Windtree Therapeutics, Inc. (WINT) Earnings Call Transcript & Summary

Good afternoon, and welcome to the Windtree Therapeutics R&D and Investor Day. [Operator Instructions]. As a reminder, this call is being recorded, and a replay will be made available on the Windtree website following the conclusion of the event. I'd now like to turn the call over to Craig Fraser, President and Chief Executive Officer of Windtree Therapeutics. Please go ahead, Craig.

Thanks, Tara, and hello, everybody. Good afternoon and good morning. We were looking forward to giving all of you an update on all of the various activities that Windtree has going on. It's going to prove to be a very eventful next set of quarters and we put a lot into motion. So I think now is a great time to be learning a little bit more about Windtree and about our programs. Today, I'll be making some forward-looking comments. I really encourage everybody to go to our website to look at our public filings and to review them and further information. But here's what we're going to be covering today. I'll be speaking. I'm the President and CEO of Windtree. I've been here at Windtree as the CEO for nearly 8 years, been in the industry. However, for 33 focused on specialty cardiovascular and other specialty type of biologics. And I will be doing an introduction to Windtree getting oriented to the company, talking a bit about our lead program and that landscape in the area of cardiogenic shock. I'll also then be turning it over to Dr. Steve Simonson, our CMO. And Steve will be covering istaroxime, how it works, talking about the rationale that we had for picking the focused areas that we have for development and specifically talking about the last trial that we ran called the seismic study. And that was a study in patients experiencing cardiogenic shock or early cardiogenic shock. I'll talk about the results. And where do we go from here, what our plans are. And then we will have the star of the show, if you will, Dr. John Teerlink, who is one of the top heart failure experts in the U.S. and really globally is joining us today to give a clinical perspective of the need, what's going on with these patients and where istaroxime could fit in therapeutic options for treating these patients and helping them. And then I will wrap up by giving some additional perspective on heart failure, business development, talk about cash and cap table, and we'll open up for some Q&A on the back end of that. So let me jump right into this. Windtree is a biotech, biopharmaceutical company that's focused on patients that are in the hospital due to a heart that is failing. And we're really treating patients at their moments of crisis, oftentimes in critical care, certainly, decompensated and less stable patients that are in the hospital. And we have a drug and an approach that we believe and has been demonstrating the opportunity to really help these types of patients. And we trade on NASDAQ under WINT. But specifically, istaroxime has been under development in the area of patients hospitalized due to their heart failure or acute heart failure as we call it, and more recently, in cardiogenic shock. But here's the thing. -- istaroxime now has been through 3 Phase II global studies. And there's been a high consistency of results. And this is a consistency of results across a wide range of severity, across all areas of the world, in all the regions and across many, many measures, not 1 or 2 -- and it has demonstrated a profile that's very unique and very attractive. And in fact, when we first brought istaroxime a number of years ago in a merger and acquisition, and we gather the top key opinion leaders from the U.S. and some from Europe. In fact, it was the profile of the product even more so than the positive Phase IIb results that the thought leaders were really giving us an appreciation for. But this profile is one where we not only significantly improve the functioning of a failing heart. But we do so in a manner that doesn't trade off blood pressure. And in fact, we also rapidly and significantly improve blood pressure. Most often, that's a nice to have in the area of acute heart failure. It's a critical thing to have in the area of cardiogenic shock as we'll be telling you about today. But at the same time, the uniqueness of the profile finds that it has a favorable effect on things that are associated with myocardial oxygen demand, such as heart rate as well as improving renal function, which is a really big deal in these patients. And what so far has been a differentiating safety profile. And more specifically, the recent positive Phase II results in cardiogenic shock has created a unique opportunity for the company, an opportunity that we believe can be a program that's relatively faster and less expensive than typical programs because of the primary endpoint that you need to achieve and just has an attractive regulatory and developmental landscape and it creates a lot of optionality for the company. Therefore, cardiogenic shock has become our lead program, and we've really dialed the organization into the execution of cardiogenic shock. We, at the same time, our highly engaged in business development activities. I'll talk to you about that at the end, including exploring potential strategic opportunities. And while we won't be talking about it in the rest of the presentation, I do want to point out that one of the strengths of Windtree is not only are we a lean, very capital-efficient operation and we've really doubt in our burn and all of that is great, but it's being run by a group of highly experienced people across all of our functions. People like Steve Simonson that you're going to hear about our CMO. It's a group of people that have been there and done that many decades of successful experience in drug development, doing deals, launching products. And we don't often talk about people versus the science, but in my personal experience, having done this a number of times and start-ups that have really worked out, the people are the important dimension as well, and we have that covered. So this is our portfolio. Istaroxime is in the lead. Istaroxime has 2 potential