Greetings, welcome to the Spectral Medical Tigris Trial and Corporate Update Call. At this time, all participants are in listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Ali Mahdavi. Thank you, sir. You may begin.
Thank you. Good morning, everyone, and thanks for joining us for today's investor conference call to discuss the top-line results from the Tigris trial. Joining me this morning are Chris Seto, Chief Executive Officer of Spectral Medical, and Dr. John Kellum, our Chief Medical Officer. Following remarks from Chris and John, we will open the call for a Q&A session. Before we begin, we are required to provide the following statements regarding forward-looking information, which is made on behalf of Spectral Medical and all of its representatives on this call. Remarks and answers to your questions today may contain forward-looking information about future events or the company's future performance. This information is subject to risks and uncertainties that may cause actual events or results to differ materially. Any information regarding forward-looking statements is made as of today's date, and the company does not undertake to update any forward-looking statements.
I'll now turn the call over to Chris.
Thanks, Ali. Good morning, all, thank you for joining us today. This is a pivotal moment for Spectral Medical. Over the past several years, we have been steadfast in our mission to bring a targeted life-saving therapy for endotoxic septic shock, or ESS, to the U.S. market. Today, we are not just pleased but very excited to discuss the results, which we released yesterday afternoon from our pivotal Tigris phase III trial. Tigris and the top-line results we're sharing today represent the culmination of close to two decades of focus for Spectral Medical, beginning with the EUPHRATES phase III trial and now confirmed and strengthened by Tigris. EUPHRATES provided the first large-scale evidence that PMX hemoadsorption could improve survival in a clearly defined population of patients with ESS. Tigris has built directly on those insights.
Together, these trials form a powerful and coherent body of evidence supported by decades of real-world use globally that gives us confidence that PMX can transform care for ESS, which is one of the most challenging and deadly conditions treated in the ICU. While I'm not going to get ahead of the data John will present in a moment, I can tell you this. What we will share today reflects the strength of our science, the consistency of our results to the EUPHRATES trial subgroup, as well as observed global data with PMX outside of our clinical trials. Ultimately, our belief that PMX can address one of the most pressing unmet needs in critical care. We believe these results reinforce the foundation for our FDA regulatory submission, and if approved, a successful commercial launch in the U.S.
Before we get into the details, I want to thank patients and families who participated in Tigris, the clinical investigators and study coordinators across our sites, our strategic partners, Baxter and Toray, the Spectral team, and certainly our shareholders for their commitment to this program. Without them, today's discussion would not be possible. With that, I'll turn it over to Dr. John Kellum, our Chief Medical Officer, to discuss the top-line results from Tigris. John?
Thanks, Chris. As Chris already noted, we are indeed quite pleased and excited to announce our primary results from the Tigris trial. Before we get into the numbers, I'd like to just remind you what we set out to accomplish with this trial. First of all, Tigris was designed as a confirmatory trial to reproduce the results from a subgroup of our previous trial, EUPHRATES. The subgroup was based on two additional criteria over and above what was used for enrollment in EUPHRATES. These criteria were high organ failure, and we used the multi-organ dysfunction score greater than nine, and an EAA that was not just above 0.6 but was less than 0.9.
The rationale for these criteria involves selecting patients with high enough risk for 28-day mortality endpoint, something that's referred to as prognostic enrichment, and selecting patients that are likely to respond to therapy, which we refer to as predictive enrichment. MODS provided the prognostic enrichment, while EAA provided both prognostic and predictive enrichment. Second, Tigris used a Bayesian statistical approach. What is a Bayesian approach? Rather than determining whether something might occur by chance and reporting this out as a P value, Bayesian statistics combine prior data and update that data with new data and report something called a posterior probability of benefit. The posterior probability of benefit represents the likelihood, based on all available evidence until that point, that the treatment is effective, in this case, indicating a mortality benefit.
