DiaMedica Therapeutics Inc. Price & Performance (DMAC)

Following the prepared remarks, the phone lines will be open for questions. I would now like to turn you over to your host for today's call, Mr. Rick Pauls, DiaMedica's president, and chief executive ops officer. Mister Pauls?

Thank you, operator. Hello, everyone, and welcome to our full year twenty twenty four conference call. I'm joined this morning by Scott Kellen, our Chief Financial Officer and Doctor. Lorienne, Masuoka. Our Chief Medical Officer. We're happy to be here today to update you on the progress of our two main clinical development programs. Seeing that our next expected clinical milestone is for our preeclampsia study, I'll ask Lorianne to start with an update on our preeclampsia program then we'll turn to our stroke study.

Thanks Rick. Starting with preeclampsia, we are very pleased with our progress in this clinical program. Less than a year ago, our collaborators submitted the first draft of the protocol to the Tiger Berg Hospital's Ethics Board. Since then, we have obtained ethics approval, clearance from the South African Health Products Regulatory Authority, South Africa's equivalent of the US FDA, and have begun dosing preeclastic mothers. This marks the first study of DM199 in a pregnancy related condition, a vulnerable setting where both the mother and fetus are considered patients. We believe these significant accomplishments within a short timeframe underscore DM199's potential as a treatment for this serious condition. All of this was made possible by the strong collaborations we've built with leading KOLs and trialists. Our partners at the University of Melbourne and Stellenbosch University were immediately drawn to DM199 for its promising safety profile, its ability to produce nitric oxide, and its potential to lower blood pressure. Most notably, DM199 is a protein of a sufficiently large molecular size that it is not expected to cross the placental barrier. Offering a key safety advantage for the developing fetus. In contrast, small molecule antihypertensives passively diffuse across the placental barrier and some are contraindicated in pregnancy because they cause fetal harm.

We have repeatedly demonstrated that DM199 can lower blood pressure in humans and believe that this supports the hypothesis that DM199 can lower blood pressure in pregnant women. Compared to other therapeutic areas like oncology, which have advanced more in recent years, the treatment of pregnancy complications remains outdated. No FDA approved treatments exist for preeclampsia. Despite the growing burden of this disease. To our knowledge, DM199 is the only novel agent currently being in pregnant women with preeclampsia. Existing blood pressure medications used in preeclampsia do not enhance nitric oxide signaling. Which is critically impaired, leading to reduced blood flow to the fetus. Nor do they improve preeclamptic endothelial dysfunction, They merely manage symptoms. Preeclampsia is a progressive disease, and these outdated treatments lose effect effectiveness or fail over time. By augmenting nitric oxide signaling, we hope that DM199 can not only lower blood pressure but also improve underlying endothelial dysfunction offering benefits such as increased blood flow to the fetus. And reduction of dangerously high blood pressure in the mother going beyond symptom management. For context on the limitations of existing hypertension treatments, the PRESERVE-one study of early onset preeclampsia in The United States found that approximately fifty percent of women delivered within five to six days of study enrollment due to refractory or uncontrolled hypertension despite receiving maximal intervention.

On average, participants delivered before thirty weeks of gestation, exposing the baby to significant risks. This highlights the aggressive and progressive nature of preeclampsia and underscores the urgent need for therapies that can successfully manage symptoms and ultimately go beyond this to target the underlying endothelial dysfunction. At these early gestational ages, every additional day of prolonging pregnancy is crucial. Turning now to our investigator sponsored phase two trial, we are currently dosing women in Part 1a the dose escalation portion of the study. Each dose cohort consists of three patients, If no safety concerns arise, we proceed to the next cohort at a higher dose. Part 1a may include up to 10 cohorts with the lowest IV dose starting at zero point one microgram per kilogram and the highest at two point five microgram per kilogram. For reference, our IV dose in the stroke program is zero point five micrograms per kilogram. Once a dose is identified in Part 1a, that achieves clinically meaningful blood pressure reductions without causing hypotension, we will advance to Part 1B and expansion cohort of 30 additional patients designed to confirm the optimal dose. We are pleased to report that multiple dosing cohorts in Part 1a have been completed.

With DM199 appearing to be well tolerated and no serious adverse events or signs of pathological hypotension being reported. We look forward to sharing results from Part 1a, which we anticipate in the second quarter. Turning to our stroke program, We are pleased to announce that we have activated 30 clinical sites which we describe as our critical mass to generate a more steady stream of enrollments. Increasing overall activity levels in communications between sites is important in creating that healthy, professional competition to keep our study front of mind amongst our study sites. I would note that the bulk of these sites are operating under our latest protocol version five point zero. This version of the protocol, among other things, allows DM199 to be stored at refrigerated temperature and expands the eligible population include patients not responding to thrombolytic treatment. Refrigerated storage enables the study drug to be sent with the participant when they leave the hospital, potentially the logistics of the participant receiving their subcutaneous injections for the entire three week treatment period. And for patients who haven't improved for at least six hours after thrombolytic treatment, providing the remaining enrollment criteria are met, they may be enrolled in our trial.

