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

Greetings. Welcome to the Windtree Therapeutics Corporate Update Call. [Operator Instructions] And please note that this conference is being recorded. I will now turn the conference over to John Hamill, CFO of Windtree Therapeutics. Thank you, sir. You may begin.

Thank you, operator, and thank you all for joining the Windtree management team today. On today's call are Craig Fraser, our President and Chief Executive Officer; Steve Simonson, our Chief Medical Officer; and Eric Curtis, our Chief Operating Officer. We previously announced the positive topline result from the SEISMiC Phase II study in early cardiogenic shock, and that further details were under embargo due to the acceptance of the late-breaker at the European Society of Cardiology Heart Failure meeting. That late-breaker presentation occurred earlier today, and we also issued a news release sharing those more detailed results from our study. Please note that certain information discussed on the call today is covered under the safe harbor provision of the Private Securities Litigation Reform Act. We caution listeners that during this call, we will be making forward-looking statements. Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified by the cautionary statements contained in Windtree's press release issued today and the company's SEC filings, including in the annual report on Form 10-K and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, May 23, 2022. Windtree undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. With that, I will turn the call over to Craig.

Thanks, John. Hello, everybody, and welcome to the live update from the European Society of Cardiology Heart Failure meeting in Madrid, Spain. We were excited to be joining you this evening to tell you about our trial results and everything that has been going on the ground here and what our plans are for our next steps. As John mentioned, the study was accepted for the late-breaker session at this ESC conference, and we've been able to get the data out from under embargo with that presentation. Earlier today, the presentation was conducted by Dr. Marco Metra, who was a study principal investigator. And Dr. Marco Metra is a Professor of Cardiology at the University of Brescia in Italy, and is really a true global leader in the area of heart failure and cardiogenic shock, guidelines and development. Since announcing just the topline result without any additional details, we have been looking forward to being able to share with you what we're seeing that makes us so excited for continuing development of istaroxime in cardiogenic shock. So today, we're going to present some additional key data furthering information on primary endpoint, the secondary measures associated with blood pressure changes, systolic and diastolic cardiac function, renal profile, safety and tolerability and some information regarding dosage. We'll also be discussing the area of cardiogenic shock. And given these positive results, the next steps in our clinical development plan and for our company going forward. Let's begin with a quick introduction of the management team participating in the call today. I'm Craig Fraser, CEO and President. And I've been here as the CEO for just over 6 years. After spending time in the Marine Corps in the Army, I came into this industry 32 years ago and have been building and running biopharmaceutical and device products and businesses globally for both start-ups and large companies. Joining me today is the Chief Medical Officer, Dr. Steve Simonson. Steve is a critical care pulmonologist by training a practice from Duke, with more than 25 years of pharmaceutical industry clinical trial expertise, including all phases of drug development. Eric Curtis is our Chief Operating Officer and has 25 years of biopharma experience in large companies and small companies, like the one he came from before joining Windtree where he was the CEO of a small private oncology start-up. And finally, John Hamill, who you just heard from, our CFO has 30 years of strong experience in financial management, investor relations and public company executive management. And we really do have a great team at Windtree, which in my personal experience is critical when you're doing a smaller startup. An example of their ability to execute really has been seen in the past 1.5 year or so as the team successfully executed 2 global studies and the headwinds of a global pandemic, making things very challenging, especially in intensive care units where we conducted our studies, including this cardiogenic shock study. I'm really proud of the job they do, and thankful for all our investigators and their staff to help bring this study successfully across the finish line. So we have a lot of exciting information to share with you today, and we'll start with how istaroxime works and the scientific rationale that set up early cardiogenic shock. Istaroxime is a first-in-class novel dual mechanism agent that works in both cycles of the heart to improve both systolic and diastolic cardiac function. The first mechanism increases the force of contraction through the inhibition of the sodium potassium HEPH. And then the novel second mechanism is a complementary action that facilitates myocardial relaxation through activation of the SERCA2a, calcium pump, enhancing calcium reuptake. This causes a greater relaxation of the heart between each and every heartbeat leading to greater fill volumes of blood and more calcium available for the next contraction. It's these 2 mechanisms working together that have created a very unique clinical profile that we're now seeing reflected in cardiogenic shock as well. Istaroxime has been under development for patients hospitalized with acute heart failure. This is a very common and very large market as it's the #1 reason for hospitalizations in the U.S. and Europe in the elderly. And despite significant unmet need and the size of the market, there has not been any new therapies for nearly 2 decades and Ista appears to be the only late-stage therapy for the acute stabilization for these acute heart failure patients in development. For AHF, we had a positive Phase IIa study where 120 patients were treated with Ista at 0.5, 1.0 and 1.5 milligrams per kilogram per minute infused over 6 hours or placebo. The IIa study met its primary endpoint of reducing pulmonary capillary wedge pressure, which is the feeling pressures of the heart and also had statistically significant improvement in stroke volume and systolic blood pressure as well as lowering the heart rate, which is very unique and beneficial. Istaroxime also went on to have a positive Phase IIb study in AHF where 120 hospitalized patients were treated with istaroxime 0.5,1. This time infused for 24 hours versus placebo. Again, Ista met its primary endpoint with a statistically significant improved EDE Prime, which is an echo assessment of blood pressure. At both Ista doses, Ista demonstrated improved cardiac function without unwanted side effects of existing therapies, making it a very unique potential addition for treating these patients. By examining the data, however, when you really look at this unique profile, it was a very attractive profile versus existing therapies, and it's the information that led us to thinking Ista may have the potential to treat early cardiogenic shock as well. The first graph on the top left shows the primary endpoint of E/e' Prime significantly being improved as well as the significant improvements in stroke volume which is the amount of blood coming out of the heart with each contraction. Importantly and very uniquely, this efficacy did not come at the expense of reducing blood pressure as seen with many other available agents. And in fact, systolic blood pressure significantly improved. Further, unlike many agents, GFR and the measure of renal function also significantly improved with the upper 4.0 dose. So Windtree became interested in early cardiogenic shock because of istaroxime's unique characteristics of raising systolic blood pressure as this is the key and urgent need in cardiogenic shock patient treatment. We were hearing from interactions with regulators and our scientific advisers at meetings encouraging us to look at early cardiogenic shock based on this profile, and so the potential for an attractive development, regulatory path for possible approval. Initially, the question for us going in was whether we would have the therapeutic effect on blood pressure we saw in the AHF studies and a much more severe, and thus, population and thus have a potential treatment in an area that we knew had a big need for acceptable treatments. We're happy to report the answer to this question from our SEISMiC study is a clear yes. Eric, can you start off by telling us a little bit about the opportunity in shock?

