Dear ladies and gentlemen, welcome to the conference call of Idorsia. At our customers' request, this conference will be recorded. As a reminder, all participants will be in a listen-only mode. After the presentation, there will be an opportunity to ask questions. If any participant has difficulties hearing the conference, please press star key followed by zero on your telephone for operator assistance. May I now hand you over to Andrew Weiss, who will lead you through this conference. Please go ahead.
Thank you, Aurelie. Good morning, good afternoon, everyone. Welcome to today's Idorsia call on the launch of the phase III trial for selatogrel into suspected AMI. Before I hand over the microphone to our participants, I do need to remind everybody that we will be making forward-looking statements in this call. With me on the call today, slide three, please, are our CEO, Jean-Paul Clozel, our Chief Scientific Officer, Martine Clozel, and our Head of Global Clinical Development, Guy Braunstein. To make his introductory comments, I hand over to Jean-Paul. Thank you.
Thank you, Andrew. Thank you for the introduction. Next slide, please. When we created Idorsia four years ago, we had very clear strategic priorities. Number one, to deliver at least three products to the market in a short amount of time. Number two, to build a world-class commercial organization. Number three, to bring Idorsia to sustainable profitability. While we were doing that, we need to continue to fuel our pipeline with new discoveries, new drugs coming from our own research. Finally, to use the state-of-the-art technologies to drive innovation. Next slide, please. As I can show it on this slide, we really made very good progress for our pipeline. As you can see, daridorexant has got the phase III results. The NDA has been filed, and we should get the approval at the beginning of next year.
We also got very good results with clazosentan in Japan for subarachnoid hemorrhage. We should have the results of lucerastat, another phase III program, at the end of this year, aprocitentan in the middle of next year. cenerimod at the end of this year. You see that we have made very good progress for our pipeline. Next slide. Today, I would like to speak of another phase III program, which is going to start and which is addressing a very important clinical problem. As you know, cardiovascular disease is the number one cause of death, before cancer, in developed countries. In developed countries, 1/3 of the deaths are attributed to heart attack. 80% of the deaths caused by cardiovascular disease are due to heart attack or stroke. In the U.S., each year, 800,000 people get a new heart attack.
This is not only true for men, but it's also beginning to be a very significant problem in women. Each year, more than 3 million women have a heart attack worldwide. Next slide. In the previous slide, before joining the pharmaceutical industry, I used to treat patients with cardiovascular problems. There was always a very difficult question to answer. It was when the patient was asking me, "Can I go to holidays at this place? Can I sail? Can I go on this cruise?
Can I go on the top of this mountain, or can I take a long flight?" It was very difficult for me to say yes, because I knew that if this patient, who already had a heart attack, would have a new heart attack while he were on this boat, while he was on this mountain, it would take him 4, 5, 6 hours to go to the first hospital to be treated. That during this time, he could die.
Most of the time, I would say, "No, it's not prudent to do this long trip." When one of our scientists, Sébastien Roux, who was also a cardiologist, came with this idea to treat these patients at a very early stage, my first question was really, do we have the drug which would be able to treat the patients at the beginning of their heart attack, as soon as they start to feel pain? Really, the first question, of course, was, do we have the drug to do that? Martine is now going to tell you why selatogrel is indeed an ideal product to deal with this very significant clinical problem. Please, Martine. Next slide.
Thank you. Thank you very much, Jean-Paul. Good morning or good afternoon to all of you joining us today. It is my pleasure to share more information about yet another exciting discovery coming from our team. Slide nine, please. As many of you know, existing P2Y12 receptor antagonists are used in the treatment and prevention of arterial thrombotic events. Next slide. The class has an established efficacy and a well-known safety profile, with millions and millions of patients treated to date. Despite the success of this class and other effective interventions, there remains a distinct unmet medical need in the treatment of AMI. Next slide. Which is a treatment during the time between the onset of symptoms and the receipt of first anti-thrombotic treatment. Next. A study of AMI mortality showed that at least 20% of patients experiencing their first myocardial infarction died before reaching a hospital. Next slide.
