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spk01: Good morning, ladies and gentlemen, and welcome to the Diomedica Therapeutics for Quarter 2021 conference call. An audio recording of the webcast will be available shortly after the call today on Diomedica's website at www.diomedica.com in the Investor Relations section. Before the company proceeds with its remarks, please note that the company will be making forward-looking statements on today's call. These statements are subject to risk 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 Questionary Statement Note Regarding Forward-Looking Statements in the Company's Press Release Issued Yesterday and under the heading Risk Factors in DIAB-Medica's Most Recent Annual Report on Form 10-K. The AMEDICA'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 15, 2022, and may no longer be accurate at the time of any replay or transcript rereading. The AMEDICA 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, the America's President and Chief Executive Officer. Mr. Pauls, you may begin.
spk04: Thank you, Julie. Good morning, everyone, and welcome to our year-end 2021 business update and earnings call. Yesterday, after the market closed, we issued a press release summarizing our fourth quarter 2021 financial results and providing a general update. At the time, we also filed our quarterly report on Form 10-Q. Both documents can be found in the Investor Relations section of our website at DiMedica.com. I'm joined this morning by our Chief Financial Officer, Scott Kellan, our Chief Medical Officer, Kirsten Gross, our Chief Commercial Officer, Dominic Condari, and our Senior VP of Clinical Operations, Harry Elkhorn. I'd like to begin today with introducing you to our two newest members of our executive team. Kirsten is a board-certified neurologist, experienced in both clinical medicine and drug development. She practiced and taught at the University of Michigan and the State University of New York in Syracuse. She began her work in drug development with Pfizer and has experience working with large and smaller organizations, including heading one of the neurological divisions at Roche, and brings direct experience moving multiple compounds through the clinical and regulatory process in both the US and Europe. Dominic Condari has over 30 years of commercial experience with Genentech, including managing the growth of the Activase or TPA franchise as it became the first approved therapeutic for treating acute ischemic stroke. Dom also provided the commercial leadership for Lucentis, the blockbuster macular degeneration treatment. We're extremely grateful to have both of these individuals join our team, and we thought that you may want to hear from them, from these two, and get their perspective on what attracted them to joining our team. So let's start with Dr. Gross.
spk03: Thanks, Rick. So there were three main factors that attracted me to the company. First, the repeat findings from numerous randomized controlled trials described in the peer-reviewed medical literature from Asia consistently demonstrating clinical improvement in acute ischemic stroke patients receiving the human urinary derived form of KLK1. Second, the mechanism of action of KLK1 to selectively vasodilate arteries, and this may improve collateral blood flow to the area of the brain with ischemia, resulting in improved recovery from stroke. In addition, this improved collateral blood flow may also reduce the potential for stroke recurrence from a reocclusion of a blood vessel. Third, that the company took the time to match the PK profile of DM-199, the recombinant form of KLK1, to the urinary form of KLK1 that has previously demonstrated in repeat trials clinical improvement. This would optimize the dosing regimen of DM-199 in stroke clinical trials. So taken together, these three factors are what drew me to the company as they increased the probability of success of a clinical trial of recombinant DM-199 in acute ischemic stroke.
spk04: All right. Thank you, Kirsten. We're very excited to have you join our team. Now let's hear from Dominic.
spk06: Yeah, thanks, Rick. When I researched Diametica and DM-199, my first impression was that DM-199 is not incremental. It's not an incremental therapeutic modality, but a treatment that can significantly advance stroke care for a large number of ischemic stroke patients. Over the past couple of decades, my focus in acute ischemic stroke has been working with hospital neurologists on the front end with a zero to 4.5 hour treatment window for TPA. Unfortunately, only about a third of the acute ischemic stroke patients get to the hospital within this narrow treatment window. And of those, only about half are eligible for TPA. So the net result is that only about 8% of all admitted stroke patients get TPA. Typically, a stroke patient will have a hospital stay of five or six days with physician monitoring and perhaps an additional look at CT or MRI and maybe an anticoagulant or an antiplatelet is added to the treatment regimen. Now, looking ahead, based on Phase 2 data, DM-199 can potentially reduce disability and reduce the likelihood of recurrent stroke. And with an expanded treatment window from 0 to 24 hours annually, over 500,000 acute ischemic stroke patients can fall within this treatment window. there is a significant opportunity to advance stroke care for a large number of patients during the recovery phase of stroke. I might add that the mode of action for DM-199 is well explained and understood. Secondly, there are, you know, numerous clinical trials with human-sourced KLK1 demonstrating safety and improved stroke recovery in terms of reducing disability and reducing stroke recurrences. I might add that a recombinant form of DM-199 will assure purity of the product and abundant supply. And last, I believe that DM-199 will be well received by the neurology customer base. Thanks, Rick.
