Hello, this is Sten R. Sörensen. I'm the CEO of Cereno Scientific. I'm pleased to welcome you to this first webcast to the investing community from Cereno Scientific. This is the first of a series of similar events that we will hold to keep you updated about what's going on and what's exciting about our development. Today, we will focus on our lead project, CS1, which is being initiated in a phase II clinical trial in the rare severe disease, pulmonary arterial hypertension. We've put together a very nice program for you with speakers to cover this important topic. Let me show you the agenda. I'm gonna start with a couple of slides about Cereno, and then I'm very pleased to have our principal investigator, Dr. Raymond Benza, present from Ohio in the U.S. He's Professor of Medicine, Director, Division of Cardiovascular Diseases at Wexner Medical Center at The Ohio State University. Welcome, Raymond. Next, Dr. Phil Adamson, Divisional Vice President and Chief Medical Officer for the Heart Failure Division at Abbott, will speak about the CardioMEMS cutting-edge technology that's being used in our trial in these patients. Following will be Dr. Björn Dahlöf, Chief Medical Officer at Cereno Scientific, and he will present our study and details of the study for you. Then I will make some closing remarks. Welcome, hope you find this agenda exciting. What are Cereno about? Well, we are on a mission to develop new drugs that are more effective and safer than the drugs for rare and common cardiovascular diseases. We have three programs in development, one in phase II, which is what our focus today, and we have two preclinical programs, also them in cardiovascular disease. Why cardiovascular disease? Well, it's the most common cause of death on the planet. It's double that of cancer. There is a major unmet medical need for these patients. They need more efficacy, and they need safer drugs. That's what we are about. Now, what's our global presence? Well, we have our major activities, actually in the U.S. The company is founded and it has its headquarters in Gothenburg, outside AstraZeneca's research facilities. But we have also established a daughter company in Boston, Kendall Square, and we are doing major research programs for Cereno in the United States. This is a clinical study that we will focus on today, but also two preclinical development programs in collaboration with University of Michigan in Ann Arbor. This is a short picture of our pipeline. The leading project, which we focus on today, is CS1, and it's an HDAC inhibitor that has epigenetic modulating capacities that are very exciting. We are studying that now in our first indication, pulmonary arterial hypertension. You will hear a lot about that today. The other two preclinical programs are CS585. That's a prostacyclin analog that we have seen looks to be very potent, selective, and stable, and there is a need for new prostacyclin agonist in cardiovascular field. The third program is CS014. That's also preclinical program and also an HDAC inhibitor with epigenetic modulating capacities. All these three programs are for cardiovascular disease, rare and common diseases. Now, with those words, I'll let Dr. Raymond Benza, principal investigator for the trial, in and he will talk about pulmonary arterial hypertension. Welcome, Ray. Thanks so much for that, kind introduction, and I'm really excited to be here today to speak about pulmonary arterial hypertension and the role that CS1 will have in this very deadly and rare disease. What exactly is a pulmonary hypertension? Let's go over a little bit about what the problem is. Well, these are the faces of my patients. Pulmonary hypertension is a progressive chronic disease that affects primarily women in a 5-to-1 ratio and with a mean age of 50 years of age. Pulmonary hypertension is characterized by a narrowing of the pulmonary vessels, ultimately leading to right heart failure and death. The median life expectancy for our patients is 2.5 years without therapy, which has been extended to 7.5 years with monotherapeutics. In a disease that affects primarily middle-aged women, an additional 7.5 years of life is not where we wanna end. Pulmonary hypertension as a whole is prevalent in modern societies. As you can see here in the community evaluation, up to 50% of patients that we see in the clinic routinely with no history of cardiovascular disease can have an abnormal pulmonary artery systolic pressure. Although pulmonary arterial hypertension is rare, pulmonary hypertension is a global disease with extreme presence. There is no cure for pulmonary arterial hypertension except for lung transplantation, which is why there is a need for new therapies to treat this disease. Unlike left heart failure, there are no long-term acceptable mechanical options to treat right heart failure. The drugs that we have currently designed to treat this disease have really made use of three pathways. They can either accentuate the prostacyclin pathway or the nitric oxide pathway, or they can mitigate the endothelin pathway. Now, the problem with these three medications or pathways is that the drugs that we currently use to effectively treat this disease do so mainly through a vasodilatory component to the blood vessel with a very, very small amount of vascular remodeling. Hence, that is the reason why these drugs have not yet cured this disease or increased the life expectancy to that which we want. Now, this is the pathology of the disease, and you can