Good morning ladies and gentlemen and welcome to the DiaMedica Therapeutics Third Quarter 2024 Conference Call. An audio recording of the webcast will be available shortly after the call today on DiaMedica's website at www.diamedica.com in the Investor Relations section. Before DiaMedica 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 appears 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 the third quarter 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 14, 2024 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, the phone lines will be open for questions. I would now like to introduce your host for today's call, Mr. Rick Pauls, DiaMedica's President and Chief Executive Officer. Mr. Pauls, you may begin.

Thank you, operator. Hello, everyone and welcome to our third quarter conference call. I'm joined this morning by Dr. Lorianne Masuoka, our Chief Medical Officer; and Scott Kellen, our Chief Financial Officer. We're making solid progress on both our stroke and preeclampsia programs and we expect 2025 to be a truly transformative year for our company and our shareholders. Although activating our top U.S. sites in our AIS study has taken longer than anticipated, I'm pleased to report that we now have 13 of our top 15 sites, either fully activated or with signed clinical trial agreements, negotiating this agreement stage is typically the most time-consuming part of the site activation process. We anticipate that these sites, especially our top 5 will enroll a disproportionately large number of patients. Houston Methodist, the first of our top 5 sites to be activated went live in September. Chattanooga, Tennessee and Oregon Health are 2 more of our anticipated top 5 priority sites. We have signed contracts with them and their site initiation visits have been scheduled. We anticipate all of our top 5 U.S. sites to be activated in recruiting by the end of the year. Canada will also add 5 to 7 sites that should rival the recruitment rates of our U.S. priority sites as well, with the first sites activated before year-end. Lorianne will discuss this in more detail but at the same time, we're bringing on these Tier 1 sites. We're implementing a protocol update designed to further accelerate enrollment and target high-quality patients with significant unmet medical needs. We've taken this sites feedback into account and made several small yet impactful changes. Most notably, we're now using a newly manufactured drug lot that allows for a refrigerated storage of our investigational product. Previously, the drug was frozen requiring an investigational pharmacist to dispense the drug and often these pharmacists only work on Mondays through Friday, from 9 to 5. With refrigerated vials, we believe sites will be able to enroll patients after hours and on weekends by storing the drug in the emergency departments. Our preeclampsia program is also making tremendous strides. We are pleased to have quickly secured regulatory approval from the South African Health Products Regulatory Authority and just yesterday, the first pregnant participant with preeclampsia was enrolled. We believe DM199 has the potential to be disease-modifying in preeclampsia and hope to demonstrate this in the Part 1a of the study which will be announced in the first half of 2025. We believe DM199 has both first and best-in-class potential for preeclampsia. And unfortunately, there are no currently approved therapies in the U.S. today. Now let me turn you over to Lorianne.

Thanks, Rick. Today, I would like to start off by covering the recent updates to the ReMEDy2 protocol and statistical analysis plan. I will be referencing slides displayed on your screen for our web-based listeners. These slides were also filed with the SEC in a Form 8-K last night. I joined DiaMedica in late January of this year and I couldn't be more excited about the opportunity. It quickly became clear that we needed to transform the medical organization and bring clinical site-facing activities back to DiaMedica because we were not getting acceptable results from our contract research organization. I am very pleased with our progress and we'll share more details about this momentarily. With that transition underway, the next area of attention that we brought to focus was the trial design and statistical analysis plan. If you reference Slide 2 of the presentation, we've implemented a series of updates and further clarifications to the ReMEDy2 protocol which we believe are very positive for our trial. These updates were submitted to the FDA at the end of August. And as we have received no comments as of yesterday, we are implementing the new protocol modifications. The 2 primary updates to discuss are the inclusion of patients who did not respond to thrombolytic therapy that is treatment with thrombolytics that is activator or tenecteplase and the increase of the interim analysis sample size from 144 to 200 participants which dramatically enhances the power of the Bayesian simulation used to forecast the total required sample size and therefore improves the precision of and confidence in the final sample size determination for the trial. I'll discuss each in detail but know that these changes will help us achieve the following outcomes. Number one, accelerate per site enrollment rates. In previewing these changes with…