Approximately another 10% died during hospital admission. Slide 14. An antithrombotic treatment for use at the very onset of AMI symptoms would need to be rapidly absorbed and potent, working quickly to inhibit thrombus formation at the very early stage. The inhibition should be reversed after a few hours to avoid interfering with later treatment decisions. Finally, it must have an appropriate safety profile for use prior to formal diagnosis of AMI. Fixing the right P2Y12 receptor antagonist to be administered as close as possible to AMI symptom onset represents an exciting opportunity to address this unmet need and improve AMI outcomes. Next slide. As Jean-Paul introduced, the scientists at Idorsia have developed a P2Y12 receptor antagonist called selatogrel. We believe selatogrel has the potential to provide the treatment benefits in addition to standard of care when administered at the onset of suspected AMI symptoms.
I will now explain in the next several slides the properties of selatogrel that support our trust and our excitement about its potential. Slide 16. Let's first look at why the onset of AMI symptoms can be considered the actual optimal time to treat with a P2Y12 receptor antagonist. Next. From the moment the symptoms start, everything goes very wrong very fast. Thrombus formation in one of the coronary arteries progresses, and ischemia will rapidly cause irreversible damage to the heart. In the very initial stages of thrombus formation, the role of platelets, in particular platelet aggregation, dominates, a process in which the P2Y12 receptor plays a key role. If left untreated, the thrombus will become fibrin-rich, and we see it on the slide. Progressively, fibrin fibers start to cover the platelets, which are adhering and aggregating and activated.
At that point, platelets will have a more limited role in thrombus formation. Next slide. This suggests that P2Y12 receptor antagonists could have a very important role to play in the initial stages of thrombus formation. Slide 19. Selatogrel has demonstrated properties that indicate that it has the potential to provide the treatment benefit in addition to standard of care when administered at the onset of suspected AMI symptoms. Next slide. Data gathered during preclinical and clinical development have shown that selatogrel is a potent and highly selective antagonist of the P2Y12 receptor, but in addition, has a fast onset and a short duration of action. Next. Pharmacokinetic and pharmacodynamic studies have shown selatogrel is rapidly taken up into the bloodstream following subcutaneous injection. Next slide. Demonstrating its fast onset of action.
On slide 23, we can see that these studies also show that the effective anti-platelet activity of selatogrel is going down rapidly after its maximum and lasts for about six to eight hours at the dose selected for further development, demonstrating selatogrel's short duration of action. Slide 24. In pharmacology studies, preclinical data from a modified Folts model in Antares suggested these properties by demonstrating that thrombus formation was inhibited within 10 minutes of subcutaneous injection in the guinea pig of selatogrel. Next slide. We can see from this Folts model that following a mechanical injury to a, in that case, carotid artery, a thrombus begins to form, resulting in repeated cycles, which you can see here by the Doppler measurements of blood flow velocity translated into blood flow, resulting in repeated cycles of vessel occlusion, followed by dislodgement of the thrombus and reopening.
Following subcutaneous injection of selatogrel, the occlusion dislodgement cycle continues for about 10 minutes, at which point, and you can see it in front of the white arrow, the blood flow is restored into the artery. Work in this model has also hinted that selatogrel may have the potential to dissolve an already formed thrombus. Slide 27. In animal models of thrombosis and hemostasis, at a dose providing anti-thrombotic effect which was equivalent to that of ticagrelor, selatogrel resulted in a much lower level, a very low level, of surgically induced blood loss. We later learned that this could be explained by selatogrel being highly selective for the P2Y12 receptor. Next slide. These properties combined differentiate selatogrel from overall P2Y12 receptor antagonists, which have a slower onset of action, particularly during acute myocardial infarction, and persist for longer, and are less selective for the P2Y12 receptor. Slide 29.
The properties are suggestive of a compound with the potential to provide a treatment benefit in addition to standard of care when administered at the onset of suspected AMI symptoms. Crucially, in addition, as a result of its solubility, selatogrel is suitable for subcutaneous injection in humans. All of these factors had our scientists thinking, how can we take advantage of the properties demonstrated by selatogrel to develop an effective treatment for use in the very early stages of AMI?
Next slide. Acute myocardial infarction is such an emergency, because there is no time to await an ambulance and even less medical intervention in a hospital, one of our scientists, Sébastien, had the idea of a self-administration by the patient at the onset of symptoms. Self-administration is currently used to treat a number of other emergency situations. Why not AMI? With that, I would like to hand over to Guy to tell you how we are going to assess whether this idea can become a life-changing innovation for patients. Guy, the floor is yours.