In the case of Tigris, we are looking to find a posterior probability on the odds ratio comparing the treatment with PMX to the standard of care that would be less than one. We are hoping to see this probability to be greater than 95% in an analysis which is adjusted for baseline severity of illness. Why are we adjusting for baseline severity of illness? Simply put, this allows us to control for differences amongst patients to achieve a more precise estimate of the treatment effect. Adjusted analysis have become really the standard in clinical trials, especially for small, complex studies like ours. As outlined in June, our top-line data readout will include both the primary and key secondary results, which is the 28-day and 90-day mortality by study arm. These will be analyzed using our pre-planned Bayesian analysis adjusting for baseline severity.
We also said we would report results without adjustment for completeness. These results include the posterior probability of benefit, the risk differences, and the odds ratios. As you can see from the top-line results, we met our primary endpoint by exceeding 95% posterior probability of benefit at 28 days. Our posterior probability was 95.3. We also calculated the size of the effect using an unadjusted analysis, which demonstrated an absolute risk reduction of 8.3%. Also, as we promised in June, we're reporting the same analysis for 90-day mortality. Mortality at 90 days became our key secondary endpoint because the same Bayesian analysis, the same model statistically, can be used to calculate a posterior probability of benefit at 90 days. 90 days is obviously more important to patients than 28 days, especially since many patients may still be in the hospital at 28 days when they have septic shock.
As you can see from the results at 90 days, we clearly exceeded expectations. Mortality in the standard of care arm was 60.8%, while in the PMX arm it was 43.4%, a difference of 17.4%. When these results are combined with the prior data, we see an adjusted odds ratio of 0.54 and a posterior probability of benefit at 90 days of 99.4%. The 90-day unadjusted absolute risk reduction is 12.3%. This would result in a relative risk reduction of 20% and a number needed to treat of 8.1. This means you would only need to treat eight patients to save one life. This is a very strong NNT, especially for mortality. For example, the NNT for Xigris, the last approved drug for sepsis, was 16, meaning that you would have to treat twice as many patients to save one life.
By reference, the NNT for statins is more than 250. As we noted previously, an important aspect of regulatory review of products like this that are used in other jurisdictions is that they are generally based on the totality of evidence. This includes safety and efficacy data from other sources in addition to our own results. We believe this is an advantage for us because there's an extensive safety history for the product, there's a large body of evidence from retrospective studies showing effectiveness, and these reports will provide additional support for our application. Finally, we're submitting a manuscript with the complete results of Tigris and all of the analyses later this month or early September at the latest. The manuscript will provide detailed analysis of other secondary endpoints, safety analyses, et cetera.
While we can't control the publication timeline, it's quite possible that the manuscript will be published by the end of this year, early 2026 at the latest. Next, I'd like to just comment on our timeline. As we reported previously, our FDA submission is planned for October of this year. The FDA has already accepted our non-clinical modules, and we're working with them to finalize these. FDA will take a bit longer to review the clinical, but as we've reported previously, we expect this to be concluded in about nine months, delays are always possible. That's the best information we have at this time. Back to you, Chris.
Thanks, John. As we look ahead, we'll further increase the focus on turning this clinical achievement into commercial reality. That's where our partnership with Baxter is key.
Vantam brings decades of experience in delivering advanced therapies to critical care settings with a commercial infrastructure that reaches deeply into U.S. hospitals, including many of the leading centers for sepsis care. Together, we're preparing to bring to market what we are calling TREA Therapy, which you may have noticed in our joint press release yesterday. This stands for Targeted Rapid Endotoxin Adsorption. It's a precision medicine approach to septic shock that combines our FDA-cleared Endotoxin Activity Assay with the PMX hemoadsorption cartridge. This integrated diagnostic plus therapy model is designed to give clinicians the ability to act rapidly and decisively in the life-threatening condition of endotoxic septic shock. With commercial groundwork well underway and subject to FDA approval, we are confident that TREA Therapy can be rapidly adopted in the U.S., bringing a long-awaited targeted solution to patients and their care teams.
We'll now open up the call for your questions.
Thank you. We will now conduct a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two to remove yourself from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Once again, that's star one to ask a question at this time. One moment while we poll for the first question. The first question comes from Scott McAuley with Paradigm Capital. Please proceed.
Morning, Chris and John. Congrats on the data. It's definitely been a long time coming, very excited to see. A few questions from me. Obviously, one of the important things for the Bayesian analysis is kind of the equivalence of the patients between the two studies. Just checking in that kind of from what you saw, those patient populations were quite equivalent, and you're very confident that it meets that requirement for the Bayesian analysis.
