Hello, everybody. We're back. We have AIM ImmunoTech, ticker AIM. Tom Equels, CEO, joins us once again. It's been a little bit, but a lot of it, I think, has happened, you know, over that time, with AIM. And just as a reminder, the company has an asset called Ampligen. It's really a synthetic double-stranded RNA. You know, once you put that into a person, it kind of tricks the body into almost an antiviral immune response. It has a lot of applications in terms of oncology indications. They're doing some tremendous work right now in pancreatic cancer. They've had good data there. They've been in ovarian cancer. They're doing all kinds of things, plus that drug is actually approved ex-US in Argentina. It's one, a South American country, for chronic fatigue syndrome. There's a lot of overlap here, and I think once you boil it down and you look at where oncology and these indications are for combination therapies and our understanding of what things like an Ampligen do to change the immune environment, sets up this tremendous opportunity for combination therapies. I think for AIM, it's been a long road, lots of investigator-sponsored trials, lots of, call it, bits and pieces of data here and there. But now, as you look at the company today, they're in a mid-stage trial in pancreatic cancer. It's got a bit more traction, and I think it's worth paying attention to. So Tom, welcome back. I think it would be most ideal if you give us just a brief overview of the company, and then we can get into kind of the bits and pieces of the trials that are ongoing. Thank you very much, Jason. We're an immunology research and development company. We trade on NYSE American, ticker symbol AIM. We have a primary exploratory drug that we're developing in oncology, as well as with certain antiviral and immunodeficiency-related applications. Specifically, our focuses right now are in three areas: late-stage pancreatic cancer, advanced recurrent ovarian cancer, and long COVID-expressing chronic fatigue-like conditions, which is very similar, if not identical, to chronic fatigue syndrome in many respects. Our clinical progress there, as you mentioned, has been significant over the past two years. I'm prepared to discuss those issues, but before I do, going back to a point you made, it's important to understand with this molecule why it has such great potential. It's a first-in-class drug that we're working with, and it's a highly selective double-stranded RNA that stimulates the Toll-like receptor 3 pathway, and only the Toll-like receptor 3 pathway, with minimal inflammation, no cross-activation of other TLR pathways. And as a result, we have an extremely well-developed safety profile involving hundreds and hundreds of subjects with extensive experience with infusion therapy with Ampligen. Now, that safety profile becomes very important because Ampligen's role in stimulating and activating, as an agonist, the Toll-like 3 receptors, is a role that, by its very nature, has broad-spectrum applicability. So the way it works in solid tumors, for example, the data that we're getting in pancreatic cancer tumors, stage 4 triple-negative breast tumors, ovarian cancer tumors. You know, these solid tumors all have something in common. They're very much composed of epithelial tissues, which are rich with Toll-like receptor 3, and so when we show that Ampligen works in pancreatic cancer, we show that it works in ovarian cancer, it's only logical to assume that it will probably work in a similar fashion, maybe not. You know, a little bit better in one case than another, but in a similar positive fashion in a very wide spectrum of solid tumors. Similarly, the way it operates in conjunction with other immunotherapies, like checkpoint blockade therapies, we've taken the time to test it with different checkpoint blockade therapies, and we're seeing the same broad-spectrum potential there. Because what the Ampligen is doing is allowing the immune system, and similarly allowing the checkpoint blockade drug, to identify the tumor and work. You know, many of these checkpoint blockade therapies are extremely successful in a certain segment of the population, but all of them, even the most successful ones, like Keytruda, have significant refractory patients, patients who don't respond. We believe the reason they don't respond is the microenvironment of the tumor is such-... that the checkpoint blockade drug can't target the tumor, and we believe Ampligen highlights the tumor so that it can be targeted and dealt with by the checkpoint blockade drug. So we see a lot of potential here in Ampligen's future as a therapeutic in oncology, and also in long COVID. I can go into that a little bit later. I wanted to talk about that, yeah. Yeah. Mm-hmm. So- Well, sorry, go ahead, Chad. Why don't you go ahead? Yeah. Yeah. Before, just starting with the oncology programs, now you're in two different phase IIs in pancreatic cancer. You know, one in locally advanced, the other in metastatic, in