spk04: Thank you, Don. We're equally excited to have you joining our team. And ultimately, we feel the real winners here are going to be the patients. So now I'd like to provide an update on our lead program, our Phase 2-3 Remedy 2 trial of DM-109 in the treatment of acute ischemic stroke, referred to as AIS. The design of the Remedy 2 has some interesting and unique aspects. The trial is randomized, placebo-controlled, a study that will enroll approximately 350 patients at clinical sites in the U.S. What is unique about the design is that we're planning to assess two separate independent primary endpoints with the same study population. These endpoints include an evaluation of stroke recoveries, can the patient return to normal physical function, so things like being able to eat, bathe, drive on their own, and the rate of recurrence of acute ischemic stroke in the three months following the initial stroke. Each of these endpoints is clinically meaningful and could greatly benefit stroke patients as well as their families and caregivers. This also gives us two opportunities to achieve an approval outcome with the FDA. The adaptive design of the study is a second unique feature. For the study, adaptive refers to the interim analysis we are planning after approximately 40% or 140 patients have completed enrollment. The Data Safety Monitoring Board, the DSMB, for the study will review the results from these patients to evaluate the effects of DM-19 is having on stroke recoveries and the rate of recurrence. Based upon this evaluation, the DSMB will take action from stopping the study for futility or overwhelming efficacy, to continue the study as planned, or increasing the number of study participants. The benefit here is having the ability to increase the sample size. If the actual benefit is looking like it's coming in below the planned benefit level, having the opportunity to increase the number of patients gives us the opportunity to ensure that we achieve statistically significant outcomes. and have a successful clinical trial. Utilizing the adaptive trial design allows us to better manage the clinical risk, increase our chances for completing a successful trial. Note that we will be blinded to the results of this analysis and only know if and how the DSMB recommends that we move forward. Let me also briefly highlight that DM-109 received FDA fast track designation for the treatment of AIS last year. This is an important milestone and underscores the significant unmet medical need that exists among patients suffering from AIS where there hasn't been a new or meaningful therapeutic advancement in over 25 years. The FAST-TRACK designation provides us with the opportunity for more frequent interactions with the FDA and may eventually qualify DMA-9 for accelerated and priority review. As an update on sites, we have 10 sites now under contract and adding the sites currently in startup phase, we have engaged with over 70% of our targeted numbers of sites for the trial. Startup sites represent sites that have been vetted, interested in participating, and are proceeding towards activation to be able to enroll patients. Unfortunately, we can't control COVID, but our clinical team continues to work with members of our scientific advisory board and other physicians in our network to reach out directly to the neurologists at key study sites to support making remedy to a priority study for their institutions. Well, it's unfortunate that the startup process has been a little slow up to this point. We are encouraged by the fact that our issues have been COVID-related and not related to concerns about DM-19 or the study design. At the current rate of COVID, infections and hospitalizations have rapidly been declining. We're optimistic that hospitals will be able to restore their research staffing. We're also in the process of evaluating additional steps to potentially support site contracting and patient recruitment. We believe that we are well-positioned to then engage them and advance this clinical trial. In terms of our expected timing, as we've discussed, the ultimate timing for the completion of our interim analysis and the study itself will be driven by the rate at which our study sites are able to enroll patients. Our current plans are based upon a fairly conservative projected enrollment rate. We are more optimistic after the recent quick declines of COVID cases, as I mentioned. We believe that the combination of our longer treatment window of 24 hours from stroke onset combined with our safety profile and the potential to improve both stroke recovery and reduce the risk of stroke recurrence may drive a better enrollment rate. We will keep you updated as we get more clarity on both the site activation and enrollment rates as we hit milestones. I would like to also reiterate that the Remedy 2 is our primary focus right now, as we believe it has the fastest path to commercial approval. Turning to our REDUX, our Phase II CKD program, we recently completed enrollment and are working through the final patient follow-ups and cleaning the study data to prepare for the final analysis and reporting. As most of you know, REDUX is a basket or a signaling study in which we are evaluating three different causes of chronic kidney disease and two different dose levels of DMY-9 over approximately a three-month treatment period. Currently, the key takeaway from REDUX is that the CKD represents an attractive development opportunity for DM-19. We believe that the study is directing us towards targeting subgroup of hypertensive African-Americans and or IgE nephropathy patients who have moderate to severe kidney disease. Patients who are both improving kidney function and controlling blood pressure could greatly improve their quality of life. We look forward to updating you on the next steps after we complete the final analysis of the Redux data and in terms of the next steps and potentially discussing our results with the FDA. Now, I'll ask Scott Kellen to take us through the financial results for our fourth quarter. Thank you, Rick.