Yeah, I can answer that, Scott, good morning. Yeah, these are sort of secondary and even tertiary data points and what we have in front of us right now that's sort of locked is all the top-line data. I don't have complete picture on all of that.
What I've seen so far, it looks like there's equivalence both between arms, meaning the PMX versus standard of care, and also the data appear to be very similar between the previous trial, the subset of patients from EUPHRATES and the new data. Once we have all of that data locked and analyzed, we'll be reporting that in our manuscript.
Absolutely. That's great. I guess similarly on the safety side, again, I know you kind of highlight that you've seen the safety was in line with what's been seen historically and internationally. Just checking in on that, again, what you've seen so far is that this is a very safe product, adding to the efficacy we're seeing today.
Yeah. Again, those data are still being sort of polished up, but I'm very confident that we're not going to see any surprises in the safety data.
That's great. I guess on the press release, it was great to see a joint issue, press release between Spectral and Baxter. I guess is there any color you can give in terms of that process? Was this something that they had approached you to do as you were ramping up to put out the release? They kind of see the data and then say that, hey, they wanted to issue this jointly. Any color you can give on that? Obviously it's a great confidence boost that not only do they have a quote, but they issued the press release themselves jointly with Spectral.
Yeah. Scott McAuley, it's Chris Seto. Thanks. Thanks a lot for the question. Yes, it was Baxter that certainly wanted to move towards a joint press release. I think they have a view of certainly how important this product is for their portfolio, going forward in the overall growth of Baxter. In terms of the process, certainly I don't think they would've been part of a joint press release if we didn't have results such as this. I think certainly on the back of poor results, I don't think that they would have certainly wanted to be part of the release. I'm not sure if that fully answers your question or not, Scott McAuley.
Yeah, no, I think, but that they approached you about it, which I guess you said, and that they were very involved in the process and are, again, they're putting their name on this more than just a quote.
Yeah. I mean, look, they're putting their name on it. Their chief medical officer for Baxter Global certainly is quoted in there. Obviously they've taken this process seriously. I think once again, as you see, they've amplified the press release and the results through their own social media and their own press releases that they're pleased with what they've seen.
That's great. For the balance sheet and on the financing, obviously there was that promissory note with Baxter and one of the tranches was unlocked or is unlocked on this data release. Any commentary on that in terms of when we'll hear or if we'll hear on Baxter paying that out?
Yeah, I would expect in short order, Scott. I don't think it's certainly much of concern given that they continue to be part of this joint press release. A couple of things that I could talk about with respect to the triggers. I know in the conditions it was a 7% at 28-day and 10% at 90 days. Certainly on the 90 days, on just a raw data perspective, we blew that out of the water. At 28 days, it was slightly under on a raw data basis. If you look at the intent of what that 7% was, it was based on our pre-specified, and which in fact was to reach a 95% posterior probability at 28 days.
We achieved that, but not only that, I could bring all sorts of other data behind it, but the modified intent-to-treat, reversing out those six randomized not treated patients, on a raw data basis, that was 8.1%. I'm highly confident that this second tranche is going to be advanced and, I'd say keep a lookout for it in the next few days.
That's great. John, this is a big difference between that 28-day and 90-day numbers. Obviously fantastic to see in the comments that obviously 90 days more important from a clinical perspective. Even just with comparing to the prior EUPHRATES, the 90-day here is significantly better than what was even seen before. Any insight or thinking you have kind of around that on what's driving that?
Yeah. Thanks, Scott. I mean, obviously this is going to be a curious thing for lots of people looking at this. I have to say in retrospect, it's not maybe so surprising. I think Claudio Ronco, Professor Claudio Ronco from Italy, who's the most experienced with anyone in the world with this therapy, I think hits it with a very reasonable hypothesis around why this occurs. Which is that patients are still on life support often at 28 days, and those patients often don't do very well. If you can get your organ failure reversed and get out of the ICU, you have a much better chance of being alive at 90 days.