Thank you, Martine, and greetings to everyone following our presentation today. I think we should be on slide 31 now. You have heard from Martine about the properties of selatogrel that gives us great confidence in our program. I would like to share with you the work that has gone so far to prepare the selatogrel phase III registration study. Next slide 32. These diagrams schematically depict what happens today. Heart attack symptoms on the left of the slide can be sudden and intense and sometimes cause sudden death. In other instances, heart attacks are not painful or less painful, but can start with mild symptoms that develop gradually, and symptoms are sometimes mistaken for less serious issues such as indigestion. Typically, patients will only take the symptoms seriously when they worsen, and they then call the emergency service and make their way to the hospital.
The patient's failure to recognize the symptoms and to take action results in the first period of delay. Depending on the speed of emergency response, there can be a further delay once the alarm has been raised. On average today, first medical contact can be delayed by up to four to six hours. Early intervention as quickly as possible at the occurrence of symptoms suggestive of AMI is crucial to preserve the heart muscle damage. The longer the blood flow to the heart muscle is restricted, the more heart muscle damage will occur and the worse the outcome for the patient short-term and long-term. Early intervention in AMI has therefore the potential to abort the thrombotic process, saving heart muscle to improve long-term outcome and potentially saving lives. Next slide 33.
An early intervention means here, prior to first medical contact and decision being made by the patient, which implies a number of things. First, the symptoms have to be recognized by the patient. This means that patients have to be trained to recognize the different ways a heart attack presents and also to minimize the risk of diagnostic errors. Second, to intervene with a product that is safe, and it is important to also minimize the safety risk in case no formal diagnostic is made and there may be diagnostic error. The product has to act fast to optimize its efficacy in the short-term treatment window when the clot is still present at the platelet- rich and not yet fibrin- rich, as shown by Martine. Fast-acting means being effective within a few minutes.
The treatment should be short-acting, as also mentioned by Martine, to preserve the amount of care upon medical contact, to avoid interaction with the procedure that will take place later when the patient reaches medical contact, and also to minimize the risk of bleeding at that stage. The effect should therefore disappear in a few hours. Finally, if the patient has to administer the product themselves, it should be easy to use, and especially in the context of the highly stressed emergency context. Next slide, please. Slide 34. Let's look now at how we have addressed these prerequisites in preparing for our registration study. Next slide 35. This chart models the phase I pharmacokinetic results presented by Martine a few minutes ago on the left side, and the slide shows how the PK profile translates into inhibition of platelet aggregation on the right side.
Our modeling shows that rapid IPA inhibition of platelet aggregation onset within 15 minutes. More than 90% of participants have more than 80% inhibition 15 minutes after dosing. The strong inhibition of platelet aggregation lasts for approximately six to eight hours. Having shown this in healthy people, it was also important to confirm this PK and PD profile obtaining less individuals in patients. Therefore, two phase II studies in two different settings were established. Next slide 36. Our phase II program evaluated the safety pharmacokinetics and pharmacodynamic characteristics of selatogrel in two groups of patients. The first group was in chronic coronary syndrome. That was a larger study, which allowed to give a safety database of a different size. The second study was done in acute myocardial infarction. It's a smaller study, but more relevant to the real-life situation of interest. Next slide, please. Slide 37.
Both studies demonstrated significant inhibition of platelet aggregation. On the slide here, you see the inhibition of platelet aggregation on the vertical axis over time and the horizontal axis in patients with chronic coronary syndrome upon injection of placebo, the triangle or round symbol, 8 mg selatogrel, the pink dots, or 16 mg selatogrel, the purple squares. The subcutaneous administration of selatogrel 8 mg and 16 mg induces a rapid platelet aggregation inhibition with onset of action within 15 minutes, and the height of its effect extends over four to eight hours, depending on the dose. The phase II study in patients with acute myocardial infarction showed similar results. These two studies confirm the efficacy profile we had seen in healthy volunteers. Slide 38. Next slide. Safety is important, as I mentioned before. Treatment-emergent adverse events in chronic coronary syndrome studies suggest that selatogrel is safe and well-tolerated.
An excess of dyspnea was noted with both doses of selatogrel compared with placebo, with most of the events being mild. This is a known adverse event from other reversible P2Y12 antagonists. Bleeding events were also observed in this study. They were mostly trivial, related to venipuncture as part of the procedural intervention of the study and bruising at the subcutaneous injection of the study drug. Importantly, there was no treatment-emergent serious bleed. Overall, the safety of selatogrel was good, and the drug was well-tolerated. Next slide, please. Slide 39. We see from this phase II data, from the phase II clinical development so far, that we can tick three boxes. Safe product, fast acting, and short duration. Selatogrel induces profound platelet inhibition. It is fast acting within 15 minutes of administration with appropriate duration. Selatogrel was well-tolerated at both doses with no major bleed.