This change, in addition to increasing the number of potential patients for REMEDY two brings in a patient population, that can be a good group for evaluation in our trial. In our initial stroke trial, REMEDY one post hoc analysis of similar participants showed the most favorable improvement in the rate of full or nearly full recovery. The protocol also allows for enrollment of patients with occlusions of the M2 segment of the middle cerebral artery and the posterior arteries. This is a very significant change given the recent negative results of three mechanical thrombectomy of middle sized vessel occlusion studies announced at the IST Conference last month, I can share with you that sites are very positive about version five of the protocol. Building on this, our clinical and medical affairs teams continue to work on ensuring that once activated, study sites feel comfortable and well supported to enroll participants. In particular, they need to be comfortable that any participant they enroll will be able to receive treatment through the three week dosing period as the participant moved from the hospital to any intermediate care facility and ultimately home. Developing this comfort level requires a great deal of personal contact between our clinical team and the study sites.

By the end of last year, we had a wide variety of resources available to provide any assistance the site might require and open lines of communication to ensure that the sites are aware of such options. Complementing these efforts, our medical affairs team has been investing time meeting in person with study teams to discuss the potential benefits of DM199 and the importance of the remedy two trial. This is done in a lunch and learn format to maximize the number of site personnel that can hear and engage with us on the trial. The team has also been coordinating peer to peer calls between study coordinators so that these professionals can share directly with each other thoughts and ideas on the things that work and don't work in managing participants through the study. Members of senior management have also been visiting the site's projected to be high enrollers. As we look back on the progress we've made to we note that even with highly interested physician investigators, it has been and is taking significantly more time to get sites through the engagement, planning, and setup process. We believe this is related to lower staffing levels in research units in this post COVID world.

In hindsight, our expectation that restoring support for research at study sites would have been a higher priority. But in the end, we underestimated the required startup time. As I described, we've increased our level of engagement to overcome these issues. And though we're very encouraged by the uptick in enrollments in 2025, we've updated our expectations for the interim analysis to the first half of twenty twenty six. We'll provide a further update after we hit enrollment of 25%. In other ReMEDy II related developments, we've had a great experience the February twenty twenty five International Stroke Conference. This was held in Los Angeles and our booth received considerable attention and we hosted a reception for our current and potential study sites. Which was very well attended. At this conference, results from three studies of mechanical and medium vessel occlusions were announced. None of the studies reported success. These results have the potential to benefit REMEDY two in that these patients are candidates for our trial. The European Stroke Conference is coming up in May, we look forward to another opportunity to build awareness of DM199 and our REMEDY two trial. And as we announced yesterday, the scheduled safety review of the new IV dosing rates implemented upon resumption of our trial was completed in January.

Our independent data safety monitoring board conducted a comprehensive review as safety data from all then enrolled participants and no significant safety concerns were identified. Their conclusion was that the REMEDY two trial should continue without modification. Also in February, a paper providing an analysis of the mechanism of action of DM199 and its potential benefit for AIS patients appeared in a peer reviewed publication entitled recombinant human tissue countercrime one for treating acute ischemic stroke and preventing recurrence. This publication is now available online and was published in the February 2025 issue of Stroke, This paper provides scientific insight into DM199's mechanism for increasing collateral circulation and salvaging brain tissue at risk from infarction following an AIS. I'll now turn the call back to Rick. Thanks, Lorienne. I want to take a minute to thank Mr. Dan O'Connor for recently joining our Board. He's a tremendously accomplished leader in biotech and in particular in building companies. We're grateful to have his wisdom and guidance, as we move DiaMedica and DM199 forward and we'll take every opportunity to learn from his past successes. Before I turn the call over to Scott, I'd like to add that our team really believes DM199 will be an effective treatment for both stroke and preeclampsia patients.

I would also like to recognize our team's hard work and accomplishments over the past year, and I look forward to continuing working with the team as we advance our clinical programs. Know that we are fully committed to moving both clinical programs forward as we have an important opportunity to provide options for patients who currently have no therapeutic treatment options today. Now, I'd like to hand the call over to Scott Kellen to review this quarter's financial results. Thanks, Rick, and good morning, everyone.

