Thank you very much for joining today's webcast hosted by SynAct Pharma. We look forward to provide you with a company update and to give further details and the rationale behind the planned rights issue announced to the market this morning. If we go to slide number two. As we will have some forward-looking statements during the presentation, a short disclaimer. If we go to slide number three. The presenting management today is Jeppe Øvlesen. I'm the CEO of the company. We also have on board Thomas Jonassen, he's the CSO and also the founder of the company. We have the CFO, Patrick Renblad, to join this webcast today. If you go to slide number four. The topics that we will cover today is a short overview of where we are with the company.
We will go a bit into details on the pipeline development. Some of the pipeline development is completed in 2021, but also about the exciting plans that we have for this year and for next year. We will cover a short status on the business development, and I'm sure that a lot of our investors have a specific interest in this point, and we can show good traction on this, and we look forward to enlighten you a bit about where we are. Patrick will talk about the rights issue, some of the details in it, and also the strategy going forward. We will end up with a session for a Q&A. Slide number five. Just a short overview of the company and where we are right now.
SynAct is focused on the development of a novel and best-in-class treatment targeting inflammatory diseases. It's a target that we have worked with since 2000, and we have actually created three companies around this product. The first one was Action Pharma, second one was TXP Pharma, and then in 2012, we established SynAct Pharma. We work with a very interesting area in inflammatory diseases, and as you will see in the presentation, we have reached a level where we are now just as effective as other compounds in the market, but that we are in a position where we have a safety profile that is a lot better. 2021 was a very, very important year for SynAct. We actually managed to show efficacy in two different indications in a phase II study.
That is strong and compelling data that we will talk about a bit more in the presentation today, and also data that has ensured that we get to the table with partners for partnering discussions. On the right side of the slide, a few facts and figures. Company founded in 2012. We managed to list the company on the stock market in 2016. We are in the planning and in the preparation of an uplist to the Nasdaq main market. We have 14,000 shareholders, and we are proud of that. We have really had good journey with most of the shareholders and a long journey with a lot of them joining also from the IPO. We are also very motivated in the management. We hold 20% ownership at this point in time.
We go to slide number six. This slide gives you a bit of an overview of the activities that we have completed in 2021. As mentioned before, we managed to get positive data in our COVID study in Q2. Later on in the year in Q4, the best data that we could bring up in our RA study with positive data in our phase II late that year. Data that has really proven that the compound works and that we get in front of partners that could take on the project at a later stage. We have also during the year supplied additional IP protection of our compound. That is really a critical milestone because it gives protection to the compound up until 2042.
We've also produced additional toxicology studies so that we can now dose in a 12-week study, and that is another very important milestone for us. In addition to that, we have produced a tablet that we have also shown that works with good compelling data and that enable us to do further studies in different kind of indication. Move to slide number seven. Thomas will take over.
Yes, thank you very much. Rheumatoid arthritis is an autoimmune and inflammatory disease, which is the main focus for our development of our lead compound AP1189. Rheumatoid arthritis affects primarily a chronic disease that affects the joints. It affects up to 1% of the global population. It has a very high business opportunity with a market size expected in 2025 to reach $30 billion. Importantly, the treatment of the current treatment options do not secure optimal treatment for up to 47% of patients. First-line treatment is methotrexate, what is called a DMARD, is working well and in more than 50% of the patients. The onset of action is slow, so you cannot expect the full effect before three months.
Importantly, a large number of patients do not respond adequately to the treatment and need additional treatment options like secondary and third-line treatment, including biologics as TNF blockers and oral small molecule compounds as the JAK inhibitors. All in all, with the profile of our compounds, we believe and find rheumatoid arthritis as very attractive opportunity for development our compound with the aim to be a novel potential game-changing treatment option in the disease. Next slide, please, which is slide number eight. This slide gives an overview of the current pipeline, focusing on our lead compound AP1189.
As Jeppe highlighted, we completed the first clinical study in rheumatoid arthritis, the BEGIN study, last year, where we reported high-level data just around December first. That gives us the opportunity. That study was conducted in previously treated patients where we added or we gave the compound in combination with the first-line treatment methotrexate. This gives us now the opportunity to continue development in first-line treatment. As I will show you, a little in one of the next slides, we have designed a study and aim for filing a clinical trial application in Q2 this year.