I think on a more data sort of perspective, I think everyone realizes, and this is not anything new, but people looking at survival curves for sepsis trials have noted over the last several years that the curves are still separating or there's still dynamic changes that are occurring at 28 days. It's not a great endpoint. It's just been sort of an historical endpoint that's been used. A lot of trials have moved toward longer-term endpoints at 90 days. For example, most of the NIH trials that look at sepsis and other critical illnesses, frankly, have moved out beyond 28 days. We have a lot more analysis to do to sort of look into that and really sort of test those hypotheses with data. I think that's a very reasonable explanation for what's going on here.
That's great. That kind of follows up that the why 28 day the primary versus that 90-day, and sounds like the 28 day just historically been that number, but there's the move to focus more on 90 or plus.
Yeah. In fact, the FDA told us that they really wanted to see 90 days, a lot of that, to speculate what FDA's thinking is not what I want to do, but they see a lot of results at 28 days, which then disappear, that get worse by 90 days. It's really, particularly if you're still in the hospital or even in the ICU, being alive in 28 days but dead at 90 isn't really so great in terms of patient-centered outcomes. I think they're very interested, as is the public and as the academic community, at sort of understanding whether or not patients really, when they survive, that they're really going to survive long-term, and not be in the hospital or even in the ICU.
I think 90 days is probably. We may see that get hardened with data like this, where people are really not interested in the 28 days and become much more interested in outcomes like 60 or 90 days.
Yep. That's great. Maybe lastly, from the regulatory side, submitting to the FDA, do you feel like the package you have here is confident in terms of getting that approval, but also in terms of the potential label that might be attached to any approval? You're happy with approaching the FDA with what you want and think that you'll get an appropriate label claim to support that commercial launch?
Well, to sort of answer the second question first, I think this was a very precise trial in the sense that the population that we're selecting, we never claimed to be effective in all forms of septic shock and certainly not all forms of sepsis. We're already sort of narrowing down to a very specific population that's based on our diagnostic as well as some clinical phenotyping. I would expect all of that to be in the label, and I think that's appropriate. We were never intending to say that this therapy is for everyone with sepsis. That said, there are 140,000, 150,000 people in the U.S. per year, maybe 30,000 in Canada, who develop this syndrome. Mortality is in excess of 50% in these patients. My view is that we'll expect a label that is sort of consistent with the trial design.
In terms of confidence, all I can say is that I think the FDA makes these decisions on the basis of effectiveness as well as safety. I've already commented on both of those, and I think they're quite strong.
Just sorry, one more. Obviously, Baxter has been very supportive in doing a lot of work on the commercial preparedness and getting ready for that. Are they assisting in any way on the regulatory side? Is that something that you guys are focused on independently and they're there to kind of catch the product once you get that approval and hit the ground running from a sales and marketing perspective?
In parallel, as you may know, in parallel, Baxter conducted or we conducted it for Baxter, but Baxter funded a sub-study which involved delivering the therapy for a subset of patients in the Tigris trial using their device, their software, their infusion sets, that's in order to provide the data that's necessary for 510 to simultaneously or as near simultaneously as possible to get approval for PrisMax to deliver the therapy at the same time that the PMA would be approved for PMX. That's a little bit of an issue for anyone trying to work in this space because you can't get approval for a device to deliver a therapy unless that therapy is already approved.
It's a little bit of a catch-22, and working closely with Baxter on the regulatory side is trying to get us to line up, and obviously working with FDA, who's been, I think, very helpful in terms of helping get us coordination between the 510 approval that Baxter would have to get for their device, their delivery system, and the PMA for us. We're working closely with Baxter on that.
That's great. That's it for me for now. Thanks again, guys, and again, congrats. It's been a long time coming.
Thanks, Scott.
The next question comes from Mena Abdel-Nour with Bloom Burton & Co. Please proceed.
Hi. Again, congratulations on the trial. I think, like Scott said, it's a long time coming. I just have one question really around the data and thoughts, if you could speculate a little bit on reimbursement in the future. The fact that there is this difference or greater difference at 90 days versus 28 days, do you think that's going to raise the barrier for reimbursement or because it's taking a bit longer or the difference is greater at that time point, that this is going to create some issues? Yeah, love to hear your thoughts on that.