With this data, we selected 60 mg as a dose for further investigation. As mentioned before, it's important also to have a convenient mode of administration. Next slide, please. Slide 40. Idorsia chose to work with a leader in the field of auto-injector to select and customize the right delivery system. Antares has a proven track record in developing drug device combination products that are tailored to the therapeutic need and patient-friendly. Together, we have developed a drug device product combination, combining Idorsia selatogrel product with the Antares subcutaneous QuickShot auto-injector. Next slide 41. The Antares auto-injector was chosen for several reasons. First, its robustness, as it will be carried by patients in their bag or their pocket wherever they go, 24 hours a day, 7 days a week, 365 days a year.
The product has to be reliable all the time. Given the emergency use indication for the selatogrel drug device product, technical reliability for successful autoinjection is a key criterion. Ease of use and emergency readiness are essential for patient and caregiver to handle the device confidently during very stressful condition. During the development of the device, Idorsia conducted several human factor studies, including a validation study in patients and caregivers of relevant age range in both sexes and in subjects with or without experience of self-injection. Next slide 42. The final validation study in the relevant population was conducted in situation mirroring the real-life experience. The results of this study demonstrated that the autoinjector, the on-device label, and the instruction for use allowed the users to perform their task. Next slide, please. Slide 43.
With these results, we can tick another box here from the prerequisite list, the easiness to use. To a very important criteria, symptom recognition. This is important to our concept because it needs the right product injected at the right time by a patient that will be empowered to take actions. As a result, the patients must receive adequate training. Next slide, please. Slide 44. It is important that patients and their caregivers understand when and how to use a study autoinjector. The training material was developed with the education experts, cardiologists, nurses, feedback from patients post-AMI on symptom recognition, assessing when the patients have to inject and how to do it. How to use a study autoinjector and to call emergency services right after the injection. In the study, patients will also have to successfully practice a placebo injection prior to being randomized. Slide 45.
With that said, we can now tick all the five boxes of all the prerequisites, and we are ready to discuss the phase III registration study. Next slide, please. Slide 46. With the study named SOS-AMI, we will now put selatogrel in the hands of the patient. Next slide 47. The concept to be tested in the study is whether an early intervention, namely the self-injection of the P2Y12 antagonist selatogrel upon symptoms, prior to formal diagnosis and medical contact, leads to improved outcome. To do so, the SOS-AMI has been designed in collaboration with leading experts and has been discussed with health authorities. It is an international, multicenter, double-blind, randomized, placebo-controlled clinical trial. In SOS-AMI, the patient is empowered to make self-treatment decision at the very onset of suspected AMI symptoms. This empowerment requires engaging the patient in recognizing AMI symptoms and taking immediate actions.
Next slide 48. One of the key questions is who will be enrolled in the study? Subjects will be enrolled in the study within 4 weeks of a recent AMI, either at high risk of recurrent AMI. Patients are considered high risk if they have either had another myocardial infarction within the previous year, or if they have several other factors such as diabetes, age over 65, active smokers, and so on. Of course, prior to being randomized to study, the patients will have to be trained and demonstrate that they can placebo inject themselves. This leads us to the next slide 49, which depicts how the study will be operationalized. Here you see a schematic of the study.
Patient that had a recent AMI and are at high risk of repeat heart attack will be enrolled in screening phase, during which they will receive the training by the qualified trainers, including the practice of a placebo injection. They will go within four weeks of the recent AMI into a randomization in a 1:1 fashion to either selatogrel or placebo. They go about their normal life, carrying the auto-injector with them at all times. They will have regular telephone contacts with the trainers, which minimizes the burden of both patients and the study sites. When they experience and recognize any symptoms suggesting of an AMI, they will perform the required two actions, first self-injection of selatogrel, and immediately after, call the emergency service to be taken to hospital. They will be followed with post-treatment assessment for a one-month period. Next slide 50.
