritis, you need to have a good safety profile.
The bottom line from this curve here, you can see the placebo, the methotrexate, which do induce side effects, we know that. The 50 mg and the 100 mg was quite comparable. No serious side effects and only mild to moderate, which is quite important. Remember that all these patients, they got methotrexate in addition also then to the 50 and 100 mg AP1189. All in all, the bottom line here is that we have a good safety profile, which will be important. However, this was 4 weeks, and we needed to do longer studies, and the EXPAND is a follow-up on the BEGIN. The EXPAND do target exactly the same group of patient as BEGIN, newly diagnosed patients with severe rheumatoid arthritis.
Why did we do a 12-week study? Yes, obviously, we want to see the efficacy and the safety after 12 weeks. This was also an important question to the potential partners we are talking to in order to take this this even further was quite important. That's why we are doing this, and we just finalized the recruitment. This is AP1189 in 100 mg. You remember that this was actually where we saw the best effect, and with the placebo, and the placebo is still methotrexate. They are not allowed to get any corticosteroids, and that's important. Quite a few studies that has been done, has been done also including corticosteroids. We don't do that here. We want to have a, as clean picture as possible.
12 weeks, once daily dosing, 60 patients per group, and we randomized actually totally 127 in a very short period of time. That was really well done. Primary endpoint is the ACR20. As you remember, this is really the endpoint coming from the FDA, the U.S. regulatory authorities. The secondary endpoint is the others that we talked about, the C-C-line score, but also the DAS28 score, which also was significant in the first study, and FACIT-Fatigue, of course. In addition to that, we have a sub-study looking at the inflammation in these patients. We are doing MRI, looking at the different, see if we in 12 weeks time can alter the inflammatory response in the joints.
That's also an important important question to to answer also in terms of the mode of action. The second study is the RESOLVE study. This is the so-called DMARD-IR. These patient have gone through methotrexate treatment, but it doesn't work really anymore. Then we add 1189. This is the next cycle in the treatment. First one was really first line. This is when methotrexate doesn't work anymore. Can we then add on and get them to respond? Important question. It's a kind of approval of a concept, I think, for these group of patients.
Remember, a rheumatoid arthritis patient is like, for example, other diseasesIs they kind of shift phenotype from time to time because they don't respond anymore for one treatment, then you add another treatment and so on and so forth. Here we have dosing once daily with different doses of AP1189. We have the primary efficacy endpoint is still ACR20 and the secondary endpoint exactly the same as in the EXPAND. We're also doing an MRI sub-study on the part B of this. When we get the results in the second half of this year, we'll see do also these patients respond?
If so, then we go into a part B, which will be a 12-week study with selected doses of 1189. Important questions to be answered in the second half of this year. When we look at the profile of 1189 right now, it looks quite favorable in terms of the treatment regime in rheumatoid arthritis. Once-daily oral dosing is important because if you are a patient, you want to take a pill per day. You don't want to be dependent on going to the hospital and maybe having the injections and so on. It's important, it's convenience.
Quick onset of action, actually, both in the COVID-19 study as well as in the BEGIN study, we saw quite a quick time to efficacy. That's also quite important. You know, steroids do have very quick onset to action if you take enough. However, you have all the side effects. Here, you have also a quite a quick onset to action, however, not with the same side effects at all. The high degree of efficacy. Remember that some of the compounds that we do compare us with is, for example, the JAKs, oral, good efficacy, however, with a lot of safety issues. We want to be almost as effective as the JAKs, however, with a much better safety profile.
That's the profile of the, of the drug. Steroid-free mode of action, right? No inhibition of the immune system, just a balance of the immune system that makes you fight the inflammation, and then compatible with the methotrexate. I think we always already shown that in the, in the first BEGIN study. If we take that into the patient room, where could this fit in? And we'll know much more about this when we get the results in the second half of this year, of course. Newly diagnosed, very severe patients could get into a balance in the immune system, balance in the symptoms more quickly. We also have some markers that make these patients more severe that we can look for.
That is definitely an opportunity. The DMARD-IR, as we talked about, the second study that we get read out this year, where methotrexate doesn't work, and then you can add on. As you can see here, there are the 1st line and then 2nd line, 3rd line and 4th line. That means that the patients go through different cycles. What they are treated with doesn't work anymore, and then they add on. We hope that AP1189 is a basis for treatment all the way through. I talked about the highly active, newly diagnosed. When we did the market research lately, this was quite a attractive group of patients to treat.