Thanks, Greg. Cardiogenic shock is a serious condition that occurs when the heart cannot pump enough blood and oxygen to the body and eventually the brain, kidneys and other vital organs. It is characterized by very low blood pressure and hypoperfusion accompanied by high pulmonary capillary wedge pressure and decreased urine output. Cardiogenic shock is considered a medical emergency and to be treated immediately. It has high inpatient mortality, approximately 30% to 40% when in full shock and substantial morbidity in survivors. We were interested in the total market potential of cardiogenic shock, but to our knowledge, this has not been done before as of lack of attention in this space. So Windtree did the evaluation with an experienced vendor. Using cardiogenic shock patient U.S. hospital claims and worldwide prevalence data, Windtree estimates that the worldwide total market value of cardiogenic shock to be $1.25 billion. This estimate is calculated by multiplying the patient numbers from the largest markets by assumed various regional prices of drug treatment consistent with other acute care therapies of similar incident rates. The addressable market for istaroxime will be a subset of the total market value of $1.25 billion. Windtree also did market research to better understand the need of the disease. From a commission's perceptions, there's no satisfactory drug treatments to reverse cardiogenic shock. The drugs that are available have unwanted side effects such as arrhythmias, decreasing blood pressure, renal dysfunction and potentially increases in mortality. As such, they are often reserved as rescue medications, a therapy that can be used earlier to increase -- rapidly increase blood pressure and improved cardiac function without side effects is needed. Windtree conducted market research to understand how one of its main customer groups views the need for innovation in this disease. The physician market research asked 100 U.S.-based clinical cardiologists who treat cardiogenic shock patients, how needed was new drug innovation in SCAI, which stands for Society for Cardiovascular Angiography and Intervention, stage IIb cardiogenic shock patients. Now Windtree refers to these groups of patients as early cardiogenic shock patients. 99 out of the 100 clinical cardiologists responded that there is a high need for pharmacologic drug innovation in SCAI Stage B cardiogenic shock patients. Additionally, when shown a blinded clinical profile reflective of istaroxime, 84% of the cardiologists responded, they would be likely to extremely likely to use a drug with a profile reflective of istaroxime for early cardiogenic shock patients. The majority of the cardiologists also responded that they would position a drug with a profile istaroxime for utilization before use of other existing classes of drugs available today, such as inotropes and vasopressors. These very strong results from the market research suggest Istaroxime could fill a significant unmet need, if approved by regulatory authorities in the future. Now I'll turn it over to Steve to speak about our regulatory potential opportunity and the seismic study results. Steve?

