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spk01: Good morning, ladies and gentlemen, and welcome to the Diametica Therapeutics first quarter 2023 conference call. An audio recording of the webcast will be available shortly after the call today on Diametica's website at www.diametica.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 Note regarding forward-looking statements in the company's press release. issued yesterday and under the heading Risk Factors in Diametica's most recent annual report on Form 10-K and subsequent quarterly report on Form 10-Q. Diametica's SEC filings are available at the SEC's website, www.sec.gov, and on its website. Please also note that any comments made on today's call speak only as of today, May 16th, 2023, and may no longer be accurate at the time of any replay or a transcript rereading. Diametica 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.
spk04: Thank you, operator. Hello, everyone, and welcome to our Q1 2023 conference call. I am joined this morning with Dr. Kirsten Gruss, our Chief Medical Officer, and Scott Callen, our Chief Financial Officer. I am happy to report this morning that our complete response requesting the lifting of our clinical hold is being finalized as we speak, and we plan to submit to the FDA this week. Much hard work has been performed to get us here. The FDA requested a new study was completed in April. This was performed at an independent laboratory and consisted of two parts. Part one simulated actual use in a hospital of drug being administered and part two evaluated worst case scenarios such as varying storage durations, temperature and light exposure. We believe that the data from part one confirmed our conclusions that the effects of the change in the IV bag material was the cause of the hypotensive events leading to our halting of enrollment in the study. Results from Part 2 of the in-use study were substantially consistent with Part 1, which means that there will likely be no new special handling instructions required for the IV administration of DM-109. I would also point out that part one results were consistent with the results of the IV bag testing we completed in the fall of last year, where we proposed revising the IV dose to 0.5 micrograms per kg to match our phase two stroke trial IV dosing levels. We hope that this consistency will contribute to a favorable decision by the FDA. And just to remind everyone, there are no proposed changes to the ensuing three-week subcutaneous dosing under the study protocol. I'm also very pleased to report that we have recently completed a Phase 1c in healthy volunteers trial. Even though the FDA did not request or suggest human testing, we planned and initiated a Phase 1c open-label single ascending dose study of DM-49 administered using the PVC IV bags planned to be used in the Remedy 2 trial at 0.1, 0.025, and 0.5 microgram per kg. This study was conducted in Australia. The results have confirmed to us with human data that a proposed revised IV dose of DM-49 of 0.5 micrograms per kg would be generally safe, well-tolerated, and achieved a blood concentration level that reached the desired therapeutic range as seen in our prior Phase II acute ischemic stroke trial. The results from this Phase 1c study give us further confidence that a proposed DM-19 IV dose revision to 0.5 micrograms per kg for Remedy 2 will minimize the risk for clinically significant hypotension and reach the targeted range. These results will be included as additional supporting data in our clinical hold response. We also believe that this study and the resulting data will demonstrate our commitment to patient safety and provide greater comfort for our prior and new principal investigators and study sites to engage in and support the Remedy 2 trial. As a result of all this work, we are optimistic that we have fully identified the cause for last year's unexpected hypotensive events and will be providing the FDA with adequate data to support our analysis of the cause of the prior hypotensive events. We believe the results of the Phase 1c study further support our proposed revision to the IV dose of 0.5 micrograms per kg and demonstrate the safety and tolerability of DM-49. All in, we are cautiously optimistic that this will allow the FDA to lift the clinical hold. With the expansion of our team this past year, I'm confident that we have the right team in place to execute the Remedy 2 trial, which we believe will be a pivotal trial. Once we hear back from the FDA and if the response is positive, we will provide an update on the next steps and expected timing for relaunching the Remedy 2 trial. We've also recently expanded our management team with the addition of David Wambach as our Chief Business Officer. Dave brings over 15 years of relevant life sciences, capital markets, M&A, and investor relations experience to Diomedica. He was actually the lead banker on our 2018 initial public offering on NASDAQ and has been one of my most reliable and trusted outside advisors over the past five years. And as well, he has an extensive understanding of our DM-109 programs. He also brings key relationships across the biotech and investment communities. David's committed to advancing DM-109, as you can tell with his recent purchase of $750,000 of Diametica's common stock. We're grateful to have him part of our team. 