indications, cardiogenic shock and acute heart failure that we believe is Phase III ready as well, drafting off of the work that we're doing in cardiogenic shock. And then behind istaroxime are the next-generation SERCA2a activators. SERCA2a is the novel mechanism that is in istaroxime. Steve will tell you about this. But we have next-generation SERCA2a activators. And SERCA2a has been a much sought-after target in the world of heart failure for decades, really. And -- but it's been elusive to development in companies. And we really have been the first company to get a clinical stage SERCA2a istaroxime, being a first example. But we have next-generation SERCA2a activators that could be fast follow-ons or treat other areas that also have oral bioavailability unlike [indiscernible] that's an IV for hospitalized patient, these have potential in development to be chronic medicines, outpatient medicines. I'm not going to talk about rostafuroxin -- it's for genetically associated hypertension. We're going to sell it. And we also had a legacy acute pulmonary care part of our business, focused on little preterm babies, drug device combination that last year, we did a global out-license of it. So that's potential value to our shareholders, and we have a partner advancing that. But again, this heart failure platform is a multi-indication on the lead, multi-asset platform that is really attractive, we believe, for licensing or acquisition and there's just a lot of opportunity. So I'm just going to do a quick introduction of cardiogenic shock before turning it over to Steve. The cardiogenic shock is a condition where the heart is really failing to meet the body's demands. And in fact, that's the definition of heart failure itself. And heart failure is a condition that we probably have all had relative with heart failure or congestive heart failure. It's very common. There's nearly 8 million patients in the United States with heart failure. And these patients will have these episodes where they'll go into a bit of a downward spiral, what we call decompensating where the bodies -- well the heart is failing to really pump adequately, and the body has a way of sensing that and having reactions to that. Like if the kidneys are sensing a drop in blood pressure, it will start to kick in the renin-angiotensin- aldosterone cascade that starts to retain fluid and try to get volume up, which becomes problematic, different hormonal things will kick into gear. And all this creates a downward spiral where the patient goes into the hospital, pulmonary edema, fluid overload. Now some of these patients that are in heart failure, their heart failure is going to be severe enough or more unstable so that the heart is really failing to adequately meet the body's demand to the point that even vital organs will start to be starved of flow, perfusion, oxygenation and vital organs will start to become impaired, like brain, kidneys and so forth. This condition is cardiogenic shock and the start of cardiogenic shock. And there's systolic blood pressure in this case because the heart, the pump is not filling up the pipes, if you will, and therefore, the blood pressure measured within those pipes, their systolic blood pressure is down into 80s, 70s, maybe even down into the 60s. And as opposed to [ URI ] systolic that top number is about 120. And this becomes a treatment emergency. It's a really urgent situation to start turning this situation in the downward spiral that many of these patients are on and get the blood pressure back up above 90 and get the patient stabilized. And when they're in full-blown classic shock mortality, 20% to 40%, it can become even worse for the ones that are way beyond even what we're going to be treating. Now because there hasn't been any new products in this area, we needed to go out and value it, we gathered all the claims data from the U.S., and we did a proper valuation, and it's about a $1.25 billion market potential in terms of valuation globally. And again, I'll talk about this later, there's nothing else in development. So it's a pretty wide open field running. Now we wanted to make sure that this area had a high need. Of course, we were hearing that. We know that from working in this space in Korea. We were hearing it from our scientific advisers. In fact, we looked at shock coming out of a meeting with the FDA on acute heart failure in our data. It was a great meeting. We picked up a fast track designation coming out of that. But in fact, the medical reviewer mentioned to our CMO, -- have you guys considered cardiogenic shock with this profile? And there's also this big need in cardiogenic shock because the agents that we have to work with and Dr. Teerlink will illuminate this a bit more, have their issues. And you don't reach for them casually or quickly. You can get blood pressure up and shock if we give somebody, for instance, start an infusion of norepinephrine, adrenaline, or catecholamines. All that will kick up heart rate a lot. And with that can come arrhythmias,myocardial oxygen [indiscernible], the heart work harder. So these things tend to come at a cost and oftentimes get a bit reserved until patients really back is against the wall. And we went out and talked to 100 U.S. clinical cardiologists who treat cardiogenic shock. And we ask these 100 physicians, how much need there was for a new therapy. 99 out of 100 responded, it's highly needed. Now like I said, I've been doing this for 33 years, leading some big portfolios and some of the largest pharmaceutical companies. So I've seen a lot of market research. It's hard to remember -- I can't remember seeing 99 out of 100 physicians agree on something. And when they saw a blinded profile for Ista, and this was before we had the [ SHOP ] data, but just the profile of it, 84% responded that they would be likely to extremely likely to use it. And the majority said, it has that profile will be the first thing I would use. So with that, I'm going to hand this over to Steve, and I apologize for us using the same computer right before we started this call, my computer decided to reboot. So I'm going to get out of Steve's Chair and turn it over to him.

