DiaMedica Therapeutics Inc. Aktie

Thank you. Medica Therapeutics Second Quarter 2026 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 forward-looking statements on today's call. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these statements. More information, including factors that could cause actual results to differ materially projected results appear in the section entitled Cautionary Statements, Note Regarding Forward-Looking Statements in the company's press release issued yesterday and under the heading Risk Factors in Diomedica's most recent annual report on Form 10-K, recent quarterly report on Form 10Q. Diomedica'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 to the committee's decision to Only as of today, August 11, 2026, and may no longer be accurate at the time of any replay or transcript rereading.

Following management's remarks, we will open the phone lines for questions. I would now like to introduce your host for today's call, Rick Pauls, Diomedica. President and Chief Executive Officer. Mr. Pauls, you may begin.

Thank you, Morgan, and thank you all for joining us today. With me this morning are Dr. Julie Kropp, our Chief Medical Officer, and Scott Kellan, our Chief Financial Officer. Q2 was an important quarter for Diomedica with progress across D-19 in early onset fetal growth restriction, pre- preeclampsia and acute ischemic stroke. We advanced our pregnancy-related clinical strategy, continued preparations for our Phase 2 early-onset preeclampsia study in Canada and the U.K., and made further progress towards reaching the planned Phase 2-3 Remedy 2 interim analysis in acute ischemic stroke. There are four key updates I would like to highlight. First, With respect to the IST being conducted by Professor Kluver, enrollment has been completed in the first cohort of the Phase II Early Onset Fetal Growth Restriction Study.

The cohort consists of six participants treated at the 5 microgram per kg dose level. This is important as it expands the clinical use of the of DM-19 into a second serious women's health disorder for which there are no approved therapies. We plan to host a Key Opinion Leader event in September with Professor Kathy Kluver, the study's principal investigator, and other experts to discuss the potential of DMV9 in fetal growth restriction and share top line results for the completed first cohort open label phase two trial. Second, the extension cohort from the Part 1A of the IST has been completed. This was the initial dose escalation cohort treating women with late-stage preeclampsia. The combined results from the dose escalation and extension groups were important, as noted in the earnings press release, as they provide the clinical support driving the selection of the mid-dose range for the evaluation both for early onset fetal growth restriction and early onset preeclampsia studies. Julie will review the data later in the call.

And third, we continue to advance our early onset preeclampsia programs on the regulatory and operational fronts, which I will discuss in a moment. And fourth, Remedy 2, our phase 2-3 acute ischemic stroke study is approaching the 200th patient required to trigger the pre-specified interim efficacy analysis. Although enrollment slowed somewhat in July, we now have surpassed 85% of the enrollment target and we anticipate the interim analysis readout in the first quarter of 2027. As a reminder, DME9 is recombinant form of the naturally occurring human KLK1 protein. KLK1 is a serum protease that acts through the BK2 receptors present in the enthalial blood vessels to restore the body's natural ability to increase levels of nitric oxide, prostacyclin, and end-of-field drive hyperpolarizing factors. We believe that this novel mechanism improves vascular biology, makes DM-19 both unique and well suited to address the endothelial and perfusion-related dysfunction common in preeclampsia, fetal growth restriction, and acute ischemic stroke. As I mentioned, we are pleased to report today that enrollment has been completed in the first cohort of the open-labeled Fable Phase II IST Fetal Growth Restriction Study.

The first cohort consisted of six participants treated at the 5 microgram per kg dose level. This study is enrolling early onset fetal growth restriction patients with or without concurrent preeclampsia. This expansion of our development program allows us to evaluate FGR, a related yet distinct clinical indication to preeclampsia. Early onset FGR is a serious complication of pregnancy associated with inadequate uteroplasental blood flow. There are currently no therapies approved to treat FTR, just early delivery, which can have very serious consequences for the babies. The study is evaluating three dose levels. With the first cohort now fully enrolled, enrollment in the second cohort at 10 micrograms per kg should begin shortly.

The dose for the third cohort will be between 1 and 15 micrograms per kg and will be based on the results from the first two cohorts. Key FGR study endpoints. safety and tolerability, prolongation of gestation, flow-mediated dilation, among other measures. This is an important study. It's the first time that DM-1A9 has been used in early onset patients. We plan to host a Key Opinion Leader event in September featuring Professor Kuhler, the study's principal investigator, where rationale for DM-1A9 in treating fetal growth restriction will be discussed, along with along with top line results from the completed first cohort. We are excited about this indication because it represents an expansion of DM-109's potential reach based upon the demonstrated improvement in the pulsatility or the resistance index observed in the initial preeclampsia Part 1A study. We also anticipate the first patients to be dosed shortly in the IST early onset preeclampsia and continuous IV infusion preeclampsia studies. Based on the results of the recently completed late onset preeclampsia study, a protocol amendment was filed in July to adjust the dosing regimen to provide more flexibility on dosing at the mid-2040s. to lower level range.

Dosing will start shortly after the acceptance of the protocol amendment is completed in coming weeks. Moving to the Global Phase II Early-Onset Preeclampsia Program, Health Canada authorized initiation of our open-label Phase II dose-ranging study in early-onset preeclampsia patients earlier this year. The study is also designed to enroll approximately 30 patients at three dose levels. We are working with SISIM Canada and Anticipate to Dose. the first patient in Q4 of this year. We're also working to expand the study to the United Kingdom later this year, subject to regulatory authorization and site readiness. The results of the multi-preclampsia and FGR studies will be important in defining the dosing for the Phase III registrational trial in one or both indications. Turning to expanding the early-onset preeclampsia trial into U.S. sites, as we announced in June, we believe that based on the FDA feedback, our previously completed RET reproductive toxicology study may be accessible to support a US IND application, provided that we can demonstrate sufficient evidence of DMOE9 exposure and enzymatic activity throughout the previously completed rat study, as well as the adequate pharmacologic effects in rats to support their use as an appropriate toxicology species.

To address FDA's request, we are conducting a pharmacokinetic and pharmacologic activity study of DM-19 in rats. Following completion of the study, anticipated in September, and reports in October, we plan to present results to the FDA and work with the agency towards initiating clinical development in the US. Finally, turning to the Remedy 2, our ongoing Phase 2-3 Acute Ischemic Stroke Trial. Enrollment has now surpassed 85% of the 200 patients required to trigger the pre-specified interim analysis, which is expected in Q1 of 2027. We currently have approximately 70 active sites across the U.S., Canada, the UK, and six countries in Europe. Site activation in Europe are adding meaningful enrollment capacity. The interim efficacy analysis, which occurs after completion of the protocol-defined 90-day follow-up, will be conducted by the Independent Data Safety Monitoring Board, or the DSMB, and is intended to assess whether a sample size re-estimate is warranted.

The final The final size may range between 300 and 728 patients or futility. Diomedica will remain blinded to data and treatment effect estimates reviewed by the independent DSMB. And I'll turn the call over to Julie to walk through the late onset preeclampsia phase two part 1A clinical update in more detail.