Yeah. This is John. I don't think it's going to create any reimbursement issues. I frankly don't think the reimbursement when you're talking about mortality differences, I don't really think that they impact reimbursement very much. I think that when you have softer endpoints and there's question about what's the value of being off mechanical ventilation, for example. Every patient would tell you there's great value in that. You get into issues about, how much is something worth if it doesn't save a life, right? I think the fact that we're able to demonstrate such a robust difference at 90 days, which is really, as I said before, is much more important to patients, really will, I think, support the idea that the value of this product is quite high.
Maybe just a quick follow-up to that. In addition to the mortality, which I think everyone agrees that is clearly the most important endpoint, I imagine that you will be collecting and reporting in the coming days or months additional data like time on life support or additional support required by these patients and whether there is a difference there. The reason why I ask that is there is a little bit of a catch 22 if you improve mortality for the hospital, there is increased costs. I think that is something that I am quite curious about with respect to adoption. I would like to hear your thoughts on that if you have any kind of.
Yeah, that's a great question. I think you're spot on in sort of trying to work through how this plays out in terms of adoption amongst hospitals. I would say yes, we have much more data collection or data analysis that's underway to sort of unpack all of that. We will expect to put some of that information in the Tigris manuscript. The speculation obviously is tied to, again, to Claudio Ronco's hypothesis that these are patients that are still in the standard of care arm, are still in the ICU, and obviously that's much more expensive than being out of the ICU.
If that all holds up in further analysis and we actually do see patients that are out of the ICU, even maybe out of the hospital at 28 days in the treatment arm versus standard of care, then that in and of itself, even if there wasn't a mortality difference, would probably drive clinical adoption just because of the health economics around it. I think that's just a hypothesis at this point. I think that we sort of need to look at the rest of the data to sort of have a better understanding of that.
Thank you very much. I have no other questions. Again, congratulations on the trial. Scott said it. It's a long time coming.
Yeah. Thank you.
The next question comes from Kevin Vinstro, a private investor. Please proceed.
Yeah.
Thank you for the excellent presentation and also congratulations on all the hard work. Reiterating the other comments. Just a few questions from me. Question number one, this is for Dr. John Kellum. I'm wondering if you can just provide a little bit of commentary around the comparison between Tigris and EDEN. I know EDEN was very different, but in terms of mortality and things like that, are they pretty lined up in terms of what you would expect?
Thanks, Kevin Vinstro. I think probably not everyone's aware of the EDEN study. The manuscript is in press but hasn't been published. There was an abstract published back in February. I'll just tell people what that is. The EDEN study was an observational study, in which we enrolled patients that included patients that could not be enrolled in the Tigris trial, usually because they either had an exclusion criteria or they failed to meet inclusion criteria. These were all people with septic shock. We wanted to understand the relationship between both organ failure scores using MODS and SOFA and the EAA levels, both within the range that we enrolled in Tigris, 0.6-0.9, but also outside that range. To sort of understand what the natural history of this disease process is.
Obviously in the Tigris trial, we're only including patients that meet our pre-specified criteria. What we observed in that study, and as reported in the abstract and what's in the manuscript, is that it does look like the patients in this kind of high organ failure, defined by a MODS greater than 9 or SOFA score greater than 11 and EAA greater than 0.6, really does represent the super high mortality population that had a 60% population, 60, almost 61% mortality rate in that study at 28 days. There's two cautions about that. One is that that also included some patients, I can't remember how many now, but there were some patients that were above 0.9, so that may have driven the 28-day mortality up a bit. There weren't very many of those patients, but there were some.
Secondly, because this is not an intervention study, this is obviously all, if you will, standard of care. It probably also reflects the fact that every time you do an observational study, there are slightly increased mortality relative to the treatment studies, mostly because getting into a treatment study requires some additional screening and enrollment criteria that wasn't applied. That said, I think it's quite remarkable that the 28-day mortality in that subgroup in that analysis was 60%. Actually, we got the 60% mortality in the standard of care group. It just took a bit longer in Tigris. It took 90 days. I think there is a lot of similarity, and I think a lot of consistency across both the observational data, the interventional study, and the subset of patients that we analyzed and used as our prior for the Bayesian from the EUPHRATES trial.