In addition, we also intend to make a parallel development of the compound in what is called DMARD IR patients, meaning the rheumatoid arthritis patients who do not respond adequately to the first-line treatment, methotrexate treatment, and therefore have a need for second-line treatment. That is, from a business perspective, a very attractive opportunity. We are currently setting up the development program in collaboration with the U.S. authorities, FDA, meaning that we aim to have an agreed program by the end of Q2 this year so that we can file the first clinical application, what's it called, an IND in the U.S. in Q3 this year.
We do also have an ongoing program in nephrotic syndrome, where we are currently working on redesigning the study to gain from the newly developed tablet as well as the possibility to dose longer. We will within the next week come back with an updated study design to present to you all in this potentially very attractive development path.
As Jeppe also highlighted, we did have and we did generate positive data in COVID-19, where we were able to show that the compound giving an add-on to standard therapy was able to reduce time to recovery, meaning reducing the need for oxygen supply by almost four days compared to placebo treatment, and was also associated with a faster recovery and shorter hospitalization. We are currently working to broaden this out to other viral infections, mainly on a pharmacology program, and we will focus on influenza, and we will come back with an updated development plan in the second half this year.
Finally, we do have an inflammatory, or we do have a next-generation compounds discovery program that we look very much forward to to develop further in the next year. Slide nine. Thank you. This slide highlights the main high-level data from our BEGIN study. The study was a randomized placebo-controlled double-blinded study in previously treatment in the rheumatoid arthritis patients who were offered to participate in the compound. If they were eligible for methotrexate, the first-line treatment applied to rheumatoid arthritis, they were offered the possibility to participate in our study. Then were tested either with placebo or either 50mg or 100 mg of our AP1189, given as a suspension.
Very importantly, we found that the compound was very well-tolerated, especially 100 mg group was very, very promising safety profile compared to the placebo and to what could be expected at this following fourweek treatment. Importantly, as I highlighted some of the other treatment options, for example, JAK inhibitors very early develop side effects that potentially then end up being treatment limited. Most importantly, immunosuppression. We did not see that at all with our compounds. From an efficacy point of view, and perhaps the most important here is that the primary readout was the ability to reduce disease activity measured by what's called Clinical Disease Activity Index. What we saw was that the 100 mg dose given once daily for four weeks significantly reduced disease activity compared to placebo.
15.5-point, as highlighted here, is actually not only significantly higher than the placebo effect, but it's also what is considered clinically meaningful response in a four-week treatment period. To the right, we do have readouts on one of the very important secondary readouts, the ACR scoring, the American College of Rheumatology's scoring system for disease for improvement in disease activity. The higher numbers you get here on ACR20, ACR50, ACR70, the better. ACR20 mean that you have an overall 20% improvement in or reduction in your disease, not only on a broad-based number of readouts.
What you can see here is that we have 60%, more than 60% of our patients treated with 100 mg responded to the treatment and qualified for an ACR20 compared to 33% in the placebo group. This is a clean, again, a clinically meaningful readout. With this in mind, we were of course very encouraged about the data, and importantly, we intend to go on with development in rheumatoid arthritis. Please go to slide number 10. Here, the 61% reduction in ACR20 as we saw here on 100 mg is clinically meaningful, and very importantly, also an effect that is very comparable to what has been reported for other compounds.
Most importantly, here we highlighted compared to the JAK inhibitors, a class of compounds who have a very large market share, market position with an annual revenue of several billion dollars, that recently has been one of the only oral treatment options in rheumatoid arthritis. JAK inhibitors has recently been highlighted to induce a number of side effects that has limited the use and recommendation from the FDA is now that you use them as third line rather than second line treatment.
In any case, it's one of the most potent compounds, and what we find very, very encouraging with our treatment is that we, following four weeks treatment, do have a response rate that is comparable to what has been reported with JAK inhibitors in these first-line, as a first-line treatment. You could say that that would be the target effect of our compound, would be that we expect that giving the compound for prolonged treatment periods, we could reach a treatment effects that again would be comparable to the JAKs and would be a very, very attractive to moving forward, pending that we continuously have the safety profile as we have seen in the BEGIN study.
The target profile of this compound would be once daily dosing as an alternative to what is on the market today with a benign and attractive safety profile. Could we go to slide number 11? On slide number 11 here, I highlight that the emerging clinical profile of AP1189 and how we see it positioned in rheumatoid arthritis. We do have a compound that is orally available for once daily dosing, and we now have a new tablet with a very attractive plasma profile following dosing. We do have a quick onset of action. It induces efficacy within days.