Thank you, Rick. As Rick notes, the Part 1A Extension cohort has been completed with the dosing of the final 12 patients at Stellenbosch University site in South Africa. The cohort enrolled women with late-stage preeclampsia who had severe hypertension and were expected to deliver within 72 hours under the current treatment protocol. The purpose of the extension cohort was to more fully characterize the highest dose of DM-199 and provide additional dose response, safety, pharmacokinetic, and pharmacodynamic information to support dose selection for subsequent studies. highest dose analysis including 15 patients, three from the initial dose escalation phase, and 12 additional patients enrolled in the extension cohort. Following DM-199 administration, we observed statistically significant and sustained reductions from baseline in both systolic and diastolic maternal blood pressure. At the pre-specified assessment five minutes after completion of the IV infusion, mean systolic blood pressure decreased by 29.1 millimeters of mercury from a baseline of 169.3 millimeters of mercury with a p-value less than 0.001. Mean diet systolic blood pressure decreased by 17 millimeters of mercury from a baseline mean of 103.7 millimeters of mercury with a p-value less than 0.01. Mean systolic blood pressure remained below 160 at all measured time points over 24 hours, an important threshold blood pressure for required delivery to reduce the risk of brain hemorrhage in the mother.

These findings were consistent with the previously reported dose-responsive reductions in systolic and diastolic blood pressure. Across the dose-ranging cohorts, the most clinically meaningful pharmacodynamic effects observed in Part 1a of the study were produced in the mid-dose range cohorts 4 through 8. These participants showed clinically meaningful reductions in both maternal blood pressure and the uterine artery pulsatility index. Note that reductions in the pulsatile index are consistent with reduced uteroplacental vascular resistance, suggesting improved blood flow to the baby, which we believe is key to potentially modifying the underlying disease process in these patient populations. These findings support studying dose levels from the mid-dose range for further clinical evaluation as we move to the early onset preeclampsia and fetal growth restriction studies. The dose levels for the next studies will begin at 5 micrograms per kilogram and advance to 10 micrograms per kilogram in the second cohort. The dose level for the third cohorts will be selected based on results from the first two cohorts and will range somewhere between 1 and 15 micrograms per kilogram.

This is intended flexibility to further define the optimal dose range based on the emerging data. Taken together, we believe these findings provide evidence of a mechanistically on-target pharmacodynamic response for DM-199 in preeclampsia. The study investigators plan to present the full dataset, including safety, pharmacokinetic, and pharmacodynamic analyses at an upcoming medical conference and and submit the results for publication in a peer-reviewed journal later this year.

We now turn the call back to Rick. Thanks, Julie. I'd like to now ask Scott to review the financial results for the quarter.

Thank you, Rick, and good morning, everyone. So, in walking through the financial results for the second quarter, as of June 30, 2026, our cash, cash equivalents, and short-term investments were $43.5 million. Current liabilities were $6.6 million, and working capital was $37.7 million. compared to cash and investments of $59.9 million, current liabilities of $5.1 million, and working capital of $55.5 million as of December 31, 2025. We continue to believe that our current TASH position will fund our planned clinical studies and corporate operations through 2027. Net cash used in operating activities for the six months into June 30, 2026 was $17.2 million, compared to $14.7 million for the same period in 2025. increase resulted primarily from the increased net loss in the current year. Turning to the income statement, R&D expenses were $8.2 million and $16.1 million for the three and six-month time periods ending June 30, 2026. This was an increase from $5.8 million and $11.5 million for the same time periods in the prior year.

The increases are primarily due to the expansion of our clinical team, continuation of our Remedy 2 clinical trial, including its global expansion, related to additional reproductive toxicity testing being performed in support of our PE program in the United States increased manufacturing and development activities, and increases in non-cash share-based compensation. We expect that our R&D expenses will moderately increase in future periods relative to recent prior periods as we continue both our Remedy 2 trial and continue the expansion of our DM-199 clinical development program in preeclampsia. Our general and administrative expenses were $2.3 million and $4.8 million for the three- and six-month time periods ending June 30, 2026. expenses increased slightly compared to the same time periods in 2025, which were $2.2 million and $4.7 million, respectively. The increase for the three-month period was driven primarily by increased non-cash share-based compensation and professional fees, while the increase for the six-month period resulted primarily from increased personnel costs incurred in conjunction with expanding our team, partially offset by a reduction in current year legal and other professional fees. We expect G&A expenses to remain relatively consistent in future periods as compared to recent prior periods. In summary, we remain well-funded with a cash runway through 2027. This covers through our major upcoming milestones, including the Remedy 2 interim analysis, planned data readouts from our preeclampsia and fetal growth restriction programs, and continued advancement of our Phase 2 preeclampsia program in Canada and the United Kingdom.

With that, let me ask the operator to open lines for.

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 Josh Shimmer with Cantor. Your line is open.

Great, thanks for taking the questions, two quick ones. First, just trying to understand the commentary around dosing while you're focusing on the four to eight microgram per kilogram cohorts, not the higher doses for the late onset preeclampsia program, but then you are exploring higher doses. the early onset preeclampsia program so we can kind of square that and help us understand that strategy. And then for the fetal growth restriction program, are there any inclusion criteria that you're using to try to focus on patients who you might think might be most likely to respond and or have evidence of impaired placental perfusion?.

at baseline thank you sure thanks thanks Josh yes for so what we've what we're seeing from the part 1a as we've seen in other clinical trials that there's really a sweet spot for dosing DM1 dm-199 and you believe koki one selectively improves uterine blood flow while also controlling blood pressure but what we see is happening if we go too high, we think we're still controlling blood pressure, but we think that we run into receptor desensitization, and because of that we see less of the dilation. And so this is consistent actually what we've seen in glucose studies and for type two diabetics, we've seen the same effect in kidney disease studies looking at EGFR and UACR, where we see a greater clinical effect at the 3 microgram compared to the 15. And then in addition, you know, we also have an issued patent as well on this nonlinear dose response curve. So I So I think for us it's important that we've got some flexibility here that we can adjust the dose, but really more targeting this mid-range. In regards to your second question, in terms of FGR, these are very severe patients. These are FGR between weeks 27 and 32. And they'll be patients that earn the 3% or less percentile in terms of body weight.

So they're very severe. these babies typically, if they were not being treated, that they would be delivering between one and six days. And so we think, you know, extending the gestational days, dilating the intrudern arteries and other factors, you know, we think this could be very exciting. So this really is focusing on, you know, on the dilation. And then we also believe that if we do see positive signals, this will be encouraging ahead of early onset preeclampsia because there we think we can also be controlling blood pressure in addition to the dilation. So we're really excited to have this KOL event in September.

Your next question comes from Stacy Koo with TD Cowan. Your line is open.

Hi, good morning. Thanks so much for taking your questions and congratulations on all the progress. So first on the fetal growth restriction, let's say cohort one data that we're going to get in September, maybe just help us understand the importance of, of maybe that chronic dosing that we're going to see. How many doses do you think you might disclose? Again, I know very early days, so just to help us understand that, kind of that dynamic. And then as we think to maybe the growth restriction and what's maybe clinically meaningful, is it a week of extension before delivery? Is it longer than that? Just help us understand the type of dynamics or maybe even a little sneak peek for the KOL event when it comes to the unmet. So that's the first question on FGR. The second is on maybe your learnings. for early onset preeclampsia. Just remind us, what are the, I guess, ongoing thoughts around IV versus subcutaneous? administration, maybe what kind of refinements you might be applying as you think about the different cohorts.

