DiaMedica Therapeutics Inc. (DMAC) May 19, 2026 Conference Transcript

session. Today, my name is Nevin Varghese. I'm with RBC Capital Markets, one of the analysts here. And I'm joined on stage by Rick Pauls, who is the CEO of Diamedica Therapeutics. Rick, thank you for joining us today.

Great. Appreciate the opportunity.

So earlier this year, you had presented some interim data from an investigator trial, a phase two trial. Can you remind us about what the lead drug 199 demonstrated in late onset preeclampsia? How was the safety? And can you remind us about what the potential, especially for 199 to cross the placental barrier and how de-risk that data is now?

Sure. So what we're developing is a recombinant protein called tissue calocrine. It's a critical protein. It's in all of us. It turns out that patients that have or at risk of preeclampsia have low levels. And so from our interim results from our late onset preeclampsia patients, first and foremost, we wanted to look at safety. And a critical aspect of safety is that does our drug cross the placental barrier? So when you're dealing with preeclampsia, you're dealing with two lives. And if a drug passes the placenta, there's just a lot of risk. You don't know what's going to happen. So first and foremost, we wanted to see whether or not a drug is safe and well tolerated. So what we're able to show over approximately 30 patients that our drug did not cross the placenta and did not really provide any risk to the baby so that it's safe and well tolerated. We also wanted to determine at what dose can we see a blood pressure drop. And the premise is that today the main reasons why mothers have to deliver early is because when systolic blood pressure gets over 160, that's really when the OBGYN doc's starting to prepare for delivery. So what we saw, these patients came in, They were on maximum tolerable dose, typically on libidol and nifedipine. And the unfortunate part about preeclampsia, that there really isn't anything else you can give these mothers. You can't give these mothers ACE inhibitors. You can't give them ARBs. You can't give them PDE5 inhibitors because they've all shown to cross the placenta and cause harm to the baby. And so, again, these mothers were on maximum tolerable dose. They're basically on a trajectory that blood pressure was going to continue to increase at a rapid rate. On average, they had a systolic blood pressure of 167. And within five minutes of starting the IV infusion, blood pressure was coming down. And what we saw really at the targeted range of dosing, we saw about a 25 millimeters drop in systolic blood pressure. So very clear, very immediate. And it held all through the 24-hour treatment window. We also wanted to see if our drug could dilate the intrauterine arteries. So the root cause of preeclampsia is that the baby, there's not getting enough blood flow to the baby. And so everything that comes from nutrients all comes via the placenta. And so what we also saw was a 13% overall absolute reduction in what's called the intrauterine pulsatility index, which is a direct measurement of blood flow. So the lower the resistance, the more blood flow. So although this was a small study, we saw this immediate effect as well. So it wasn't just the blood pressure control, but also the dilation of the intrusion arteries. And most importantly, the drug has been shown to be very safe and well-tolerated, which is really important when you're talking about treating a mother. This is a naturally occurring protein. We just made a synthetic recombinant form of it.

Okay. Makes a lot of sense. And then have you had any regulatory meetings or interactions following that data set? And how has the feedback been from regulators on the, I guess, on the amount of information that we've seen so far on the lack of placental transfer of 199?

Sure. So we've gone to the FDA. So the FDA has asked us to, so we previously had run a host of RepoTalk studies. The FDA has asked us to run an additional 10-day rabbit study, which we did. And we continue to see a tolerability issue. So when we're giving a recombinant humanized protein to a rabbit, it has not been well tolerated. And it's not tolerated at any dose. Having said that, from the data we've had thus far in the rabbits, we've had over 200 rabbits been born. No tolerability issues, no deformations. But the FDA has asked us to run an additional RepoTalk study that we have proposed that we'll run that in a rat model. We're anticipating getting results, getting feedback from the FDA shortly. In the meantime, we've recently had clearance from Health Canada to start our Phase 2 trial, and then we're also planning to expand into the UK. So while we're meeting the requirements from the FDA, we're going to be running the study in Canada, the UK, and if there's time, we'll run in the US. But ultimately, as long as we can get the last remaining requirement from the FDA completed before Phase 3 next year, then we'll be good to go.

And then can you remind us about, or is there any particular reason why this was an issue specifically in rabbits, but perhaps not in rodents or, you know, is this something that you can run in other animals like dogs, perhaps, or their canine models? And then for this proposal to the FDA, what is the timeline looking like? When might regulators respond? And then is there potentially any risk to some of these other trials that you're starting in other geographies as a result of this rabbit tox, or is it just that U.S. regulators are a little bit more stringent about?