see on the upper panel a normal blood vessel with a very wide lumen. What happens with this disease initially is a very potent vasoconstrictive effect on the vessel in which the lumen is narrowed. As this chronic vasoconstriction continues, vascular remodeling ensues that is characterized by neointimal formation, muscularization of the artery, inflammation of fibrosis that eventually occludes the lumen and then enables the body to try to constitute the vessel by making these very small plexiform lesions. In addition, because the vessel is so narrow now, microthrombosis is a very important component of the pathophysiology of this disease, and this is important when we describe some of the mechanisms of CS1. Well, managing PH can be very difficult because we know that people who progress and have adaptive right ventricular remodel, a responsive disease, are the ones who are gonna survive the longest. Now, the problem here is that we do not know what causes the transition between adaptive remodeling and maladaptive remodeling. This disease can progress at a very unknown rate. Knowing who is the most vulnerable to die from this disease is incredibly important in our management. That's where risk calculators and risk tools have come into common practice with pulmonary arterial hypertension. As you can see, as we select the medications to use for pulmonary hypertension, we're constantly assessing the risk of this patient to die or have a clinical worsening event from this disease. That's how we use our medications based on risk. Well, we've developed some very sophisticated systems now because we believe that one test does not paint the whole picture. Using one, two, or three clinical variables really doesn't tell us all the risk that's lying beneath the surface. I think our community agrees that there's a need for a collective measurement tool to really predict survival in the modern era of pulmonary hypertension therapy that supplements our clinical gestalt, particularly for our experienced providers, most importantly, serves as a key decision tool for less experienced providers because this is where the majority of our patients are being seen today. These are an example of some of the tools that we use to predict risk. The one that is globally accepted now is the REVEAL risk score, which is shown on the left-hand side of this panel. An abbreviated version of REVEAL Lite 2 is shown on the right-hand part of this panel. As you can see, it's a collection of easily obtainable variables that are derived from demographics, comorbidities, functional capacity, and several diagnostic tests that are summated to a score, and the score predicts the survival that a patient will have. This is currently what we use globally now to predict survival and to intelligently use our armamentarium of drugs to match risk with the intensity of therapy. Now, there have been many PH trials over the last several years. We're finally catching up in this disease state. As you can see, over the last two decades, the majority of the development have been in those three initial pathways that I illustrated earlier, which work again by a major vessel relaxation mechanism. We need better drugs that can actually remodel the blood vessels if we want long-term survival. That is where the shift in drug development is now going to. We're now looking at drugs that directly will remodel the blood vessel by looking at metabolic pathways, proliferative pathways, inflammatory pathways, and even looking at developing drugs that can mitigate or activate the genes that we know cause this disease. One of the biggest new directions that we're going in is in the epigenetic modification of pathways to slow down the progression of the pulmonary vascular remodeling. You can see now that we have lots of clinical trials targeting metabolic pathways in pulmonary hypertension, targeting inflammation in pulmonary arterial hypertension, and also drugs targeting other signaling pathways like the estrogen pathway, the PDGF pathway, and others. Now, unfortunately, we haven't had a lot of success in this new area, and we've had a lot of trials looking at novel pathways that have either failed or become neutral, again, because they haven't actually worked on the essence of pulmonary vascular remodeling. That's where new pathways for treating pulmonary arterial hypertension are really coming into play. This slide demonstrates some of these new trials that are currently being conducted in these different areas focused on vascular remodeling. Well, this is where CS1 comes in because this is a drug that truly can remodel the pulmonary vessels and goes beyond the main mechanisms of pulmonary vasodilation. It has antithrombotic activity by restoring tissue plasminogen activator and reducing PAI-1. As you remember, microthrombosis is a major part of the pathology of this disease. It has anti-inflammatory activity, antifibrotic remodeling activity, and it reduces pulmonary artery pressure. All the key things that we're looking for for a new molecule that truly remodels the blood vessel and just doesn't vasodilate. We're going to be using this drug, as Björn Dahlöf will tell us a little bit later, in a phase II prospective randomized open label blinded endpoint multicenter study that will investigate the safety and tolerability of three doses of CS3 in patients with pulmonary arterial hypertension. We're going to use some very novel endpoints in this study. We're going to be using the contemporary