We are planning to randomize 14,000 patients at approximately 250 sites in about 30 countries. The special protocol assessment has been agreed with the FDA. The FDA has also designated investigation of selatogrel for the treatment of a suspected AMI in adult patients with a history of AMI as a Fast Track development program. The next slide shows the data flow. Slide 51. The primary objective of the study is to assess the clinical efficacy of selatogrel when self-administered upon occurrence of symptoms suggestive of an AMI in patients at risk of having a recurrence. The success of this will be measured by the grading of MI on the scale from no myocardial infarction up to death. All events will be blindly adjudicated by clinical event committee to ensure consistency across the many sites and countries around the world.
Similarly, the primary safety endpoint of bleeding will be blindly adjudicated by the clinical event committee. Slide 52, coming back to what happens to MI today. With selatogrel, we're addressing the delay between symptoms and treatment, the period during which patients are most vulnerable. With selatogrel, we empower patients to take decisions prior to formal diagnosis, with the purpose of saving lives and improve long-term outcome. Slide 53. How could MI be managed in the future? As we see here, the self-administration has the potential to change the life of the patient by slowing or stopping of the heart attack. Early intervention leads to better outcomes short-term and long-term.
The keywords to remember are self-administration of selatogrel using the auto-injector as early as possible at the onset of MI symptoms by empowered and powered patients. It could change the treatment paradigm of MI. SOS-AMI is the next study on the selatogrel development. We look forward to reporting the outcome of SOS-AMI in approximately 2.5 to three years from now. With that said, I will now hand over to Andrew for the Q&A session.
Thank you, Guy. This concludes our prepared remarks. We've come to past the top of the hour. We have now at least 25 minutes to be able to address questions. Operator, may I ask you to open the lines for the Q&A session, please?
Yes, of course. Ladies and gentlemen, we will now begin our question-and-answer session. If you have a question for our speakers, please dial zero and one on your telephone keypad now to enter the queue. Once your name has been announced, you can ask a question. If you find your question has answered before it is your turn to speak, you can dial zero and two to cancel your question. If you are using speaker equipment today, please lift the handset before making your selection. One moment, please, for the first question. The first question is from Peter Verdult Citi. Your line is now open. Please go ahead.
Yeah, thanks. It's Peter Verdult from Citi. Thanks for doing the call. A few questions from me, please. Firstly, just the anticipated cost of the phase III program, and anything you can say about the powering of the study. Then looking ahead, if this does become a success, is this a market you're looking to build yourself, or would you seek a partner? Then related to that, just in terms of how this market gets built, what sort of KOL buy-in have you got? Are there any significant heavy hitters that you've got on your advisory board or that you've got advocating the use of selatogrel in acute AMI? I just want to get a sense of how much buy-in you've got from the key KOLs in the U.S. and Europe.
Okay, Peter, thanks for that. That's a boatload of questions. Okay, we've got one on anticipated cost, two on what are the powering assumptions of the trial. Beyond just what the patients are, but what we are expecting in terms of number of events that would be happening. In case of market success and we get the great data out there, would we do this on our own or partner? Fourthly, what are the KOLs thinking about this and how's our interactions been with them? I will address quickly the cost one, and I will refer the powering assumption one to Guy, and then have the partnering and KOL buy-in by Jean-Paul. The anticipated cost, regularly, we don't break down individual costs of the different trials.
I think we've been able to indicate in the past so far that we don't think that the trial costs will exceed those that we had for daridorexant as we developed that phase III program, which took about three and a half years from beginning to end. It's been indicated in previous conference calls that those costs were somewhere around CHF 200 million- CHF 220 million in total over the whole lifespan of the phase III program. Guy, do you want to address the powering assumptions of the trial, please?
Yes, I can take that question. Sure. There are a number of components to this question. The first one is based on the rate of recurrence. Of course, this is based on analysis of databases that we have collected, and we know that not all patients are going to have a recurrence within the observation period. The number two is also based on the probability that the patient will recognize the symptoms and decide to inject. Both of those are relatively unknown, and therefore, we make a number of assumptions o n these numbers to end up with a number of patients that have to be randomized of 14,000.
Maybe your assumption is about the effect size or the size of the effect we want to observe, better than to say the effect size. We estimate that we may be able to reduce the occurrence of events. It's a bit complicated here because we have a multi-level endpoint. As I mentioned, we fixed level from no event to death. Therefore, it's not totally the same for all different levels. Overall, it's a 25% reduction in event rate on active complex placebo.
Thank you Guy, Jean-Paul. On partnership?