I know you just talked about the receptor desensitization, but just help us understand what's the most up-to-date thinking on the frequency of dosing, et cetera. And then the last question is a clarification. on the FDA IND submission, is it fair to assume after we finish this enzymatic study, sounds like it's going to be completed in October, that you'll be able to kind of submit the.

and to the FDA. Thanks so much. Yes, sure. So starting with the first question. So for FGR, I think what's important here is that we think we've got very encouraging data thus far with the late-onset patients, where the patient's got one dose IV and then one dose subcutaneous. But this is really going to be the first time that we've actually dosed early-onset patients. And the the patients will come in, they're getting subcutaneous dosing every three days until delivery. And as I mentioned, we think that Standard of care, which basically is really limited, we were anticipating somewhere between one and six days. So from our perspective, I mean, we had indicated earlier that if we could get another five, six days, that could have a profound impact in terms of outcomes for these babies.

Hopefully we'll get a few weeks on that front. In terms of the early onset preeclampsia, One of the changes as well we've made is that we're dropping the IV infusion and focusing on subcutaneous dosing every three days, three times. until delivery. One of the cohorts coming up for preeclampsia is a continuous IV infusion, and that'll be in late onset patients. And the premise there is that we believe by adjusting the dose, we can dial in the blood pressure to the targeted range. And so if we see positive effects there, what we would then intend to do for phase three for preeclampsia is that we're dosing every three days until systolic blood pressure approaches 160 and then at what point we would switch over to continuous IV infusion that can hopefully get us even a few extra days. And it goes well with the rat study that's already been initiated, it's ongoing. We should be completing that in the early part of September.

The plan would be then to submit for a US IND. When we did meet with the FDA to discuss this topic, The last comment they had indicated to us that this was the last piece that they thought we needed to open up the IMD.

Thank you so much. Your next question comes from Thomas Flaven with Lake Street. Your line is open.

Good morning. Thanks for taking the questions. Rick, just following up on the FTR, what's clinically meaningful, what's not. So you mentioned days of gestation. Is there going to be an endpoint looking at what percentile the baby grows to? I know you said these are third percentile or less. Are you trying to get the baby up to fifth, tenth percentile I don't really know what the number would be, or is this simply gestational extension, which hopefully leads to an improvement in baby weight too?.

Yes, we'll be looking for changes to that. I think the two main ones we're looking at initially is the gestational days because we do believe keeping your baby and mom longer should result in larger, healthier babies. also be looking at the dilation of interuterine arteries. Typically, if a mother is not getting a treatment, there's no effect that that dilation should be worsening with time. So if we can even see a stabilization to an improvement, that would be super encouraging. Yes, and there will be a series of other endpoints that we'll be looking at as well for the study.

And then just for the Part Ia data that you shared today, I'm assuming you did, you tracked the same endpoints that you did in prior cohorts around placental transfer, uterine dilation, intrauterine artery dilation. Will that be presented at some point or how do you think about disclosing those other endpoints?.

Yes, so our collaborators are preparing to submit for publication in a peer-reviewed journal.

and sharing the full data set there. Got it, and then one final one on Remedy2. assuming you know enrollment pace picks up from July once you hit the 200 and get past the end point for the data to get to the DSMB how close will you be to that initial target of total enrollment do you think at that point when you do the interim analysis readout.

Yes, so after patient 200 is dosed, there'll be a 90-day follow-up for the primary endpoint, and then there'll be another, you know, four to six weeks for the primary endpoint. for the data analysis and then at what point we'll provide a public update. And during that period of time we will continue to be dosing patients. So hopefully we'll be getting closer and closer to 300 patients that we think would be potential the base case in terms of the study.

Got it. Thank you. Your next question comes from Matthew Caulfield with H.C. Wainwright. Your line is open.

Hi, thank you. Hi, Rick and team. Congrats on the interim data set. So for the Phase 2-3 remedy trial, the interim analysis looks like it's slightly shifted from fourth quarter to early 27. You've noted the 85% enrolled towards the interim analysis. Have there been any nuances for the recruitment process? to date or how that could possibly translate to the ease of real-world patient selection in the future?.

Thanks a lot. Yes, I mean, this trial's been very interesting. It's, We'll get one month where we get very significant enrollment and then the following drops up substantially. And so it's odd in terms of how it goes. But in terms of practical, in terms of real world use, I think the big benefit of this drug here is the safety profile. So we think this drug will be able to be used. in community hospitals. And so because of that, I think we're very excited about the prospects of... getting this drug, you know, getting complete this trial and, you know, getting this drug to patients and starting to treat them.

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

Good morning, everyone. Thanks for taking the questions. This is Jake on for Chase. I was wondering, for the company-sponsored phase two, can you just walk us through the timelines to be in the clinic in both the UK and the US?.

Yes, so we are for the company sponsored trial for the early onset preeclampsia, we're targeting late this year. And then for the UK, we're just going through the regulatory process. And so hopefully, you know, similar time maybe that's into early 2027.

Okay, and is there any more detail on the regulatory process in the UK that we could.

No, we're just going through the process we've identified. The submission process, we have identified three great sites and we're working through them in terms of getting the study to launch. So in total we've got five sites. So we've got three in the UK and two in Canada. And again, in total, we're targeting 30 patients. And the protocol is very similar to the IST that's also running concurrently.

Thank you, appreciate that, Keller. That concludes our Q&A session. I will now turn the conference back over to Rick Pauls for any closing remarks.

All right, thank you, Operator. So before we close today's call, I want to say to please keep an eye out for a press release announcing the date of our KOL event focusing on early onset fetal growth restriction. At that event, we look forward to sharing scientific rationale for using DM-49 to treat FGR along with top-line results from the first patient cohort in our open-label Phase II trial. We believe DM-19 represents an important opportunity in treating pregnant mothers with FGR, and we're really excited to share more details with you soon. Thank you again for joining us today and for your continued interest and support. We look forward to updating you on the progress.

in the coming months. Operator, you may now close the call. This concludes today's call. Thank you for attending. You may now disconnect and have a wonderful rest of your day.

This live transcript is auto-generated without human intervention or review.

[Call has ended.]

Good morning, ladies and gentlemen, and welcome to the DiaMedica Therapeutics First Quarter 2026 Earnings Conference Call. An audio recording of this webcast will be made available shortly after the call today on DiaMedica's website at www.diamedica.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 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 sections entitled Cautionary Statement Notes regarding Forward-Looking Statements in the company's press release issued yesterday under the heading Risk Factors in DiaMedica's most recent annual report on Form 10-K and most recent quarterly report on Form 10-Q. DiaMedica's SEC filings are available at www.sec.gov and on its website. Please note that any comments made on today's call speak only as of today, May 7, 2026, and may no longer be accurate at the time of any replay or transcript rereading. Please -- following management's remarks, we will open the phone lines for questions.

I would now like to introduce your host for today's call, Rick Pauls, DiaMedica's President and Chief Executive Officer. Mr. Pauls, you may begin.