As the operator mentioned, we announced our full year 2024 financial results and filed our annual report on Form 10 ks yesterday, These documents are both available on either the DiaMedica or the SEC websites. As of 12/31/2024, we reported a total combined cash and investments of $44,100,000 current liabilities of $5,400,000 working capital of $39.2 This compares to a total combined cash and investments of $52900000.02800000.0 dollars in current liabilities and $50,900,000 in working capital, as of the December. The decreases in combined cash and investments and in working capital were due primarily to the cash used to fund our operations partially offset by net proceeds received from the approximately $12,000,000 private placement we completed in June of twenty twenty four. Net cash used in operating activities for the full year 'twenty four was 22,100,000.0 compared to 18,700,000.0 for the full year '23. The increase in cash used in operating activities was driven by the combination of our increased net loss and the advance of deposit funds to vendors supporting our REMEDY two trial during 2024. These were partially offset by changes in operating assets and liabilities during 2024 particularly the increase in accrued liabilities related to our REMEDY two trial and ongoing manufacturing development activities as of 12/31/2024.

We anticipate that our current cash and investments provide us a runway into Q3 of twenty twenty six. Turning to the income statement. Our research and development expenses increased to 19,100,000.0 for the year ended 12/31/2024. Up from $13,100,000 in the prior year. This increase resulted primarily from cost increases driven by the continuation of the REMEDY two clinical trial, the expansion of the clinical team, and increased manufacturing and development activity. Partially offsetting these increases were cost reductions, related to the completion of prior clinical and non clinical trial work in 2023. We expect that R and D expenses will increase moderately relative to recent prior periods as the company expands REMEDY two globally and continues our site activation enrollment activities and as we continue to pursue our DM199 clinical development program into preeclampsia. Our general and administrative expenses were 7,600,000.0 for the full year of 2024, down from $8,200,000 for the full year 2023. This decrease was driven primarily by the combination of decreased legal fees incurred in connection with our lawsuit against PRA Netherlands and reductions in directors and officers liability insurance premiums. These decreases were partially offset by increased personnel costs associated with expanding our team and increased non cash share based compensation costs.

DiaMedica expects G and A expenses to remain steady compared to prior periods. Our net other income for the full year of 2024 was $2,300,000 compared to $1,900,000 for 2023. This increase was driven by our higher level of interest income being recognized related to higher average marketable security balances during 2024 as compared to the prior year. With that, let me ask the operator to open the lines for questions.

Thank you so much. Ladies and gentlemen, we'll now begin the question and answer session. You will hear a prompt that your hand has been raised. Should you wish to remove yourself from the question and answer session, please press star followed by two. If you're using a speakerphone, please lift the handset before pressing any keys. Just a moment for your first question. And your first question comes from Thomas Flaten with Lake Street. Please go ahead.

Good morning. I appreciate you taking the questions. Lorienne, a couple for you on REMEDY two. Of the 30 sites that are activated, how many of those are the 15 top sites that you've previously identified And how many of the 30 are actively enrolling versus being activated?

So of the 30 active, or sorry, of the 30 sites that we've identified and activated, the top 15 comprise about 13 or so. So the vast majority of the top 15 are activated and many of them are currently enrolling.

Got it. And then with respect to the DSMB review that you said I believe you said took was completed in January, how much data did they have on those patients? Was it just from the very acute phase or did they have a full treatment period? To review for safety?

So they had the entire database which means that all of the data that had been entered for those patients were available to the DSMB. What we do is we establish a cutoff date and then after that cutoff date, look at all of the data for that patient. So it's their entire experience that they have gone through up until that cutoff date.

Understood. Excellent. Thank you for taking the questions. I'll get back in the queue.

Thank you. Your next question comes from Chase Knickerbocker with Craig Hallum. Please go ahead.

Good morning. Thanks for taking the questions. Sorry if I make you repeat some details here, but maybe just help us out with a couple of the assumptions to kind of get us to a first half twenty six interim assessment Just maybe relative to kind of the last updates we received, what are your expectations around enrollment rates? And as we look at these 30 centers, I mean, is kind of your ultimate expectation for trial sites activated? Thanks.

Start there. [indiscernible] Go ahead, Loraine.

So we have 30 new sites that are currently active in The United States, but please remember that we are going to also that we also have five centers that are very active in Georgia. We are going to be opening sites in Canada in the next few weeks and we're also going to be moving into Australia and into Europe. So we'll have more than 30 sites. What we anticipate from the interim analysis is the opportunity. The reason why we increased our sample size from 144 to 200 was the opportunity to decrease the sample size that is needed overall. [indiscernible] were looking at a 14% improvement over placebo and with a three sixty four patient population. With the 200 interim analysis, we have the possibility if we see that same efficacy rate of having only three hundred patients We anticipate that the interim analysis, although delayed as compared to the original interim analysis in large part due to increasing the sample size for the interim analysis could overall save us time and money by reducing the sample size.