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 announced our first quarter 2023 financial results and filed our quarterly report on Form 10-Q yesterday afternoon. These documents are both available on either the Diametica or the SEC websites. Starting with our balance sheet, as of March 31, 2023, Our combined cash and investments totaled $28.7 million, down from $33.5 million as of the end of 2022. Our first quarter 2023 cash usage was $5.1 million, compared to $3.9 million in the prior year period. The increase in our cash usage was due primarily to the in-use and the Phase 1c studies. We believe that our current cash will support the clinical development of DM-199 and our operations into the fourth quarter of next year. Our research and development expenses increased to $3.6 million for the three months ended March 31, 2023, up $1.6 million from $2 million for the first three months ended March 31, 2022. The increased costs were driven by a number of factors, including increased manufacturing and process development costs, costs for the in-use and the Phase 1c studies, and increased personnel costs associated with the expansion of the clinical team. These increases were partially offset by decreased costs incurred in the Phase 2-3 Remedy 2 stroke trial due to the clinical hold. Our general and administrative expenses were $1.9 million for the three months ended March 31, 2023, up from $1.6 million for the same period in the prior year. The increase was primarily due to recruiting costs incurred in conjunction with the expansion of the company's team and increased legal fees incurred in connection with the company's lawsuit against PRA Netherlands. Speaking of which, let me provide a quick update on our ongoing lawsuit against PRA Netherlands, which as of July 1st, 2021, was acquired by ICON PLC. Last month, the Netherlands Commercial Court issued its ruling on the matter of our ownership of the study data and records from the trial that PRA slash ICON ran for us in 2013 and 2014. In that ruling, the court declared that Diomedica was the rightful owner of the study records, both paper and electronic, as stipulated in the original study agreement. The court ordered PRA slash ICON to, quote, allow and tolerate, end quote, that Diomedica exercise its right as owner of documents and to cooperate with the surrender of both the physical documents and the digital data. The court further ruled that PRA slash ICON had no legal basis for withholding the study documents. After all these years, that ruling was quite the vindication. We now look forward to obtaining the records and conducting a proper audit of the study and to evaluate the inconsistent messaging from PRA. We are currently taking steps to enforce the court's ruling and to get access to the study documents. PRA, however, does have a right to appeal this decision. This right lasts until mid-July of this year. At that time, we'll be able to provide some clarity on the timing for the next steps through the Netherlands legal system. So thank you, and with that, let me turn the call back over to Rick.
spk05: Thanks, Scott. With that, we'd like to open the call for questions. Operator, if you could please introduce the first analyst.
spk01: If you would like to ask a question, please press star 1 on your telephone keypad now. You'll 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 1 on your phone now.
spk07: And our first question comes from Thomas Flatton of Lake Street Capital.
spk01: Your line is open.
spk06: Thanks. Good morning, guys, and I appreciate you taking the questions. Rick, I was curious, and maybe I misunderstood from the last call, that the Part 1C was kind of a back-pocket data set that you could use in the event that FDA had ongoing questions, but it's now going to be submitted as part of your formal response with the in-use study. I was just curious if you could comment on that. Was it more just that the timing worked out, or was there a change in strategy there?
spk04: No, really good question. So it really was a question of timing. And so we were preparing to submit our complete response in April, the end of April, with combining both the part one and part two of the in-use. And then we realized that the phase one scene, healthy volunteers, was moving along very quickly. And so recognizing that in just a couple more weeks, we could actually do a complete response that would actually include human data And encouragingly, that human data now supports the in-use data and also supports the IV bag study we did last fall. So we think overall, the combination of the in-use study, the Phase Ic data, we believe provides a very compelling basis for the FDA to allow us to resume the trial.
spk06: And thanks for that. And just looking back a bit, when you guys conceived of the one microgram per kilogram dose, I'm assuming that was a translation from either the porcine or the human urinary form that you had come up with that dose. I was just curious, now that it's having the same effect at half the dose, I was just curious what you guys have maybe gone back on a post-mortem basis to understand. Should you have been at one microgram in the first place? Maybe some post-mortem thoughts on that.
spk04: Yeah, so if you go back, so we initially did a phase one trial in healthy subjects that looked to match the PK profile, the IV dose of our drug compared to the human urinary form that's being used today in China. And at the time, we'd used the polyoferon bag, and using that bag, we came up with a one microgram per kg dose levels. Fast forward, that was the same bag that we used for our phase two, that we had the phase two results. And then when we progressed and moved to our phase two slash three that initiated last year, we pivoted to a PVC bag. And that's where we had the three serious adverse events of large drops in blood pressure. Last summer, we went back and looked at what changed from the phase two to the phase two slash three. And that's where we recognized that really the only thing that we could determine was changing the bags. Did additional work both last summer and then further with the in-use. And what we now realize is that the polyoferrin bag, that effectively half the drug was sticking. And so effectively, the one microgram per kg using the PVC bag was giving patients twice the dose. so that we thought that they were getting. So with this new in-use study in the Phase 1c, we were able to basically match up to a similar PK profile using the PVC bag as we did with the previous bag.
spk08: Got it. Thanks, Rick.
spk07: And our next question comes from Alex Nowak from Craig Hallam.
spk01: Your line is open.
spk05: All right. Great. Good morning, everyone. To continue off Tom's questions there, I think the work that you've done here is really interesting. To go back and just confirm the dose levels, will you plan on publishing that work just showing all the steps you took from you know, root cause identification, how you ended up solving it, the studies that you've done, either publish this at a conference or publish it in an abstract somewhere, just so I think we could have some more hard support, hard evidence around the kind of changes in the studies design.