In the COVID-19 study, the RESOVIR-1 study that we conducted and reported during the summer last year, we saw already effects of the compound on the ability to improve oxygenation within the first 24-48 hours, indicating that the compound given in the right dose actually will induce a very fast onset of action. The efficacy following the four week treatment was, as I showed on the previous slide, comparable to the JAKs. The safety was very good. We did not see any severe adverse events, and importantly, overall, very benign and very attractive immune safety profile, and importantly, no immunosuppression, which in many cases is a treatment limiting problem with most other compounds targeting rheumatoid arthritis.
We do not have any steroid hormone-induced effect of the compound, which is quite important. There's one other compound that mimics the mode of action of our compound, that's on the market in the U.S., that's Acthar Gel, and that is limited by its treatment effect as it has a much more broad-based receptor targeting, including stimulation of glucocorticoids and thereby inducing steroid hormone side effects. We do not do that with our compound. That's very important. Then it's effective in combination with methotrexate, and most importantly, not less importantly, we do have an intention to grant given for a combination treatment, meaning that we can control the combination from our IP perspective with methotrexate all the way up to around 2040.
To the right, we highlight the different treatment options in rheumatoid arthritis. First line treatment, that is what we tested in the BEGIN study, meaning going in early in the disease at the time where anti-rheumatic treatment is initiated, we see a clear opportunity with our compound early, fast onset of action, good safety profile, and potentially as effective as the JAK inhibitors would given at a very attractive treatment opportunity. We continue to develop the compound in first line, as a first line treatment. Then DMARD IR. That's very, very important, as I said, very important and large business opportunity. But also, not least because there's a lot of treatment options to these patients who do not respond adequately to standard first line treatment.
Most of these compounds are associated with side effects, and in many cases, the physician has to test different compounds in order to find the right dose regimen for the patients. One of the things that is what we are discussing with the FDA is the development path in DMARD IR as a very attractive development path and potentially giving a very large and very interesting business opportunity. At the end, we also have flares, but that would attractive opportunity to treat, but that would be not what we are focused on in the years to come. The next slide, which is slide number 12, please.
This highlights a very high level, how we intend to develop our continued development in our, as a first-line treatment. We call the study that we are setting up here and make the clinical trial application here in Q2 this year, we call it the EXPAND, where we test our newly developed compound, newly developed tablet of 100 mg once daily compared versus placebo in a 12-week study in previous treatment-naïve rheumatoid arthritis patients in combination with methotrexate. It would be 12 weeks dosing, and we expect to run and take benefit of the network of investigators that we have worked with during the BEGIN study. Set the study up file here in Q2 with the aim to have high-level data next year in early Q3. Next slide, please.
That is slide number 13. On this slide here, we highlight the intended development plan that we are discussing with the FDA and where the intention is to have their input finalized here by during the spring in Q2. Overall, the intention is to run an adaptive study with a part one, part A, where we test the compound either four to six weeks dosing, three doses versus placebo, with then to identify the most attractive doses to bring into the second line, which would be a 12-week study. This study would be set up under, as I said, in under an IND with the aim to file the IND in Q3 and then be up dosing by the end of the year.
Again, with the aim to have data from the first part of the study over the summer next year. That is very important for us to highlight that what we are going to do in the next year is very focused to initiate two clinical trials in rheumatoid arthritis. EXPAND study, which is first line to confirm the effect of the BEGIN study, and importantly, to have 12 weeks data, which is very, very important to have a full efficacy and safety profile and also from business perspective, very important. Then initiate our development program in DMARD-IR patients. With that, I will give the word back to Jeppe.
Yes. If we move on to slide number 14, I will give you an update on where we are with the business development. Thanks to strong data received from the phase II study in RA, we have and still are in positive discussions with potential partners. It is big pharma companies, but it's also more specialized biotech companies. We have since data point four months ago, spent most of our management time on these discussions and will continue these interactions over the coming months. We have been reaffirmed in these discussions that the program and the study has been well-designed, and we are triggering the trends seen in the market, thereby meeting patient needs and filling the market gaps. At the same time, our competition, the so-called JAK inhibitors, have faced increasing problems with side effects, including black box warnings with the FDA.