So that is indeed a very good group of patients with clear medical need. The DMARD-IR and going into the second line of treatment, the market opportunities there is very, very big. Obviously, that's where you want to be. We'll get some of the first answers when RESOLVE part A reads out. When we asked the high prescribing US doctors, we also asked high prescribing European doctors, what do they want? What is the need in RA? Describing the profile of AP1189 and for DMARD-IR, the second study, degree of interest is high and anticipated use definitely very high as well. Quite a few of these patients, they go into antibodies.
TNF-alpha antibodies is one of them. They work for some patients, but doesn't work for others. So definitely also there is a good opportunity. Then we asked the doctors, "Okay, with this profile, what else would you test?" There were quite a few different diseases. Psoriatic arthritis being one of them. Lupus is also an autoimmune disease like rheumatoid arthritis with some of the same inflammation mechanisms, which we believe could be extremely interesting to test. Ankylosing spondylitis is another one. As I started by saying, this could really be interesting as a general anti-inflammatory, where you help your body to balance the immune system to the better and help. I think we did that.
Help your own body to conquer the inflammation. This is what AP1189 do, I believe. If you look at the different treatments that are out in the market today, you see a lot of different indications, a lot of different diseases that are treated in a quite a broad way. However, as you can see, black box warnings. Black box warnings mean that the U.S. FDA have put on some warnings for this drug. As you can see, quite a few of them have that. If we could come through this development without severe side effects, I think that would really add on the benefit of AP1189.
Building SynAct Pharma further, I'm taking over as the CEO on Thursday after the AGM. And we're shifting because now SynAct Pharma is really coming into a extremely exciting period of time. Jeppe Øvlesen has been the CEO since we started the company, has been instrumental in developing it. However, he's an entrepreneurial. I'm a pharma guy, and this is what we need at this point of time. Talking to investors and also talking to potential partners. This is the value. This is how we want to build SynAct Pharma in order to create even more value. Thank you.
Thank you. The Q&A time. Do I have any questions from the audience? We have. Microphone is coming.
Now, normally when you introduce a new drug, you are allowed to start with fourth line and work yourself towards first line. You indicated that you hope to rather quickly end up in the first line. That's my first question. The other one is, if this works for rheumatoid arthritis, how allowed will the clinicians be to use this drug for all the other inflammatory diseases without huge studies on each and every one?
Yeah. Very good question. In terms of the first one, first line or second line, we have used the first line, the more severe patients, newly diagnosed as a kind of proof of a principle and concept. Can we really damper the inflammation where they are quite, you know, naive in terms of treatment? That has been. It's also, as I said, the more severe patients, I believe is a good market opportunity there. However, the big market opportunity is in the second line. That is where we are going to focus for the next, the next trial to phase 2B in Resolve will be in that segment when methotrexate hasn't been.
Then, of course, there is also, okay, when methotrexate doesn't work, what about the more expensive antibody treatments, right? That will also be something that could be looked at. We do the development from a drug development point of view. It's all about answering different questions, as you know. I think we answered with the results coming in the EXPAND study. We have kind of answered the questions about newly diagnosed. 100 mgs, where do we get it in terms of efficacy and in terms of safety in 12 weeks? That is important also for potential partners. Then the DMARD-IR and the second-line treatment will be the focus, I think.
You can go back because what is interesting is that none of the none of the DMARD, the disease-modifying treatments today can be used in first line actually because of the side effect profile. My dream is really to have AP1189 as a basis in the different lines and see how far we can go. Maybe we could even prolong the time where you don't need to have additional treatments. You know, there are many questions to be answered on that. In terms of the different indications, you know, doctors are only allowed to treat when you have an approved drug in that indication. Otherwise, it's off-label, and that is not allowed.
That's probably also why we need a partner to take care of the further development also in the phase 3, further development of AP1189. You know, maybe we get it after we see the data now, maybe we get it when we have done the next study. We will have a focus on that.
Even so, if you prove that this is harmless, off-label use is commonplace.
Yeah, well, some are using, yes. You know, from a strict regulatory perspective, you need to have the indication.
We are overdue. If any one of you needs to leave, it's okay to leave, of course. We have some questions from the people viewing this online. I think we will take the questions in quite a fast manner. I would like to address them anyway. If anyone, anybody needs to leave, it's okay, of course. Life hack. Is it okay for you if I ask the question, the first question, it's a long one, in Swedish, and you answer in English?
Yeah.
Because you're Danish.
I can answer in Swedish as well.
Okay. Perfect. All right. The other questions comes in English. När man fördjupar sig i forskningen gällande melanokortinsystemet, rätta mig om jag har fel, inser man ganska snabbt att det är ett av kroppens viktigaste regleringssystem när det gäller inflammation. Det blir då ganska uppenbart att studierna inom RA endast är en del av helheten. Finns exempelvis otroligt mycket preclin-studier där man testat melano. Hur uttalar man det?