spk04: Yes, it's something that we're talking about. I mean, I guess we're not going to commit to it, but it would be something that's important, and in particular for the, you know, the principal investigators at these sites. So if we can give greater clarity on We'll be looking at how to get that, you know, to get that data out so that it's very clearly we've identified, you know, what happened and why we believe that we'll be able to avoid these events for the most part going forward.
spk05: Okay. No, that's good. And, you know, anything from the in-use study of the Phase Ic data that's going to make the FDA go, huh, okay, great, thanks for providing this, but have you considered XYZ? You know, what could we be still surprised by the FDA's response here?
spk04: You know, we've done what we think has been a very extensive review. We've used a number of different, you know, outside consultants as well to help us to review everything. You know, we thought we had the data with the in-use, and then we feel by taking this even further and running a study in humans, you know, that I mentioned on the prepared remarks, was not required or indicated or alluded to by the FDA. You know, we think this is ideally, this will give them more comfort in in terms of we're doing everything we can regarding patient safety. Other aspect too that we've also done is some revisions to the protocol. And so in particular, we'll be starting the infusion for the first 15 minutes slow. And if there are any signs of drops in blood pressure that are significant, then the sites can dose these patients over a few hours later. We think that'll be important. And then we also are doing a 24-hour washout if a patient was previously on an ACE inhibitor. So these three patients were all on ACE inhibitors that had this serious adverse event. And so we know there is an interaction with ACE inhibitors in terms of the mechanism of action. So we think these additional precautionary steps that Kirsten and the clinical team have added I think will provide more comfort as well in terms of prevention. Until we get the feedback from the FDA, we don't know, but we believe we've answered everything. There's some additional questions that the FDA had also asked regards to trypsin and our assay, and they've already responded that they thought that the work we've done has been acceptable. So we'll plan to file this week, and then the FDA will have up to 30 days to get us a response.
spk05: Okay, that's great. And then maybe just two quick questions. One was I think you mentioned in the prepared remarks there was new principal investigators in the study. Can you just elaborate on that? And then just remind us on the PRA lawsuit. What study was PRA conducting going back almost 10 years now? What data is there that you'd like to get or you're going to get, and what could be helpful in that data for the ongoing development of DM-199?
spk04: Yeah, so the first part is my prepared marks in reference to, you know, we had, you know, 15 sites that we had under contract and on clinicaltrials.gov. And then we have numerous others that, you know, we've had different layers of interaction that as soon as we get the whole feedback from the FDA and coming off, we'll be full steam on getting as many of these sites up as quickly as we can. And then maybe let Scott take the PRA question.
spk03: Hi, Alex. Yeah, good question on PRA. It's been a while. They were doing the original first-in-man work, so the original dose tolerance studies, a number of single and multiple ascending dose studies that culminated in a small proof-of-concept study for type 2 diabetes. And the lawsuit issues revolve around that proof-of-concept study where You know, their representations as to what we would expect, what we could expect from the outcome of that study didn't match what they initially reported as the outcome. And then they refused to allow us access to perform a proper audit of the study to truly understand what actually happened. So we're waiting to see the data to understand whether or not we have a signal for efficacy in the type 2 diabetic indication or not. And, you know, principally, any positive data was beneficial for the overall development, but we'll wait until we see what those results are before we form an opinion on whether or not we should be looking harder back at type 2 diabetes.
spk05: Yep, absolutely. It will be great to see that data. All right, appreciate the update. Thank you.
spk07: Thanks, Alex.
spk01: Thanks, Alex. As a reminder, if you do have a question, please press star 1 on your touchtone keypad now. And we have a question from Francois Bisbro from Oppenheimer.
spk07: Your line is open.
spk08: Hi, this is Dan.
spk02: Sorry about that. Hi, this is Dan on for Frank. Thanks for taking my question. Regarding the P1C, you mentioned the 0.5 microgram per kilogram achieved the exposure levels similar to remedy one. Of course, these are healthy volunteers, but were there any PD parameters that were part of the data collected? If you're able to share at this time if there was any dose response in the PKPD parameters across the three doses, any additional granularity you can share this time on the P1C. Thanks.
spk08: Kirsten, do you mind taking that one?
spk04: No, I think we've been having some troubles here with the roster here. Dan, no, I mean, this was, these patients were healthy subjects. And, you know, I'll point out that, you know, the study design was quite similar to our phase one trial we did in healthy subjects before launching our phase two study for stroke.
spk08: Thanks. Thanks for taking my questions.
spk07: Thanks, Dan. Thank you.
spk01: And seeing no further questions in queue at this time, I'll turn the call back over to our host.
spk04: 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. This concludes our call.
spk01: The meeting has now come to an end.
spk07: Thank you for joining, and have a pleasant day.
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