Yeah, we feel this is just a U.S. thing. And in particular, when we look at Health Canada, when we did our submission, they had, you know, basically they gave us clearance within 30 days. And so this rabbit issue does not occur with other drugs. We know, for example, TPA, also actually being used for stroke, one of our indications, has the same issue. So even on to be giving TPA to rabbits. And so we feel it's the same situation. So we do believe it's just a check the box. There are other species that we could be looking at. And we know that, for example, mini pigs, we have some really good tolerability data there. But rabbits are known to be very sensitive species. And they're just very sensitive to our recombinant protein. We don't think this will affect anything else in terms of our other studies. We're running a pivotal trial for stroke. We're running in preeclampsia in South Africa, and there's no additional work that any of these other jurisdictions are asking for. Okay.

And then to follow up on that, has the data that's been generated in humans so far been something that you've been able to submit along with this?

And is that something that could potentially convince the FDA to allow the rat tox study to be sufficient in order to move forward with this? or is that data that they already have on hand and this is just kind of the you know last check the box before yeah so as part of our submission we did share the results of the data we have in south africa for preeclampsia and 30 plus pregnant mothers again very well tolerated both mother and the baby but the fda really wants to focus on basically want to want to focus on the preclinical work. And they actually asked us why we're going into, why we went to South Africa first. We went there really because we're dealing with the world leader in preeclampsia that now has dosed more patients at her site than all other sites combined. So we do really believe that it's just a additional check the box. This is a very vulnerable patient population. So nobody wants to be harming babies. So we just do believe that it's just a check the box exercise that we're through. And so if the FDA comes back and they agree with the RAD study, it's about three months to run the RAD study. Okay.

And then going back to the data, we had seen from cohort six to nine, I believe, that's where we had seen the strongest blood pressure response, where we had seen an average from 167 to about 142 or so, that 25 drop you were talking about earlier. But we're going to be seeing some expansion data from an additional 12 patients later this quarter as well. So just wanted to know what the status update on that was. And if you could set some expectations for what exactly we might see, how much fallout we might see, if we're going to see any additional kind of, you know, endpoints there that might be relevant.

Yeah, the big thing there is that we'll be dosing. So the extension data that we'll have out later this quarter, so in June sometime, that's going to be at the highest dose. So that'd be a cohort 10. So it'll be three patients in the cohort 10 plus 12 patients extension. And really we want to see most importantly is that of course safety, tolerability, but we really want to see any difference in terms of blood pressure drop. So we're already dropping blood pressure to really getting pretty close to the targeted range. So in these patients, ideally you want to have systolic and close to the 140 range. You don't want to be dropping blood pressure down to 120 or below. But so this is, I think, really really confirmatory that at a higher dose, the highest dose tested, can we continue to see very significant drops in blood pressure. We also believe that if a patient doesn't have as high of a blood pressure baseline, the drop's not as high. And we've seen this in other studies, other indications is that when blood pressure is very high, we see a larger drop. When it's not as high, it's not as large. If blood pressure is normal, we also don't seem to drop blood pressure, which is important.

So I guess the thinking is that there might be a stabilization at some point where, you know, even at a higher dose, cohort 10, there might be a possibility that, you know, we don't really see any further reductions past.

Right.

Whatever.

Right. Which will be important as we go into the early onset. So the next cohorts will be running. These mothers will be coming in with a blood pressure more under control. So when they first get diagnosed, they'll initially go on libido-lonifedipine and then they'll go on to our drug. And the premise there is that there we'll be looking to more preventing how long it takes before that blood pressure to start rising. Got it. So if we can get drug on board, helping to control, we're basically, we think we're improving endothelial health. And if we're doing that, then we should really be able to extend how long it takes before the blood pressure starts to increase. We're not going to cure the disease. If we can keep baby and mother for another week, that'll have a profound impact in terms of reducing the number of these severe neonatal events occur for these mothers.

How are you thinking about what a primary endpoint for a study in early-onset disease might look like? Is that just prevention? Would it be the extension of time? Would it be fetal weight, perhaps, or some other innovative way to potentially look at? How are you kind of thinking about that?

Yeah, so the written feedback we had from the FDA were a composite of neonatal events, what they've given us. And we've been able to basically map out that if we can get, for example, a seven-day extension in neonatal events, a seven-day extension in gestational days, that directly correlates to a very significant reduction into neonatal events. So if we could see five, seven-days extension, we think powering on a pivotal trial at 90% will be around 240 patients. So a manageable study size for the pivotal trial.

And then I know you're also planning some PKPD modeling to better inform some of these dosing decisions. How do you expect this analysis that you plan on doing to kind of refine that approach? And particularly if you can also touch upon the timing of the subcutaneous versus IV dosing, because we had seen some mismatches there and how that might translate to the early onset patients. And this is also going to influence your dosing strategy for the upcoming UK and Canada studies.

