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spk08: Good morning, ladies and gentlemen, and welcome to the Diomedica Therapeutics second quarter 2023 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 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 Diomedica's most recent annual report on Form 10-K. 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 only as of today, August 15, 2023. and may no longer be accurate at the time of any replay or transcript rereading. Diomedica disclaims any duty to update its forward-looking statements. Following the prepared remarks, we will open the phone lines for questions. I would now like to introduce your host for today's call, Mr. Rick Pauls, Diomedica's President and Chief Executive Officer. Mr. Pauls. You may begin, sir.
spk06: Thank you, Paul. Hello, everyone, and welcome to our second quarter conference call. I am joined this morning by Scott Kellan, our Chief Financial Officer. Before we begin this morning, I want to take a moment to welcome Dr. Richard Kuntz to our Board of Directors. Dr. Kuntz recently retired from Medtronic. where he was the chief medical officer, chief scientific officer, and a member of the executive committee. Prior to that, he served as a senior vice president and president of neuromodulation of Medtronic. Before Medtronic, he was the founder and chief scientific officer of the Harvard Clinical Research Institute in Boston. He also served as an associate professor of medicine at Harvard Medical School, chief of the division of clinical biometrics, and as an interventional cardiologist in the Division of Cardiovascular Diseases at the Brigham and Women's Hospital in Boston. He also served as an advisor to multiple national and regional committees in the National Academy of Medicine and National Institutes of Health. Dr. Kunz has directed numerous multicenter clinical trials and has authored over 200 original publications. We are grateful to have Rick join our board. His experience complements and broadens the knowledge and skill set of our board. Turning back to our update, The second quarter saw two important milestones for Diametica and her shareholders. The FDA's lifting of the clinical hold on a Remedy 2 stroke trial and the completion of an at-the-market financing, raising gross proceeds of $37.5 million. Starting with the FDA, on June 21st, we announced that the FDA had fully lifted the clinical hold on a Remedy 2 Phase 2-3 clinical trial, studying DM-19 as a treatment for acute ischemic stroke, or AIS. With this decision, we immediately reengaged with our study support vendors and have selected a new contract research organization with strong current experience in the stroke space. As many of you know, there is a great deal of work involved with preparing for a pivotal registrational clinical trial. I can assure everyone that our entire team is excited and focused on working with our CRO, the supporting vendors, and key advisors for the resumption of the trial. Recall that we have a bit of a leg up as we have approximately a dozen sites already under contract from last year. Additionally, we are now also evaluating the addition of clinical sites outside of the U.S. to increase our enrollment rate in countries viewed as being able to enroll more quickly than their U.S. counterparts. Our goal is to deliver a complete and clean clinical data package to the FDA at the conclusion of the Remedy 2 trial, enabling the FDA to accept and approve DM-199. It has been with this objective in mind that we expanded our clinical team over the past year. As of today, all key vendors have been engaged and are actively pursuing preparations for the resumption of patient enrollment. The estimated timeline has not yet been finalized, but based upon discussions with our CRO and multiple others, we are optimistic that enrollment for the interim analysis can be completed before the end of 2024. The final timing will come down to the actual pace of enrollment. I want to stress that with our recent capital raise, which brought in significantly more capital than anticipated, we are able to pursue expanding the study globally in order to increase the enrollment rate with the intent to ultimately reach both the interim and final analysis more quickly. We expect to be able to provide more clarity on the overall timeline at our Q3 earnings call. On a related note, and as we've previously discussed, we are conducting a phase one C, open label single ascending IV dose study of DM-189 in healthy volunteers using the same PVC IV bags as in the Remedy 2 trial. The first part of the study demonstrated the safety of our planned 0.5 microgram per kg IV dose level to be used going forward in the Remedy 2 trial. It also demonstrated that this dose level achieved our targeted KLK1 blood concentration level, a level that we believe is the desired therapeutic range similar to our prior phase two stroke trial and the reported drug levels of the human urine-derived KLK1 protein widely used in China under the product name Calicang. We were able to report today that we also completed a fourth cohort in the phase one C study consisting of three hypertensive patients on ACE inhibitors. These patients received the 0.5 microgram per kg dose using the updated methods plan for the remedy two trial. We are pleased to see that all participants received the full IV dose and there were no instances of hypotension or large drops in blood pressure. We believe that the additional clinical data from these combined results will provide further assurance to current and potential physician investigators that the correct IV dose level has been identified and patients, including ACE patients, may be safely enrolled in the Remedy 2 trial. Turning to our second milestone, we also significantly strengthened their balance sheet during the past quarter. In June, we completed an offering of straight carbon shares, no warrant coverage, priced at the market. Gross proceeds from the offering were $37.5 