DiaMedica Therapeutics Inc.

Good morning, ladies and gentlemen, and welcome to the Diomedica Therapeutics Full Year 2025 Earnings Conference Call. An audio recording of this webcast will be available shortly after the call today on Diomedica's website at www.diomedica.com. in the Investor Relations section. Before the company proceeds with its remarks, please note that the company will be making forward-looking statements on today's call. These statements are subject to risks and uncertainties that could cause the actual results to differ materially from those projected in these statements. More information including factors that could cause actual results to differ from projected results, appear in the section entitled Cautionary Statement Note Regarding Forward-Looking Statements in the company's press release issued yesterday and under the heading Risk Factors in Diamedica's most recent annual report on Form 10-K. Diamedica's SEC filings are available at www.sec.gov and on its website. Please also note that any comments made on today's call speak only as of today, March 31st, 2026, and may no longer be accurate at the time of any rent replay or transcript rereading. Diomedica disclaims any duty to update its forward-looking statements. Following the prepared remarks, we will open the phone lines for questions. I would now like to introduce your host for today's call, Rick Pauls, Diomedica's President and Chief Executive Officer. Mr. Pauls, you may begin.

Thank you, Morgan, and thank you all for joining us for our fiscal year 2025 earnings call. With me this morning are Dr. Julie Kropp, our Chief Medical Officer, and Scott Kellan, our Chief Financial Officer. Looking back for a moment, 2025 is a year in which we made significant progress across our pipeline, achieving a number of key milestones. As most of you know, our lead candidate, DM-109, is a recombinant form of the naturally occurring KLK1 protein, a serum protease, that acts through the bradykinin-2 receptors in the walls or endothelium of our blood vessels. to increase the level of nitric oxide, prostacyclin, and endothelial-derived hyperpolarizing factor. The combination of these factors has the potential to more effectively enhance blood flow and vascular health than any other factor given by itself. We believe that this mechanism is why DM-19 is so well-suited to improve patient outcomes for preeclampsia, fetal growth restriction, acute ischemic stroke, and other indications associated with vascular pathology. And I'll turn the call over to Julie to provide an update on our preeclampsia and stroke programs.