So what we're seeing, so the late onset study that we're just completing here, what we're starting off with the first dose IV, and then we do subcutaneous dose. What we're seeing thus far is that we feel that by just actually adjusting the IV dosing, we could bring in the blood pressure into a targeted range. So what we're looking for are upcoming phase two trials in early onset. that we'll be dosing subcutaneous every three days until delivery. And then separately, we've got a 30-patient study that's going to be doing just IV infusion. And the idea there is that we'll start IV infusion and we'll basically continue IV infusion until delivery. So we think that for phase three, what we anticipate is we'll be dosing every three days until systolic gets close to 160. And then when it gets close to 160, then we'll move to continuous IV infusion. And we think that potentially alone could get us a couple extra days. So if we could get a week or so plus extension with sub-Q, then a few extra days with the continuous IV infusion, I mean, we're hoping we'll get a few weeks when we just need probably five to seven days is what we need.

And I know the rate of that IV infusion also makes a difference as well. So is that something that you've kind of determined already what that might look like? Because I believe, you know, you've said previously that kind of a rapid infusion of this can drop blood pressure a little bit too much maybe. And so there's this kind of steady state that I suppose you have to get to. So is that something that you've already determined? And with this IV, continuous IV infusion, is there any particular kind of operational considerations to take into account?

Yeah, so looking at the Part 180 that we have right now, what is pretty clear is that if we kind of start in that cohort 6 to 9 in the study that we just completed, starting off in that dose range for a two-hour IV infusion starting, but then just letting the sites adjust the IV dose as needed. And so what we're seeing firsthand, by just adjusting the IV dose, they can really dial in the blood pressure into the targeted range. And so that'll be very important so we can give the sites the flexibility. OBGYN docs already have the flexibility when they give short-acting libidolol. So when libidolol and nifedipine, the oral starts to wear off after a few days. They will often give libidolol for a few hours just to stabilize the mother before delivery. We believe a similar way they can use our drug, adjust it. But more importantly, I think we can adjust this potentially for a few days versus just a few hours that's used today with libidolol. Okay.

Then I guess actually going back to the cohort 10 that we're going to see some more data from as well. Just given that you are including some early onset pre-eclampsia patients in this case. How do you think insights from that will inform the design for any future trials that you conduct?

Yeah, so this is going to be a little bit of a different patient population than the early onset. I think the important piece is we believe that this drug is, you know, we think almost every patient is a responder. I think that's really the key takeaway. It's not like, hey, we're looking for 67% responders. We feel almost every single patient that goes on drug sees an immediate effect. So this will just be helping to confirm in a larger patient population and also a larger safety data set. We have been reported that some of these mothers coming in, they've got edema that's swollen like this, and within a day of getting the IV infusions resolving before delivery. And so we think that's maybe some indications of improving endothelial health because, if anything, that edema should be getting worse, not improving.

And then moving to AIS, you've met the interim enrollment for the Remedy 2 Phase 2-3 trial. The interim analysis is in the fourth quarter. So can you remind us what the interim will be looking for and what the powering of that interim might be? And is there a chance that maybe this trial could be stopped for superiority or do you anticipate needing to maybe resize the total trial population?

So what we're expecting is having our interim analysis in the first 200 patients by the end of the year. And so the interim analysis will be blinded to the data, but first there will be a futility. So if we're not seeing a drug effect, the study will be terminated. Otherwise, there will be a resample size somewhere between 300 and 700 patients. And so that will really help us. So if we're seeing a drug effect that's, I'd say, comparable to our Phase II data, comparable to the human urine form of the protein in Asia, we would be anticipating around 300 patients. At the time of the interim analysis, we should be getting pretty close to 280 patients. So if the final study size is, call it 300, we should be very close. We do not have an early stopping for futility because we feel this single study should support registration. But to do that, we think we need a minimum of 300 patients in terms of total sample size. The primary endpoint, we'll be looking for the modified Rankin score. So this is a score of 0 to 6. So 6 is considered death. 0 to 1 is a full recovery. And so the modified Rankin score of 0 to 1 would be a primary endpoint. It's a very straightforward endpoint from a neurologist's perspective. And it's a very simple way of looking at it. If you're a plumber, can you go back to doing your job? It might be a little bit slower, but can you go back to doing your job? Standard endpoint that's used very frequently with studies from TPA and also with mechanical thrombectomy. So we feel very good in terms of the endpoint. What's unique about the stroke program is that in China, there's a form of this protein that's being used to treat stroke. Last year, almost a million patients were treated, and that's currently been marketed by Shanghai Pharma. So there's a lot of data, 200 clinical papers published showing the clinical use of this protein. And we think all that data from China, we call it basically a playbook in terms of what patients we think would be best responder, what dose, how long to treat them. So a lot of information that could take some time, multiple phase two trials to really figure out best responders. We think we can really rely on the clinical use. And I'll just mention for stroke, it's been a hard indication, been lots of failures over the years. But what we know that works for stroke is blood flow. So no protectants, oxidative stress, they've repeatedly failed for stroke. But what has worked is blood flow. TPA, you dissolve the clot, mechanical termectomy, pull at the clot, blood flow gets reestablished. And what's really unique about how our protein works from a mechanism for stroke is you have a stroke in that ischemic area that's at risk of dying. Following the stroke, you have these bradykinin-2 receptors on athelium that are upregulated 30-fold. But what the body is missing is the ligand bradykinin. So tissue calicoin, KLK1, it releases bradykinin, which passes the blood-brain barrier, and then it basically attaches to where those receptors are. Because those receptors are all upregulated in the ischemic area, now it focally vasodilates, pulling in blood flow from other parts. And what's unique about some of the more recent papers coming up with the urine form in Asia, they actually have imaging. We actually can see where the brain lights up in terms of where that blood flow gets reestablished after getting the human urine form of this protein. Got it. That's why we think that this this mechanism is a lot different than the challenges we've had in the past with stroke trials. OK.