spk05: Good morning, everyone. As Rick mentioned, we did announce our full year 21 financial results and filed our annual report on the Form 10-K yesterday after the markets closed. These documents are both available on either the Diametica or the SEC website. Now going through the financials, our net loss for the full year of 21 was $13.6 million, or $0.65 per share, which compares with our prior year net loss of $12.3 million, or $0.78 per share. Our cash position remains strong with $45.1 million of cash, cash equivalents, and marketable securities. as of December 31, 2021, which is up from $27.5 million at the end of the prior year. We believe our current cash will support the clinical development of DM-199 and fund our operations into early 2024. Our research and development expenses increased slightly to $8.8 million for the year ended December 31, 2021, up from $8.2 million for the full year of 2020. This increase was primarily due to a combination of the additional costs incurred for our Phase 2-3 Remedy 2 trial and increased personnel costs associated with adding staff to support our expanding clinical programs. This increase was partially offset by decreased costs incurred for our earlier Remedy 1, the Phase 2 AIS study, which completed during 2020, and then decreased costs for the Redux trial as the number of enrollments in the trial declined through 2021 as the study neared completion. Our general and administrative expenses were $4.9 million and $4.5 million for the full fiscal years 2021 and 2020, respectively. The increase was due to a number of factors, including increased costs associated with professional services, the payment to Catalan of a milestone obligation under our technology license agreement with Catalan, increased directors and officers liability insurance costs, and increased personnel costs to support the company's R&D operations. These increases were partially offset by a reduction in our non-cash share-based compensation costs. Turning to the cash flows, our net cash used in operating activities for the year ended December 31, 2021 was 12.3 million compared to 9.2 million for the full year 2020. This increase relates primarily to our increased net loss in 2021, partially offset by share-based compensation and the effects of changes in operating assets and liabilities. And importantly, as I mentioned earlier, we believe our current cash will support the clinical development of DM-199 and our operations into early 2024. Now let me turn the call back over to Rick.
spk04: Thank you, Scott. As you can see, we've had a very productive 2021. which is continuing into 2022, including significant progress with DM-49, our clinical trials, and building our team. And with a strong balance sheet, we're well positioned to continue to execute on the plans we have reviewed for you today. With that, we'd like to open the call for questions. Operator, could you please introduce the first analyst?
spk01: Thank you. At this time, I would like to remind everyone, in order to ask a question, press star one on your telephone keypad. Your first question comes from Alex Nolak from Craig Allen Capital Group. Please go ahead.
spk07: Great. Good morning, everyone. Kirsten, I appreciate the intro and kind of your background on what attracts you to the company. Just curious, beyond the pivotal stroke study that's going on, can you walk through some of the additional studies, lab or bench data that you're looking to generate here over the coming months to years to help position the company's product of DM-199 for
spk04: Yeah, maybe I'll take this. So right now, really our focus with our clinical team is on the Remedy 2 trial. And so while we're working on that, we are starting to looking at what the next steps, potential steps are for the kidney program. But we just want to be sure that we're very focused here right now on the stroke pivotal trial.
spk07: Okay, understood. And maybe refresh us, and this is, I guess, a broader question, refresh us from the regulatory landscape for chronic kidney disease in the U.S. now? Because we saw the CRL from Riyadh recently. I mean, they were kind of paving the path forward. So does the broader CKD space, do we need to, I mean, do we know necessarily the path necessary to get through FDA approval at this time? Do we need to reset it with kidney metrics we need to focus on, like UHDR or EGFR? Just any thoughts there?