million and net proceeds were $36.1 million, bringing our cash balance to over $60 million at the end of the quarter. The financing was led by existing investors who contributed a significant portion of this capital raise and who remain enthusiastic about DM-199 and its potential to offer a compelling new treatment option for stroke patients. We also had excellent participation from our management team and board who collectively invested $700,000. We are grateful to our investors who have put us in a position where we believe we can now drive our destiny. We believe that we now have the sufficient capital enabling us to complete the interim analysis with a remaining cash runway of approximately one year. We focus on the interim analysis as it has the potential to signal a beneficial impact of DM-19 to stroke patients, a patient set that has not seen a significant therapeutic development in over 25 years since the approval of TPA. Before I turn the call over to Scott, I also want to call your attention to a new video and slide in our corporate deck that had created which further illustrates the DM-189 mechanism of action as it applies to stroke patients. Specifically, DM-189's role in increasing collateral circulation. The key updated mechanism message is that in response to ischemic conditions caused by a stroke, the bradykinin-2 receptors expressed on the cell cells in the arteries of the brain are highly upregulated locally in the ischemic penumbra. This increase may be by as much as 40-fold higher based upon testing in animal models. By augmenting with DM-19, we believe a significantly greater number of the upregulated bradykin-2 receptors may be activated, causing the beneficial focal basal dilation in the affected area of the brain, the ischemic penumbra, to increase blood flow and oxygen. We believe this improved collateral circulation will salvage brain tissue in the penumbra and lead to improved patient outcomes. This video can be found on our website at www.diametica.com and scrolling down to the front page to the section titled Advancing Patient Care with Innovative Treatments. I would like to now turn the call to Scott Kellan to review the financial highlights.
spk03: Thanks, Rick, and good morning, everyone. As Rick mentioned, we strengthened our balance sheet considerably in June with the completion of a $37.5 million private placement with accredited investors. Net proceeds from the transaction were approximately $36.1 million. And also, when David Wombeck joined us as our chief business officer in April, he invested $750,000. As a result, Our June 30, 2023 total cash, cash equivalents, and marketable securities increased to $60.6 million, up from $33.5 million at the end of 2022. Our cash usage was $10.1 million for the six months ended June 30, 2023, compared to $6.4 million in the prior year period. The increase in our cash usage was due primarily to a combination of factors, including the completion of the in-use and the Phase 1c studies, ongoing manufacturing development work, our expanded management and clinical team to support the Remedy 2 trial, and our lawsuit with PRA. We believe that our current capital will support the clinical development of DM-199 and our operations into 2026. Our research and development expenses increased to $2.5 million for the three months end of June 30, 2023, up from $2 million in the prior year period. R&D expenses increased to $6.2 million for the six months end of June 30, 2023, compared to $3.9 million for the six months end of June 30, 2022. The increase for the six-month comparison was due primarily to costs incurred for the in-use study performed to address the recently lifted clinical hold on our Remedy 2 trial, and costs incurred for the Phase 1c study determining the DM-199 blood concentration levels achieved with the new IV dose of DM-199. Also contributing to the increase were increased manufacturing and process development costs, costs incurred to finalize the clinical data and perform the related analyses for the Redux trial, and increased personnel costs associated with expanding our clinical team. These increases were partially offset by decreased costs incurred for the Remedy 2 trial, which until late June had been on clinical hold. Our general and administrative expenses were $2.2 million for the three months ended June 30, 2023, up from $1.4 million for the three months ended June 30, 2022. G&A expenses were $4.1 million for the six months ended June 30, 2023, and this was up from $3 million for the six months ended June 30, 2022. The increase for the six-month comparison was primarily due to increased legal fees incurred in connection with our lawsuit against PRA Netherlands and increased personnel costs associated with expanding our management team. Increased professional service fees and non-cash share-based compensation also contributed to this increase. Now, before I turn you back over to Rick, let me also provide a brief update on our ongoing lawsuit against PRA Netherlands. As many of you will recall, in December of 2022, the Netherlands court, at our request, seized our study records from PRA. Then in April 2023, following a March 2023 hearing, the Netherlands court issued a ruling affirming our ownership of the study data and, importantly, stating that PRA had no legal basis for withholding the study data. Now, PRA appealed this decision in June, and while this appeal may take nine to 12 months to resolve, it is not holding up our main damages lawsuit. This hearing is currently scheduled for December 7th of this year and we look forward to presenting our case against PRA and providing our analysis of the damages caused by PRA's actions. It's also interesting to note that the same three-judge panel that oversaw the hearing on our ownership of the study data is scheduled to oversee the hearing for the main lawsuit. For more information regarding the background to this lawsuit, please see our SEC filings. Now, let me turn the call back over to Rick.