Thank you, Andrew. The first partnership is with Antares. I have to say Antares made a fantastic job to really come with us to the design, to the adaptation of their device for selatogrel. We have a very good collaboration with Antares, and I'll take this opportunity to thank this very good company in the U.S. This is important because I think the device and later on its fabrication or its making is very important. That's the partnership that is very important for us. For the development, clearly, we are going to do it on our own. Frankly, if the study is positive this drug and this combination will be prescribed by cardiologists. It will be a very specialized type of market, and therefore we are thinking of selling it ourselves without a partner.
Thank you, Jean-Paul. Do you want to address the KOL community that is interested and how interactions there have been with the FDA?
I think, first of all, the first community which is important is the FDA. Really I can say, this was very clear at the time of the COVID, because we did receive a lot of inquiries of cardiologists who wanted to have our device because as you know, the number of patients during the COVID crisis hospitalized because of myocardial infarction in New York was, for example, decreased by half, by 50%. People hesitate to go to the hospital because, of course, contagious, but also they really were afraid to be contaminated, and therefore it became a very significant problem. It was very clear that this auto medication is very interesting.
The FDA knows, especially in United States, and as you know, in the United States, it is very different to get a myocardial infarction if you are in the middle of New York or Boston or if you are in the middle of Oklahoma or Wisconsin. The time, the chances you get to be treated is very different. This is why the FDA thinks that this is a very useful tool and that if it really is shown to work people in very far remote location will have this auto-injector at home and could treat themselves while they will be transported to sometimes seven or eight hours travel to the first clinic.
The key opinion leaders, especially in the U.S., are very in favor. Of course, they want to see the results, but we had no problem to find centers interested into the study. I have to say that both in Europe and in the U.S., this concept is getting more and more traction and gets a very big support from key opinion leaders.
Thank you.
The next question is from Greg Svorinich, Goldman Sachs. Your line is now open. Please go ahead.
Greg, good morning, good afternoon. Thanks for taking my questions and thanks for the presentation. Just a question on the trial design. I know that a key element is to get patients to recognize the symptoms of a heart attack. How do you think you'll be able from a clinical trial perspective to kind of normalize for that? I'm just wondering how this is going to actually play out, and whether there is a certain element of variability that may confound the trial. If you could address that'd be great. And then I'll follow up with a second question.
Yes. I can address the question. We have developed a training package specifically with patient educators, with physicians, with nurses, and with patients that had myocardial infarction before. This package has been tested. This package is being translated into all the different languages in the different countries. Every country has a trainer, and every trainer of the trainers, every site has a trainer. Through this cascade of trainers that we train the site trainers, we believe we'll be able to reach harmonization across the different sites and countries. As you have seen also from the graphical on the slide, the main contact for patients along the observational period is with the trainer, which will be done through phone calls. There will be reinduction regularly of the training done by these trainers on every site. We have paid a lot of attention on the training.
As you rightly point out, this is absolutely crucial to the study. It is crucial because we want the patient to recognize the symptoms. The harmonization is also very important for the reasons you highlighted. This is why we have put in place this way of training the patient, developing the master training program, as well as recruiting the trainers in the different countries and the trainers at the site level that will work under the supervision of the country trainers.
Guy, I can add something because I suppose this was maybe part of the question, is that about the confusing the results. If the patient does not recognize the symptoms, which might happen, and we know it will happen, he will not inject himself. Therefore, he will not be included into the final analysis, which is only taking into account the patients who have injected themselves. That's very important. This is why this type of, it's not a detail, this type of important element was agreed with the FDA because, of course, we didn't want to have patients who do not inject themselves and who are included into the study. I think it's important to know.
Thanks, JP. Maybe a quick follow-up to that, and then my second question, but the follow-up is, as it relates to those who inject themselves, and you just mentioned those are the ones that will be counted, but is there a consideration for the potential that perhaps you'll have subjects in the trial who inject themselves and actually are not having an actual AMI, perhaps it's a false positive? Are they being accounted for in a particular way?
Sure. This can happen as well, of course. These patients, as I mentioned, we have six categories in the endpoint going from no event to death. The patient that will inject when actually they have no myocardial infarction and maybe they are confusing the symptoms with something else, will be counted as having no impact, no death. They will be in that category number six. This is accounted for in our sample size calculation, of course. It's at the moment, of course, difficult to estimate how frequently this will happen. We are going to monitor that during the course of the study. Of course, this is a possibility and this is accounted for in the statistical model.