That's great. Second question, and I asked this question before. I know with the Tigris and EUPHRATES, there's always that kind of time gap between actually randomizing individuals or I should say, getting approval from the next of kin versus once this becomes kind of standard of care, assuming FDA approval, you would actually not have that requirement. And again, this is more of a speculative question, I guess, but is it fair to say that you would expect the mortality benefit to be even stronger once you get rid of that kind of approval process?
Yeah. You and I have talked about this before, Kevin. I think it's a reasonable hypothesis. It's a reasonable question to ask. I do agree with you that when you don't have to formally have people sign a consent form to participate in a research study, and usually the family has to think about it for a while, and it delays for the process. When all you're doing is getting informed consent to treat patients, that's a much quicker process. I do think that we will shorten the time between presentation with endotoxic septic shock and the sort of definitive therapy. Obviously when you're removing a toxin that's floating around the bloodstream, the faster you can get that out, the more likely there's going to be a benefit. I think that your hypothesis is quite reasonable.
I do think that may well be borne out in data going forward. There is a little bit of data out there already from analyses that have been done, I think, in Europe, which suggests that's exactly what you see, that faster therapy results in better outcomes. We'll have to see how that plays out in the marketplace.
Okay. Just one last question for you, Dr. Kellum, around multiple cartridges. I know with the EUPHRATES, Tigris, it was limited to two, and I guess you're still poring over the data, but when you do submit for FDA approval, are you going to extend it to basically say, "Hey, guided by the EAA, there's reason to believe, or we think that there's opportunity for multiple cartridges on a case-by-case basis?
Not at this juncture. I think that the FDA is really quite keen to keep the label and the IFU for the product to match the clinical evidence. I think we didn't design this trial as a prognostic-based approach where you sort of treat to the EAA levels. Future work could focus on that and potentially extend the treatment and the population. At this juncture, really the label is going to almost certainly say that your two treatments based on initial EAA level. That said, physicians have some latitude in terms of what they want to do, and certainly we do see patients occasionally who have relapses. They get better from endotoxic septic shock treatment, and then five days later, they're back in the ICU with the same syndrome again.
We did not re-treat those patients because it wasn't in the protocol, but you might imagine that you might think about that if their EAA levels are back up again, would you go ahead and treat them again? I think all those are fair game for future speculation. At this point, I think we're going to be locked into very specific criteria based on our study design.
Okay. That's great. Just two quick questions for Chris. First one is around ramping up production of EAA and availability of PMX pending FDA approval. What are your plans with respect to that?
Kevin, I think we've addressed this before, but I think certainly there's enough capacity both on PMX production as well as EAA production. As you know, we produce EAA here in Toronto, and we have significant capacity to fulfill what we think are going to be projected orders going forward. On the PMX side, I think that certainly at some point there will need to be an expansion of the production facilities out of Toray. It's like that movie "Jaws" where the sheriff tells the captain, "You're going to need a bigger boat." Well, that's certainly our message to Toray. Is it going to be tomorrow? No. I think it could potentially be sooner rather than later.
Okay. That is great. Just one more question for you. In respect to the up to CAD 100 million offering, can you give any color in terms of what you may or why you would do that and what the money may be used for?
Yeah, Kevin. Certainly we don't have any intention to utilize the base shelf at this point in time. I think it gives us maximum flexibility going forward. As you know, and if you look at our balance sheet, we carry a number of converts and Vantiv has worked hard with us in putting forward a facility in the form of a promissory note. As we know, that's debt. I would expect that those convertible debentures get converted. They are deep in the money, but one never knows. We don't have a unilateral forced conversion feature on that. I would like to have as much flexibility around our balance sheet and to right size the balance sheet as possible. Is that something where, at today's share price, we would avail ourselves of that? Likely not.
If certainly there was a significant uplift in the share price, and I'm talking significant, that it would blunt any form of dilution, we'd have to consider it. Once again, it's just another tool that gives us maximum flexibility around our balance sheet.
Okay. Thank you so much. Appreciate it from both of you.