Thank you, Eric. Improvement in blood pressure in setting a shock is very important. So much so that the FDA has approved a drug in the setting of shock using [ beet ] blood pressure as a key endpoint along with a safety profile comparable to the control group. That drug is GIAPREZA for distributive or septic shock. Thus, there may be an opportunity in cardiogenic shock for istaroxime to follow a similar path. In our Phase II program, istaroxime has demonstrated a dose-related ability to increase systolic blood pressure. There are several factors that make this potential endpoint attractive and exploring this potential opportunity was the impetus for this study. The SEISMiC study was designed to evaluate the potential of istaroxime to improve blood pressure in heart failure patients who have worsened to the point of SCAI Stage B cardiogenic shock. The SEISMiC Phase II study is an international, randomized, double-blind, placebo-controlled study that enrolled 60 patients with SCAI Stage B early cardiogenic shock due to heart failure with systolic blood pressures between 75 and 90 millimeters of mercury. Patients were randomized on a one-to-one basis to placebo plus standard of care versus istaroxime plus standard of care with 2 istaroxime target doses utilized in the treatment arm. 1.5 micrograms per kilogram per minute and 1.0 micrograms per kilogram per minute. Patients received the infusions for 24 hours. The primary endpoint was the difference in systolic blood pressure area under the curve for the first 6 hours after initiating the infusion. Secondary endpoints included characterization of blood pressure changes over 24 hours, echocardiographic assessments of systolic and diastolic cardiac function, assessment of renal function and safety and tolerability. As we've been happy to report, SEISMiC was a positive study. Blood pressure endpoints were met with a very significant result on the assessment of systolic blood pressure profile over 6 hours. Additionally, the significant increase in blood pressure profile was maintained throughout the 24-hour infusion. Cardiac function was improved, renal function was maintained and having both target doses of 1.0 and 1.5 in the study provided valuable information for evolution of our dosing regimen going forward. As you will see, these results add to the rationale for development of istaroxime in acute heart failure as well as justification to progress the program in shock patients. Let's look at the primary endpoint of the study, blood pressure AUC over the first 6 hours. You can see that the blood pressure increase was rapid with istaroxime and stayed above the control group for the entire 6 hours. The p value for this comparison was 0.017. This slide shows the blood pressure response over the entire 24-hour infusion. Istaroxime increased blood pressure within the first hour compared to placebo, and it continued to increase over the 24 hours of the study drug infusion. This comparison was also significant with a p-value of 0.025. Additionally, there was no decrement in blood pressure over the 96 hours of close monitoring. Echocardiography demonstrated improvements in systolic and diastolic cardiac function, extending the observations from previous Phase II studies in acute heart failure. Importantly, systolic function was substantially improved with significant increases in cardiac index and a substantial increase in stroke volume that just missed statistical significance. Cardiac index is the amount of blood pumped by the heart per minute. Stroke volume is the amount of blood ejected with each contraction. These are important measures in determining how well the heart is working. Additionally, left atrial area, left ventricular and diastolic or end systolic volume and left ventricular and diastolic volume were significantly reduced. These changes are important because they reflect the improvement in cardiac function, not only around contraction and systolic, but also diastolic improvement. This slide shows renal function over 96 hours. You can see there is no decrement in renal function during or after the istaroxime infusion compared to placebo. In fact, there was an increase in GFR in the Istaroxime group at 24 hours, similar to the improvement we saw in our IIb study in acute heart failure. It's interesting to note that istaroxime treated patients had numerically greater diuresis and weight loss with a lower cumulative dose of loop diuretic, but this did not achieve statistical significance in this small study. This last point wasn't an end point, just an observation in the study. As I mentioned, this characteristic of istaroxime to maintain or improve renal function has been seen in the previous Phase II studies and is a very important feature. Avoiding injury to the kidneys and maintaining renal function is very important in these patients and may be an important differentiator for istaroxime. This slide shows that serious adverse events were comparable between istaroxime and the placebo group. And as has been seen before, there are more gastrointestinal adverse events reported with istaroxime primarily dose-related nausea and sometimes vomiting. Additionally, there were more reports of infusion site discomfort in the istaroxime treated patients. These particular effects were expected and did not lead to any treatment discontinuations. As mentioned earlier, reducing the target dose from 1.5 micrograms per kilogram per minute to 1.0 approximately mid study gave us the opportunity to do a post hoc comparison of the 2 doses versus placebo. This slide shows the blood pressure by dose over the period of the primary endpoint for the study. The placebo group is represented by the dotted line. High dose istaroxime is represented by the gray line and the low dose istaroxime is in green. The blood pressure results of both ista doses were greater than placebo and the 1.0 microgram dose was numerically superior to the 1.5 microgram dose. Besides a favorable early blood pressure profile, the 1.0 microgram dose was also associated with more echocardiographic improvements of cardiac function. A further comparison of the 2 doses can be seen here. The first row shows the systolic blood pressure profile over the 24 hours with both doses increasing blood pressure greater than placebo. With respect to clinical events by dose, the 1 microgram per kilogram per minute dose group generally performed numerically better than both the higher dose ista group as well as the placebo group on a number of important clinical event parameters listed here. You can see that the ability to look at both doses in this study was extremely valuable and will help us plan dosing going forward. So to summarize the data from the SEISMiC study, the systolic blood pressure was significantly increased by istaroxime. The increase began within the first hour and was sustained through the 96-hour period. Cardiac function was improved and renal function was maintained. It appears that we are seeing most of the efficacy at the 1.0 microgram per kilogram per minute dose and higher doses are not needed to produce the desired effect. We did this study to see if istaroxime can increase blood pressure in patients with early cardiogenic shock, and that was a reasonable question to ask in a 60-patient study. And the answer is definitely yes. Despite having only 60 patients, we saw positive results on cardiac function, confirmed our renal profile and have valuable dose response relationship data. This study has been a treasure chest of information that has helped us to move into our next clinical studies. This study adds to the solid foundation of data indicating that Istaroxime has the potential to be a meaningful therapeutic intervention not only for acute heart failure, but for more severe heart failure patients with early cardiogenic shock. Istaroxime has uniquely shown an increased cardiac output, increased blood pressure and preserved renal function in a very difficult to treat group of patients that can benefit from all 3 features.