Thanks, Rick, and good morning, everyone. Starting with our preeclampsia program, 2025 marked a very strong year of progress. In July, we announced positive interim results from Part 1A, the ascending dose portion of our investigator-sponsored Phase 2 trial being conducted in South Africa. These results showed that DM-199 produced statistically significant reductions in blood pressure and in the uterine artery pulsatility index, consistent with reductions in vascular resistance that suggest a potential improvement in blood flow to the placenta. Importantly, the interim data demonstrated that DM-199 did not cross the placental barrier. These interim results were observed in hypertensive women expected to deliver within the next 72 hours. We believe these results demonstrate an on-target mechanistic response, which supports DM-199's potential to be a first-in-class disease-modifying therapy for preeclampsia. Key findings from the interim analysis of Part 1a, specifically from Cohort 6 through 9, in pregnant women with preeclampsia planned for delivery within 72 hours include the following. First, blood pressure data demonstrated clear dose-dependent and statistically significant sustained reductions in both systolic and diastolic blood pressure, underscoring DM-199's potential to control maternal hypertension associated with preeclampsia. Second, DM-199 significantly reduced the uterine artery pulsatility index, a Doppler-based measure of arterial resistance that suggests improved uteroplacental perfusion. Third, and most importantly, DM-199 did not cross the placental barrier, placing it in a unique position with respect to safety and reduced fetal risk in this highly vulnerable patient population. Through additional analysis, we have also demonstrated that DM-199 does not pass to babies through breast milk, further reinforcing its confinement to the maternal circulation. This advantageous safety profile combined with DM-199's novel mechanism of action may enable earlier initiation and longer treatment duration, which has the potential to drive meaningful prolongation of pregnancy without added safety burdens. We believe the observed improvements in vascular resistance reflect restoration of normal endothelial function consistent with an on-target mechanistic response to DM199 therapy. By improving endothelial health, DM199 has the potential to address the underlying vascular dysfunction driving the disease that should result in stabilization of maternal vascular pathology and prolonged pregnancy, as opposed to current therapies that simply manage symptoms. Taken together, the ability to reduce blood pressure, improve uteroprocental perfusion, and restore endothelial function reinforces our belief in DM-199's potential to be a first-in-class disease-modifying therapy for this life-threatening condition for which there are currently no approved treatment options. During the fourth quarter, under the leadership of Professor Kluver, enrollment continued in the Part 1A expansion cohort, which will include up to 12 additional patients to provide us with a more comprehensive data set. We anticipate completion of this cohort in the first half of 2026. Protocol amendments are being finalized for Part 1B and 2 of this study. Part 1B will enroll up to 30 hypertensive women with late stage preeclampsia expected to deliver within 72 hours to further confirm the Part 1A results. These participants will receive continuous IV administration of DM-199 that will be titrated to maintain blood pressure in the targeted range. Part 2 will enroll up to 30 women with early onset preeclampsia who are candidates for expectant management where the therapeutic goal is to prolong the pregnancy as long as possible while also providing increased blood flow to promote larger, healthier babies. These protocol amendments represent refinements to the previous treatment regimens based upon learnings from Part 1A. The fetal growth restriction cohort will be enrolling patients without preeclampsia but with impaired placental function, further expanding the potential application of DM-199 across placental vascular disorders. The first patient in that cohort is anticipated to be dosed in Q2, 2026. Importantly, we have also recently received regulatory clearance from Health Canada to initiate a global phase two clinical trial of DM-199 in early onset preeclampsia. This is an important regulatory milestone for our PE program. We are currently finalizing plans to commence site activation in the second half of the year. We intend this trial to be a global Phase II study. It is an open-label, dose-finding trial designed to enroll approximately 30 participants with early-onset preeclampsia between 24 and 32 weeks of gestation. This expectant management population represents patients with the greatest unmet medical need where safely prolonging pregnancy can have the most meaningful maternal and neonatal impact. The study will evaluate the safety, tolerability, and preliminary efficacy of DM-199 with dosing anticipated to continue until delivery. We are assessing three dose levels to inform dose selection of the optimal regimen for Phase III. Primary study endpoints include maternal pharmacokinetics and further confirmation that DM-199 does not cross the placental barrier, an important safety consideration for both regulatory review and patient acceptance. In addition, we will evaluate clinical and biomarker outcomes, including prolongation of pregnancy, blood pressure control, uterine artery blood flow, circulating pathogenic biomarkers, and renal function. We are also preparing to seek approval to expand the study to include sites in the UK. And with respect to the additional reproductive tox study in rabbits requested by the FDA, preliminary results from a dose range finding study in rabbits suggest that rabbits may not be a suitable animal model for reproductive toxicology studies with DM-199. This is likely due to an unusual immune response to the recombinant human protein unique to rabbits that has not been seen in rats, monkeys, or humans thus far. Most importantly, from our perspective, there were no teratogenic effects observed in the approximately 200 pups or baby rabbits produced in a prior study. This included no external visceral or skeletal malformations. We are currently evaluating an alternative animal model to address the FDA's request and we will work with FDA to find a solution in parallel to initiating the Phase 2 trial in Canada and other potential jurisdictions. Turning to our Remedy 2 trial, 2025 was also a good year for our stroke program. Over the past several months, we have intensified our engagement with study sites to share best practices and build friendly competition. We've also added additional resources to support sites through the enrollment and follow-up process, and we continue to work on additional ways to support our study sites. These activities, along with increased site activations globally, have resulted in encouraging enrollment momentum over the last few months. At present, I'm very pleased to report that with these additional efforts in the United States and Canada, along with expansion into the UK and Europe, we have achieved almost 70% of the required enrollment of 200 participants for the interim analysis. We currently have close to 61 active sites, including four in the UK and an additional 12 across Europe, and approximately 25 more sites are expected to activate in the coming quarter. With our recent progress, we are reiterating our guidance to complete the interim analysis by the second half of 2026. Since the last earnings call, an independent data safety monitoring board meeting was conducted after the enrollment of 100 patients. Following review of the safety data from these participants, the independent DSMB unanimously recommended that enrollment continue without modification. I will now turn the call back to Rick.