Thank you, operator, and thank you all for joining us today. With me this morning are Dr. Julie Krop, our Chief Medical Officer; and Scott Kellen, our Chief Financial Officer. Given that our last call was only 5 weeks ago, we'll try to keep our remarks short. We are pleased with the progress we've made so far in 2026 as we continue to advance DM199 across both our preeclampsia and acute ischemic stroke programs. Most importantly, for our shareholders, we're poised to deliver multiple clinical milestones between now and the end of 2027, all of which could provide significant validation of the value of DM199. We also weigh the risks and advantages of providing interim updates as clinically meaningful data emerges ahead of formal readouts.

We're particularly interested in completing the interim analysis for our stroke program. We've been working diligently on the ReMEDy2 stroke trial for a long time, battling through some significant challenges emanating from the COVID pandemic. With enrollment having surpassed 70%, we expect that the interim analysis will validate all of the hard work that has gone into the program.

I now turn the call over to Julie to provide additional detail on our preeclampsia and stroke programs.

Thank you, Rick. In the Phase II investigator-sponsored trial, enrollment is near completion in the extension cohort for the Part 1a dose escalation study in late-onset preeclampsia patients. Late onset patients are planned to deliver within 72 hours. This cohort will allow us to detect the dose or doses we plan to use for the upcoming cohorts of the IST. We expect to complete this cohort and provide a data update later this quarter. As you may recall, the interim results from this study demonstrated DM199's potential to reduce blood pressure and improve placental perfusion without crossing the placental barrier. While we only have data in a relatively small number of patients, the results we observed were highly consistent and encouraging.

We look forward to sharing the data from the extension cohort to further support the interim results. Additionally, learnings from Part 1a are guiding protocol amendments for the 2 remaining preeclampsia study groups. The first group referred to as Part 1b is an expansion study with up to 30 additional late-onset preeclampsia patients who will receive DM199 as a continuous IV infusion until delivery. In this cohort, we hope to learn more about the ability of doctors to use DM199 to effectively support blood pressure control management at this late stage of the disease. The second part referred to as Part 2 will study up to 30 early onset preeclampsia patients. Three doses will be evaluated to support dosing for a Phase III trial and an optimal dose level to extend the time mom is able to carry the baby, increasing the gestational age at the delivery.

As you've seen in our investor presentations, the medical complications for the baby are expected to decrease significantly the longer mom carries the baby. With the potential for DM199 to help manage blood pressure and improve blood flow to the placenta, we believe DM199 has a chance to be a transformative therapy for preeclampsia. Initiation of these 2 preeclampsia cohorts which will recruit concurrently, is expected to begin after the completion of the ongoing Part 1a extension cohort.

The IST also includes a study in women experiencing fetal growth restriction. In this group, we will be evaluating the effects of DM199 on fetal growth restriction in patients without preeclampsia. FGR is a condition with diminished fetal growth due to a poorly functioning placenta, the life support system of the unborn child. FGR is the leading cause of stillbirth and for infants that survive the FGR pregnancy, it is associated with enduring adverse health effects over the child's lifespan. In this cohort, we will evaluate the potential for DM199 to increase placental perfusion and improve fetal development.

Enrollment of the first patient for this study is expected in the current quarter. In parallel with the IST, we are advancing our global Phase II study in early onset preeclampsia. We intend to conduct this study in North America, both the United States and Canada and the United Kingdom. In March 2026, we received approval from Health Canada to initiate this study and study sites have been selected. We are working to initiate enrollment in Canada by the end of this year. We expect to file a clinical trial application in the U.K. in the current quarter. With respect to the status of the IND submission in the United States, as we discussed previously, the FDA requested an additional nonclinical 10-day modified embryo fetal development and pre- and postnatal development study in a rabbit model. Results of a non-GLP dose-ranging study in rabbit suggest that the animals developed an adverse immune response to DM199, preventing us from completing the requested modified pre- and postnatal development study in a rabbit model.

We have proposed to the FDA performing this study in a second rodent model and are awaiting their response. That said, I would highlight for everyone that we are moving forward in parallel with the study in Canada and are planning to add U.K. sites while we complete any additional preclinical work requested by the FDA. This study will evaluate 3 dose groups of DM199 in patients with early onset preeclampsia to further establish safety, pharmacokinetics and pharmacodynamics in a more ethnically diverse patient group prior to initiating a registration study.

Turning now to our stroke program. We are encouraged by the continued progress on the ReMEDy2 trial. Enrollment has now surpassed 70% of the target required for the interim analysis. Site activations and enrollments have recently commenced in Europe as well. In addition to the United States, Canada and the U.K., we've added 6 additional European countries and now have approximately 70 sites activated. In April, we sponsored an investigator meeting for our European study team that was well attended and had many productive sessions and discussions, which we believe are the key to getting the study teams excited about and focused on patient enrollment.

And we are reiterating our intention to complete the interim analysis by the end of 2026. As a reminder, in the Phase II ReMEDy1 stroke study, treatment with DM199 was associated with clinically meaningful improvements in functional outcomes for the patient group that most closely resembles the patients enrolling in our ReMEDy2 trial. In the subset of patients that did not undergo a thrombectomy, we observed a 15% absolute increase over placebo in the proportion of patients achieving favorable recovery as measured by a score of 0 or 1 on the modified Rankin Scale. Furthermore, ReMEDy2 is enrolling patients presenting with moderate stroke severity defined as an NIHSS score between 5 and 15. Looking at that subgroup in the ReMEDy1 study, there was a 19% absolute improvement over placebo in functional outcomes. There was also a 50% reduction in the number of patient deaths and a 13.3% reduction in recurrent strokes compared to placebo. These data inform the design and powering assumptions for the ongoing ReMEDy2 trial. I think you can understand why we are eagerly awaiting the results of the interim analysis.

Let me now turn the call back to Rick.

Thanks, Julie. I'd like to now ask Scott to review the financial results for the quarter.

Thank you, Rick, and good morning, everyone. We announced our first quarter 2026 financial results and filed our quarterly report on Form 10-Q yesterday after the markets closed. As of March 31, 2026, our cash, cash equivalents and short-term investments were $51.3 million, current liabilities were $5.7 million and working capital was $46.6 million compared to cash and investments of $59.9 million, current liabilities of $5.1 million and working capital of $55.5 million as of December 31, 2025. We anticipate that our current cash and investments will be sufficient to fund our planned clinical studies and operations through 2027. Net cash used in operating activities for the first quarter of '26 was $9.1 million compared to $7.1 million for the first quarter of 2025.

The increase in cash used in operating activities resulted primarily from the increased net loss for the current year period, partially offset by changes in operating assets and liabilities during the current year quarter.

Turning to the income statement. Our research and development expenses increased to $8 million for the 3 months ended March 31, 2026, up from $5.7 million for the same period in the prior year. The increase is due primarily to the increased costs resulting from the continuation of our ReMEDy2 clinical trial and its global expansion, the expansion of our clinical team and costs related to additional reproductive toxicity testing being performed in support of our PE program in the United States. These increases were partially offset by net cost reductions in manufacturing development activity related to work performed and completed in the prior year period.