Thank you, Craig. Let me start by saying a few words about how istaroxime works because it's a very interesting molecule. Istaroxime is a small molecule that's administered by intravenous infusion. And it has 2 mechanisms of action. The first mechanism is to inhibit a pump called the sodium-potassium ATPase and this results in an increase in calcium inside the cell that produces a stronger force of contraction. The second thing that istaroxime does that is perhaps more unique is it activates SERCA2a. And SERCA2a takes that calcium and sequesters it in an organelle inside the cell, the sarcoplasmic reticulum. And that facilitates relaxation of the heart muscle and contributes to better ventricular filling. So istaroxime has an impact on both systolic or the contraction phase and diastolic or the relaxation phase of cardiac function. And istaroxime may have a direct action to increase blood pressure by an effect on the vascular smooth muscle. The rationale for looking at istaroxime in cardiogenic shock came from our acute heart failure Phase II program, as Craig was telling you. What we've seen in that program is a consistent improvement in cardiac function, and this is primarily driven by an increase in stroke volume or the amount of blood that is pumped with each heart beat. And we see lower cardiac filling pressures, and these are typically elevated in acute heart failure decompensations and contribute to the congestion that is seen in heart failure-related decompensations. We see dose-related increases in systolic blood pressure. Istaroxime maintains or increases renal function and there are dose-related decreases in heart rate. And to this point, we have not seen any increase in clinically significant arrhythmias. So this is a very unique profile that may provide the potential to fill the unmet medical need for acute heart failure and cardiogenic shock. So we embarked on a study that is called the SEISMiC study in early cardiogenic shock. We enrolled 60 patients who had their early cardiogenic shock due to acute heart failure. Their systolic blood pressures were between 75 and 90 millimeters of mercury. We infused study drug for 24 hours. Patients received istaroxime or placebo. And within the istaroxime group, 2 target doses were evaluated. 1.5 micrograms per kilogram per minute in the first group and 1.0 microgram per kilogram per minute in the second group. The primary endpoint was the systolic blood pressure profile over the first 6 hours of the infusion comparing istaroxime to placebo. We looked at several secondary measures, as you might expect, the systolic blood pressure profile over 24 hours and at specific time points, we did echocardiography to look at systolic and diastolic cardiac function. We looked at renal function and various safety and tolerability measures. This graph represents the primary endpoint of the SEISMiC study. The cross-hatched area represents the placebo blood pressure profile over 6 hours, and the green area represents the istaroxime group. You can see that there was a statistically significant increase in the blood pressure profile for the istaroxime group over this period of time. This shows the actual blood pressure values over the 24-hour duration of infusion. And you can see that istaroxime produced a greater increase in blood pressure over this time period. And if we look at the left-hand side of this graph, the separation between istaroxime and placebo began at the first time point measured at 30 minutes. And that's a characteristic you'd like to see in a drug treating condition like cardiogenic shock. I mentioned we did echocardiography to assess systolic and diastolic cardiac function. And as we've seen in the other Phase II studies with istaroxime cardiac index or the amount of blood that the heart pumps per minute was significantly increased. And this was driven by an increase in stroke volume, and that's the amount of blood that the heart pumps out per beat as opposed to increasing the heart rate. We also saw improvements in other parameters, including left atrial area being reduced, the left ventricular and systolic volume and end diastolic volumes were reduced as well. This graph shows the effect on renal function as reflected by the estimated glomerular filtration rate. And it's consistent with the kind of graph we've seen in our Phase II programs with -- or studies with istaroxime to date. The dotted line represents the GFR for the placebo group, and the green line represents the istaroxime group. And you can see that during the infusion, congruent with the increase in blood pressure that we've seen, we have an increase in GFR in the istaroxime-treated patients. We looked at 2 doses of istaroxime in SEISMiC. And what we're looking at here is the blood pressure values over the first 6 hours of the study, the primary endpoint of SEISMiC. The dotted line represents the placebo values. The green line represents the high dose istaroxime group, and the yellow line represents the lower dose istaroxime group. And this gave us some valuable dose-related information on istaroxime. It showed us that we don't have to push the dose of istaroxime to get the kind of blood pressure increases that these patients need to improve. And that will serve our program well going forward into future studies. So to summarize the SEISMiC results, systolic blood pressure was significantly increased. That result was seen rapidly and it persisted throughout the 24-hour infusion period. We monitored blood pressure over 96 hours, and that increase in blood pressure was sustained over that period of time. We saw improvements in key secondary endpoints of systolic and diastolic function of the heart. Renal function was maintained, and we got valuable dose information to integrate into our program moving forward. So this study and these data substantiate and advance the rationale for istaroxime as a potential treatment for cardiogenic shock and support the data that we have from the program from acute heart failure. So building off this positive proof-of-concept study, where do we want to take istaroxime. There are 2 pathways of study that we would like to pursue. The first is what we are calling the SEISMiC extension study, and this is a study where we want to extend the dosing interval and do some additional characterization of istaroxime. The second pathway of study is to go into more severe patients, what are referred to as SCAI Stage C cardiogenic shock. And these patients are sicker and have hypoperfusion in addition to hypotension, and they may have evidence of end-organ dysfunction due to their cardiogenic shock. When we have these 2 pieces of information in hand, we will be in a position to engage the FDA to talk about an end of Phase II meeting and iron out the details for the Phase III program. So the SEISMiC extension study, as I mentioned, we dosed istaroxime for 24 hours in SEISMiC. And in parallel with that, we completed a toxicology study to allow us to dose istaroxime longer. What we want to do in the extension study is dose istaroxime up to 60 hours, and we want to employ a dosing regimen where patients start out with a higher dose and then the dose is decreased or tapered down over the rest of the dosing period. This allows us to evaluate the ability of istaroxime to reverse the decline that these patients may have, stabilize them and continue to provide benefit with lower doses of istaroxime for longer periods of time. We also want to eliminate and characterize the benefits associated with SERCA2a activation. Istaroxime has that dual mechanism of action with sodium-potassium ATPase inhibition and SERCA2a activation. The terminal metabolite of istaroxime has a somewhat longer half-life. So longer dosing will produce a longer period of SERCA2a activation that we want to characterize in this study. This is going to be a double-blind placebo-controlled trial in SCAI Stage B patients. We're going to enroll up to 30 patients who have systolic blood pressure very similar to the first part of the SEISMiC study. We'll be doing this in the United States, Europe and Latin America. We'll have 2 dose groups of istaroxime versus placebo. And as I mentioned, they'll be dosing for up to 60 hours. This study will take about 8 months to execute, and we're looking forward to having the first patient in later this summer. The second pathway of study I mentioned was to go into SCAI Stage C. And this is a busy probably unreadable slide, but it's here just to show the classification system that we're using. And the SCAI Stage A patients might be the kind of patients that we would enroll in our acute heart failure program. They are at risk to deteriorate into a shock stage, but they don't have shock at that point. The Stage B patients, the kind of patients we studied in the SEISMiC study have systolic blood pressures that are low, but they don't have elevated lactate or evidence of hypoperfusion. The stage C patients are sicker. They have hypotension and hypoperfusion. And this table just lists some of those characteristics that we can use to identify and characterize those patients. So in the SCAI Stage C study, I just want to say that in this study, because of the upstaged raise that we did earlier this year, we are able to begin working on this SCAI Stage C earlier than we had planned, and we're going to execute this in parallel with the SEISMiC extension study. The extension study, as I mentioned, is a bit further along, and we're ready for first patient in later this summer. But we're hoping to have the SCAI Stage C study ready to begin enrollment by the end of third quarter or beginning of fourth quarter. At that time, we will confirm a decision to proceed and provide specific guidance, including the timing of the data. And right now, our thinking is that we will deliver this in the same kind of time frame that it will take to do the SEISMiC extension study. So the details around the SCAI Stage C study. We're going to begin with 20 patients with this type of shock. And the protocol will be written to allow additional enrollment after the review of these first 20 patients. Istaroxime or placebo will be added to initial standard of care. The study will be blinded. The reason that we're adding istaroxime to standard of care is that these patients require relatively immediate therapy to reverse their condition. They don't have time to wait for study consent or to get to the study drug from the pharmacy. So they will begin on standard of care with a vasopressor or inotrope and then istaroxime will be added to that. There will be a period of stable therapy for about 6 hours to assess the primary blood pressure endpoint. Of course, if the patient's condition dictates it, the changes in medications will be allowed. But we want to try to assess the effect of istaroxime in this setting with the existing standard of care therapy. After that initial 6 hours, we will taper the initial shock therapy and istaroxime or study drug will be supporting the patient. The key measurements in this study will include the systolic blood pressure over 6 hours. We'll be doing a vasopressor inotrope scoring system. This is a published scoring system that will allow us to quantify the burden of support that these patients need. We'll be looking at safety parameters like clinically significant arrhythmias, renal function and the need for additional shock therapy and progression to a greater stage of shock. So that is our program of study going forward. And now I'll turn it back over to Craig to talk about the addressable market.