collaboration with AstraZeneca. Could you just walk us through those two programs, and, you know, the differences between the two? Yeah, the program with AstraZeneca is combining Ampligen with AstraZeneca's drug, durvalumab, also known as Imfinzi. durvalumab is a PD-L1 checkpoint inhibitor. We have prior experience with PD-1, showing what appears to be a tremendous synergy or enhancement of the impact with the PD-1 drugs. But we wanted to explore, in pancreatic cancer, the opportunity to work with Ampligen in combination with PD-L1, because our preclinical data suggested that PD-L1 checkpoint inhibitors might be a more effective combination in the pancreatic tumor. Now, that study is moving very rapidly. It... Because we were combining Ampligen with durvalumab for the first time, we had to conduct a safety clinical program as a lead-in to the full opening of the trial, and that was a three-by-three step-in of Ampligen plus durvalumab. Thus far, there have been no significant safety issues. It's been generally well-tolerated. We're almost at the end of that, but the data just from that run-in period related to disease stabilization has been fairly significant. Because this is being conducted in the Netherlands at Erasmus, and because they have patients who are in a parallel track at Erasmus not receiving the therapy, we're looking at their progress related to disease stabilization or disease progression, however you wanna look at it, and the progress of the Ampligen cohort. And many of these subjects will start to be enrolled once we've finished the phase Ib part of this and moved into the phase II. But what's significant, and we can see so far, is for those who have reached the six-month stage, we have disease stabilization at six months with over 60% of this Ampligen plus durvalumab cohort. Whereas this comparator group, that's being looked at at Erasmus, has only approximately 20% disease stabilization at that stage. So this is a very powerful initial signal, and we're very excited to, once we finish up that phase Ib part of the study, to have this fully open. And there's a very strong demand to get in the study, which is important. But again, the distinction here is, one, the combination with durvalumab, and two, that these are metastatic pancreatic cancer patients in this study. Now, AMP-270, which we've had some difficulty getting moving forward because, you know, the late stage pancreatic cancer is, as everybody knows, a very fast-acting and highly lethal cancer. We're working, you know, on the cutting edge of oncology when we're trying to help these subjects. And to some extent, not the approved standard of care, because the approved standard of care is what we were trying to use in locally advanced as a baseline to replicate our early access program data. But in many cases, there are all these other therapies that are followed up just because of the desperation of the situation. And so we're working to modify the inclusion criteria there, and we're in the last stages of that to address some of these follow-on, like radiotherapy, things like that. And we have to analyze too, if we continue to see these tremendous successes in combination with durvalumab, it may make sense to modify the AMP-270 concept into a similar combination therapy. Because there is if it's working in metastatic, we believe it will have a similar impact in locally advanced. We saw in the early access program that Ampligen by itself had a, this is with 57 subject, had a very strong impact in both locally advanced and metastatic pancreatic cancer in terms of disease stabilization, prolongation of progression-free survival, and overall survival, well beyond the standard of care. But even more importantly, we identified through exploratory biomarkers subsets that we believe are indicative of who will respond extremely well to Ampligen, and there the extension of overall survival is just outstanding. So there seems to be a lot of Ampligen's been around for a while, right? It, it's got an approval. It was chronic fatigue, right? It's, it's been, it's a, it's a validated approach to immune stimulation. But, you know, sometimes I think some therapies like cancer vaccines, that were a little bit ahead of their, their time, so to speak, right? Where with the, with, with the movement of checkpoints into basically every indication that's out there, there's been a lot of movement towards understanding the kind of antiviral, antimicrobial response. You have a double-stranded RNA, you're mimicking a viral response. We saw Genenta this morning, they're doing something, just putting alpha interferon into, into cancer cells. And, and we had Indaptus just a, just an hour ago, using whole bacteria. You get this antimicrobial response, and movement towards adding checkpoints in. So, I wonder, you know, while it's been some time and you've collected a whole lot of data, that is now the time for AIM, that there's all this movement with this innate immunity and the antiviral response