spk06: Thanks, Scott. With that, we would like to open the call for questions. Paul, if you could please open the line for questions.
spk08: If you would like to ask a question, please press star 1 on your telephone keypad now. You will be placed into the queue in the order received. Please be prepared to ask your question when prompted. Once again, if you have a question, please press star one on your phone now.
spk07: And our first question comes from Thomas Flatton from Lake Street Capital.
spk04: Your line is up. Thank you. Good morning, guys. Appreciate you taking the questions. Hey, Rick, with respect to the patients that were enrolled in the study prior to the clinical hold, I don't know if you've told us how many there were, but will they be kept in the efficacy analysis set or will they be censored out?
spk06: Yeah, Thomas. So we haven't disclosed that number, but we do plan to have those included in the analysis.
spk04: Got it. And then for the interim analysis, given the change to the endpoint, is the number of patients still the same for the interim analysis?
spk06: Yeah, we're still planning for 144 patients. for the interim analysis.
spk04: Got it, got it. And then you're still shooting for a total of 75 sites, is that right?
spk06: So the current plan is currently being revised kind of live as we move ahead. Currently, we're working towards 40 sites in the US, 10 sites in Australia. And then, as I mentioned on the prepared remarks, with additional capital that came in, we're also looking at going further ex-US. We're looking at Canada and Europe. There's some work right now just seeing what it's going to take in terms of timelines to add. But I think it's important for us if we can expand internationally to increase the enrollment rate for the trial.
spk04: Excellent. Appreciate you taking the question.
spk01: Thank you. Thanks, Thomas.
spk07: And our next question comes from Alex Nowak of Craig Hallam Capital Group. Your line is open.
spk01: One moment. We seem to have lost him from the queue.
spk07: I apologize for the technical difficulty. For those that were in the queue, if you could please press star one again.
spk01: All right, and Mr. Nowak, your line is open.
spk05: Okay, hopefully you can hear me this time. I'm not sure what you could hear, what you couldn't hear, Rick. But, you know, just with regards to getting the clinical hold lifted and searching for the new CRO, what were some of the new requirements that you had this time when searching for a CRO compared to when Remedy2 was initially started? It sounds like maybe some more international exposure was a new requirement, but anything in addition?
spk06: Yeah. So, Alex, so that, you know, we're in a different environment today. So we're, you know, a year plus now past, you know, COVID. So it was important for us to take the learnings we had previously, and then we were looking for a global CRO that could really help us with expanding outside of the U.S. as well, but also importantly having a CRO that has recent experience with stroke trials. So that was an important piece. So the CRO we've selected has extensive experience with a number of more recent trials, better understanding, I'd say, of a good understanding of sites that could ideally be strong enrollers for this trial.
spk05: Okay, understood. And then maybe expand on the expected international uptake of DM-199 in the clinical study versus domestic uptake. Why would international necessarily go faster? Just from your conversations, what do you think in there?
spk06: Yeah, so as we were looking at enrollment rates of past trials, What we did see in particular in Europe that the enrollment rate per site per month was a fair bit higher than what's been seen for U.S. trials. And part of that may be associated with socialized healthcare. But based upon this, we think it's important if we seriously can look at ex-U.S. expansion.