All right. Back into the CMO seat, I feel smarter already. But to give you a quick perspective on the market, right? Steve mentioned Bs and Cs and As. And Dr. Teerlink is going to illuminate this a bit further as well. But I want to give a perspective on what we're covering here. When you look at the patients that are from early shock all the way through very extreme, those extreme patients, that's not where our program will be. That tends to be a device world where they need mechanical intervention, right? But when you look at Bs and Cs, that represents about 86% of these patients that are in different stages of cardiogenic shock. And that's the focus of this program. And that's why we want to get a little bit of experience with the Cs. But let me talk about Bs for a second, that 56% where we did our study, we really see a great opportunity. When you look at istaroxime and its profile, not only reversing the condition and getting the blood pressure up and moving these patients, systolics back up above 90, where they're much more stable patients. But that effect on what is causing the condition, the lack of cardiac function, if you will. And what we saw in such a small study to reach statistical significance on many of those measures that Steve mentioned, even exceeded our expectations to take very dilated, lose hearts and tighten them up, to see that stroke volume to that degree, increase and so forth. Give us a lot of promise that if you -- if we can keep this agent relatively clean, if you will, on the side effect profile and differentiate, it, it will be used earlier where other therapies tend to be not used in reserve, i.e., an early shock. And it will be fantastic if we see -- because there's a portion of those patients that move from B into C. It's a very unstable patient. And if we can keep a bunch of those patients from moving down into C, right? But then at the same time, we want to include the C and need to include the Cs. That justifies a systolic blood pressure as a surrogate endpoint, if you will. But the Cs also have a lot of need, a lot more events. So hence, the focus. And then As will be, as Steve just alluded to, tend to be the focus of what we'll do as a heart failure drug in our acute heart failure work, patients and heart failure add with lower blood pressures. And again, Dr. Teerlink will touch on this as well. So we think we really have the majority of the market covered. And I'll end our section of cardiogenic shock by saying this landscape is really, really very rich to make a difference. If you have an agent that works because these patients, I want to give a perspective on how sick these patients are and the ability to create really good evidence-based positioning, if you will. First of all, the average length of stay for a patient who's been diagnosed in cardiogenic shock is 19.5 days in the U.S. And their cost tend to be north of $200,000, even approaching $0.25 million. These are very sick patients with a lot of high costs and we've already been talking about the morbidity and mortality aspects of this. And Dr. Teerlink also will touch on that. So if you have an agent that works, what we see is a tremendous opportunity to one be used earlier and therefore, expand the market. And two, when an agent is used to be the preferred agent based on our profile. I also want to point out there's a couple of other drivers of potential value or opportunity. One is, besides the current agents having these undesirable side effects and even poor outcomes in many cases. And the high cost that you see here, we can generate pretty good evidence in the face of what also is no new therapies in development and the therapies are there or older agents that are not actively promoted. I can't remember a such a pronounced need where it's wide open field running to have a therapy that you can do something with. And then it just ends up being a very good drivers of valuation, if you will, around time risk, cost, return and so forth. So we're excited about the program and the opportunity, most of all, to potentially help patients that are really in a high need that we believe. Now let me turn this over to the person who's been on the front lines treating these types of patients and patients in heart failure and helping to shape the thinking about this. And that is Dr. John Teerlink, and we're really fortunate to have a great set of advisers to this program, really right from the start, but a real standout is Dr. Teerlink. Dr. Teerlink's background includes medical school at Harvard, followed by residency at UCSF. He also did a post doc in Switzerland and then fellowship back at UCSF, where he then subsequently joined the faculty and as a Professor of Clinical Medicine at UCSF, Dr. Teerlink is a Director of heart failure and the Echo laboratory at San Francisco VA, which is also associated with the university and he's an active leader truly in U.S. and European health heart failure, medical associations and has just authored so much. He's been a principal investigator on many, if not the majority of the largest heart failure studies and cardiogenic shock work. He even previously served on the FDA's cardio renal advisory committee and has a nice understanding of the regulatory landscape as well. So with that, Dr. Teerlink, I'll turn it over to you.

