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.
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