Thanks, Julie. We're also pleased to note the paper titled Endothelial Triple Pathway Vasorelaxation as an Adjuvant Strategy in Resistant Hypertension was recently published in the Journal of Hypertension. The article authors included Dr. Luke Laffin, a recognized key opinion leader in the treatment of resistant hypertension. This publication underscores the need for new treatment approaches to lower blood pressure in patients with chronic kidney disease. It also highlights findings from our prior Phase II Redux trial, which demonstrated DM-109's ability to significantly reduce blood pressure in patients with elevated levels over a three-month treatment period. DM-109 was also observed to lower serum potassium levels in patients whose potassium levels were elevated, placing these patients at risk of developing hyperkalemia. We look forward to sharing more on the potential use of D-109 to control blood pressure in patients with chronic kidney disease in the future. I would like to now ask Scott to review the financial results for the quarter.

Thank you, Rick, and good morning, everyone. We announced our full-year financial results for 2025 and filed our annual report on Form 10-K yesterday. As of December 31st, 2025, our cash, cash equivalents, and short-term investments were $59.9 million. Current liabilities were $5.1 million and working capital of $55.5 million. Compared to cash and investments of $44.1 million, current liabilities of $5.4 million, and working capital of $39.2 million as of December 31, 2024. The increase in cash and short-term investments is due to the net proceeds received from the sale of common shares in the company's July 2025 private placement and under its at-the-market offering program. We feel confident about our cash position and anticipate it will fund our planned clinical studies and corporate operations through the end of 2027. Net cash used in operating activities for the full year 2025 was $29.1 million compared to $22.1 million for the full year of 2024. This increase is primarily a result of the increase to net loss for the full year of 2025 as compared to the prior year period. Turning to the income statement, our research and development expenses increased to $24.6 million for the year ended December 31, 2025. up from $19.1 million for the prior year. This $5.5 million increase is driven by a combination of factors, including the continuation of our Remedy 2 clinical trial and its global expansion, the expansion of our clinical team in both the prior and current year periods, and increased non-cash share-based compensation costs. These increases were partially offset by cost reductions related to manufacturing process development work performed and completed in the prior year period. Our general and administrative expenses were $9.8 million for the full year of 2025, up from $7.6 million for the full year of 2024. G&A expenses increased by $2.2 million due to a number of factors, including increased non-cash share-based compensation expense, increased personnel costs, increased investor relations expenses, and increased patent prosecution costs. With that, let me ask the operator to open the lines for questions.

Thank you. We will now begin the question and answer session. If you would like to ask a question, please press star then the number 1 on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star 1 again. Your first question comes from Stacy Koo with TD Cowan. Your line is open.

Good morning, everyone, and thanks so much for taking our questions. So we have a couple. If we could just stay with preeclampsia for now. The first question is on kind of your update with the Revit preclinical trials for the U.S. IND approval. So just help us understand what are your early thoughts on the alternative species with the FDA. What other preclinical models are best for reproductive tox studies? So that's the first question, if you could maybe further elaborate there. And then as we think about the ISP and clearly a lot of great signals that we're going to get there, what key learnings are you hoping to carry into the early onset preeclampsia kind of cohort as we think about Part 2 and Part 3, so fetal growth as well. Is there any potential that we can get an update later this year to just help us understand where you all are in potential timing there? And then, of course, ahead of the US trial, Julia, we kind of heard all the high level of preparation. ahead of moving forward in the U.S., but just help us understand how our conversation's progressing. What criteria is the team focused on when it comes to enrolling the right preeclampsia study investigators? And then if I could sneak in a tiny question on CKD, clearly a big opportunity. When could we expect a detailed plan or a more detailed plan for pursuing DM-199 and treatment-resistant hypertension in CKD patients? Thanks so much.

Right, thank you. So I'll start off maybe with the CKD, the fourth question, is that we're very excited about the opportunity for our drug to lower blood pressure. We've clearly seen it in numerous trials. I think there's a huge clinical need, in particular in patients with chronic kidney disease, as many of these patients have elevated levels of potassium that puts these patients at risk of hyperkalemia. So I think first we can treat these patients, control their blood pressure when they frankly don't have a lot of options. And what we did see in our previous trial, the ability to lower potassium levels, which could be a very exciting opportunity. Right now, really, the focus, though, is on our preeclampsia and stroke program. And at the appropriate time, we'll look at potentially advancing into CKD. But right now, we want to make sure we're really focused here near term on our other two programs. And then maybe I'll hand it off to Julie. Thank you.