Thanks, Steve. We're very pleased with the results of this study. Going in, as we said, we wanted to be able to see whether we would have essentially the therapeutic effect to raise blood pressure in these really unstable, very severe patients where their heart's failing. And despite the relatively small study, as Steve was just mentioning, when you get to a study that's 30 versus 30, we -- this exceeded our expectations with regard to what we were able to see in the various measures that are not just biomarker measures, but the various echo measures and assessments of cardiac function to hit statistical significance across so many of those, really were showing the power and the potential of the istaroxime. And additionally, the SEISMiC study again reinforced this nice renal profile that everybody is looking for to seeing further study. I can also say that here at the ESC meeting, in meeting with many, many experts over the last couple of days, particularly in this area around cardiogenic shock, the constant theme that we have been hearing from them is that they really do need a therapy in this space that's adequate, appropriate. They feel like they don't have anything adequate in this space at all, reinforcing that need. And in particular, really talking to us about how unique it is to have a drug that improves cardiac output in the pump function of the heart, and at the same time, is positive towards blood pressure and perfusion because existing agents, besides having negative side effect data, the existing agent typically have to do a trade-off from one or the other. So we're excited about carrying this forward. But I also want to point out that this study represents more than just the potential ista program in cardiogenic shock that needs drug innovation. This work is relevant to acute heart failure program itself as well. As an indication, it would be highly complementary to HF because we build confidence in that product's power and deliver additional clinical utility. But very importantly, for the company and our shareholders, it also represents a potentially faster and less expensive indication. We also believe that the seismic trial results in early cardiogenic shock directly relate and contribute to the progress of clinical development in AHF. As the patient in this trial were not just by Stage B early cardiogenic shock patients, but also happen to be there because he had severe, less stable acute heart failure. So after the previous studies in classic less severe heart fire, we now have tested ista efficacy in a much sicker population and we like it's holding. This, along with other learnings from the trial will be applied to HF development and cardiogenic shock development. As you've seen reflected in Dr. Marco Metra's quote in the press release, as an acute cardiac treatment ista is proving to have the potential to effectively treat patients without reducing blood pressure or renal function, which are the common side effects of the rescue medicines. Steve, can you take us through the cardiogenic shock development plan and strategy?