Can you remind us about what the manufacturing for one nine nine is? Have there been any considerations for changes in the manufacturing just given, you know, potential expansion into these other or as you move forward into other trials in different geographies? Yeah, I guess if you can just give us a brief overview of what the manufacturing looks like.

Yeah, so basically we're using Chosella and we're working with Catalan, and we're doing 250 liter runs. We think that's going to be our commercial scale. We're dosing this, you know, we're basically dosing this at, you know, 3 to 5 micrograms per kg. So we think each manufacturing run will give us several hundred thousand doses. So we'll be looking at, you know, maybe a couple dollars per dose. We'll start off, you know, commercially. We think that this is something we do five, six. You know, we can easily do five to six manufacturing runs a year. But we've already locked down our commercial scale and done multiple batches. Very, very stable protein. It's stable at room temperature for a year. So it's got wonderful, wonderful CMC characteristics. And the big challenge we've been able to do is being able to manufacture an active recombinant form. And so we know that over the years, there's been at least five other companies have tried to make the recombinant. We know that companies like Amgen, Bayer, Takeda have tried to make recombinant. But a lot of those were back, you know, multiple decades ago. So by us being the first ones to manufacture an active form of the protein, we've got issued composition of matter patents. We've got dosing, route of administration as well. So I think a very clear pathway on the manufacturing side and patents. Okay, got it.

Yeah, and if you can quickly touch on the patents as well, what the IP looks like for this.

Yeah, so the key piece was the composition of matter patents in terms of how we make the protein. And so what it turned out that through a lot of trial and error, it was the glycosylations, how they're attached. So we basically have a 50-50 mix of high and low glycosylation that was critical for activity. Without this glycosylation, there was no activity. And we discovered this in a non-obvious manner. And because it was not obvious, we got issued composition matter patents. And then we also have a series of dosing in terms of route of administration, in particular subcutaneous. And then, of course, as a biologic, there's also the 12 years of market exclusivity as well. But also part of the manufacturing process, we kept those trade secrets because there were some steps involved. I'd also mention we also made two changes to the amino acid sequence that was important in terms of improving the manufacturability in terms of being able to manufacture an active form of this protein.

And then depending on how the stroke program reads out or even what we see from some of the data in preeclampsia later on, how are you thinking about potentially partnering this or working with a partner on this or are you thinking about going this off?

Yeah, so these are both really huge, very large market opportunities where these patients for both stroke and preeclampsia, there's not a treatment options today. Ultimately, it's the same drug. So we would anticipate that we'll need to have the same partner that would commercialize for both. The nice thing is that both of these will be acute care sales forces that will be in the hospital setting. Importantly, we also think that from a pricing perspective, we feel that ultimately the preeclampsia pricing is probably five times higher in terms of the value that it'll be able to provide. But we also feel we'll likely be dosing at five times higher. So ultimately, I think the drug will be priced on a per milligram basis. And for both indications, if it gets approved, if we look at something very similar analogy to TPA today, that, you know, TPA will be given to pretty much every patient that can get to the hospital in four and a half hours because the alternative is, you know, a lifelong potential of challenges. And we think the same thing here for both stroke and the preeclampsia if it gets approved. Probably some serious litigation risk for the hospital if they don't give it to a patient because the alternative is serious and it's not like you can come back a week later and get re-dosed again, seeing if it improves outcomes. Sounds.

And then lastly, can you remind us about what the cash runway looks like?

Sure. So we got last reported $51 million in cash. They'll give us a runway through 2027. so that'll be enough cash to you know to complete to complete the phase three trial for stroke and we'll get um four readouts um for for preeclampsia and also um readout uh phase two readout for fetal growth restriction so we think a lot of really important um readouts coming up that uh that we're funded through yeah big year um rick thank you so much thank you all for uh Tendek.

Great. Thank you. Appreciate it.