Yeah, hi, Stacy. All very good questions. I think, you know, it's premature right now to say exactly which species that we're going to focus on. We want to first be able to, you know, submit a package to the FDA, and we're having a discussion with them further on appropriate models. There are several appropriate models we're considering, but again, we'll hold back until we will give an update once we have that discussion. And then with regards to your question around what have we learned from previous cohorts, I think we understand the PK better after running the initial studies, and one of the learnings we're taking forward is for our early onset studies using the subcutaneous only and probably reserving the IV for the later onset as we've been doing previously. So that's one element. I think it's, you know, as far as site selection, we are, you know, highly focused on selecting sites that have both experience with preeclampsia studies as well as a practice that's well-suited for early onset, you know, expectant management, which is Something, you know, some sites are very adept at and other sites are more conservative about when to deliver patients. So, again, it's that tightrope between tweeting, you know, between the mother's health and the baby's health and making sure that we select centers that are comfortable, you know, keeping the mother even though there's some, you know, severe, there's potentially severe complications going on. It feels like they can stabilize them enough. to prolong the pregnancy. So those are kind of the considerations that we're focused on.

Incredibly helpful. Thank you so much.

Your next question comes from Josh Shimmer with Cantor.

Your line is open.

Thanks for taking the questions. Two quick ones. For the Evaluation of DM-199 and earlier onset preeclampsia, how do you think about the potential risk of the protein crossing the placental barrier at that stage, and what evidence do you have to suggest that it, in that setting as well, will not cross in any meaningful extent to the placenta? And then for the interim analysis for the Phase III stroke program, what are the potential outcomes there? stopping criteria, either positive or negative, or resizing criteria. Maybe you can share a little bit more about what you expect the intern to inform. Thank you.

Sure. Thanks, Josh. So, starting off with the early onset and crossing of the placenta, we don't think it'll happen. I mean, we've done now over 35-plus patients uh with with um more late onset pre-cancer where we didn't see this crossing um to cross the placental barrier is about five besides the cross will be about 500 dollars where our protein is about 26 kilodaltons so you know 50 times larger so it would be very shocking if it did occur we also did an earlier study in the rat model we also did not see it so I think right at this point here, another check the box, but we feel very good the fact that in the South African patient population, we didn't see it. With regards to your second question, the ongoing phase 2-3 stroke program, for the interim analysis, first off, if we're not seeing a drug effect, we will terminate the study for lack of efficacy. Otherwise, there'll be a resample size, and the resample size will range from 300 to 728 How we designed this trial, and we believe, you know, base case that, you know, if we're seeing a drug effect that's comparable to our phase two, which is comparable to the many studies that have been shown with the human urinary form of the study in China, looking at the modified Rankin score of 0 to 1 as the primary endpoint. We're anticipating that if we see, again, drug effect comparable, we'll be looking at something ideally in the 3 to 350 range. If we need to go above 500 patients, we'll have to really evaluate the next steps of the program in light of the high prospects, I think, as well for the pre-cancer program.

Thank you. Your next question comes from Thomas Flatton with Lake Street.

Your line is open.

Hey, good morning. I appreciate you taking the questions. Just a question on the Part 1A expansion cohort. It strikes me that it's taking a bit longer than I might have thought in my mind, given how many patients Dr. Kluwer sees on a weekly basis. Is this a slow and deliberate approach she's taking, or has something else been going on there? Just some additional color on that expansion cohort would be great.

Sure, yeah, it's a good question. It really has been a result of some staffing challenges that Kathy Clivers had at her site. We've recently provided some additional financial support, and with the hiring of a couple new nurses just in the last few weeks, you know, we anticipate that enrollment's going to pick up again.

And then, following on from that, if I understood the press release in your commentary correctly, Are Parts 2 and 3, or Parts 1B and 2, sorry, dependent on the completion of the expansion cohort, or will they initiate prior to the full completion of that cohort?

So, we've made a few protocol amendments that are going through shortly, and so we're anticipating later in Q2 that those two cohorts should initiate. Parts 1A expansion study is ongoing and will be completed as well in Q2.

Got it. Understood. And then just a quick one on Remedy 2. You mentioned some acceleration or some momentum building. I was wondering if you could just give us a sense of in the first quarter of this year, You know, how many patients did you enroll compared to what you did in the fourth quarter of last year, just to give us some kind of scope and scale of that momentum?