Thanks, Craig. Now that we've shared the positive SEISMiC results with you, we want to tell you how we're going to progress the development to put us in the best position for planned regulatory authority discussions on a potential Phase III program in cardiogenic shock. We will be enrolling a small number of additional patients in 2 pathways of study. First, we will extend the SEISMiC study to incorporate longer dosing and evaluate tapering dosing regimens. We will characterize the physiological and clinical responses. Additionally, we will get experience in a sicker patient population within cardiogenic shock, a group referred to as SCAI Stage C patients. This is a logical progression for our program. Once we have this data, we believe we will have a good package of data to take to regulatory authorities to align on the Phase III program. In the SEISMiC extension study, we want to take another step to quickly answer some important questions in a short period of time. By doing an extension as opposed to a new study, we're able to leverage a portion of hospitals already up and running with SEISMiC. The goals of the extension study are to characterize the physiological and clinical effects associated with longer istaroxime dosing as well as evaluating a tapering dose regimen commonly used with vasoactive medications in the ICU. Additionally, we plan to more fully illuminate the effects and potential benefits associated with the second mechanism of istaroxime SERCA2a activation. We feel this will support our clinical and regulatory strategy for istaroxime. The study is a double-blind, placebo-controlled study in 30 patients with 2:1 randomization with systolic blood pressure between 70 and 100 millimeters of mercury conducted in sites in the U.S., Europe and Latin America. We'll increase the time with the infusion to 48 to 60 hours in the following scheme. Group 1 will begin at 1 microgram per kilogram per minute for 24 hours then decrease to 0.5 micrograms per kilogram per minute for 24 hours, then decrease to 0.25 for 12 hours. The second group will get 1 microgram for 12 hours then 0.5 for 36 hours, followed by a placebo taper to off. So total dosing duration in that group will be 48 hours. The third group will receive a placebo schedule matched to Group 1 or 2. These patients will be extensively monitored and we'll measure physiologic parameters associated with cardiac function, blood pressure and safety. The second plan of investigation will be a small study of SCAI Stage C patients. The objective is to support our regulatory and clinical strategy by gaining experience in a sicker type of cardiogenic shock patient where drug treatment is needed. The patients we studied in our SEISMiC trial were SCAI Stage B patients. And the difference between SCAI Stages B and C is that the C patients are experiencing hypoperfusion and are at even greater risk for organ dysfunction. We believe there is good rationale for istaroxime to be effective in stage C patients because of the characteristics we saw in SEISMiC, specifically improving cardiac pump function, raising systolic blood pressure, which is a primary goal for treatment for these patients, and doing so while protecting the kidneys. I'll turn it back over to Craig now for further comments on our company strategy with istaroxime. Craig?