spk04: Yeah, that's a really good question, Alex. If we look in 2019, there was new guidance from a working group with the National Kidney Foundation, the FDA, and EMA that really is looking at surrogate endpoints for approval. And so our understanding, in particular when we're looking at rare forms of kidney disease, is that there's the potential to have conditional approval based upon UACR, the albinuria levels, and guidelines of, you know, ideally over 30% reduction over six plus months for the conditional approval, and then full approval over two years based upon a slowing in the rate of decline of EGFR. And I think we can look at the recent approval of Caldeas, you know, based upon their UACR, just going back to a few months. So I think we're very encouraged in terms of the potential regulatory path here for for chronic kidney disease. And so what we're currently looking at, we have a few different potential pathways to move forward in terms of kidney disease, focusing more so on the hypertensive African Americans and maybe a subgroup of these patients and or IgA nephropathy. So again, we want to look a little more carefully at our data to really see which cause of kidney disease we think would be the best fit for our therapy and also in the context of the competitive landscape. So we're very excited about the potential and we just want to make sure that before we come out and provide an update to the market, we have a very clear indication of what that cause and what that regulatory path will be going forward.
spk07: Yeah, I understand. It makes total sense. And then just a clarification question around the enrollment. So you said 10 sites were under contract. are those the number of sites that are actively enrolling patients? And if not, what is that number of actively enrolling? And then how long to convert the 70% of targeted sites under discussion to active enrollment, just based on where things are trending in the last month or so?
spk04: Yeah, so we can actually follow live on clinicaltrials.gov. Usually it's a couple weeks late. But we've got four or five sites right now that are actively recruiting sites. Our intent here is to provide everyone with an update on enrollment milestones along the way, and just with a little bit of additional color here. So with the COVID variant, both the Delta and the Omnicom surging in the second half of the year, there was some challenges with the sites that were shifting their staff away from research. But what we can share with you this time is that we're not having any troubles getting interest from the sites that have the research teams in place. Once committed, they've been steadily moving this process forward. Combining that with the response that we got at the recent International Stroke Conference, we don't have concerns about the interest. It's really about now converting these sites over. We're talking over 50 sites in total here that are contracted and or going through the process. The other piece to this that we're also refocusing is Really focusing on those sites that we believe can enroll greater than one patient per month. Really focusing on those sites we think will be the optimal enrollers. And we're still targeting the first half of 2023 for the interim analysis.
spk07: That's great. Thanks, Rick, for the update. Appreciate it.
spk04: Yep. Thanks, Alex.
spk01: Your next question comes from François Brissereau from Oppenheimer. Please go ahead.
spk02: Hi, this is Daniel on behalf of Frank Brisebois. Thanks for taking the question. Just a quick one. Could you add some more color on the importance of the interim look, particularly in terms of efficacy? And you already talked about the enrollment rate. So just wondering how the enrollment is going on, given that you have this sweet spot of patients who need to have a small blood Vessel occlusion enrollment within 24 hours just to talk about the some color on the interim look that'd be great.
spk04: Thanks Sure. Yeah, so at the interim analysis So after you know 40% of the patients have completed therapy that the data safety monitoring board will review the results and make a recommendation to us and how to proceed and There's really you know, three different options, you know, three different potential scenarios here that we anticipate So the first is to continue the study as planned and Second is to increase the number of patients. And then third will be to stopping the study for either overwhelming efficacy or for lack of efficacy. So the premise here is that DiMedica will be blinded, but it will be an opportunity really here to, most importantly, to increase the study size if needed to potentially reach statistical significance.
spk02: Great. That makes sense. And just one more question on the REDUX side of things. Are you sharing anything on when we can expect to see the final CKD data? And as a related, are you planning to move forward with the program yourself? Or is there any thoughts about partnership on that end?
spk04: Yeah, so later this year, we're not anticipating any material difference from what's been reported. And in particular, you can look at the ASN poster presentation we had back in November. And right now we're exploring a number of different options and the potential for partnership is one of the pieces that we are looking at as a potential next steps. I think what we want to be very careful about here is we don't want to do anything that will jeopardize our capital use funding our stroke program to get into that interim and then to still have a runway post interim, which is most important in terms of our capital budget right now.
spk02: Great. Thanks for taking the questions. Thank you, Daniel.
spk01: And there are no further questions at this time. I will turn the call back over to Rick Paul, CEO, for closing remarks.
spk04: All right. Again, we would like to thank everyone for joining us this morning. We appreciate your interest in Diomedica and your continued support. With this, we conclude our call.
spk01: This concludes today's conference call. You may now disconnect.
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