REVEAL risk score to really give us an idea who we're bringing into this trial to make sure that we're enriching the trial with the right patients and to be able to follow the efficacy of this drug using the appropriate and most contemporary endpoints. We're using the best imaging agent that we can to look at the remodeling of the right ventricle, which is cardiac MRI. Then we're using the CardioMEMS device, a novel device that has been approved for the use of heart failure, to actually monitor the effects of this drug on pulmonary pressures. I'm going to tell you why that's very important here in a few minutes. We're also looking at novel biomarkers as well as our traditional endpoints, which are six-minute walk test, echo, and some other biomarkers. Now, this is where I feel why the CardioMEMS device is going to be so good at really giving us the earliest indication of remodeling in these patients. As you can see on the right-hand part of this panel, there are a number of things that we follow in clinical trials, like six-minute walk tests, NYHA changes in weights and symptoms, changes in heart failure symptoms. These are really late manifestations of the disease and very late manifestations of the vascular remodeling that we see in this disease. If you look all the way to the left of this slide, changes in hemodynamics, which the CardioMEMS device gives us, gives us a huge gain in time to identify these very subtle changes in progression and remodeling of the pulmonary vessels. Hemodynamics are a very, very important part of how we manage our patients. Currently, what we do right now is repeated right heart catheterizations to measure these pressures. There are a lot of shortcomings to doing a right heart cath. It's invasive, there's some risk involved, and it really is a single time point measured in a supine or risk condition. Not something very good to visualize remodeling over a period of time. That's where the CardioMEMS comes in, which is this device that I'm illustrating now, which is implanted into the pulmonary artery through a right heart catheterization procedure. With this type of device, you can see on this lower panel that we can measure the pulmonary artery pressures very concisely. In this panel, the red is the pulmonary artery systolic pressure, the blue is pulmonary artery mean pressure, and the green is pulmonary artery diastolic pressure. You can measure this every single day in the course of a patient. This is just an example of one of my patients treated with traditional drugs. You can see how this person has responded in terms of their pressure to these drugs, and in the corresponding MRI pictures on the top, how the right ventricle is also remodeled with this. With these slides, I hope I gave you a general idea of the absolute need for these new medications, the novel endpoints we'll be utilizing in this study, and particularly the importance of utilizing the CardioMEMS to give us daily touch points with our patients to see early effects of this drug on vascular remodeling. With that, I thank you for your attention. Thank you, Dr. Benza, for an excellent presentation and for taking time out. There was some noise in the background. I know you are at the airport. Have a good flight later on. Now I'd like to introduce Dr. Phil Adamson from our partner in this study, our collaborator, Abbott, and he will talk about hemodynamics and the device CardioMEMS, which as you heard, is being used in this trial. Welcome, Phil. Thank you, Sten, and thank you, Ray, for that great background in pulmonary hypertension, World Health Organization Group 1 disease. What I'd like to do is give you the background as to the use thus far of the CardioMEMS sensor and the system in patients with World Health Organization Group 2 pulmonary hypertension, which is secondary to left heart failure. The management of this disease. It really started many years ago with the recognition that pressures increase as patients who have chronic ambulatory left heart failure begin the process of decompensation. Many years ago, we discovered this phenomenon and looked at that very carefully. What we found was that these pressures, when examined with automatic detection algorithms, actually changed long before patients developed symptoms, as Ray mentioned. That's given rise to the hypothesis that a superior way to manage patients with heart failure is to base that management on what we now call hemodynamic congestion. Let me talk you through this slide. You've seen it already, but it demonstrates that the first insult that a patient's physiology has in their ambulatory stability is an increase in cardiac filling pressures. This increase comes from a shift of volume, either from the splanchnic circulation or exogenous fluid overload, leading to these pressure increases which occur 2-3 weeks before patients develop symptoms. Very predictable physiologic and pathophysiologic changes occur. These reproducible changes include autonomic adaptation to this insult. It includes the detection of congestion in the pulmonary vasculature. All of this time, which we call now hemodynamic congestion, is in the absence of symptoms. With the ability now to monitor these pressures, we're now able to treat the patient before they come to us with symptoms, because as Ray mentioned, it is very true both for WHO Group 1 as well as WHO Group 2, and probably for the whole progression of this disease and most cardiovascular diseases, is that its clinical symptoms are a