Okay. Thank you for that Guy . My last question, then maybe I'll jump back in the queue, is with regards to your SPA that you have in place with the FDA, can you perhaps provide additional color as to what exactly is in that SPA? In other words, should we have a view that if you do hit on a primary endpoint that the FDA has agreed that it will approve the drug or is there some other element of the SPA that's important for us to keep in mind? Thank you.
That's in general the interpretation of SPA. The SPA agreement means that if we conduct the study and we conduct it well, this is an important component as well, and the study delivers the results that are expected, the likelihood of approval is very, very high. It's never 100% commitment, as you know, with agencies. There are always things that can happen that may lead to different decisions. It gives us a very good comfort in respect to the potential for being approved, assuming that the study is well conducted and the results are aligned to what we expect.
Okay, thank you.
The next question is from Rajan Sharma with Deutsche Bank. Your line is now open. Please go ahead.
Hi, thank you for the question. First one, could you just give us a sense of how many patients at present experience a second event within 12 months? On that point, just thinking about market sizing, do you have a sense at the minute of how successful patients are in successfully identifying an AMI? For example, do you have any data to tell us how many patients when they experience symptoms actually contact emergency services? Thank you.
Yeah. I will not give you exact numbers but estimate because of course t he study has not started yet, and these estimates are going to be revised as the study is going on. Overall, we anticipate that approximately a third of the patients will recognize the symptoms and self-inject. This is just a rough estimate at the moment. That's what we anticipate. It may be a bit less, it may be a bit more, but it's approximately that. That's why we need such a large study, because the majority will probably not have symptoms within this period of observation.
Okay, thank you. Then maybe if I could just follow up with a quick one, just in terms of going back to the commercialization. Going back to your comments about it being a specialized niche indication, what do you think is the right size for a commercial organization? What kind of infrastructure would you need?
Okay. Jean-Paul, do you want to address how large you think the heart attack survivor patient actually is?
I think that there is a very big mistake, is always to address the market size and to confuse the market size with the recruitment criteria. If I take the example of pulmonary hypertension. When we did a study in pulmonary hypertension, we did a study in patients with a certain amount of limitation in walk distance. It has never been in our label something which was required to treat a patient with pulmonary hypertension. It was something which was allowed to characterize the patient during the study and to be sure that we were treating patients which were sick. It was also giving us a chance to get a positive response. This is the case with our study.
In fact, what we want to show is that when you have an initial myocardial infarction, and you treat the patient with our auto-injector, he will save him, maybe in a very large amount of time. We say at least 30%, it will save him from a myocardial infarction. It would be impossible to do a study, or it would be very time-consuming and very difficult. We will need maybe 50,000 or 60,000 patients if we would do a study, for example, in patients at risk of myocardial infarction and who never had a myocardial infarction, who also would not be able to recognize otherwise a myocardial infarction. It doesn't mean at all that the FDA is going to limit our indication exactly to the criteria of inclusion in our study. That's number one.
Therefore, the market is really clearly not only the patient who got a myocardial infarction one year before. Because if they got it two years, their risk of a new myocardial infarction is lower, but it is still there. If they got three years before myocardial infarction and they have diabetes, they still have a high risk of myocardial infarction. Depending on the result, depending on the extent of the effect, the market is going to be much larger than patients who got in the year before or in the month before a myocardial infarction. This is really something that people have to keep in mind.
If the study is positive, of course, the size of the marketing is really addressing the cardiologists of the U.S., because I really do believe that only cardiologists would prescribe such a drug, and I think it's quite a limited market. It's a limited size of medical representatives. I do believe that it will be very difficult for a patient who is known to be at risk not to carry such a device, because it's really, if our study is positive, it could really save his life.
I think that the adherence, like for the EpiPen, it was a huge success because it's an insurance, it's a safety for the patient to carry something. Today, imagine to get a myocardial infarction on a golf course or in the middle of nowhere. It's quite terrible because you have to wait very often for a long time. I think that cardiologists will prescribe it and it will be limited cost of marketing.
Thank you, Jean-Paul, for those clear statements. Operator, do we have any other questions?
Yes, we do have a final question from Barbora Blaha, Credit Suisse. Your line is open. Please go ahead.
Thank you for taking my questions. First one, maybe I missed it, how long do you think will this study take?