Thanks, Kevin.
The next question comes from Daniel Murphy, private investor. Please proceed.
Hi, gentlemen. How are you?
Good, thanks.
I'm a longtime investor. I have been with Spectral for about 11 years. I also have two personal friends who've died from sepsis shock. I hope this all works out. As a lay person, I just have a question, is where is it that you think PMX and Spectral will be successful, and what are the advantages it has over the previous trial from Eli Lilly that wasn't successful? What's the difference in the product and how and why are you confident that this is going to work much better than something that was tried? What's the differential?
Yeah. No, thank you very much. This is John. Thank you very much for that question because I think that is exactly the question that people should be asking. I think the story really kind of plays out quite well. Xigris, drotrecogin alfa, was a drug that was really quite effective in a subset of patients who had activated protein C deficiency. Even in patients with protein C levels that were lower than normal, the drug worked exceedingly well. Because that subgroup of patients drove the overall result, Eli Lilly really wanted to have an indication for all patients with sepsis, and therefore played down this kind of personalized medicine. Now, this was many years ago, and personalized medicine wasn't such a hot topic in medicine. You might argue that it was because Eli Lilly sort of wanted the whole show.
As a result, when they conducted a second trial, that efficacy, just because of differences in case mix perhaps, really sort of waned. They had another problem, and that was some serious bleeding complications where the number needed to harm actually started to look somewhat similar to the number needed to treat. Those kinds of things really complicated the story for Xigris. Nevertheless, I'm an ICU doctor, used a lot of Xigris in select patients in the days that it was available, and I think for some patients it was quite effective.
Here we know exactly the population that we should be treating, patients that have a level of endotoxin in their bloodstream that is both high enough to kill you, but not so high that therapy can't be effective and that you have evidence of development of significant organ dysfunction, meaning that you're at high risk of death. We're already sort of preset to say this is the population we think that the product should be used on. We're not trying to say that it should be used on everybody that has a clinical syndrome of septic shock and hope that we can help some patients but maybe not help others.
I think that's the big difference. I really think you're asking exactly the right question that we should be asking. I think trials in sepsis going forward will be much more focused on making sure that they've selected a population that's really the target population that can be treated.
Great answer. I really appreciate it. As I said, having known two people that have died from septic shock, I really hope that this goes through, and thanks for all your hard work, gentlemen.
Thank you.
The next question comes from Michael Wilk, a private investor.
Good morning, fellas. Congratulations on your results. Just a quick question. You've got 28-day data and 90-day data. Moving forward, is there any data that will be looked at that exceeds and goes past 90 days?
Yeah, thank you for that question. We did collect and are frankly still collecting data on 12 months. That data's not locked yet. I can't say anything about it. We do expect to be able to report on the long-term outcomes, the 12-month outcomes at least, at some point because we are collecting that data. Obviously, the trial, still a lot of patients are still pending outcome at 12 months. That data won't be locked for a while. Once it is, we do expect to present a subsequent follow-on analysis. The only thing I can say about what we think about the longer term outcomes is that we do see, I would say the survival curves beginning to stabilize somewhere past about 60 days.
The expectation is that longer term outcomes, let's say at 12 months, will be very similar to what we see at 90 days. We'll have to wait and see what the final analysis shows once all the data is in.
Thank you very much.
The next question comes from Prashant Rao, a private investor.
Good morning.
Hi, Prashant.
Hey, good morning. Congratulations on the excellent results. I do have two questions. Can you please clarify the zero percent mortality reported in the modified intent-to-treat group? I want to understand how many patients does it reflect and were there any key balances or exclusions?
Yeah, I can comment on that. This is actually fairly common in device trials, and it's actually why the modified intent-to-treat is used as a primary endpoint historically in many device trials. The FDA doesn't really like it. They prefer an intent-to-treat, which is why we have that as our primary endpoint. However, the reason that it exists is that unlike a drug, which you can get up from the pharmacy and just deliver to patients, and if somebody drops the drug on the floor, you can get another dose of the drug from the pharmacist. Devices have a habit of either breaking down or something not being available.