On the overall number of sites, how how how high do you expect to to go at this point? And then on the kind of enrollment rate, can you just kind of help us on how we should think about it with kind of existing sites and your experience ramping these up now as far as what gets us to that first half twenty twenty six interim?

Yeah, so we're anticipating doubling the number of sites that we are going to be having enrolling. And we currently are targeting sites that can enroll about one to two patients per month.

And of the sites that we've enrolled so far, you know, kinda what number of those are kind of at that kind of rate of one to two per month at this point? And kind of is there an idea of kind of how long it takes at this point to kind of get them to that rate?

It generally takes about six to twelve months to get a site up and running. And once they're up and running, it takes several weeks for them to start activating and enrolling, they need to get everything ready for enrollment into the trial. We're not at the moment disclosing how many of those sites are enrolling, how many patients. We'll give you a fuller picture when we hit twenty five percent enrollment.

Great. Thank you.

Thank you so much. Your next question comes from Francois Brisebois with Oppenheimer. Please go ahead.

Hi. This is Dan on for Frank. Thanks for taking our questions. Since the amendments that were disclosed last time particularly with regard to the tPA non responders, are you starting to see an improvement in the enrollment rate in this particular subpopulation among the activated sites.

Yeah, and I have one follow-up.

Sure, Dan. Yeah, so the beginning of the year we have seen a very encouraging increase in terms of enrollment. It's still not kind of where we want to be at. But definitely a significant increase that has been driven in part with this protocol amendment where we are including patients that receive tPA that do not respond M2 patients. And so keep in mind that for the protocol Version five most of the activation of those that protocol occurred at the end of twenty twenty four and then coming into early into the new year. Thank you. And in regard to the recent ISD conference that you highlighted, could you give us some more color on like the KOLs feedback on DM199 in light of the other studies that were reported there at the conference?

Sure. Mean, as Lorien mentioned in the prepared remarks is that the big takeaway was that there was a lot of excitement before the conference on mechanical thrombectomy for these mevo study patients. So these are medium vessels typically the M2s And most of the physicians had thought that those studies would be very positive. And would have potentially had a negative impact in terms of our trial and our patient population. The fact that three of those studies failed, one of them actually showed some safety concerns was very encouraging for our sites, our Scientific Advisory Board. Beyond that there really wasn't anything exciting at the conference. And so that was really the big takeaway. And so because of this, think there were a number of other trials that now we've heard have are not moving ahead the mechanical thrombectomy from miVo. So from a academic research perspective I think that's going to be very positive for additional capacity for sites to be able to enroll a trial like ours. Both those sites that are currently activated and those sites that are coming on board for our trial.

Great. Thanks for taking our questions.

Thank you so much. Your next question comes from Matthew Caulfield with H. W. Wainwright. Please go ahead.

Hi. Good morning, guys. Thanks for the updates. For the preliminary top line in preeclampsia expected in the second quarter, is there a meaningful threshold for impacting maternal blood that would offer the best read through or de risking for heading Yeah, what we're looking for what we're looking for is about [indiscernible] What we're looking for is about a ten to twenty drop in systolic pressure. We wanna get systolic pressure down to about 140. So that they're safely in a good range.

And we are also anticipating that on the safety side there won't be any evidence that DM199 passes the placental barrier. And we're also looking at dilation of the intrauterine arteries using Doppler measurements. To measure something called pulsativity index, which assesses resistance to blood flow in the uterine arteries. We're looking for a lower positivity index, suggests that there's lower resistance and better placental perfusion. Those are the three things that we're going to be looking at. Primarily in the phase 1a trial. And if we see positive signals in those three areas, then that's a huge signal for us to move forward.

Great, very helpful. I appreciate that. And then just one final question from us. For REMEDY two, with the inclusion of the thrombolytic non responders, has the amended statistical analysis plan been finalized with the FDA at this stage?

Thanks again. Yes, it has. Okay, great.

Thank you, guys.

Thank you so much. There are no further questions at this time. I would like to hand the call back over to Rick Pauls for closing remarks.

Thank you, Marissa.

We'd like to thank everyone for joining us this morning and for your continued support. We We are particularly excited about the momentum that we're building in both our stroke and pre cramps programs as we advance DM199 a potentially transformative therapy for patients who do not have a treatment option today. The dedication of our team combined with your support position us strongly a very meaningful progress in 2025. We look forward to sharing updates with you soon. Thank you again. With us, this concludes our call.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.