very late phenomenon. We are very robust creatures, and we are able to take a lot of change in our physiology before symptoms restrict our ability to do things. Our traditional clinical congestion is now known not to be very helpful in preventing hospitalization for this disease. We've learned a lot about heart failure pathophysiology, but let me tell you first of all about this device that will be used in the trial. We're very excited to be a collaborator in this Cereno trial. This is one of the first, if not the first, corporate-to-corporate collaborations we've done as Abbott, the medical devices, with a pharma company. This is extraordinarily exciting process for us, and we're enthusiastic about supporting the success of this endeavor. The CardioMEMS heart failure system consists of three components. It consists of an implantable sensor, which I'll tell you about in a moment. By the way, this sensor is a microelectromechanical sensor that does not require a lead or a battery. It's permanently implanted in the pulmonary artery. The patients then interrogate this device from an antenna embedded in a pad that they lie back on. They press a button, and that information then is sent and encrypted and sent to a secured website that then displays the hemodynamic information, as Ray mentioned already. The implant itself actually occurs through a typical right heart catheterization. The only addition is a limited angiogram to identify the appropriate blood vessel for the sensor and a guide wire for the over-the-wire delivery system. The sensor itself then is deployed. The antenna is this little gold thing, which I'll show you actually here. This antenna supports the microelectromechanical system, and that antenna is wired to a capacitor. The capacitor then moves in nanometer deflections that result as a result of the pressure changes in the pulmonary artery, and that then changes the frequency of interrogation. This is the secret of the microelectromechanical system, is that we're able to convert then this linear relationship between the frequency change and the pressure on the sensor inside the body. Again, this is a passive sensor. It's not continuous. It actually is only active when interrogated, but creates a beautiful digital pressure waveform that's robust and very accurate and precise over time. You can see the United States coin here and as a reference for the size of this device. The Nitinol loops that you saw in the previous illustration really are to anchor the device in the pulmonary artery itself. This sensor then is, as Ray mentioned, allows the patient to upload PA pressures or pulmonary artery pressures every day. That trend that happens when the patients upload every day allows trend analysis for decision-making in this patient population. When we've examined this process, we've examined this process and the approach for congestive heart failure, left heart failure in several thousand patients, two prospective randomized clinical trials involving nearly 1,000 patients in one and 550 in the first trial that we did called CHAMPION. We've performed multiple single-arm studies, retrospective propensity-matched control group outcomes in thousands and thousands of patients. Consistent results in reduction of heart failure hospitalizations have been seen regardless of the geographic area, multiple medical cultures, including the United Kingdom, Germany, France, Ireland, the Netherlands. We've seen this of course in the United States as well. This has been a remarkably consistent approach that's demonstrated superiority of monitoring patients, but not just monitoring them from their pulmonary perspective, but also then acting on that, those pressures to guide medical therapy. Our very exciting collaboration with Cereno now allows us the opportunity to consider a potential regulatory pathway for use of this device in patients with pulmonary hypertension. Currently our United States indication was actually updated this week based on the GUIDE-HF trial. You see what is different in blue. The updated indication in the United States alone is now for New York Heart Association Class II or III heart failure patients with a previous hospitalization and/or elevated B-type natriuretic peptides. The data is used to manage heart failure, but also to control pulmonary artery pressures to reduce hospitalizations. For CE marking, our original indication has continued, but is being updated as we speak for Class III patients with a previous hospitalization. We look forward to the Cereno collaboration because we are anticipating through a collaborative effort of the Device Division of the U.S. Food and Drug Administration and the Drug Division for a regulatory opportunity to demonstrate safety and efficacy of this system in patients with WHO Group 1 pulmonary hypertension. This is a very important and exciting collaboration for Abbott, and we look forward to actually benefiting these patients and actually measuring the pulmonary hypertension that's the root of their disease. With that, Sten, I appreciate again the opportunity to share, and I'd be happy to answer any questions as the day goes by. Thank you, Phil. Very good presentation. Yes, indeed, you and I know from the past that this is a unique collaboration between Abbott, who's never done this before, with a pharma from the tech division or the device division. We are super excited about this collaboration and having both you as a partner in this study but also being able to use