Fantastic. Thank you. And I think we may have to give Craig an honorary MD given his nice explication of the patient's course and with the cardiogenic shock. These are my disclosures. Obviously, my career has been committed to trying to help development of novel both drugs and devices to treat patients with heart failure and cardiogenic shock. And this is a fantastic continuation of that journey. And what I'd like to do is build upon the great talks by Craig and Steve to try to give a more clinical perspective to some of these things. So this is going to be touching upon issues that have already been addressed to some part, but giving a little different perspective. Of note, while I am President of the Heart Failure [ side ] of America and have association with the VA as well as UCSF, these viewpoints are obviously my own. So I'd like to just quickly go through kind of how we define heart failure and cardiogenic shock. Talk about the outcomes of patients with cardiogenic shock. The current pharmacologic therapy of these patients and then fit istaroxime profile and data into that context. So starting with how do we define cardiogenic shock? Well, the first parts of this were defined in clinical trials. And these clinical trials, the common denominator in all of them is hypotension. And so this is the key point for all the trials in terms of if you have a systolic blood pressure less than 90, that is the entry criteria for all the criteria, for all these trials and guidelines. So that becomes a [indiscernible] for what we call cardiogenic shock. And there have been multiple, multiple classifications. The European site of cardiology classification is along the top row here. And then the SCAI, which is the Society for Cardiovascular Angiography and Interventions, classification is below that. And the important point from this is to recall that this is a continuum. Even though we like to make little boxes of people, these patients are always teetering between these stages. And as a clinician taking care of them, we don't necessarily look at them specifically, "Oh, this is just a SCAI Stage B patient." This is a cardiogenic shock patient who is teetering on becoming -- and we don't know whether they're going to become classic cardiogenic shock where they start having more evidence of hypoperfusion and more multi-organ dysfunction or whether they're going to go all the way to meeting transplants and other things -- other more dramatic mechanical interventions. So I want to stress that this is really a challenging continuum to take care of and that these patients are dynamic along this line. The next thing that I want to bring in part is -- and this is just actually for your reference. I know one of the things that I've been very impressed with in dealing with the investment community, is how well you folks are educating yourselves. So this is more -- it's a very busy slide, but it's a reference for you to look at in terms of what's the most current work on cardiogenic shock from the cardiogenic shock working group classifications and it just tries to refine what we've been talking around here, which is clearly the SCAI classification. And that has been globally adopted. And the point you've already heard about this classification. But the thing I want to stress, and this is something that's unusual for actually a sponsor to do that I think I actually understated the percentage of BMC I want you to recall that these stages are developed and investigated the epidemiology of this is investigated in shock centers, in places where they specialize in this. And often don't include the broad base of community centers that actually have to deal with the Stage A, B and C cardiogenic shock on a routine basis. So my personal opinion is that while 86% is a very impressive number, I think it's actually even greater than that in terms of our -- the patients that we see. And just for perspective, I work at a Veterans Affairs hospital, which is much more along the lines of a community care hospital. And we see a lot of BMC cardiogenic shock. So you'll be hearing lots of numbers. And sometimes, these numbers just wash over us. And I just want to put a bidding perspective, and this is nice on the left-hand side, is a nice graphic from [ Steve Greens ] Article where he pointed out that the atherosclerotic cardiovascular disease risk scores categorize a risk of -- in 1 year of myocardial infarction, ischemic stroke. If that gets up to 7%, that's considered a very high risk. And in-hospital mortality for myocardial infarctions, which would be epicardial blood clot there, the in-hospital mortality for those is 6.4% to 9%. So with that as a perspective, when you look at what happens to our cardiogenic shock patients in red is the mortality of Stage B, C, D and E patients in hospital based on their outcome distribution of baseline, SCAI Stage on the left and then the maximum SCAI Stage on the right. So right away, even if you have just Stage B, you have a 21% chance of dying in the hospital. When -- if you -- when you present with that. The other thing to notice is that actually if you can maintain or if you can subsequently move patients into B or C, you can actually have significant impact on reducing their mortality risk. So if you can keep patients in these lower stages of cardiogenic shock, you have the real opportunity to dramatically improve outcomes. Just to finish up what the key here is the red is the mortality. Blue is the native heart survival and then orange is the heart replacement therapy, and this includes transplant and LVADs. So this gives 2 messages to me. One is that it's very important to treat these patients because intrinsically, they have high morbidity, mortality, but that it's also important to treat these patients aggressively early on because you can have the possibility of preventing them from going on to more dangerous forms of cardiogenic shock. So this is a blown-up version of just looking at the in-house or mortality at the baseline SCAI Stage. And once again, you can see that the -- is just dramatic in-hospital mortality that would be considered extremely high risk in any other scale. So what do we do to treat these patients? Well, we have these agents that are listed and they go from norepinephrine down to vasopressin, all of which are what we call typical vasopressors and then dobutamine, milrinone and then internationally, there's levosimendan and those are considered more inotropic agents. The challenge with these agents are that -- when you look at the vasoconstriction agents, they will improve blood pressure, but oftentimes, they actually worsen and organ perfusion and so we're balancing the -- trying to balance the challenge of perfusing the brain to let the patient continue to no longer not have altered mental status while not killing the kidneys because you're squeezing the blood vessels so tightly that actually the blood flow itself. The blood pressure stays fine, but the blood flow itself has decreased to a level that can no longer sustain the organs. So that's one of the dramatic problems with those agents. And then in addition, they tend -- many of them tend to increase heart rate, which increases myocardial oxygen demand and can increase ventricular wall stresses, all of which culminate in making patients with heart failure cardiogenic shock, do much worse. And then finally, we have the inotropic agents. And these agents, while they improve contractility, many of them will increase myocardial oxygen demand by increasing heart rate. And so viewed from another direction, these agents all work by solely increasing intracellular calcium which then can increase heart rate, decrease blood pressure, increases oxygen demand, decreases from cardiac efficiencies and increases arhythmias, including lethal arhythmias. So that had led and despite all of this, there has been a huge history of developing [ inotropes ] that have failed because they did the same thing over and over and over again. They only increased intracellular calcium in ways that were deleterious to the cells and following Einstein's definition of insanity. So you've already heard that istaroxime is unique. And one of the things that's special about it is that it actually not only can improve contractually by providing that transient increase in calcium, so more calcium is available for increased contractility, but then it also increases the reuptake of that calcium. So that can actually improve the ventricular myocardial relaxation and decrease of ventricular filling pressures which can also result in increased wall stresses, which can then result in decreased myocardial oxygen demand that then result in decreased ischemia and decreased risk for arrhythmias. So this is a really important differentiating factor from all of the prior inotropes. And you've already heard some data from the SEISMiC trial. I want to go back a little and share some of the information from a study that I was also involved in where patients -- 120 patients were enrolled with acute decompensated heart failure. And this provides some of the background for the development program, patients with reduced ejection fraction and elevated NT-proBNPs and what we've seen in this program was that the E/e Prime, which is a measure of ventricular filling pressures was significantly reduced by istaroxime at the same time that stroke volume was increased. So confirming this beneficial effect of its dual mechanism of action. In addition and importantly, at the 1 microgram per kilogram per minute dose, there was a significant decrease in the heart rate, while there was an increase in systolic blood pressure. And this was the real trigger to say, "Wow, this might actually be really effective in cardiogenic shock." Importantly, 24-hour Holter monitors were done during this study as well. And in the green, you have the placebo and the blue you have -- in blue and orange, you have the istaroxime doses. I draw your attention to the right-hand panels where there is no increase in arrhythmias across the board between baseline and day 2 and no increase in the -- from baseline to day 2 in the istaroxime groups at all. So this is very important to show that istaroxime did not, and these studies show any increase in arrhythmic effect. And then you've already seen the importance of SEISMiC showing this increase in the area under the curve in the blood pressure with a very reasonable and no significant adverse events related to this agent. So how does this all fit into taking care of patients? Well, when I was at a bedside with a patient who is having reduced -- so low blood pressure and is teetering on the edge of, are they going to have reduced worsening renal function? Or are they going to have altered mental status? Are they going to have worsening lung function? In all of these settings, I look -- want to look for other agents to take care of them, but I'm reluctant to do so because those agents have such dramatic side effects and dramatic downsize. And so one of the great things about istaroxime is that this mechanism of action can potentially avoid all the literious effects of the current therapies mean that physicians who want to use a therapy to try to intervene on their patient will be able to do so earlier. And they'll be able to do so in a way that directly addresses the pathophysiology by augmenting stroke volume, improving the diastolic function and increasing the blood pressure. And as I mentioned before, there's no increase in this end organ dysfunction, arrhythmias or heart rate in this early clinical experience, which gives us the confidence to go ahead and do this. And so because of this, I really feel that istaroxime does have the potential to treat patients with this early heart failure, cardiogenic shock pattern, and prevent progression to clinical worsening as well as being able to directly treat patients who already have mid-level the classical heart failure, cardiogenic shock and this fills a crucial unmet need in treating these patients. So thank you, and then I have to put on quickly my [ hat ] is Heart Failure [ site ] of America President, and invite all of you that if you want to talk to heart failure experts, come on to Cleveland and see us, sorry for that unpaid announcement. There you go. So looking forward to answering any questions. Craig?

