Windtree Therapeutics has announced the results from the Phase 2b study of its lead drug candidate, istaroxime, in the treatment of cardiogenic shock due to heart failure. The data from the study will be instrumental in determining the optimal dosing regimen for a potential Phase 3 program.
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NewsTranscript
00:00Hello, everybody. My name is Craig Frazier. I'm the Chairman and CEO of Wintry Therapeutics.
00:09Today I'm going to make some forward-looking statements. I encourage everybody to look
00:13at our SEC filings. We are a public company. We trade on NASDAQ under Winty. And we're
00:20a company that's focused on people and treating patients in their moments of crisis, when
00:25they're hospitalized in intensive care units with a heart that's failing, with or without
00:31going into cardiogenic shock. And we have this really innovative and novel lead drug
00:37candidate called Estoroxime. And now Estoroxime's been through four phase two studies. We've
00:43treated over three in our patients. And we're seeing this very attractive profile that I'll
00:48tell you about. Our company also has some business development deals and licenses already
00:54in place. We just recently did $139 million license earlier in the year with a bigger
01:00pharmaceutical company that can be possible deal revenue. And we have an early pipeline
01:05of cardiovascular and cancer assets. We're led by a team that's been there or done that,
01:11a team that has many decades of experience and success. Now, Estoroxime has this really
01:17attractive and unique profile of taking people whose heart is failing and getting their heart
01:22tuned up and better functioning out of their heart and doing so without trading off blood
01:26pressure. In fact, getting blood pressure up, getting the kidneys working better, keeping
01:31heart rate down and the amount of demand on the heart. And these attractive positive results
01:37have led us to studying a severe population called cardiogenic shock. Now, cardiogenic
01:42shock is a condition where the heart is failing to pump and failing to perfuse the body. Even
01:49vital organs are starting to be starved of oxygen and flow and they begin to shut down.
01:55And it looks like blood pressure crashing out and the patient's in big time trouble.
02:01In fact, classic shock has 20 to 30 percent of these patients won't survive. So it's an
02:06urgent situation. It's a big market where there is nothing else in development other
02:11than Estoroxime as well. It's over a billion dollar market. Now, the ideal agent to treat
02:17cardiogenic shock would be one where you're getting the heart functioning better, you're
02:22getting blood pressure rapidly and significantly up to get the organs perfused or not one that
02:28doesn't damage the kidneys, unlike the current agents and one that also doesn't cause pacing
02:33problems or heart rhythm disturbances and can really help the patient pull up out of
02:39shock. But unfortunately, that agent doesn't exist in the current products that hits on
02:44all of those categories and desires. The current agents, these old agents, maybe have
02:50something that can help have a better effect, but they cause lots of bad side effects that
02:56can lead to bad outcomes. And the doctors are saying to us they really need a new drug
03:01innovation. In fact, this is some of the strongest market research I've seen in my 35 years saying
03:07how much of a need there is. Now, Steve's our chief medical officer is going to tell
03:11us about the most recent results that we're all really excited about.
03:16I'm Steve Simonson, chief medical officer at Wintry Therapeutics. I'm a pulmonary critical
03:21care physician by training. I began my career at Duke University Medical Center and I've
03:26been in pharma for more than 25 years. I've been at Wintry for the last 10. I'm very pleased
03:33to be showing you the exciting results coming out of the seismic trials in early cardiogenic
03:37shock.
03:39Isteroxime is a very interesting molecule. It's given to hospitalized patients by IV
03:43infusion, and it has two mechanisms of action. First, it inhibits the sodium potassium ATPase,
03:51resulting in an increase in intracellular calcium, creating a stronger force of contraction.
03:57The second mechanism and the unique aspect of isteroxime is that it activates SERCA2A.
04:04SERCA2A acts to decrease intracellular calcium after a contraction takes place. It actively
04:10pumps calcium into the sarcoplasmic reticulum in the cell, where it's held until the next
04:15contraction. This allows for a more effective relaxation of the heart muscle.