Thanks. The year ahead is very exciting for Windtree as our plans have several important milestones and events. As you heard from Steve, we plan to conduct a SEISMiC extension study and the SCAI Stage C cardiogenic chalk study to further optimize istaroxime dosing and prepare us for the planned cardiogenic shock Phase III program. These studies should take about 6 months or so with data currently expected at the end of Q1 2023. Besides executing additional studies, we plan to meet with regulatory authorities to share our whole istaroxime data set and discuss the strategy and additional studies and to discuss the development path to potential approval. Our plans call for us being in Phase III for cardiogenic shock next year. I will plan to provide additional updates and guidance in the next couple of months. Further with additional adequate resourcing, Windtree is set to start the next AHF study. This AHF Phase II study will help us become Phase III ready with optimizing our AHF dose and testing secondary endpoint measures that regulatory authorities have indicated to us would be suitable for Phase III primary endpoints. Importantly, Windtree is also engaged in business development activities on multiple fronts for the potential of partnership, which could provide financial support for our development plan, particularly for heart failure and a potential nondilutive cash milestones and royalties. So in summary, ista has been successful in 7 studies with approximately 300 patients treated thus far. To our knowledge, istaroxime is the only drug in Phase II or III development for acute stabilization of heart failure and cardiogenic shock. In the AHF studies, that had positive 2a and 2b results demonstrating approved cardiac function without coming at the expense of blood pressure and renal function and has a well-tolerated profile. Cardiogenic shock has significant unmet need as we've discussed today, and our positive seismic results have created a valuable additional program and option for the company. This pathway to potential approval is expected to be both faster and less costly and the program has a scale fitting of Windtree while being complementary to the bigger area of AHF. With that, I'll turn things over to our operator for questions.

[Operator Instructions] Our first question comes from the line of Leland Gershell with Oppenheimer.

A few questions for me here. First, Craig or Steve, maybe you already discussed this, and my apologies if I missed it. But if you could just walk us through the rationale behind what looks like that sort of inverse dose response on the SPP versus the dose levels in the study. And also wanted to ask about -- if you could comment on any concomitant therapy, any pressures, dobutamine, et cetera, that may have been used in the patients in the study? And I also want to ask about where you may be with respect to partnering discussions, whether here or in other countries.

It's Steve, the inverse dose response or the difference in the systolic blood pressure dose responses and whether pressers or backbone therapies were...

So addressing that last point first. The patients who came into the SEISMiC study could not be on vasopressors or inotropes. And the investigator had to have a feeling that they would not need them in the ensuing hours after randomization. We did assess the need for those kind of therapies as a secondary endpoint in the trial. Addressing your first question on the greater effect of 1.0 dosing on blood pressure. I guess the first thing I should say is that the 1.0 dose, while numerically superior to the 1.5 dose because of the small numbers, that difference was not statistically significant. So from that perspective, they were comparable. I think if we go into larger numbers, that caveat may not be needed. But both doses produce improvements in cardiac function. But as the dose increases, you may see some of the vasoconstrictor effects could dominate. Unfortunately, what we found here with the seismic data is that we don't need to use as much istaroxime to achieve the therapeutic targets to improve these patients.

Great. And Craig, I guess just want to comment on maybe just strategic.

Yes. On the strategic side with regard to business development and so forth, Leland?

Right.

Yes. Yes. So we are actively engaged with a number of companies. Some of those companies have been waiting to see the cardiogenic shock data. A few of them are under CDAs with cross-functional diligence teams. And I can tell you, over the next 30 days, some both initial meetings and meetings that represent many follow-up meetings now that we have data that we have, gosh, probably a couple of dozen of those. So we are very active on that front. And Leland, I think particularly as we look at the area, as you and I have talked in the past about heart failure and the scale of it and so forth, we know this product would really benefit from being partnered frankly, the places that we all came from Pfizer, J&J and Z and so forth. And just a non-dilutive support and funding, and we see such a focus back lately into the area of cardiovascular and cardiometabolic by the big companies. After drifting away for probably 20 years, you really see that coming back. And you see a refocus on heart failure in part because of the diabetes agents for instance in chronic heart failure made a lot of gains. So heart failure and cardiovascular become a priority therapeutic area and part of the shopping list from another number of companies. So the timing is really good. Of course, any of those big strategic transaction deals, they do take time. So we'll keep people updated on the progress, but it's going to be very active set of meetings and so forth here over the next several weeks, and we'll keep you guys updated.