Thank you, Dr. Teerlink, for such a great explanation of what's going on with these patients and the clinical thoughts and decision-making. So as Dr. Teerlink talked about heart failure, just to put a perspective on it, heart failure and patients coming into the hospital and acute decompensated heart failure is the #1 reason for hospitalizations in the U.S. and Europe, really most areas of the world and people over the age of 65, 1.3 million, 1.4 million admissions per year. It's that common. And -- it has -- even itself has about a 7% inpatient mortality, not quite like shock but it is a huge area, lots of patients. If you go to an emergency department right now, even in a community hospital, you're probably going to see a heart failure patient waiting to be admitted upstairs. It is the most expensive Medicare diagnosis and there really hasn't been many treatment new coming out for the patient in the hospital with heart failure. There is some really interesting novel work being done in chronic outpatient heart failure that we've all been hearing about which is great, but there still really going to need an acute heart failure. And Dr. Teerlink mentioned the Phase IIb, the 120 patients hospice with heart failure. We also did a 2a prior to that, again, 120 patients hospitalized due to the heart failure studying, 3 different doses in that case for a 6-hour infusion. The Phase IIb that Dr. Teerlink went through the data was 120 patients using 2 different doses, the 0.501 infused for 24 hours. Now up through SEISMiC we have been limited to 24-hour infusions. But while we were doing SEISMiC, we also completed a 14-day tox study, that gives us the ability to dose this for multiple days. And we're really looking forward to seeing the additional benefit that can be afforded to patients by being on therapy for a few days, things like increasing renal function, while you're trying to offload the fluid, get the heart working not as hard as it needs to and start to dry out the patient, all of those things. These are the type of agents you tend to want to use for 2 or 3 days. And now we have the ability to do it. Hence, what is feeding our extension study to get the dose optimized. Where we go with heart failure is now that cardiogenic shock is out front, because it can move faster, less expensive, we're going to get this thing to what we believe is Phase III readiness about this time next year and can move pretty quickly through Phase III. Heart failure will be dropping right behind that. We're going to focus heart failure probably in those patients at normal to low blood pressure. Those patients that fit that profile also tend to be diuretic resistant or a lot of them and diuretics IV furosemide is a cornerstone therapy when patients come in to the hospital. You need to get them out of pulmonary congestion and a multi-day process of drying them out, but we can add on to that to improve the cardiac function. But these patients that have lower blood pressure besides being diuretic resistance tend to have longer length of stays, they also tend to be the patients that maybe we get breathing better and filling better, but are more likely to have hospital readmissions as well, which is a big deal for reimbursement and just in general, over the next 30 days. So we think that there's a really -- where the areas that we hear from the advisers like Dr. Teerlink represents about the biggest need in the treating of heart failure happens to match the profile of this agent very well. So that kind of -- we kind of are lucky on that sense and that will define and enrich our studies, if you will. So that's our focus in heart failure. I also want to remind you we have next-generation SERCA2a. And you've seen a press release, I think, even earlier this week, on picking up a USPTO ruling and recently a European Patent Office ruling on our dual-mechanism SERCA2a activators that library. That library, you should think about as the son -- sons, if you will, and daughters of istaroxime. Same dual mechanism, although the lead ones look like they have oral bioavailability. So you can have inpatient and discharge or outpatient therapies. And with everything that you learn with your lead compound, if you're successful in bringing it all the way through to a registration, getting it into the market, it makes the next-generation products that look like it, fast follow-ons. You take all that learning and you know the pathway to quickly move down. And then we have select SERCA2a activators that are just focused on SERCA2a as its mechanism. And this catches a lot of attention, may have oral bioavailability as well. This catches a lot of attention because there's a separate area or type of heart failure called heart failure with preserved ejection fracture. This tends to be oftentimes women who have stiff hearts, fibrotic hearts that just -- the nature of their heart failure is that the heart doesn't relax enough to get enough fill volume and not operating with enough relaxation of blood. And as you know, with the mechanism of SERCA2a, it would make sense why that's such a nice target for HFpEF, which really is locking therapies. So it's a multi-asset platform, and we're pending or awaiting patent information on the pure SERCA2as. But this creates, like I said, a multi-asset platform for business development, speaking of which we have a global license on AEROSURF and our KL4 platform. We will entertain discussions related to licensing opportunities with larger companies. And in fact, I do think areas like heart failure can benefit from places like we all came from the Pfizers, the AZs, the J&Js and so forth of the world. They have a lot of resources and scale. It would just benefit that much more, and our shareholders benefit from that nondilutive support financing support and so forth that can come with some partnership. At the same time, we have said publicly that we're open to exploring strategic transactions. And we do have a strategic adviser that we've brought on. And that is when companies have come to us or do come to us, be it, say, private that have great portfolio, very supportive shareholders. And if there is something that makes sense for the company and its shareholders to have more shots on goal and really build even greater value, we're certainly going to explore that and are exploring that, I should say, because we are actively engaged in that front. I'll leave it next to last slide with -- so what's our focus. For the next 4 to 6 quarters, we're going to have a lot of news. We're out with an intent to simultaneously execute 2 studies at once. Data cards in the course of the next 4 quarters, a couple of data cards, news flow along the way, but the strong trial execution of extension and our SCAI Stage C, enabling a successful Phase III readiness transition to that end of Phase II meeting with the agency. And we're doing some as you always do some select CMC type of work in for as well. I mentioned that we're highly engaged in what could be possible transformative business development. And one thing that we are intending to do with a better job than we've done in the past and that is make people known and our programs known to the outside world. So we really are -- this represents, in many ways, a launch of what you're going to see as much higher IR investor relations and public relations activity, even some dedicated media type of support and so forth. And then last but not least, is the retention and motivation of what is a fantastic team. If you look at our track record, I'm really proud of Steve and the rest of the team's ability when we say we're going to do something, in a certain amount of time, with a certain amount of dollars, the team has a strong track record of doing exactly that, even in the face of here we are doing a cardiogenic shock study in the middle of COVID, slamming hospitals and ICUs and getting that study done and having a successful study. So we have a great team, and we'll make sure that they stay retained and motivated as well. And lastly, cash and cap table, our pro forma is $15 million at the end of Q1. That includes having done a recent successful $12.4 million financing. We're really pleased with that round it slightly upside. As Steve mentioned before, we had a $9 million [ S-1 ]. And unlike most of the deals you're seeing in microcap roll these days, it was clean. 100% warrant coverage, but just straight vanilla cash warrants. And we have the money and we're in full execution mode. And that's been coupled, and we are benefit, as Steve mentioned, from having reduced our burn in having a focus on cardiogenic shock, out-licensing the KL4 platform really has given us an organization that's very lean and very capital efficient. Our common stock right now is just under 5.2 million, common stock outstanding fully diluted about 9.9 million. So with that, Tara, do we want to open up for some questions?