Thank you, Lorianne. Our focus with respect to the ReMEDy2 trial remain centered on continuing to build momentum with high-quality research institutions. By way of update, as of today, we have the majority of our 15 priority study sites have been activated. 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 and thank you for joining us on today's call. Starting with our financial position, our September 30, 2024, combined cash, cash equivalents and investments balance is $50.2 million, down from $52.9 million as of December 31, 2023. Net cash used in operating activities for the 9 months ended September 30, 2024, was $15.6 million compared to $14.9 million in the same period of the prior year. The increase in cash used in operating activities resulted primarily from the combination of our increased net loss and the advance of deposit funds to vendors supporting the ReMEDy2 clinical trial during the current year period. These increases were partially offset by changes in operating assets and liabilities during the current year period and we believe that our current cash and investments provides us a runway to Q3 of 2026. Our research and development expenses increased to $5 million for the 3 months ended September 30, 2024, up from $3.3 million in the prior year period. R&D expenses increased to $12.6 million for the 9 months ended September 30, 2024, compared to $9.4 million for the 9 months ended September 30, 2023. These increases are due primarily to cost increases resulting from the continuation of our ReMEDy2 clinical trial, the expansion of our clinical team and increased manufacturing development activity. These increases were partially offset by cost reductions related to clinical trial work completed in 2023, including our Phase Ic and REDUX trials and the completion in 2023 of the in-use study work performed to address the prior clinical hold on the ReMEDy2 trial. We expect R&D expenses to increase moderately relative to recent prior periods, as we globally expand the ReMEDy2 trial site activations and participant enrollments continue. Our general and administrative expenses were $1.9 million for each of the 3 months ended September 30, 2024 and 2023. G&A expenses were $5.7 million for the 9 months ended September 30, 2024, down from $6 million for the 9 months ended September 30, 2023. The decrease for the 9-month comparison resulted from the combination of reductions in the cost of directors and officers liability insurance premiums and decreased legal fees incurred in connection with our lawsuit against PRA Netherlands. These decreases were partially offset by increased personnel costs incurred in conjunction with expanding our team and increased noncash share-based compensation costs. We expect G&A expenses to remain steady as compared to recent prior periods. Other income net was $616,000 and $1.7 million for the 3 and 9 months ended September 30, 2024, respectively, compared to $693,000 and $1.2 million for the 3- and 9-month periods ended September 30, 2023, respectively. The increase for the 9-month comparison was driven by increased interest income recognized during the current year period, related to higher marketable securities balances during the current year period as compared to the same period in the prior year. With that, let me ask the operator to open the lines for questions.

[Operator Instructions] Your first question comes from Thomas Flaten with Lake Street.

Lorianne, just sticking with ReMEDy2, what was the original prompt for re-evaluating the protocol and statistical analysis plan? Was it just to see higher enrollment rates? Or was there some other prompt to that entire discussion that led to these changes?

It was really a combination of wanting to simulate enrollment but also extensive discussions that we had with our SAB and our KOL experts that we've been working with. They really were very excited to see what would happen with the patients who had received thrombolytic therapy but were non-responders. We work with statistical experts who said that they thought that it would be important to have at least half of the patients enroll before doing a high-quality Bayesian sample size adjustment. So we made the adjustment there based on a lot of statistical input.

Got it. And then just, I guess, a somewhat technical question. At what point will patients now be randomized, particularly those that are tPA failures because you want to balance those patients across the 2 arms and you won't really know if there are failures if you randomize them prior to getting tPA. So could you walk us through kind of the nitty-gritty on that?

Yes. So if patients are randomized, they won't receive tPA. They'll be randomized into our study. If they receive tPA prior to randomizing into our study, then we'll have to wait 6 hours before we know if they're a non-responder and can come into our study.

Got it. And then 1 final one, if I may. In the original plan that you guys laid out, the 144 patients was intended to be the interim cohort for 364 patient study. And I know you just showed us an example of the simulation you did but that was, I think, 350 patients at 200 the interim analysis. So was the -- is the 364 still a viable number? Or how should we think about that? Because those seem to be at odds with one another?

Yes, Thomas. So based on 200 patients at the interim analysis and if we had the same drug effect as previous at 144, we would anticipate a lower total number of patients so below the 364.