This has increased the interest for our programs, and further on, we have reaffirmed that the safety profile with AP1189 is one of the key drivers in reaching a deal. All up, we are as good as competing products but with a better safety profile. We have also learned a few things during the last month's discussions. One take home has been that some of the bigger partners would like to see a longer study. Not necessarily bigger studies, but instead of a four week treatment, 12-week treatment. That is exactly what we are going to prepare for and one of the main reasons for completing this rights issue. An important reason, another important reason for the rights issue is that we wish to maintain a strong position for doing a deal.
Coming from a position of strength and show that SynAct is a company that controls its own destiny. This is important in biotech, and we really believe in our compound. Therefore, we will not sit on our hands and wait for a deal. We want to move forward, make progress, optimize the value of the program, and show that we stay in control and are able to push forward on our own strategy. Slide number 15. Patrick, will you cover the rights issue page?
Yes. Thank you, Jeppe, and good morning, everybody. We are on slide 15, and let me introduce to you the high-level characteristics of the rights issue that we're pleased to announce this morning. First of all, 11 existing shares will give the rights for existing shareholders to subscribe for and buy one new share.
At a very attractive price of SEK 63. That will in all bring SEK 150 million in gross proceeds, and most importantly, the transaction is fully guaranteed by subscription and guarantee agreements. On the timelines, we launched this transaction today, and we expect to release the prospectus to the public on the 1st of April. Commencing the subscription period from the 6th of April, running over the Easter period for a close on April 22nd. We expect to announce the outcome of this rights issue to the market on or around the 26th of April. Can you move to slide 16, please?
The rights issue will provide us with net proceeds of about SEK 126 million. In addition to the tax credits that we are eligible for to receive from the Danish government, that will enable us to invest in the clinical program that Thomas has described earlier. It will enable us to continue our other R&D activities and drive the company through to the end of 2023. The clinical study program is the main investment that we're doing. The two new studies in rheumatoid arthritis and the existing study in kidney disease or nephrotic syndrome will in total drive investments of approximately SEK 80 million or 58% of the use of proceeds.
We will invest a little more than SEK 30 million, or 22% to drive the continued support of AP1189 and pipeline activities in R&D. Slightly less than 30 million SEK or 20% of the proceeds will be used to drive the company, including a significant investment to obtain the desired uplift to the Nasdaq main market. I will finish out by saying that SynAct has always operated as a very lean organization, and we will continue to do that, but we have to invest, and we will invest in building a stronger organization in R&D and support to secure sufficient capacity to deliver on our very ambitious promise. Can I have slide 17, please?
With the investments that I just described, we believe that we will be able to deliver very important clinical and corporate milestones over the next couple of years. Coming up in Q2 2022, we expect, first of all, to close this rights issue that we announced this morning. We continue our preparations and they are well advanced for an interaction with the FDA, and we expect to conclude a pre-IND interaction in the second quarter. We have promised a new set up for the clinical study in kidney disease, and we now expect to announce that new set up in this quarter too.
Finally in this quarter, the next one, sorry, the next quarter, the second one of the year, we expect to be able to list the company's share at the Nasdaq main market. The project is well underway and moves according to plan. Now in the second quarter of this year, we expect to have the IND obtained and start and dose the first patient in our EXPAND study, phase II study in RA. Following the IND in the third quarter, we expect to start the DMARD study, the DMARD-IR study, as Thomas alluded to in the fourth quarter. Towards the middle of next year, in the third quarter, we expect to read out from these two very important RA studies.
Sometime in the second half of the year, to be confirmed, we expect to complete the study in kidney patients. With that, I hand over to Jeppe Øvlesen, and please move to slide 18, please.
Yes. This slide basically describes SynAct's existing strategy in a nutshell. We have sort of a dual strategy where we go for full focus on developing our clinical programs in RA, where we create most value, and then we will continue to drive the business development as we have described in the presentation. We really believe that we have a good possibility for striking a good deal. It's all about optimizing the value of SynAct. If you move to slide 19. This slide gives a very brief summary of the presentation today, full focus on giving significant value into our clinical program.
We are focused on optimizing the partnership agreements, finding the right partners for our projects, continue the rest of the development in the other parts of the pipeline, and complete the uplisting to Nasdaq main market on time. This sums up basically the presentation that we have provided to the market today. I would like to thank all your shareholders, all existing shareholders that have been a part of our journey, and we look forward to continue that journey together with you as investors. We will be open for questions. Thank you.