Terrific. And congrats again on the [ TRIF ] data.

Our next question comes from the line of Jeffrey Cohen with Ladenburg Thalmann.

This is actually Destiny on for Jeff. I guess I would just like to start firstly with the fact that your cardiogenic shock program could potentially have breakthrough designation. Can you just remind us all what that could mean in terms of timing for regulatory submissions, approvals, et cetera?

Sure. I'll start and ask Keith to chime in. So it's -- as you saw in the landscape slide, well -- we have in the updated corporate deck as well, Cardiogenic shock again, has the potential to be a faster keeper program less expensive and so forth because of the endpoint and particularly when you get into Phase III, a lot of people want to be part of Phase III, of course, and so forth. I think we're going to have a good package put together on a regulatory strategy as we've described, taking these positive SEISMiC results, augmenting them. Now is the time to do the dose optimization, get further characterization around that SERCA2a activation and what happens particularly on the back end. And I think importantly, get the experience with these Type C patients. So it's as far less of them but we really want to validate the power of istaroxime in that sicker group. We'll have a nice package. And I think at that point, if all goes according to plan, we could be starting and should be starting Phase III in the second half of next year. Depending on the size of that and again, it would be out of place to give a whole lot of guidance on Phase III until you do your end of Phase II, but we really think from our internal planning that that's a trial that should go fairly quickly, especially as we have a machine built. So again, I think it has the potential to be an accelerated pathway particularly compared to the bigger areas. Now you asked about the regulatory support. One of the things that, in fact, this whole conversation came from is when we pick up the Fast Track designation on acute heart failure, it was coming out of those discussions with the agency where we were looking at GIAPREZA, and thinking about this area of shock. GIAPREZA did get a breakthrough designation. Breakthrough is very helpful. Well, besides it's a nice validating thing to put news out on. But where it really has its value is, of course, when you do the submission, and you want to submit for a breakthrough designation when you have your best data package put together. So how we think about first things first, Fast Track designation and then a possible breakthrough designation submission is something that will gauge in our discussions with the FDA and would be something that if we pursue it, I would say it would be a pursuit that would happen next year after we do this next set of studies. So does that answer your question? Steve, would you add anything to that?

I think that hit the nail on the head. We probably can't speculate until we get to the regulatory authorities with our data and talk to them about what's required.

Yes, I agree.

Okay. Understood. I just...

I was just going to say any other questions, Destiny?

Yes. Just one more fine. Well, technically 2 more, if I may. One is a clarification, though. So for the next couple -- so the next 2 studies, that's a total of about 50 patients, correct? And that data, when you said readout at end of Q1 '23, that was for both groups?

Yes. Yes, it is. And when you look in our corporate debt, so Destiny, these trials, we think that it will take about 6 months as you might guess, the SEISMiC extension study, the protocol, all the regulatory approvals, the same DMC, the same executive committee, all that stuff is really in motion, and it's really queued up. So -- and that's a slightly bigger one to do that SEISMiC extension, but we'll get moving on that here in the next several weeks or a couple of months. So we're targeting data by the end of Q1 for that. And the Type C, I think we're wrapping up our planning right now, and we plan to have that started here in the next couple of months as well. The one thing that we didn't say in the script today, you'll see it in our corporate deck, both of those studies to give you a little bit more information. Both of those studies, 1 study is about $4 million, the other is about $3 million. So far somewhere around $7 million, we'll have these 2 really important studies to round out our data package and understanding, put us in a good position for Phase III, we believe. And they're -- again, they're up a scale and a cost that presents a really good opportunity to progress in a very meaningful way and have a couple of data cards in the next couple of quarters.

[Operator Instructions] Our next question comes from the line of Jim Molloy with Alliance Global Partners.

Congrats on the excellent data. I had a question on the extension side. Can you walk through a little bit -- you talked about characterization and other dose levels. Can you put a little more color around what exactly you'll be looking for in the extension study? And so what would be the ideal result to come out of that?