We expect that our R&D expenses will moderately increase in future periods relative to recent prior periods as we continue our ReMEDy2 trial and continue to advance our DM199 clinical development program into PE. Our general and administrative expenses were $2.5 million for the 3 months ended March 31, 2026, and 2025. While small changes occurred within a number of expense categories, the differences were not material individually or in the aggregate and the overall net changes offset each other. We expect G&A expenses to remain relatively consistent in future periods as compared to recent prior periods.

With that, let me ask the operator to open the lines for questions.

Your first question is from the line of Josh Schimmer with Cantor.

The preeclampsia data updates that we'll get this quarter for the late onset cohort, what incremental observations should we be looking for beyond blood pressure control? Obviously, preeclampsia can affect urine output, kidney function, liver function platelets and biomarkers like sFlt. At what point will you have data to share on those parameters?

Yes. Thanks, Josh. So the expansion cohort that we're running is going to be 12 additional patients. We're almost completing that right now. It's going to be at the cohort 10 from the Part 1a. And so it's really just going to give us additional clarification here, particularly on blood pressure, dilation of the intrauterine arteries. At this point, we're really not expecting any changes in some of the biomarkers like sFlt because these patients really only got 2 doses. It's really we believe that having the drug on board for ideally a week, 2 weeks that we really would see some of those biomarkers improve.

Okay. Got it. So I think at one point, the lead investigators suggested that there was an improvement in edema at the very least maybe might be something that can improve within a short period of time. Is that something you're looking for?

Yes, that's something that if there is an improvement in endothelial health, and it is something that Dr. Cathy Cluver very clearly seen in some of these patients that the edema did resolve even within 12 to 24 hours of getting DM199, which is encouraging. It's a small number of patients, but we'll be looking to see maybe there's some additional insight there as well.

Just a couple of other quick questions, if I may. What are the steps to start initiating enrollment in the early onset preeclampsia study? Why is that not going to occur until later this year?

Yes. Julie, do you want to take that one?

Yes. Are you referring to the IST cohort? Or are you referring to the -- to our sponsored trial?

Sponsored trial.

Yes. We are in the midst of getting our dosing data from -- again, from the IST study before we select our final doses for that protocol as well as getting sites contracted up and running and our CRO selection process, all of that completed and then we'll be initiating. So it's a combination of factors, but we should be again in Canada later this year.

And then last sorry...

Sorry, if I can add. And so importantly, as we mentioned, so we have selected the 2 sites in Canada and one site in particular, is already in our stroke trial. So we're looking forward to leveraging the relationships, the existing contract that we have to basically doing what we can to expedite and get those sites activated as soon as we can.

Got it. And then last question, timelines for completing the second animal toxicology study and then ultimately reengaging with the FDA for IND.

Yes. So it will really depend on the feedback that we get from the FDA. And so it is a rat study that we proposed. And if they agree to that, that's a matter of a few months, probably 3 to 4 months to complete. And so again, while that's all happening, we'll be running the Phase II in Canada and then expanding to the U.K.

Your next question is from the line of Stacy Ku with TD Cowen.

So we have a couple of questions. So I guess, first, follow-ups. When could you expect to hear from the FDA on the mouse study? And is there a possibility the FDA could ask for another animal model? And how are you looking to prepare for all these different scenarios? It sounds like the rat study is pretty straightforward, but just help us understand how you view the next 2 necessary steps.

And again, just to clarify, it sounds like you are expecting a potential study initiation of the global Phase II by year-end. Just want to make sure you're reiterating that time line. And then we're looking forward to the updated preeclampsia results in Q2. But as we think about the early onset preeclampsia or fetal growth restriction subgroups of the IST, could we think about any potential for low-dose updates by year-end for either of these groups?

And then, Julie, just a clarification again, what is the timing of potentially starting the early onset preeclampsia IST?

And then last, just a reminder, what's the go and no-go decisions on the interim results for stroke? I can repeat some of these questions.

Okay. Great. So we'll try to take those. I'll start off here. Maybe Julie, you can help me out here. So in terms of the -- we did our submission to the FDA over a month ago. And so we're just waiting to hear the feedback. So as soon as we get clarity from the FDA, we'll provide an update. We have looked at alternative kind of backup plans in case they want something different. But we think we've got a very strong rationale for the proposed rat study. And I think it's encouraged that the Health Canada has already approved us to start the trial in Canada.

With the PE trial in terms of, yes, potential that we could get some data as soon as we have a cohort that's completed and we see some compelling data, we would look at potentially press releasing or getting that at a late-breaking conference.

And the last question that you had with regards to the outcomes of the interim analysis for the stroke program. First, we'll do a futility analysis. So if there's not a drug effect, we'll terminate. Otherwise, there'll be a resample size. And the resample size will be between 300 and 700 patients. And we believe if we see a drug effect comparable to what we see from our Phase II, which is comparable to the data we've seen with the data with the human urinary form in China, and there's about 1 million patients either being treated with that form. We would look at completing the enrollment in the following quarter.

Your next question is from the line of Thomas Flaten with Lake Street.

Rick, just following up on that last response, just to clarify, given that you've got 70-plus sites and 70% enrolled, if you -- when you said we're going to complete enrollment in the following quarter, do you mean the first quarter of '27 or the -- which quarter were you referring to on the full enrollment?

Yes. So assuming that we have the interim analysis at the end of this year, then we would anticipate completing the enrollment the following quarter, so the Q1 of next year.

And does that assume an upsize in the total population? Because it seems to me it's only May. And by year-end, when the interim analysis reads out, you should be pretty close to full enrollment on the original study size, right?

We will be. So that after patient 200 is dosed, there'll be a 30 -- sorry, a 90-day window here for the primary endpoint and then another approximately 4 weeks for the interim analysis to occur. And during that approximately 4 months, we'll be continuing to enroll. So we'll be getting closer to the 300 patient number during that period of time.

Got it. And then just to clarify a prior response. So once you get the Part 1a expansion data out this quarter, there's -- is it reasonable to assume that you would start Part 1b and Part 2 in the third quarter? Or should we expect maybe a fourth quarter start on that?

No, those should be starting here this summer. And so we're just -- we finalized the dosing that will be going into those cohorts. So we'll be doing 3 doses at 5, 10 and 15 micrograms per kg subcutaneous every 3 days until delivery. So those cohorts should be starting very soon. We had some -- we've now got our sites, Cape Town South Africa has had some challenges with some staffing and they've added some new staff. And so they've been very active recently in the Part 1a expansion study. So we feel very good that, that study will be enrolling soon.

Your next question is from the line of Jason (sic) [ Chase ] Knickerbocker with Craig-Hallum Capital Group.

One for Scott. I appreciate your comments on forward R&D, but maybe just a little bit more color there. You said kind of modest increase. I would imagine kind of enrollment is still picking up on an absolute number for stroke. And then can you just give us an idea kind of what the magnitude of that increase you expect sequentially in stroke and then kind of the incremental costs you expect for PE through the year.