spk05: Okay, understood. And then do you need a specific number of patients in the U.S. versus OUS to meet that statistical analysis plan, or is that kind of getting baked in with 40 sites U.S. and then a remainder amount OUS?
spk06: There's not. The context here also is the timelines to get sites set up in Europe will be longer than they are in the U.S. So in particular for the interim analysis, we still think it's going to be driven by the U.S. sites. and then the other ex-US sites will be supplementary.
spk05: Okay, understood. And then just a two-part question to end it out here is, at first, I think the remedy to patients with ACE inhibitors would have been excluded, but will this be reversed based on the Phase Ic's findings in that fourth cohort? And then the second part of the question is, any other protocol changes to be aware of?
spk06: Yeah, so if the patient was previously on an ACE inhibitor, there will be a 24-hour washout so that the drug will effectively be out of the system. And this is something actually is quite similar with the human urinary form of the protein in China. There's also a 24-hour washout. So all the patients will be included in the study. And just for context, again, in our phase two trial for stroke, We had about 10 patients that were previously on ACE inhibitor. Of the 46 total patients on drug, there were no instances of hypotensive events. And then we made a couple other protocol changes, learnings, I call it, from the hold. In particular, we're going to be starting off with a 15-minute slow infusion. And so if there are signs of large drops in blood pressure, then the dosing will be over three hours instead of the prescribed one hour. And so we think the hypotensive event is really the result of overwhelming the system very rapidly when the dosing first starts. So that's going to be, again, an important aspect of it. We ran the Phase 1c trial, and in particular the ACE cohort that we just recently completed. I think just to giving us, and also importantly to give the clinical site some comfort here, that we feel that we've addressed the dosing and matching the dosing to what we had previously had in our phase two trial, which was comparable to the drug exposure level with the human urinary form of the protein in China today.
spk05: Okay, it makes sense.
spk01: Well, I appreciate the update and congrats on getting the clinical hold lifted. Thanks, Alex.
spk07: And our next question comes from Francois Grisbeau from Oppenheimer. Your line is open.
spk02: Hi, this is Dan on for Frank. Thanks for taking my questions. In relation to the interim analysis, is the plan still to end the study if you see great efficacy in around the 140 patients? Any changes there?
spk06: Yeah, so similar to what we've discussed in the past, So at the interim analysis, there's really three scenarios. So the first is that we'll stop the study for futility. So if we're not seeing a positive drug effect, we'll stop the study for overwhelming efficacy. And that's based upon hitting a p-value of less than approximately 0.0072. Or alternatively, we will continue this study and we'll do a resampling size where the total size will be somewhere between 240 and 728.
spk02: Great, thanks. That makes sense. And just a quick one. Regarding the Phase Ic data in hypertensive patients, had any of the dozen sites from before requested to see additional data in patients, or was this more of a proactive move as you target new sites?
spk06: Yeah, this was completely proactive. First off, the FDA did not ask us to run this trial, so we did that proactively. And then none of the sites had asked When we talk to sites and we're talking about the hypotensive events, this is something that's manageable. By stopping the infusion, the blood pressure in the three patients that we had that were these three serious adverse events, the blood pressure returned back to normal within minutes. But this was just another, basically another proactive way of providing additional comfort in case in the future any new sites that we talk to have any concerns about large drops in blood pressure. And keeping in context here is that these neurologists, many of them every day are dealing with treating patients with TPA and realizing that 5% to 6% of patients on TPA, it causes a severe brain hemorrhage. So we think that the drop in blood pressure is manageable, but we just want to make sure we're comfortable and also for the sites as well with the dosing.
spk01: OK. Thanks for taking my questions. Thank you, Dan.
spk07: Answering no further questions in queue, I'll turn the call back over to our host for closing comments.
spk06: All right. Again, we'd like to thank everyone for joining us this morning and for your continued support. Our goal is to bring this important treatment to stroke patients as quickly as possible. We appreciate your interest in Diomedica and your continued support. With that, this concludes our call today. Thank you.
spk07: The meeting has now concluded. Thank you for joining, and have a pleasant day.
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