We are planning an observation phase of approximately one year. It may be a bit longer. We don't know at the moment. We are planning. Therefore, as I mentioned in our presentation, we should see the results in approximately 2.5 years. The time to set up the study, recruit the subject, to train them, to observe them, will take a lot longer.
Okay, thanks. Another question. I don't really understand why you have a six-point scale in this efficacy assessment. What are the other points, and could you maybe explain this a little bit?
I'm sorry, I didn't catch the details of your question.
I don't really know why you have this six-point scale of your efficacy assessment.
Basically, the worst case is that the patient will die. The best case is that there will be nothing. In between, we have several levels, non-STEMI and STEMI. We have also different levels of severity within the two categories. In total, it is six levels. It's important because we cannot just do a survival study. Death is relatively infrequent, and therefore we also want to look at STEMI and non-STEMI. We also have an interest in the long-term outcome of the patient. The long-term outcome, of course, is also driven by those who survive the acute event and maybe develop heart failure due to the repetition of myocardial infarction.
The most important is the death or AMI for the success of the study?
They are all very important because they all contribute to the hazard ratio. It's not exactly a hazard ratio, but it's [filling up] on that ratio. They all contribute, and we have an anticipation that all of the categories will have a reduction on selatogrel, except the category where there is no event. Also, there will be an increase on selatogrel compared to placebo, and for all the others, there will be a decrease. They all contribute to the severe outcome based on assumptions today.
Just something last. If there is no event, this can be either people who had no symptoms at all but falsely injected themselves, as well as people who had symptoms and then injected selatogrel and selatogrel helped to decrease this event.
Yeah.
Is this right?
Yes, and this is possible. It would be quite remarkable if this becomes the main issue, and also that if they had an extreme event, there is no biological trace of that. For example, increase in platelet level. Clearly, there is a possibility that if the event is absorbed very quickly, it may be confused by those that inject it for the wrong reasons. The blinded adjudication by the independent committee will certainly help us in that respect.
Okay. Thanks.
I think your question is very good. I just would like to complete, Guy, you can correct me if I am wrong. Please do that. I think that your question, it's an important question because it was really also the suggestion of the FDA about this continuity within the endpoint. I think they were really much in favor. This was discussed in the SPA. This is a very important element. What can happen is that a patient who would have died without our auto-injector now can survive. The number of deaths can increase. If he would have had a mild infarction, he can have a much milder infarction. If he would have, I would say, an infarction with clinical symptoms, now he can have an infarction with only enzyme issues, without clinical signs.
Every of these steps is an improvement for the patient. We wanted to capture all possible improvements for the patients, which are, I think, relevant. This is why we made these six steps, which I think is a very elegant way to capture all the potential benefits. As you know today, there is a very important clinical use of measurement of enzyme in the plasma, and therefore, we really wanted to know if we would, for example, have, in addition to this enzyme, clinical signs and other elements to characterize the extent of the myocardial event. This was asked by the FDA, and this was, I think, and we completely agree, this is the best way, in my mind, to assess the effect of this auto-injector.
Okay. Thank you.
Thanks, Barbora. Thanks, Guy. Jean-Paul for those remarks. Operator, are there any questions left?
Yes. We do have a question from Mark Purcell. Jefferies, your line is now open. Please go ahead.
Thank you.
Hi. Just take my question. Just a quick one. I'm not sure if it's been asked or not. I might have missed it. If a patient in the study does have an AMI event, and regardless whether it's a mischaracterization or not, and if they use the pen, do they receive another pen and continue on in the study for the duration or not?
Guy, you want to address that?
Yes. Once patients are allowed to self-inject several times during the course of the study, exactly as you described it, whether they have actually a first event or not, it doesn't matter. If they use the pen, the injector, they will get a refill. They will get a new pen, and they can again be followed and potentially inject another time. Absolutely.
Okay. Thank you.
Thank you, Mark. Operator, any questions?
No further questions at this point.
Thank you very much. We've come to the full hour of this conference call, including the question and answer session. I think we'll call it a day for today. Thank you very much for your attentive questions and your follow-ups. This is a very exciting moment for us and a very exciting compound. On that note, we'll close the call for today. Our next prepared remarks are going to be with the half-year results on the 27th of July. Until then, I wish you well. Take care, everybody. Thank you. Operator, close down the lines.
Ladies and gentlemen, thank you for your attendance. This call has been concluded. You may disconnect.