Sure. Thanks, Chase. Yes, with respect to the stroke, modest increases. I mean the -- and you're correct, it's all going to be driven by the enrollment rates. And to some extent, it depends on whether those patients are enrolled in the U.S. or Europe. U.S. is probably the most expensive followed by U.K., Canada and Europe. And then with respect to the incremental cost for PE, there'll be -- well, we're still working on the estimates for the Phase II trial. The financial support we provide for the IST is very modest. It's an incredible bargain. So again, moderate -- modest to moderate increases, nothing order of magnitude change-wise.

Could you just define modest or moderate for us, if you don't mind? And then just one for Rick. Just as we think about the resample, should we kind of just expect to receive the number on the resample or anything else at that point that we'll be able to provide?

Sure. For the interim analysis, we'll be providing an update on the expected timelines to complete the enrollments.

Chase, it's hard to give a specific number because there's movement inside all the different expense categories. I mean I wouldn't expect it to go up more than 10% a quarter.

I will now hand today's call over to Rick Pauls for any closing remarks.

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

Thank you for joining. You may now disconnect your lines.

Good morning, ladies and gentlemen, and welcome to the DiaMedica Therapeutics Full Year 2025 Earnings Conference Call. An audio recording of this webcast will be available shortly after the call today on DiaMedica's website at www.diamedica.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 31, 2026, and may no longer be accurate at the time of any replay or transcript rereading. DiaMedica 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, DiaMedica'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 Krop, our Chief Medical Officer; and Scott Kellen, 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, DM199, 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 DM199 is so well suited to improve patient outcomes for preeclampsia, fetal growth restriction, acute ischemic stroke and other indications associated with vascular pathology. I'll now 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 II trial being conducted in South Africa. These results showed that DM199 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 DM199 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 DM199's potential to be a first-in-class disease-modifying therapy for preeclampsia.

Key findings from the interim analysis of Part 1a, specifically from Cohorts 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 DM199's potential to control maternal hypertension associated with preeclampsia. Second, DM199 significantly reduced the uterine artery pulsatility index, a Doppler-based measure of arterial resistance that suggests improved uteroplacental perfusion. Third and most importantly, DM199 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 DM199 does not pass to babies through breast milk, further reinforcing its confinement to the maternal circulation. This advantageous safety profile combined with DM199'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 burden. 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 uterine placental perfusion and restore endothelial function reinforces our belief in DM199'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 Cluver, 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 the 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 DM199 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 expected 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 DM199 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 II clinical trial of DM199 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 expected 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 DM199 with dosing anticipated to continue until delivery. We are assessing 3 dose levels to inform dose selection of the optimal regimen for Phase III.

Primary study endpoints include maternal pharmacokinetics and further confirmation that DM199 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 U.K.

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 suggests that rabbits may not be a suitable animal model for reproductive toxicology studies with DM199. 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 II trial in Canada and other potential jurisdictions.

Turning to our ReMEDy2 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 U.K. 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 4 in the U.K. 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 Basal Relaxation 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 DM199's ability to significantly reduce blood pressure in patients with elevated levels over a 3-month treatment period. DM199 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 DM199 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 31, 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 in 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 ReMEDy2 clinical trial and its global expansion, the expansion of our clinical team in both the prior and current year periods and increased noncash 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 2025, up from $7.6 million for the full year 2024. G&A expenses increased by $2.2 million due to a number of factors, including increased noncash 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.

[Operator Instructions]

Your first question comes from Stacy Ku with TD Cowen.

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 rabbit 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? Are there -- 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 -- continue 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? So just help us understand where you all are in potential timing there?

And then, of course, ahead of the U.S. 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 conversations 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 DM199 in treatment-resistant hypertension in CKD patients?

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 2 programs. And then maybe I'll hand it off to Julie.

Yes. Stacy, all very good questions. I think it's premature right now to tell -- to say exactly which species that we're going to focus on. We want to first be able to -- we submitted 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 I think we understand the PK better after running the initial studies. And one -- 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 was one element.

I think as far as site selection, we are highly focused on selecting sites that have both experience with preeclampsia studies as well as a practice that's well suited for early onset expectant management, which is something -- some sites are very adept at and other sites are more conservative about when to deliver patients. So again, it's that tight rope between treating -- between the mother's health and the baby's health and making sure that we select centers that are comfortable keeping the mother even though there's some 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.

Your next question comes from Josh Schimmer with Cantor.

Two quick ones. For the evaluation of DM199 in 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 II/III stroke program, what are the potential outcomes there? Are there stopping criteria either positive or negative or resizing criteria? Maybe you can share a little bit more about what you expect the interim to inform?

Sure. Thanks, Josh. So starting off with the early onset and crossing of the placenta. We don't think it will happen. I mean we've done now over 35-plus patients with more late onset preeclampsia where we didn't see this crossing. To cross the placental barrier is about -- the size to cross will be about 500 daltons, where our protein is about 26 kilodaltos, so 50x 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 it's just -- I think we're 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 II/III 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 sample size will range from 300 to 728. How we designed this trial, and we believe a base case that if we're seeing a drug effect that's comparable to our Phase II, 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 ranking score of 0 to 1 as the primary endpoint, we're anticipating that if we see, again, a drug effect comparable, we'll be looking at something ideally in the 300 to 350 range. If we need to go above 500 patients, we'll have to really evaluate the next steps for the program in light of the high prospects we think as well for the preeclampsia program.

Your next question comes from Thomas Flaten with Lake Street.

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

And then following on from that, if I understood the press release and your commentary correctly, are Parts 2 and 3 -- are 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?

Those -- so we've made a few protocol amendments that are going through shortly. And so we're anticipating later in Q2 that those 2 cohorts should initiate. Part 1a expansion study is ongoing and will be completed as well in Q2.

Got it. Understood. And then just a quick one on ReMEDy2. 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, 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?

Yes. 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 2025, it was still relatively slow, but it really has picked up substantially in the last month, last 2 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.

Your next question comes from Matthew Caufield with H.C. Wainwright.

For the ReMEDy2 trial, there had been some prior discussion of some challenges with stroke enrollment formally 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 DM199 could ultimately be approved for the AIS indication?

Yes. Good question. So I think there's a difference between the challenges that we had been seeing with enrolling at more of 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 will be a wonderful drug because of that safety profile.

Your next question comes from Chase Knickerbocker with Craig-Hallum.

I was just hoping to work one more in on the nonclinical side here. Can you just maybe walk us through kind of the differences in your prior nonclinical 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?

Yes, Julie, can you take that one?

Yes. 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 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 malformations or teratogenicity from the control group in either study. But I think the concern with the FDA is finding a NOAEL effect dose where they don't see any adverse effects and the maternal toxicity that we saw, which we believe is due to immunogenicity, which is not uncommon to see in rabbits and immune responses very quickly to human proteins. So I think really, it was in both studies, we weren't -- we had maternal toxicity.

So I don't think they were really that different other than gestational ages being different and the FDA wanting us to dose primarily after the first trimester after the 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 time lines as far as when you'd expect to get that feedback that you need to continue with the different species or just kind of color from FDA on what they would like to move forward. Do you have a meeting scheduled in Q2? Maybe just walk us through time lines there.

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

Understood. And then 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 breadth 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?

Yes. And it's a combination of, in particular, over the last few months, an increase in the enrollment rate per site and also for a greater number of sites. And then with being at 61 sites now and having sites 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 our guidance for this year.