this fantastic device that you have developed. Thank you. Now, we will move on to the next speaker, and that's Cereno's own Chief Medical Officer, Björn Dahlöf, and he will talk to you about the study that we're actually pursuing together with Abbott here on these patients with Raymond Benza as principal investigator, pulmonary arterial hypertension. Welcome to the stage, Björn. Thank you. Thank you very much, Sten. It's a great pleasure for me to share with you some features and novelties of actually of this study. I think that I'm humbled to having been given the opportunity to be part of designing this study because I think it's actually it creates a great opportunity for all of us to learn more about this devastating disease and potential future improvement of therapy. I start with a summary of this of the study, and this is a phase II study that aims to demonstrate CS1 safety, tolerability, pharmacokinetics, and exploratory efficacy in PAH. As said, the primary objective is safety and tolerability, but it's a study that includes all the standard parameters of PAH studies, and it also have the validated risk scores that Raymond Benza mentioned. We will have three doses. I come in, into some more detail on how that looks. Me too would like to share my excitement about that we can use the CardioMEMS device in this trial, which I think is really, really important for the success. We will have 30 patients at around nine, 10 centers in the U.S., and the study is planned for having top-line results at the end of the year. We have already selected sites, and they are in final negotiation about to start recruiting patients. You can see that the spread around the country is quite nice. We have both in the north, on the East Coast, in the south, and on the West Coast, a number of sites. As Ray mentioned, the kind of latest contribution, I would say, to treat pulmonary arterial hypertension is epigenetic modulation. In this, I think we have in our reformulated VPA a great opportunity and that this kind of therapy could be really the future for the disease. If we look a little bit more closely on this picture, you can see that some of the hallmarks of the study, that is the proliferation and inflammation and also the effect on the right heart, actually have been shown to be beneficially affected by VPA or valproic acid. If we summarize the features of CS1, I can say that for the characteristics of the disease, which is arterial remodeling, inflammation, fibrosis, and thrombosis, as beautifully outlined by Dr. Benza, I think the epigenetic modulation we offer with CS1, with pulmonary pressure reduction, anti-inflammatory activity, anti-fibrotic, anti-remodeling activity, and antithrombotic activity, where we already have shown in man PA reduction, is really important for the mechanism. When designing a phase II study, I think it's important to cover many aspects of the design. This is an example of what is recommended to include in a phase II trial in PAH. That is safety and tolerability, and tick on that. PK sampling, tick on that. That, to look at biological and mechanistic markers, we can tick on that as well. Have a homogeneous subject group, tick on that. Use risk tools, tick on that. Change in risk as a marker of efficacy, we can look at, and we can tick that as well. Also novel biomarkers. I think we have covered all of that in our study. The design is quite simple. We have a population of PAH patients, I will come to a more exact definition in the next slide. That will be after screening and fulfilling the criteria for the study, being implanted with the CardioMEMS. Then we have a baseline period, both for the patients to familiarize themselves with the device and also to be able to have four weeks of dual antiplatelet therapy without interfering with the actual active therapy with CS1. Then the patients will randomize to three different doses of CS1, 480, 960, and the highest dose. I think the rationale for selecting the three doses have been the following. The lowest dose is actually the dose that could reduce PAI-1 in our phase I study. The middle dose is the dose that have been the lowest dose being active in animal studies of PAH. The highest dose is a dose that is double that, which to see if we can achieve more with our drug. All of these doses are lower than the traditional dose used in the former indication for valproic acid, that was epilepsy. The population of PAH patients, category, which is category one of pulmonary hypertension, and they should be symptomatic. They should have the New York Heart Association two and three group of functioning, and the REVEAL risk score, 2.06-10, which is moderate to severe risk of a future complication. They are at a good age spread, 18 to 80 years, and they should be on not more than 2 other PAH drugs. As said, the primary objective of this study is safety and tolerability, and here we have listed all the different parameters we will measure for that objective. Probably many are more interested in what we have as exploratory objectives because that is where we can see signs of efficacy for the future planning of studies. We will look at pulmonary vascular resistance and pressure from the right heart catheterization. We will look at the REVEAL risk score. We will look at pharmacokinetics as mentioned. We will have the CardioMEMS, and from that, we can not only get pulmonary pressure, but we can get some more variables, which I will show in the next slide. We will have MRI and