Yeah, I would just say at a high level, the enrollment increase really has been more so it's been this year. So even going into the end of, you know, 2025, it was still relatively slow, but really has picked up substantially in the last month, last two months. But really the more recent months is where we've seen the really uptick, and that also correlates to where we've had the increase in sites and all the work that Julia and her team have been doing has been wonderful, and I think we're now starting to see the benefits of all that work.

Great. Appreciate it. Thank you.

Your next question comes from Matthew Caulfield with HC Wainwright. Your line is open. Hey, good morning, guys.

For the remedy trial, there had been some prior discussion of some challenges with stroke enrollment formerly being slower in the U.S. due to initial triage in the community hospitals. Kind of thinking bigger picture, do you ultimately foresee any limitations for real-world access if or when DM-199 could ultimately be approved for the AIS indication? Thanks again.

Yeah, good questions. So I think there's a difference between the challenges that we've had been seeing with enrolling at more these hub-and-spoke hospitals, but ultimately for commercialization. The wonderful thing about our drug is the safety profile should be great in being able to be used very broadly at small community hospitals and big academic centers. So I think that the previous challenge we're having is really more with enrolling patients at the large academic centers. But in terms of, again, at the commercial side, I think it'll be a wonderful drug because of that safety profile.

Got it. Thank you. Appreciate it. Your next question comes from Chase Knickerbocker with Craig Hallam.

Your line is open.

Good morning. Thanks for taking the questions. Was just hoping to work one more in on the non-clinical side here. Can you just maybe walk us through kind of the differences in your prior non-clinical rabbit study that you had kind of mentioned where you didn't see any toxicity in this one? Was there kind of a different species used here? or maybe just kind of your biological rationale as to why this antibody response arose.

Yeah, Julie, can you take that one, please?

Yeah, so that's a very good question. The first study was a different gestational age time period for the pre- and postnatal rabbit study. We studied an earlier, I mean, a slightly later gestational age as well as a slightly different duration of treatment, different doses. So it's, you know, it's hard to explain. We did see maternal toxicity in that study as well. It wasn't quite as significant. But I think the difference here and the issue really with the FDA is not related to concern on the part of the fetus, I mean, sorry, the pups, if you will. The pups really did not show any increase in, you know, malformations or teratogenicity from the control group in either study. But I think the concern with the FDA is finding a Noel, an effect dose where they don't see any adverse effects. And the maternal, you know, toxicity that we saw, which we believe is due to immunogenicity, which is not uncommon. to see in rabbits, you know, immune responses very quickly to human proteins. So I think really it was in both studies we weren't established, we had maternal toxicity, so I don't think they were really that different other than, you know, gestational ages being different and the FDA wanting us to dose primarily after the first trimester, after the, you know, development, the early development of the fetus. because that's closer to the way we're going to dose humans. So it just turns out I think the rabbits just are not a good species and we're going to just have to do it in a different species.

Got it. And then just maybe a little bit on timelines as far as when you'd expect to get that feedback that you need to continue with a different species or just kind of color from FDA on what they what they would like to move forward. Do you have a meeting scheduled in Q2? Maybe just walk us through timelines there.

So we are going to, you know, we'll provide an update as soon as we have, you know, something to update. I don't think we're giving a, you know, forecast yet until we understand and get alignment from the FDA on the path forward.

Understood. And just last for me, Rick, on the stroke timing, could you just give us a little bit more color as to kind of what you're seeing from an enrollment rate perspective? I mean, is it kind of being driven by kind of breath increasing or is that depth really kind of increasing as we thought it would to kind of drive this acceleration in enrollment in the stroke study?

Yeah. And it's a combination of, you know, in particular over the last few months, an increase in the enrollment rates per site and also for a greater number of sites. And then with being at 61 sites now and having a chance to be in the trial and understand some of the challenges and opportunities of running the trial. And then I think also having a number of sites that are also on the verge of coming on board here in the coming weeks.

We feel good about reiterating guidance for this year. Got it. Thank you. That concludes our question and answer session.

I would like to now turn the conference back over to Rick Pauls, Diomedica's president and chief executive officer, for closing remarks.

Well, thank you all for joining us today. We greatly appreciate your interest in Diomedica and hope you enjoy the rest of the day. This concludes our call. Thank you.

This concludes today's call. Thank you so much for attending. You may now disconnect and have a wonderful rest of your day.