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

So just to start off a little bit to make sure I understand it. So can you help me a bit more color around kind of the assumptions to get to a quicker final readout with these changes from, again, a higher patient number at the interim? I think you might have just answered part of it but it's just with kind of greater certainty around that effect you're seeing and that allows you to resample smaller? Or is it kind of around the increased enrollment rate that you would expect for allowing tPA non-responders?

Yes. So basically, the way the Bayesian analysis works is that the more patients that you have in the interim analysis, the more precision that you can make around the sample size assessment. So as an example, if we have a 14% excellent outcome rate which is what we originally had calculated when we have the 364 patients, we could potentially bring that down to 300 with an interim analysis of 200. And obviously, that would save us a lot of money and would save us a lot of time and enrollment. So basically, by going to 200, it gives us the opportunity to significantly shave off time of the trial and to be much more efficient in terms of how much money we spend on the trial.

Got it. And you may have answered this, I'm jumping around to a couple of calls, apologies. But was there anything that you kind of saw on enrollment rates or kind of overall patient care, baseline characteristics that kind of drove these changes? Or was it mainly just around the latter point that you just made.

Yes. It's not that what we saw in the actual ongoing study was really in consultation with our statistical experts that we made these changes as we were finalizing the report for the Bayesian analysis that's going along with the SAB for submission to the FDA. So it was really based on expert opinion.

And Chase, I can add. So part of the -- of our analysis we conducted with these tPA patients that did not respond from our Phase II trial. There was a very low placebo response rate. So 0, whereas with a 25% improvement with our drug and so if we carry that into our current trial, that should greatly help the statistical analysis plan. So if we have a large number of patients that have a very low placebo but a strong drug effect, it should be very beneficial for our statistical analysis plan.

What was the end [ph] on the tPA non-responders in your previous study? How many patients was there.

A total of 20 and then I'll also add, part of our analysis included a pretty deep analysis of the human urinary form use in China today. So there's been about half a dozen clinical studies showing an incremental effect of urinary KLK1 on top of tPA and that's also consistent with the discussions we've had with a number of different groups in China with people that are treating patients there today.

Got it. And just last one for me. Does this have a -- should we think of this as having a material impact to DM199's commercial opportunity? Kind of what does it kind of expand the -- would you expect -- I guess would you expect a potential label to also include those that wouldn't respond to tPA and what could that mean kind of for the overall patient opportunity?

Yes, we do. I mean we think it will be of greater interest as well for potential partners. So as we see about half of patients who get tPA do not respond and so if we're looking at about 10% of patients that have a stroke get tPA. So 80,000 patients and I mean if we were able to expand our label and having another 40,000 patients a year, I mean there's greater than $1 billion in additional revenue in the U.S. just for that expansion alone.

Your next question comes from Francois Brisebois with Oppenheimer.

This is Dan [ph] on for Franc. Just a quick one with regards to time line here previously with the interim enrollment of 144 you had targeted for first quarter '25. Now with the 200, any guidance in terms of when we should be expecting the enrollment to complete?

Yes. So with the intended plan to have the interim analysis in Q4, we would be looking at some time next summer.

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

So for preeclampsia, there was mention of the frozen versus refrigerated vials. With the dosing now commenced, will there be any patients that would have received one versus the other? And are there any complicating factors to consider there?

So initially, the patients will receive the frozen product but it's really not an issue with this particular site. Primarily, they're going to be using the refrigerated products.

Understood. And obviously, there's no anticipation of any distinction between one versus the other?

No, they're absolutely identical.

Okay. Got it. And then also for ReMEDy2, there was mention of the no FDA comments received to date and obviously proceeding. Do you feel there's any risk the agency provides subsequent feedback at this point, necessitating trial modification once the changes are up and running.

Yes. So traditionally, the FDA responds within 30 days after submission of any protocol amendment or supplemental information. We're well past the 30-day mark. So the chances of additional FDA feedback becomes less and less over time. So right now, I would say our chances of receiving substantive FDA feedback is relatively low.

Great. I guess no answer is a good answer in that case. So I appreciate it.

That's right.

From the FDA that is?

That's right.

There are no further questions at this time. I will now turn the call back to Mr. Rick Pauls.

Great. So we'd like to thank everyone for joining us this morning and for your continued support. We look forward to a very exciting 2025 and to our next update. This concludes our call today. Thank you.

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