Yes. Thank you, Craig. So at that time, we will be conducting a question-and-answer with our speakers. [Operator Instructions] So our first question comes from Destiny Hance from Ladenburg.

I hope everyone is doing well, and this has been a wonderful and informative presentation. So thank you. Because I have Dr. Teerlink here, I just have to absolutely start with him. I know you covered a lot of the shortcomings of the alternatives, so I'm wondering, how do you make a decision on which alternative for shock is the best for each patient? How do you go about making that decision?

So Craig, if I may, I'll just directly address that. So it's a challenging decision. And every physician has a different kind of approach to it. Obviously, I'm a fairly simple kind of guy. So I look at what are the specific things I need to try to improve. And in general, if I believe that the cardiac dysfunction is the major driver, I will try to reach for dobutamine or milrinone. Milrinone causes -- can cause significant hypotension. And so it can make your cardiogenic shock in some ways, worse if the hypotensive response was greater than the inotropic response or the calciotropic response actually the term I should be using now. So -- and then the same thing with phenylephrine versus norepinephrine. In general, in heart failure, cardiogenic shock, there was 1 trial that suggested that norepinephrine may actually be a better agent in that setting. So I will tend to reach for norepinephrine in those settings. The point though is that I think most of us delay using those agents as long as possible. And it's my belief, and I want to stress it's a belief that if we were to be able to get in there earlier was something that we felt more comfortable using, we might actually prevent people from deteriorating. So did that answer your question, Destiny?

It definitely did. And I guess I also answered a follow-up question, which is how does it fall into your treatment paradigm? It sounds like it's coming sooner. And how difficult do you think it would be to make -- is the standard of care for cardiogenic shock in your opinion, of course.

Well, so the standard of care is based upon a relatively challenging evidence space, and that's a why the cardiogenic shock working group has gotten together and has been working hard to try to figure out how to group together cardiogenic shock trials and things to try to help that evidence base. But this is where development of the evidence is crucial and where you folks funding these kind of programs actually greatly advances health care in the United States, well, internationally as well. But that we need to do the trials, and we need to show that it actually -- that all this promise is actually fulfilled. Did that answer your question?

It definitely did. And I'm going to harass Craig about some regulatory things and some trials. So can we talk a little bit about the extension study. When you're talking about titrating the dosage, I know that the lower dose actually worked better or the data showed that it works better. How are you determining what dose to start at as you go into next, like the SCAI C and extension studies?

Thanks, Destiny. And even though I'm sitting in Steve's seat -- because there's been a lot of discussion about dose selection for these studies. And Steve can kind of give you a quick update on that. Steve?

Well, Destiny, I think one of the things we learned from SEISMiC is that the 1.0 dose is a very reasonable dose that we can anchor the program around going forward, and using that dose and then allowing the patient's condition to even perhaps go to lower doses is something we want to explore. And as with any therapeutic, we want to give as little of the drug as possible to achieve the desired effect, and that's one of the things we'll be evaluating in the extension.

Got it. Okay. And then the...

And Destiny, if I may say one other thing is it is really great that we explore 2 dose in SEISMiC, right? Because going into SEISMiC, if we were to back up what was our thinking on dosing, as we thought on to cardiogenic shock, the key -- and with systolic blood pressure being the primary end point. The key question that we had sitting around was -- and these are my words, well, we have the horsepower to move down the spectrum of severity and really get blood pressure rapidly and significantly up enough to pull these patients back up out and get them above 90 and so forth. And that's why we were up with the 1.5 and then decided to add to 1.0. And while both doses work, as you noted, the 1.0 looked better. The advisers, the executive committee of the study and so forth, feel good about -- that start with one because we know that rapidly and significantly its get blood pressure up. But now, as Steve mentioned and all the other reasons, it's time for dose optimization. I will also say that's where a lot of particularly small companies that might be resourced starter even and big companies that are pressured on time lines, a lot of people don't do their dosing work right before Phase III. And this is a big deal. And that's why we are putting a proper emphasis on getting the dose optimized prior to Phase III. We think we're really going to benefit the program will benefit from having done this. And it's certainly worth about $3.5 million on 3 quarters' worth of work.

Definitely, it seems like it's a clinical competitive advantage. So I 100% agree and understand. So when we're looking at Stage C study. Can you remind me how long that could take -- I thought I saw 8 months, but can you just clarify for me?

So the time frame for the Stage C study, we think it will take about the same length of time as the extension study, which is about 8 months. We're finishing up some of the features of that study, and we'll be able to give better guidance on that in a couple of months when we're further down that path.

Got it. Okay. And can you just hypothesize with me what a Phase III in cardiogenic shock could look like, number of patients, endpoints, et cetera.

Yes. And I'll ask Steve to chime in on this. First of all, let me begin by saying to everybody. We will definitively answer that question coming out of an end of Phase II formal meeting with the FDA, right? We've all done this long enough now how important that a meeting is and having your protocol the last for what Phase III looks like. Now with that said, we do believe and therefore, plan for our planning purposes and has value and think things out that a couple of things related to Phase III. One is, I do want to note upfront that unlike most Phase IIIs, the size of the Phase III here is not going to be driven by the powering around the pivotal endpoint that's usually the size what drives right size and therefore, cost and time of most studies. Here, the size of the Phase III is going to primarily be driven by what is an adequate safety database. Because, by the way, we saw even with a 60-patient study, you could achieve clinical significance. Even that 1.0 dose versus placebo in the Bs, reach statistical significance. So however, we're going to measure blood pressure, and we'll define that in an end of Phase II meeting. The driver -- but what is an adequate safety database to put a therapy on the market. And I feel okay about the FDA about proving a therapy to put onto the market primarily. Secondarily, from the company perspective, what size of a Phase III is going to deliver the other evidence-based claims. You heard Dr. Teerlink mention evidence but evidence based claims that we see signals on related to reduced ICU and hospital length of stay and readmissions due to their heart failure and just some of these other areas. But you put all that together, along with looking at precedents for similar types of agents knowing that by the time we go to an end of Phase II, we're going to have treated about 350 patients, the vast majority of them, Steve, right, having had heart failure and we had about 300 right now. So that's a pretty good safety database. And so we're thinking that Phase III would be somewhere in the neighborhood of 350, let's call it, 400. And that should do a whole lot for this program. The cost, if it is about a 400-patient study, the cost of that is about $16 million, and we believe in a Phase III, we can enroll that in about 12 to 14 months. So when you put that into acute cardiovascular real or cardiovascular or pharmaceuticals in general, those are some attractive numbers and pathways. Does that make sense, Destiny? Steve, would you add anything?

Got it. Okay. And then I would love to chat a little bit more about these potential BD partnerships, et cetera. What in an ideal world, who would you partner with or what type of company would you partner with? Is it more important that you partner the heart failure kind of path or the cardiogenic shock or you're really indifferent about which comes first or as a priority.