04:21Seismic was executed in two parts, A and B, with similar design. We prospectively plan
04:27to combine parts A and B for analysis of the primary endpoint, which is blood pressure
04:32profile over six hours. The analysis included 90 patients. Part A dosed isteroxime for 24
04:41hours. In part B, we dosed 30 patients with isteroxime or placebo for up to 60 hours.
04:48We enrolled patients with Sky Stage B cardiogenic shock due to acute heart failure.
04:56This slide shows the primary endpoint, the systolic blood pressure profile over six hours.
05:02For parts A and B on the left, and for part B alone on the right. In both analyses, there
05:08was a substantial and statistically significant increase in systolic blood pressure over this
05:13time period, a very positive result for seismic. The significant improvement in blood pressure
05:20profiles continued through the end of the infusion period.
05:25This slide shows pulmonary capillary wedge pressure and cardiac output over 48 hours.
05:31On the right panel, cardiac output, which is the amount of blood pumped out by the heart
05:35per minute, is substantially and significantly increased. On the left is pulmonary capillary
05:41wedge pressure. Wedge pressure is an assessment of filling pressures of the heart. It's elevated
05:47in acute heart failure and reflects back pressure in the pulmonary system that can lead to pulmonary
05:53edema. Isteroxime produces a marked, statistically significant reduction in pulmonary capillary
06:00wedge pressure within six hours, and the effect persists.
06:06Maintaining renal function is important, particularly in heart failure, where we need to use the
06:10kidneys to get rid of fluid overload that these patients have. You can see here that
06:15isteroxime increases renal function compared to placebo, a pattern that is common in isteroxime
06:21trials.
06:24This slide shows the serious adverse events from the trial. Serious adverse events were
06:28reported less frequently in isteroxime-treated patients compared to placebo. Although the
06:34numbers are small in Part B, worsening heart failure was reported by 18% of placebo patients
06:41compared to 5% of isteroxime-treated patients. Overall, a very favorable evolving safety
06:47and tolerability profile.
06:51There was a lot of positive data from seismic. These data and early cardiogenic shock have
06:56created a very special and unique profile for isteroxime that dovetails very nicely
07:02with the unmet medical need and the previous results we have in acute heart failure.
07:08Patients with low blood pressure and pump failure are very difficult to treat and are
07:12at increased risk for morbidity and mortality. Isteroxime improves cardiac function, increases
07:18blood pressure and renal function. And all of this was achieved with a safety and tolerability
07:23profile that was favorable and consistent with what has been reported before.
07:29And although I didn't show the data on this, importantly, isteroxime did not increase clinically
07:34significant arrhythmias compared to the placebo group.
07:37Now that you've heard from Steve with these exciting results of our studies, let me summarize
07:44by telling you, once again, cardiogenic shock is a significant opportunity for Wintry, for
07:50isteroxime and our shareholders. We can make a big difference. These patients are really
07:56sick. There's high morbidity, high mortality. The patients are in the hospital a long time.
08:02There's huge costs associated with it, over $175,000 on average. And the current agents
08:10have these undesirable side effects and can relate to poor outcomes. There's nothing else
08:15in development other than isteroxime as a drug, and it's a big market. So we're really
08:20excited. Where we go from here is the deliverables that we're going to have in the next several
08:27weeks and months, here in the second half of this year, are putting out the positive
08:32Part B study results, which we just did, the continuation of SkyState C cardiogenic shock
08:38in the more severe patients to have an interim deliverable in late Q1 of next year, so about
08:45six months from now. Also, we're supporting our partner in Asia on starting up the big
08:51heart failure study. We expect that the start of that study in the next several months,
08:56and that's going to be exciting. We'll let people know about that news. And we're going
09:00to be advancing things in our early pipeline and looking to drive value through delivering
09:07additional data, progressing the program, but also doing some more deals, some bigger
09:12deals with pharmaceutical companies. That's our objective. So stay tuned for all the excitement
09:18that's going to go on with Wintry, and we appreciate you looking at our company.