echocardiography to look at the structure and function of the right heart. We will have traditionally six-minute walk distance and actigraphy, which is measures of the functionality of the patient. We will also look at traditional things like need for additional therapy, improvement in functional capacity, quality of life, and also look at complications related to PAH and other cardiovascular diseases. In addition, we will also look at some novel biomarkers like BMP, ST2, and of course PAI-1, which is where we have shown efficacy in the phase I study. We will save biomarkers or blood and serum and plasma for future biomarker investigation. The blinded part of the study is that we look at CardioMEMS, the echocardiography, and the MRI, and also in sync with the CardioMEMS for several different parameters listed here, and that will be done blindly in core centers that have skilled readers and validated reading procedures, and they will know nothing about exactly what treatment the patients have been given. To summarize this, I think we have a cost-effective study for safety, tolerability, dose finding, and exploratory efficacy. It will be 30 patients with 3 doses at around 9-10 centers in the U.S. Safety and tolerability as a primary endpoint, CardioMEMS as a cutting-edge technology will be involved. We will have validated risk scores, and one or two of these doses will be selected for a future proof of concept study based on all the information we will have from this study. The overall conclusion of this scientific presentation from me, Ray, and Phil will be that PAH is a rare fatal disease with a huge unmet medical need. CS1 is a novel formulation of valproic acid with a putative fourfold mechanism of action through epigenetic modulation, anti-inflammatory, anti-fibrotic, antithrombotic, and pressure reducing all of relevance for PAH. The study will be a cost-effective study for safety and tolerability and all the objectives I've mentioned. We will use cutting-edge technology, and that is CardioMEMS, to demonstrate the pulmonary and right ventricular hemodynamics, as well as validated risk scores and conventional endpoints used in these kind of studies. With that, I thank you for your attention. Thank you, Björn. Excellent presentation, and it summarized it very well. That concludes the scientific part of this webcast, and I will just have a couple of slides, you know, so what happens next with this effort. First maybe, you know, what do you need to do to get here, where we are today? Well, you need to have a global collaborator for the study to actually perform it, and that's a contract research organization which we signed up last year, Worldwide Clinical Trials. You need to have a top level and the best principal investigator you can get, and I'm, you know, sure that my team here together is confident that Raymond Benza fits that model. If you could, you would love to have Abbott as a partner and their CardioMEMS technology, and that is a tick on that one. Thank you, Phil. Of course, you need regulatory approval. You need to write up your efforts, everything that's been documented on the compound, the substance, as well as information about the CardioMEMS technology to get it approved, to get this study approved by the regulatory authority in the U.S., FDA. We got that in September last year. In parallel with all of these efforts, you need to scale up your production of your clinical material so it can be produced and used with the quality parameters that are required for approval by FDA, and we did that. That was done last year. Now, of course, you need to then define, identify centers that are, have the capacity and the qualifications to perform a study like this with CardioMEMS and our drug in these severe patients. They need to be vetted and, that they have this. We have done that together with Worldwide Clinical Trials and Abbott's, support, that these centers are, there. Björn showed a slide of the centers that have been selected. What happens now? Well, we are in the midst of getting ethical approvals and signing contracts with all of these sites. When that's done, the first site is ready to enroll a patient. That's the next major milestone, and you'll probably hear about that when that happens. Then of course, these patients need to go through the procedures and then receive the drug. Of course, then we pursue the patient recruitment to be completed over this year and expect to have, as a target, top-line data by the end of this year. To conclude this presentation, you know, we have three programs in development, two programs in preclinical development that we are very excited about. I think you will hear more about that this year from us, and the data that we have found. Of course, today's topic is the major project for Cereno at this point, and I hope that you have gotten a good picture of what we're trying to do and how exciting that is, not only for us who pursue it or for the stakeholders, the patients that might be able to get this kind of drug, disease-modifying drug in this severe disease, but also for you shareholders who are part of this journey, and I thank you for your support. That concludes the presentation. Thank you very much. I should say this time, there's no unilateral discussion or Q&A responses. This time, we just do it one way, and that's from us to you. Next time, I hope we can have some questions from the audience that we can answer during the live session. Thank you, everyone. Thank you, guys.