That concludes our question-and-answer session. I would like to now turn the conference back over to Rick Pauls, DiaMedica's President and Chief Executive Officer, for closing remarks.

Well, thank you all for joining us today. We greatly appreciate your interest in DiaMedica 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.

Good morning, ladies and gentlemen, and welcome to the DiaMedica Therapeutics Q3, 2025 Earnings Conference Call. An audio recording of this webcast will be available shortly after the call today on DiaMedica's website at www.diamedica.com in the Investor Relations section.

After our speakers' remarks, there will be a question-and-answer session. [Operator Instructions] 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 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 and most recent quarterly report on Form 10-Q.

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, November 13, 2025, and may no longer be accurate at the time of any replay or transcript rereading. DiaMedica 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, DiaMedica's President and Chief Executive Officer. Mr. Pauls, you may begin.

Thank you all for joining us for our Q3 2025 earnings call. I am joined this morning by Dr. Julie Krop, our Chief Medical Officer; and Scott Kellen, our Chief Financial Officer. We've continued to make meaningful progress across both our clinical programs since Q2, and I'm pleased to share our recent developments and upcoming milestones with you today.

As most of you know, DM199 is our lead product candidate, is a recombinant form of the naturally occurring human tissue KLK1 protein. KLK1 enhances blood flow and vascular health by increasing levels of 3 key endothelium-derived vasodilating factors through activation of the bradykinin pathway.

These are nitric oxide, prostacyclin and endothelum-derived hyperpolarizing factor. We believe that this mechanism is why DM199 is well suited to improve patient outcomes for preeclampsia, fetal growth restriction and acute ischemic stroke, indications associated with vascular pathology.

Starting with the preeclampsia program. Meaningful progress has been made, since we announced the positive interim results in July from Part 1a of our investigator-sponsored Phase 2 trial being conducted in South Africa. We believe that these interim results validate the biological activity of DM199 and provide a strong basis for the expansion of this clinical study into the early onset preeclampsia and fetal growth restriction cohorts.

Additionally, this data, which includes the confirmation that DM199 did not cross the placental barrier places DM199 in an unique position with respect to safety and reduced risk in this very vulnerable patient population. We're grateful for Professor Cluver and her team as their work helped us tremendously as we prepare for our planned upcoming U.S. trial.

Just to briefly review the interim results Part 1a of the study was conducted in pregnant women with preeclampsia planned for delivery within 72 hours. We continue to believe that these interim results demonstrate that DM199 has the potential to be a first-in-class disease-modifying treatment option for preeclampsia.

We based our assessment on 3 key factors: First, blood-pressure data from cohorts 6 through 9 demonstrated clear dose-dependent and statistically significant reductions in both systolic and diastolic blood pressure.

Signaling DM199's potential to control maternal hypertension associated with preeclampsia. I would point out the importance of this, given the results of one of the more recent preeclampsia trials the PRESERVE-1 antithrombin study, in which approximately half of deliveries were initiated due to out-of-control hypertension. Suggesting that better control of blood pressure could have prolonged pregnancies in these patients.

2, improve placental perfusion. In Part 1a of our recent Phase 2 results, DM199 treatment produced a statistically significant reduction in the uterine artery pulsatility index, a doppler-based assessment of arterial resistance, suggesting improved uterine artery blood flow and enhanced placenta perfusion.

And 3, we believe that these improvements were driven by improving endothelial function believe to be an on-target mechanistic response to DM199 therapy. By improving or restoring endothelial function (sic) [ dysfunction ], DM199 has the potential to reverse vascular injury caused by preeclampsia.

Having the potential to control hypertension, improve endothelia dysfunction and improve placental perfusion, supports our belief in the potential for DM199 to be a first-in-class disease-modifying therapy for this life-threatening condition, which has no available treatment options.

During the third quarter, Professor Cluver advanced and completed Cohort 10 of Part 1a, which dose participants at 2.5 micrograms per kg IV and 15 micrograms per kg subcutaneously and further initiated dosing in the expansion cohorts of an up to 12 additional patients at the expected therapeutic dose level. We anticipate completion of this expansion cohort in the first half of 2026.

For Parts 1b and 2 protocol amendments are being implemented based on clinical learnings from Part 1a to refine the treatment regimen. Part 1b includes patients, who will be delivering within 72 hours. Part 2 will enroll women with early onset preeclampsia, who are cannabis for expected management or prolongation of pregnancy.

Part 3, the fetal growth restriction cohort includes participants with fetal growth restriction, but who do not have preeclampsia, we anticipate screening to start in the coming weeks. We're also preparing to conduct a Phase II preeclampsia trial in the U.S. We completed an in-person pre-IND meeting with the FDA, where we believe we've had a productive meeting, and we look forward to providing an update after receiving the final meeting minutes.

We anticipate the upcoming U.S. Phase 2 trial will be conducted in early onset preeclampsia patients. This treatment for this group is referred to as expected management, which is the preeclampsia patient population with the greatest unmet medical need.

Turning to our stroke program. Let me ask Julie to provide an update.

Thanks, Rick, and good morning, everyone. We continue to make steady progress in operationalizing our Phase 2b/3 ReMEDy2 stroke trial. As the trial has progressed, it's become clear that current enrollment rates are lower than what we initially projected based on historical enrollment data.

We believe this is primarily due to changes in stroke referral patterns driven by the adoption of technologies such as this AI and increases in the use of tele neurology. When patients present to smaller community hospitals and are not eligible for mechanical thrombectomy, they are currently more likely than in the past to remain at those hospitals rather than get transferred to the larger comprehensive stroke centers that typically serve as our research sites.

As a result, our participating centers are now seeing fewer of our target patient population than they did 5 or more years ago. The team continues to develop and implement strategies to offset these challenges and support our clinical sites. Based on this information, we recently updated our ReMEDy2 enrollment forecast using actual enrollment rates from our current clinical trial sites in lieu of the historical rates we originally used.

That said, there remains a lot of enthusiasm among the investigators, who are highly motivated to find additional treatment options for this high unmet medical need. We continue to make steady progress with enrollment. And as of today, are approaching 50% of our enrollment target for our interim futility analysis that includes a sample size reestimation. We now expect the interim analysis based on the first 200 patients to be completed in the second half of 2026.

As a reminder, after reviewing safety data from the first 50 participants in the study, the independent Data Safety Monitoring Board reported no safety concerns and unanimously recommended that enrollment continue without modification.

Thanks, Julie. I would like to now ask Scott to review the financial results for the quarter.

Thanks, Rick, and good morning, everyone. As of September 30, 2025, our cash, cash equivalents and short-term investments were $55.3 million, this compared to $30 million as of June 30, 2025, and $44.1 million as of our prior year-end.

Our current cash includes the net proceeds from our July private placement. We feel confident that our current cash position will fund our planned clinical studies and corporate operations into the second half of 2027. We used $21.3 million of net cash in operating activities for the 9 months ended September 30, 2025 compared to $15.6 million for the same period in 2024.