towards combination therapies in cancer. Conceptually, we were a little bit ahead of our time. When I became CEO, one of the first things I did was effectively repurpose Ampligen to have a new focus in oncology. And historically, we had been almost exclusively focused on chronic fatigue syndrome, which is even today a little understood syndrome. However, everybody understands, for example, pancreatic cancer and late-stage pancreatic cancer. So we started off in late two thousand and sixteen, getting approval from the Dutch government for an early access program of Ampligen as a single-agent therapy in late-stage pancreatic cancer patients. And there have been a number of peer-reviewed articles published outlining the successes that we achieved in that early access program in terms of therapeutic response. Now, that became a foundation for the work that we're doing in other solid tumors, in pancreatic cancer. Because we believe it, you know, has, and we've demonstrated an impact, a signal that in human clinical work, that indicates that it has an impact in different solid tumors like triple-negative breast, ovarian, pancreatic. But we are focusing now principally on ovarian and pancreatic because, you know, you can only do so much at once, especially a small company such as ours. We have a little over twenty employees and limited financial resources. You mentioned in the introduction, and I appreciate the fact you've been following us throughout, certainly during my time as CEO, that a lot of our work is investigator-sponsored studies. The reason for that is that in large part, our financial contributions are ameliorated by the fact that these studies are funded by grants from National Cancer Institute, different governmental organizations, that type of thing, or in some instances, from industry. Some of the big pharma companies have contributed, certainly to our ovarian and this pancreatic cancer work that we're doing in terms of letting us move forward with the studies that, or otherwise, would be extremely expensive. You know, that work that we're doing is now paying off because the data supports the hypothesis that we had in late two thousand and sixteen, and as you mentioned, the focus in the industry is starting to recognize that getting the immune system primed for therapy is extremely important. Now, there's another element here about Ampligen that I want to emphasize in terms of its importance in oncology. Ampligen has a powerful, I believe, the data shows a powerful anti-tumor effect in the way it operates in helping the immune system to identify tumors that might otherwise be immunosuppressed, but when we look at oncology and the causes of mortality, we also need to consider the powerful antiviral impact of Ampligen. Ampligen is a powerful antiviral with preclinical data supporting its impact in a number of different types of viruses, but certainly in respiratory viruses. When you look at that data, and you look at the causes of mortality in some of these lethal cancers, you have certainly people who die from the cancer, but you also have comorbidities that go along with that that are related to perhaps the savaging of the immune system by the cancer or chemotherapies or some combination. So that oftentimes people fail due to respiratory viruses being the actual cause of death in the course of the disease. So Ampligen brings two things to the table in that respect, which I think are very important long-term. This is why immunotherapies are gonna become more and more significant in oncology over the long term, in my belief. So what about. I think if you were to talk about COVID and long COVID a year ago or a year and a half ago, I think people get tired of it. They're just burned out from COVID, right? And you guys have done some work in long COVID during the pandemic, like a lot of groups. However, there's been a lot of activity around recognition that certain dormant viruses are being reactivated post-COVID infection, and that's actually the driver of long COVID and these chronic fatigue-like syndromes. And again, you know, there's Virios Therapeutics, right? And they're now Dogwood Therapeutics. I think just this week or last week they changed their name. But they, they've shown work with antivirals, that they're getting good results in long COVID. And then in August of this year, there was a some news out that Congress is putting through a bipartisan bill centered all around Long COVID. And it's interesting that, again, here's Ampligen, I think, a little bit ahead of its time, you know, what, 10 years ago, whatever it was, with an antiviral response, right? 