Thank you. Ladies and gentlemen, if you do wish to ask a question, please press zero one on your telephone keypad. If you wish to withdraw your question, you may do so by pressing zero two to cancel. There will be a brief pause while questions are being registered. Our first question comes from Sebastian van der Schoot with Kempen. Please go ahead.
Hey, good morning, team, and thank you for taking my questions and congrats on the share issue. I was wondering if you could maybe talk about why you decided to continue with both studies in different settings instead of prioritizing one over the other. Do you anticipate that with the current share issue that you will be able to complete both studies or reach both first inflection points? Thank you.
Should I take that, Thomas?
Yes, please.
I mean, first of all, as Patrick highlighted, within the funds of what we are raising now, we will be fully funded to run the EXPAND study, meaning the first-line treatment study, and then in parallel, initiate and complete part one of the potential adaptive study in DMARD IR, meaning that we would have a full dose range profile in DMARD IR, which then we should select the doses or potentially only 1 dose for part B. But we will know more about that when we do have the data. But that's the first part of it.
The second part is, well, we find the DMARD IR is obviously from a business perspective the way to go and also what most companies they ask for. What about the DMARDs is a question we hear and that's very logical and in many ways, and we should for sure do follow that development path. But we do also have a compound who is very attractive as from a safety profile. And as you know, that most compounds not only is developed for DMARD IR, but also for treatment naive.
We see a great opportunity here for, in a very attractive and efficient way, to generate the 12-week studies, the 12-week data in the treatment-naive to get the full efficacy of the compound and describe the safety profile as we do have a network of investigators and everything set up, so we can do that in a very attractive way. Then we actually do have both data in those patient populations.
Okay, great. If I can ask a follow-up question. Can you maybe remind us of what type of safety events you see with your compound and how that at four weeks, and how that compares to, for example, JAK inhibitors at four weeks? What are the typical safety events that you see with those drugs?
Yeah. With our compounds, the most common side effects was related to the gastrointestinal tract. Nausea was seen, but it was seen both in active and placebo. That was most likely associated to the formulation we have used, which was a suspension, meaning, and suspensions do in general have a tendency to induce nausea. We have also, from our bioequivalence study with our new tablet, nausea was not reported, and we can take it for what it is, but that at least can signal that it has to do with the suspension.
We also had some other minor side effects from the gastrointestinal tract, but importantly, which was self-limiting and was associated or described as mild in most cases. Importantly, methotrexate is associated with the risk for increasing in liver enzymes. Importantly, we did not and we saw that. We also saw that on the 50-mg group, but when we went up to 100 mg, we did not see anything at all. That is a very interesting finding that we do look very much forward to follow and understand further in the 12-week study when we move forward. One possibility could be that we inhibited some of the liver inflammation we know that methotrexate induce. Compared to the JAK inhibitors.
The JAK inhibitors, the major issue with JAK inhibitors is that they induce immunosuppression, meaning that they reduce the immune system to a degree that you have increased risk for inflammation or for infections. That is present already after four weeks in most reported studies from the JAK inhibitors. We did not see any indications of immunosuppression with our compound. From mode of action, the immunosuppression, it should not be a major way of efficacy from our compound as we induce resolution of inflammation rather than immunosuppression rather than blocking specific immune pathways.
Okay, great. Thank you very much. My final question is regarding EXPAND. Will you also have an interim analysis in that study or will it only be the 12-week data set?
We are simply working with a model where we would like to have as many patients dosed as fast as possible. You know, if we add an interim analysis, will anything else be delayed, especially if we are going to do that in a way where we base it on validated data, because that means then you should have an interim report, meaning that you had to stop dosing. Right now we intend simply just to collect the data as fast as possible and then come out with the data.
Okay, great. Thank you very much.
As a reminder, if you do wish to ask a question, please press zero one on your telephone keypad. At this time, we have no further questions. I will now hand back to our speakers for any closing comments.
Yeah. I would like to thank you all for listening in to this exciting story. I think that we have been able to provide you with a good overview of where we are and the strategy going forward. It's all centered around a dual strategy where we will push the program forward, and we will make sure that we will complete the deal in an optimized way on the best possible terms. Thank you very much for listening in, and thank you for your support.