This increase is primarily a result of the increase in net loss in the first 9 months of 2025 compared to the prior year period, partially offset by changes in operating assets and liabilities during the current year period. Our R&D expenses were $6.4 million and $17.9 million for the 3- and 9-month periods ending September 30, 2025. This was an increase from $5 million and $12.6 million for the same time periods in the prior year.

Both increases were due primarily to cost increases resulting from the continued progress of the ReMEDy2 clinical trial including its global expansion, progress with the Phase 2 investigator-sponsored trial in preeclampsia and the expansion of our clinical team during the current and prior-year periods. These increases were partially offset by cost reductions related to manufacturing process development work performed and completed in the prior-year periods.

Our general and administrative expenses were $2.6 million and $7.3 million for the 3- and 9-month periods ending September 30, 2025. These expenses increased compared to the same time period in 2024, which were $1.9 million and $5.7 million, respectively. The increases in both periods resulted primarily from increased noncash share-based compensation and increased personnel costs incurred in conjunction with expanding our team.

Increases in investor relations, patents and professional fees also contributed to the increases in both periods. Overall, our net losses were $8.6 million and $24.0 million for the 3- and 9-month periods ending September 30, 2025. These are higher than the $6.3 million and $16.5 million reported during the same period in 2024. Now let me turn the call back over to Rick.

Thank you, Scott. We'd like to now open the call for questions. Operator, if you could please introduce the first analyst.

Your first question comes from Stacy Ku with TD Cowen.

Congrats on the progress. So first, as we go a little bigger picture, maybe as we await the minutes from the pre-IND FDA meeting, can you talk about the work that you are doing with the preeclampsia KOL community and clinical trialists to increase awareness of what you've seen so far with the DM199 proof of concept.

Specifically, when it comes to U.S. clinical development, maybe also talk about the key factors you're considering right now for trial sites. That's the first question. And then second, as it relates to the protocol amendments, maybe can you go into a little bit more detail what you are thinking maybe talk a little bit more about the doses and outcomes that you all are seeing so far. Just help us understand that piece.

Sure. Great, Stacy. So starting off with the KOLs. So we've been doing quite extensive reach out with the KOLs really across the U.S. and also basically globally for that matter. And the feedback that we've been getting has been very encouraging. There hasn't been a drug in development for preeclampsia for a number of years.

And I think, first off, the feedback we're getting is the fact that the drug is not crossing the placental barrier is just a very critical safety profile. And just to see that as very encouraging and immediate drops in blood pressure and the fact that we're seeing that very consistently amongst pretty much every patient.

And then I think the upside is also encouraging, but still early is the signals of dilation of the intrauterine arteries. And so if this can consist into later-stage studies, I think, this is a clear sign of being disease-modifying.

With regards to the protocol, changes that we're looking at. So first for the Part 1b, what we're looking at doing is IV only, in IV into delivery with the ability of the positions to adjust the dosing as needed. And it's almost to be able to dial in the blood pressure to where it needs to be ahead of delivery. And then for the Part 2, we're still working on some adjustments on that. Right now, we're looking at likely using Cohort 10 from the recently completed Part 1a of the study.

In part -- in Cohort 10, we see very consistent and very clear drops in blood pressure as we've seen from cohort 6 to 9.

The next question comes from Thomas Flaten with Lake Street Capital Markets.

Just a follow-up, Rick, on the Part 1b. You kind of wedged in this 12-patient expansion cohort from Part 1a, was that intended to kind of supplement what you had originally intended to do with Part 1b, where you were going to do basically a dose expansion cohort? I'm trying to understand the purpose about the 12-patient cohort given the changes you're contemplating for Part 1b?

Yes, that's exactly it. So this cohort expansion we've done is at Cohort 10, so that's the highest dose we've gone to. And so I'd call this kind of additional work that would really replace what was previously planned for the Part 1b. And then when the Part 1b now will be IV only.

Got it. And then as you ramp-up towards a Phase 2 study here in the U.S., what is the trigger? What data are you waiting for from Dr. Cluver before you actually initiate the study here in the U.S. Is there anything in particular you're waiting for?

No. We've been analyzing the data that we received up to date. We'll be continuing to dosing more patients before that study gets initiated and not just the efficacy and the safety data, but the PK data is also very important that we've been analyzing as well. So we feel we have the data that we need to proceed.

But of course, if we get any additional data along the way, that could further help us to refine the -- that protocol is needed. And right now, the plan is for the -- that Phase 2 would be up to approximately 30 participants for the U.S. study.

The next question comes from Chase Knickerbacher with Craig Hallum.

Maybe just first, Rick. Any more specifics you'd be willing to give on what you saw in Cohort 10 that kind of led to those additional 12 patients? And then that comment on potentially that being the dose we're going to take into Part 2, just any additional detail you'd be willing to give on what you've seen in the patients you've dosed in that cohort so far?

Yes. I mean, I think what we're seeing, Chase is just very clear and immediate drop in blood pressure. Some of these patients in Cohort 10 and even in those that are in the cohort 6 to 9, these patients are all resistant hypertension. They've been on maximum tolerable alpha beta blockers, calcium channel blockers and they're refractory. They're not seeing any improvement.

Some of these patients are coming in there on, they're on short-acting IV labetalol, and there's no change in blood pressure. And frankly, within minutes of getting DM199, blood pressure is coming down very, very rapidly. And so we're just really encouraged that pretty much every patient is seeing an immediate reduction in blood pressure. So it just gives us a lot of opening statement for this treatment.

And so you've seen an incremental dose response in that tenth cohort? And then just second, on stroke, if I can. I mean, can you just maybe walk us through Rick, kind of what your expectations for enrollment rate was and kind of where it sits today? And then if you could give us an update kind of where the site activation situation sits, including kind of OUS?

Yes. As Julie had mentioned in the prepared remarks, the historical stroke enrollment rates we were looking at around 0.25 that we had previously using, and we're seeing a little less than this. And so we wanted to provide an update here revising the guidance. We currently have a little over 35 sites activated. We've got a number that are coming on board. We recently had regulatory clearance in the U.K. We believe we've got Europe coming on board as well here soon.

And so I think it's important for us here now that in past instead of looking at historical rates, we're using specific rates that we're seeing at our current sites. So that gives us a little more comfort here in terms of the revised forecast today.

What is the enrollment rhetoric that you're assuming to get to the second half target at this point?

We're not providing that at this point in time, Chase.

The next question comes from Matthew Caufield with H.C. Wainwright.

Rick and team -- so as the progress is made towards the AIS interim analysis for reaching those target 200 patients, -- regarding the Modified Rankin Scale score, what would reflect the meaningful change there in your view at the time of the interim analysis?

Sure. So we had initially the powering and really following what we saw in Phase 2. So in our Phase 2 trial, in the patients not pretreated with mechanical thrombectomy, there was a 15% absolute improvement in the MRS score of 0 to 1. And we also had made an adjustment to the protocol, excluding those with severe, severity stroke patients when they come in.

And so when we exclude those patients, we saw a 19% -- but how the study is currently powered is that we see around that 15%, we'd be looking at 300 to 350 patients for the final sample size.

This concludes the question-and-answer session. I'll turn the call to Rick for closing remarks.

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

This concludes today's conference call. Thank you for joining. You may now disconnect.