'Cause you're hitting TLR3. You know, does that bring Long COVID and these kind of chronic fatigue-like syndromes back into the picture for AIM as a company? We believe it does because, first of all, the outbreak of the Wuhan virus, you know, brought to my attention the possibility that it was a SARS-related illness. This is back in 2019, and we did a very careful analysis of the viral makeup, and it's extremely similar to SARS-CoV-1, which caused the SARS epidemic in 2002, 2003. And Ampligen was part of two different NIH contract studies with a panel of antivirals for that first SARS virus, and Ampligen was the only one at clinically achievable doses that was able to reduce viral titers in the lungs to undetectable levels, and then in a survival study, the only one that conferred 100% survival with minimal symptoms as compared to a control group with 100% fatality. I was watching to see if this was a SARS outbreak because we had that background. And also, there was a study. It was published in JAMA, but in survivors of SARS, that study was a peer-reviewed study that showed that 27% of the survivors of that initial SARS outbreak had met the CDC, US CDC guidelines for chronic fatigue syndrome. When we had the COVID-19 come on the scene, I anticipated that we might be seeing a replication of these chronic fatigue-like conditions as a result of that viral infection, very similar to what was seen with SARS-CoV-1. SARS-CoV-2 and SARS-CoV-1 are extremely similar genetically, so we anticipated that, applied for patents related to long COVID before probably anybody knew what long COVID was. This was... I think we did our first application in June of 2020, and the, you know, we never lost sight of this because what we thought might happen is actually happening, and when you look at the percentage of people who are having serious Long COVID problems, it's a significant percentage, and these are serious, sometimes fully disabling symptoms, but we've had so many people infected in the United States, that population is just growing and growing and growing, yet there's no approved therapy for it, so we've tried to step into that space, based upon our historical background in chronic fatigue syndrome, where we were showing, especially in earlier onset subjects, I believe a 51% response rate with a 33% delta between placebo and the control group. This is all laid out in a PLOS ONE article from, I think, September of 2020 or 2021. I I don't remember the exact date of the publication, but that article outlines Ampligen's impact in early onset symptoms for chronic fatigue. So we moved, based upon seeing that, into Long COVID and conducted a sort of proof-of-concept study called 518, which had, I believe, 80 subjects, but they were. We cast a very wide net as far as inclusion, so we could start to identify who the, let's call them super responders, might be. What segments of those populations would respond most vigorously to Ampligen? And that data, that final data analysis is completed. We've shown in the portion of those 80 subjects that had moderate to severe disease, which is, I forget the exact number of subjects, but there was a significant statistically significant response showing that Ampligen had an impact in improving objective criteria related to the disease. So now we're trying to move into a next phase of analysis focused on that target population. Additionally, we had exploratory biomarkers that were a part of that study, and that data analysis is not complete, but we're seeing suggestions that will help us to better identify who Ampligen responders might be. But also, some of that data may contribute to the body of scientific knowledge that goes to the real core why chronic fatigue syndrome and even Long COVID are problematic. And that is, you know, up to this point, much of the criteria for determining who has the disease is diagnostic criteria that's somewhat subjective. And, Fatigue scales are now why they're... The FDA is accepting. They have very defined, validated fatigue scales, orthostatic intolerance scales, where it was all in the last year, we're starting to see these things, and that's why I wondered if AIM is going to maybe wade back into the Long COVID chronic fatigue world. We already have the AMP-518 study results that have come in, which the complete dataset analysis clearly shows us that there's a place for Ampligen with moderate to severe sufferers of the disease, as demonstrated. We used a six-minute walk test to delineate you know this point because we see. The big difference we're seeing is right at the cusp of what would be people below that demarcation line are considered home ambulatory. Above it, community ambulatory. And what Ampligen's doing is, the signal that we see in that clinical trial is suggesting that we have a significant impact in taking people from home ambulatory into community ambulatory, which has a tremendous impact on quality of life and their ability to participate in things like work and family. Got it. 12:58 already. That's all the time we have, Tom. It's good to see you. It's been an honor and a pleasure, so Yeah, well, we'll catch up with you soon. We should chat offline once this conference is over and get caught up, and I hope to have you back soon. I look forward to it. Thanks, Tom. Thank you very much. I appreciate your interest in Ampligen and AIM.