Sure. What we want to do in the extension study is really characterize the action and the response of istaroxime during stable dosing and as the dose has changed. And keeping in mind that istaroxime has 2 mechanisms of action, the inotropic effect and the effects from SERCA2a activation. So all of the patients will have a pulmonary artery catheter for extensive cardiovascular monitoring and cardiac function assessment. We will be getting echocardiography to continue the kind of data acquisition that you've seen from our Phase II program so far. And then additionally, Holter monitoring to assess cardiac rhythm. And we've been very fortunate in the profile with istaroxime to have no propensity to cause arrhythmia to this point. And as we go forward in the program, we'll be monitoring these patients for a bit longer than we have to see if, number one, that holds up and collect that data. But also to ask and answer the question, does the SERCA2a aspect of istaroxime action, potentially provide a decreased risk for cardiac rhythm disturbances, something that this patient population is at high risk for? So that's the kind of monitoring that we'll be doing. And as I mentioned, the patients who received istaroxime seem to be having a much more effective diuresis from their severe acute heart failure. And we want to characterize the impact of that as well. So a lot of physiology as well as continuing to collect the clinical assessments that are just part of our program going forward. And I think, Steve, as we talk about the dosing and the other part of the question, right, the -- there's a couple of aspects to that. One is we clearly see we have a dose moving forward to begin to do the optimization work with the 1.0. But we believe patients will benefit from longer infusions. We needed to do some work to be able to dose it longer than 24 hours up to this point, and we've been able to accomplish what we need to to now do longer infusions. But as Steve mentioned earlier in the presentation, being able to do the titration. And you'll see 1 starts off with that 1.0 for 24 hours to anchor it with the SEISMiC data itself. And then they get titration down with 1 having an even softer landing, if you will, down to that 0.25. But if you look both longer and with the various titrations and ask ourselves, can we use even less and get the effects, particularly after maybe that initial get the blood pressure up quickly, period because we saw such a rapid rise, as you could see in the graphs. This should give us a lot of information for dose optimization. The ultimate objective is to really feel that we have a dose that's optimized for the Phase III to be as successful as it can be.

Excellent. Understood. And then kind of a follow up some more on Leland's question earlier about partnerships. Can you talk about what will be sort of the ideal in any number of partnership -- any number discussions going on. It's hard to really target when what will happen. But what will be sort of the ideal for you guys? And would you anticipate -- could likely come out of these discussions, say, 2023 or late '22?

Yes. So the companies that we're in discussions with have a varied profile and you're asking me to state who has the most ideal profile. So I'll just -- I'll stay mum on that one. The one that we ultimately feel like we can get the most advantageous and attractive deal with. But in all seriousness, all kidding aside, I really like the different profiles of the companies that we have targeted and we're talking to. We haven't talked a whole lot about our BD strategy, we'd love to do a follow-up call with you. I definitely think in the meantime, cardiogenic shock, obviously, we've got a lot of activity that we're going to be moving forward with again, heart failure, in particular, both at scale and so forth can benefit from that. And we also have kind of longer-term strategies to be a critical care company, which we have some products in and some opportunities. We have a follow-on SERCA2a activators that we're not talking about on this call. So the idea of also retaining U.S. co-promotion rights is something that Eric and have done in the past, and we think could really be advantageous here. So we can do a follow-up call and talk with you about that. But definitely somebody who has expertise in this space, has scale and resources and that we can work with. Because I think just to have a lot of opportunity to -- for us to exploit through development and see where we can take this agent.

Thank you. At this time, we have reached the end of the question-and-answer session. And I would now like to turn the call over to Craig Fraser for any closing remarks.

Well, thank you, everybody, for joining. We really appreciate it. As we said in the next several months, we're going to continue to be a really busy time for Windtree. But we have a great team to execute our objectives and to build upon this momentum. And I look forward to keeping you updated on our progress. Thanks, again, and everybody, have a great evening.

Thank you. This does conclude today's conference. You may disconnect your lines at this time. Thank you for your participation, and have a great day.