In our case, that really didn't happen. What did happen is that we had limitations of when we could treat patients because a nurse had to deliver the therapy and it had to be a study nurse. This won't be an issue in the real world because the ICU nurses can just deliver the therapy. For us, during the trial, we had to deliver it with study personnel, and study personnel were limited in terms of how late they could stay and things like that. We did have situations where, unfortunately, thinking of patients who got consented, who got randomized, and then the clock just ran out between the time that happened and the time they were able to treat the patient, and as a result, the patient ended up not being treated. That was the most common scenario.
We did have one patient, as I recall, who the family withdrew consent based on the fact that the patient was deteriorating and they really felt that it was better to not treat the patient and just keep the patient comfortable. These are complicated situations where people are having to make decisions under very adverse conditions. Things like that happen. There were exactly six patients that met those criteria, meaning that they were randomized but never received treatment for a variety of reasons, including the ones that I mentioned. I think you should interpret the modified intent-to-treat analysis, that 8.1% difference compared to the 6.4%, as a better representation of the actual effect of the therapy at 28 days. Because it's post-randomization, it's not as clean as the intent-to-treat data are. Fortunately, both of those are above the 95% posterior probability.
Thank you. Two additional questions. Do you foresee that EAA could evolve into a broader platform for ICU triage or endotoxemia management? One last question for Chris. What are the key milestones that we should expect over the next six to 12 months? Thank you.
Sorry, Prashant, could you repeat that last question?
Sure.
Key milestones. Sorry, key milestones. Yeah. Key milestones. We have several. What I would say is, FDA submission, the final module at the end of October. There is a manuscript in a major medical journal. I think we're looking to submit that by the end of this month or early September for hopefully publication by year-end. On the back of that, we would present at a major medical conference. From there, Prashant, really we would expect an FDA final decision somewhere around middle of next year. Let's call it end of June, sometime into July, possibly into August of next year.
You had another question I didn't catch about the, I think it was about the EAA.
Yeah. My question was more so to understand whether or not EAA could potentially evolve into a broader platform for ICU triage. Is that a possibility?
Well, I think there's sort of two aspects of that, right? I think that the test already could be incorporated in a broader platform in terms of screening patients for endotoxic septic shock at an earlier time than we currently do, which is after they've met clinical criteria for septic shock. You could imagine doing that sooner and put it into sepsis bundles and things like that. I think that could already be done with the existing technology. In terms of baking it in on a technology platform, that would be challenging with the current assay because the current assay is quite different. It's a bioassay that involves the patient's own white cells. No other tests really work quite that way.
A second-generation test that measured endotoxin activity that could be done on samples of whole blood where other analytes could also be measured, is something we've been working on or considering at least for several years. It's possible. I don't think it's going to be anything in the near future, however.
Thank you. I have one additional question, if I may.
Sure.
Are there any plans for trials in other indications, something like liver failure or cardiac surgery? Because I've read a lot of papers with respect to these conditions for PMX. Thank you.
Yeah. We have some observational studies actually underway in Europe using EAA to identify patients that may have an indication for PMX. On the back of that observational data, we may consider doing additional work in the future. Right now we're sort of laser-focused on getting PMX approved in the United States for endotoxic septic shock. Yeah, I think there are some potential areas to move into that are not endotoxic septic shock, but maybe high levels of endotoxin in other conditions, and I think cardiac surgery is one. Certain organ transplantation is another. Trauma, and things like that is other areas that you might consider. All of that for us is going to be post FDA clearance.
Thank you very much for the answers and congratulations once again.
Thank you.
Thanks, Prashant.
Thank you. At this time, I would like to turn the conference back over to management for closing comments.
Great. Thank you. Thank you all for joining us today. It certainly has been a journey. The Tigris results represent a pivotal moment for Spectral Medical and the patients we aim to serve. We look forward to updating you as we move towards FDA submission and ultimately commercialization in partnership with our very strong partner, Baxter, who, once again, we'd like to thank for lending part of their balance sheet to us and allowing us to move forward and ultimately to PMX commercialization. Once again, thank you all, and we look forward to updating you as we progress.
Thank you. This does conclude today's teleconference. You may disconnect your lines at this time. Thank you for your participation and have a great day.