Melanocortin.
Melanokortinagonister inom diverse sjukdomar med gott resultat. I princip alla godkända läkemedel inom immunologiområdet är godkända inom ett flertal indikationer. Mer och mer forskning visar dessutom att just resolutionsterapi öppnar helt nya indikationer. Tänker exempelvis på åderförkalkning, där man i nyligen utförda preclin-studier visat att just en MC1 plus MC3 agonist verkar väldigt lovande. Kommentarer på det. Nu till frågan då: Hur ska ni göra för att via en deal kunna få betalt för AP1189 inom flera sjukdomar än just RA och NS? Vilka ytterligare indikationer är mest aktuella i samband med era samtal med BP? Många frågor. Du får svara på det du kommer ihåg.
Jättebra frågor. Det som ju är viktigt här, som jag också sa lite under presentationen här, att melanokortinsystemet som vi jobbar med, och inflammation resolution ser ut till att vara en generell mekanism. Som Hans säger väldigt rätt, det är att till exempel innanför åderförkalkning så är det jättemycket inflammation. Innanför cancer är det jätteinflammation. Innanför Alzheimer är det mycket inflammation. Här finns det många olika möjligheter. Vi har en lista på indikationer, sjukdomar som kan, som med hög sannolikhet kan ha en bra effekt med AP1189. När det gäller en möjlig affär, hur bruker vi det i förhållande till möjliga partners? Det har vi med. Absolut. Och vi har med vad vill det ge och så vidare. Så det är en viktig del av förhandlingarna.
Hi, you have told us on several occasions that you're well-courted by the big biotech companies. If the study results are a grand slam, which we believe and hope for, do you feel that it can be a quick for larger company to intensify its discussion with you?
I definitely do believe so because this is quite... You know, we started this discussion after the BEGIN results, and we have kept the contact to all those that were interested at that point of time. We will keep them updated, and obviously quite a few of them has could have a kort startsträcka.
Startsträcka.
Yeah. Obviously we have the opportunity to do that. We all need to remember that doing a potential deal takes time.
Yeah. Peter, he wants inside information. "Could you hint anything about the deal levels you are discussion with BP in case the study results are good?
In what? Sorry.
Could you hint anything about the deal levels you are discussing with BP in case the study results are good?" I'm not sure which study results he's referring to.
Yeah, yeah.
Oh.
No, the study results that I talked about. I will never dream about starting a negotiation in this forum, although I like it.
Of course.
So, so, so-
No inside information today. I'm sorry.
One thing is quite certain, is that if there is a good results, if we see a good interest, we'll do everything to maximize the value of our shareholders. Remember that management and the board do own more than 15% of the company. We are in the same boat.
Skin in the game.
Skin in the game.
We love the skin in the game.
Yeah.
If the blind data from EXPAND study at this point in of time, enough for management to be able to forecast the readout?
No.
No?
No.
No?
No. I, in my previous life, I have looked at data looks promising for blinded, and then there were nothing. What we follow, obviously, is the safety profile, right? We cannot say anything about the outcome based upon blinded data. No.
All right. The people asking the questions are quite much more smart than I am. I'm just I'm not always sure what I'm asking for. Ulf says, "If this comes to a big success, do you intend to sell the company or take in a lot of money annually from partners and distribute it regularly to shareholders?
Yeah. I myself have been actively involved in deals for about SEK 40 billion, Each deal are different from the other. We what I can promise is that we'll do what is best for the shareholders, maximizing a potential deal value if that's what we're doing. I don't want to talk about what kind of deal structure, not at this point.
No, I'm not going to, I'm not going to force you. Of course. Last question. Microphone. Last question before ending up this wonderful day.
Just about maximizing value, would you entertain the idea of being co-financier, the company being co-financier of a phase 3 study, on a indication just to? In my view, Swedish companies do get 2 lousy deals.
Mm.
Milestones and 10%, that's it. I think that's unfair.
Mm.
We should get more.
Yeah.
In order to get more, we need to stay in the development longer. Your share price has not suffered as much as many others. If results are good in these studies that you are doing now, maybe you could attract the AP Funds to co-invest so that we still can be partake in the Phase 3.
Yeah. It's From a strategic point of view, it's a very good question as well. Again, it's as difficult to predict. However, in terms of deal-making and in terms of financing, there are several opportunities. It's all depending, as you say, on the data that comes. If they are quite good, and we can see the next phase, and not only we can see it, quite a few others can see next phase for the development. We have, both the partnering, we have the financing and, you know. Again, we will do the best for the, for the shareholders, I promise you that.
Torbjörn.
So.
Tack, tack. Thank you.
Thanks for doing that. Tack.
Swedish