Well, so let's divide BD into 2 types of BD, right? Just broadly speaking, bucket-wise. Your question, I put more in the category, a partnership and licensing. So you got the licensing partnership, somebody bigger, right? And then there's strategic transactions which is often code for things like merger and merger acquisition, right? So let me move that off to the side for a second. That has its own filters or criteria that we've thought through what would make sense. But that is you know it when you see it and you work with a bank and stuff like that. But back on the core of classic licensing -- well, cardiogenic shock is upfront, right? And you know how that's leading and heart failure will benefit from -- if you even look at dose optimizition and extension study, that's informing how to use this agent, including a low blood pressure, heart failure as well. So that's the order of things. But when it comes to licensing to companies and it's companies that have a focus on cardiovascular. It could be companies who have a focus just on hospitals and critical care. I've spent much of my career leading what we call institutional channel or critical care or hospital type of products. And you can be a bit therapeutic agnostic because it's still the same pharmacy and P&T committee and so forth. And there's a lot of -- all the bigger pharma companies, but there's many that these days, more often these days have refocused back to cardiovascular. Cardiovascular once again, is a hot therapeutic area for many of these companies. And many of them have a good understanding of hospital based. So those are the type of companies that have an interest. The follow-on SERCA2as, R&D organizations get a bit enamored with that SERCA2a activation mechanism, if you will. I will also tell you that as you get an agent and having been on the other side of the table doing lots of deals leading big portfolios or big therapeutic areas and business units and big companies that when you get an agent to what we, in this industry term, Phase III ready, like that end of Phase II clarity of Phase III that I can run the numbers on, that is really when you want to transact. You get like peak value short of it being approved. But that's kind of a sweet spot time and I think many people will be looking to, hey, SCAI Stage C patients, some active comparator in the background, clarity from an end of Phase II or ready for end to Phase II, that's a sweet spot in terms of licensing and time as we think about it based on our experience. But one of a company that's looking at cardiovascular and here getting this agent to something Phase III readiness that has multiple indications, including a really big 1 in heart failure that has next generation with oral bioavailability products behind, it's a multi-asset platform. And then when you look at shock, even if you adjusted the deal on shock, the numbers are really attractive. Things like time risk cost return for the valuation are really attractive with this particular agent in this space. So we would do a deal that makes sense for our shareholders. Shock does. The last thing I'll say, Destiny to round this out. Shock gives us an optionality that we don't have to do a deal. We could run Shock. We can go out and raise the Phase III, run it all the way through to a filing, and we can launch it in the U.S. in hospitals ourselves. We have done that as a team in a number of other places all the way back, I'm in this area because we did that at Synacor back in the mid-90s, if those of you who are old enough to remember that. So you can tackle U.S. hospitals, call on 3,500 hospitals or about 80 representatives and that's one of the reasons why whatever deal we go to do, we may even ask for US co-promotion rights. Of course, we'd like to do a global deal where we're not going to go out and start tackling the rest of the world. So Destiny, that should hopefully give you all the various dimensions of how we think about business development and why we're confident that we could have some nice engagements here that I hope we could bring across the finish line for the good of the program and shareholders.

That was wonderful and so thorough. I appreciate it. I understand it very well now. And if I have time for one more, I think from where I sit, your ability to reduce your cash burn is -- goes unrecognized. I think you don't get enough credit for the fact that you've been able to reduce your burn significantly. Just curious if that's -- where you're at now is going to be a consistent level going forward for modeling purposes?

Yes, it will -- well, the not -- let me divide it into, let's talk nonprogram burn. So that basic backdrop that is everything but the study -- but studies that you happen to do. As you know, at any moment in time when you're doing a study or 2 studies, your burn for that quarter or couple of quarters are going to go up as a total company burn. But everything beyond the studies coming and going and flexing up and flexing down, that non -- what we call nonprogram burn is pretty much a steady state. Now we're adding -- we're actually keeping things pretty steady, readjusting our structure here even as we move forward. So yes, for modeling purpose, purposes for the short to midterm, Destiny. This reduction that you see in over 50% year-on-year because we out-licensed because we dialed in, is going to be consistent for sure, even as we start some studies and flex them up on the study cost. And thank you for saying that. I will say when we went out to the market, there's -- guys let's just be honest, there's a lot of financings not getting done, right? And there's a lot of S-1s getting pulled. We were really pleased to find that we went out that within 2 days, we were getting the signals that, hey, the demand is there. And let's go ahead and get this deal wrapped up and priced -- and the story is great. But we did hear from the investors that they appreciated, at least the ones that invested, really did recognize and appreciate creating a more lean capital-efficient organization. I think it's what you have to do in these markets, and I think that's what our shareholders or potential investors expect. They want to know that their dollars, the majority of them are going to Steve and Steve's execution of studies, and that's where we are now.

Perfect. Okay. Well, that's great news. I think your upcoming milestones are very exciting, and we're looking forward to hearing more. With that, I'm going to jump back in queue. Thank you again.

Thanks, Destiny.

Yes. Thank you for the questions, Destiny. I'll now turn it over to Monique Kosse of LifeSci Advisors to read the remainder of the questions from the webcast.

Yes, we do have -- Destiny, you did a great job of asking a lot of the questions that have been coming in. So she was addressing a lot. There's just one more question here, is how would the SERCA2a activators in the Windtree pipeline be used compared to istaroxime?

Yes. And Steve, do you want to address that?

I think there's a lot of potential for the SERCA2a activators use in heart failure with reduced ejection fraction as well as heart failure with preserved ejection fraction. One of the key attributes of this family of compounds that we have that Craig mentioned, they can be given both intravenously and orally, so they can be well suited for chronic use as well if things play out. So I think that the exact placement of where the SERCA2a activators will find a home, it has to be a data-driven thing dictated by our program, but I think there's a broad spectrum of potential use. Dr. Teerlink, do you have any thoughts on the utility of that kind of a drug, a pure SERCA2a activator?

Well, I think one of the things you pointed out very accurately was there's been such a long interest in the SERCA2a activators and things. And it's really encouraging to hear that we may actually have something that can work there, and it will become a tool for us to investigate how it goes. Obviously, I think that one of the most interesting targets is for me more the heart failure with preserved ejection fraction because this is an area that is still markedly underserved and its huge. Half of our patients with heart failure have heart failure with preserved ejection fraction. And although there are some agents that are kind of getting approval for those kind of patients, is still we aren't hitting the fundamental defect of decreased relaxation response. So that is something that would be personally intriguing not to undermine I think is going to be useful across the board potentially, but that would be one of the more interesting areas for me.

And there are no further questions that have come up.

Okay. Thank you. So thank you, everybody, for joining us. I want to thank once again Dr. Teerlink, Steve. Steve, how let me use his office and all of you joining us today. I think now is a great time to look at Windtree for a whole host of reasons and because we're in full execution mode. So it should be a very busy next few quarters. When I think about the next 3 to 4 quarters, that would be very dynamic for the company. And I'm expecting -- I'm planning for a lot of progress. And we look forward to keeping you updated. In the meantime, again, I want to encourage you go to www.windtreetx.com -- windtreetx.com. Where you'll find additional information, including our public filings that will have all of our risk factors and all of the other information. So I hope everybody has a good rest of the week, and thank you, and stay tuned.