NASDAQ: IMNN
Host: Hello and welcome to the Life Sciences Investor Forum. On behalf of OTC Markets and our co-host, Zacks Small Cap Research, we are very pleased you've joined us. The next presentation is from Imunon. Their session will be moderated by David Bautz, Senior Equity Analyst with Zacks Small Cap Research. At this point, I am very pleased to welcome Stacy Lindborg, President, Chief Executive Officer, and Board Director of Imunon, which trades on NASDAQ under the symbol IMNN. Welcome, Stacy.
Stacy Lindborg: Thank you very much, and it's a pleasure to be with you. Thank you to Zacks for this introduction and for this opportunity to talk about our exciting work that is ongoing. Let me, with no further ado, move forward. Included in our deck are our disclosures and forward-looking statements. When we ultimately step back and reflect on the opportunity from an investment thesis perspective, I would say that we have an incredibly strong thesis that I'll be walking through in terms of the framing and then also the background and ultimately what stands behind and gives really robust confidence to these points.
SL: We're in the middle of a registration trial, which will be a frontline in newly diagnosed women with ovarian cancer, and the funding opportunity is to enable full funding of this trial. When we step back and think about the context of this, this product is expected, if we are successful in Phase 3, it will be a first-in-class immunotherapy in ovarian cancer. There are no immunotherapy agents that have been successful, and we'll talk a little bit about why that is and why we have the evidence that we should be the first that would be approved in immunotherapy. It would also be a first-in-class IL-12 immunotherapy, which is another conversation that I think is really important that we'll dive into in some subsequent slides.
SL: But basically, there has been no change to the standard of care. Whether you care about the mechanism and how the product is working, the frontline ovarian space has remained, and the standard of care has remained unchanged for almost three decades. We're talking about changing the lives of women with ovarian cancer. Compelling data that we have generated from a very large, well-controlled Phase 2 trial, which allows very simple interpretation, because we've actually taken patients and randomized them to receive the standard of care, which is neoadjuvant and adjuvant chemotherapy with surgery that basically is removing the cancer in between those two treatment periods with chemo. And then half of the patients were randomized to that arm, then the remaining half were randomized to receive that standard of care plus Imunon.
SL: When we compare the treatment arms, we know that this allows us to really understand and appreciate what's different between these treatment arms as a result of the novel experimental treatment. We know that this data is very strong and is unprecedented. We also know that, because of this, this represents a multi-billion-dollar unmet medical need. And this is something that's true with just the frontline indication, the first indication that we're going after with ovarian cancer. We also believe that there is a rich and broad application of this product, and then further to the technology platform that could go after other indications.
SL: This, what I'm really painting, is the smallest entry-level opportunity, and what we would expect would be peak revenue sales for frontline in really the US is already a multi-billion-dollar opportunity. We know that, and we're very aligned with the FDA. On top of the advancement of our trial, the FDA granted fast track, we have orphan drug status in the US and Europe, and we have brought in and really cultivated incredible skills within the company that ultimately will be incredibly important when we get to the commercial market. Namely, very specifically, one of those skills and capabilities is the clinical-grade GMP suite that we have in Huntsville, Alabama. We are manufacturing the core API, the active pharmaceutical ingredient for this product, and it allows us to keep cost amazingly in check and ultimately, when we get to the commercial setting, to be able to produce product in-house with robust gross margins.
SL: You'll hear over the course of my slides that we have a really strong alignment with the FDA, including already knowing and having an agreed-upon potency assay. What this really sets us up for is replicating findings that we've already observed in Phase 2, and a very strong Phase 2 that has really taken a lot of interest from the medical community. We're actively advancing this. We have the definitive endpoint, which allows for confidence in a single study filing. And on top of that, we do have, as we've discussed before, a protocol that, with the FDA's blessing, has two interim analyses that could allow for even earlier stopping and full approval.
SL: Let me go through just some background in case you're new to our story. What is IMNN-001? What is our technology platform, and why ovarian cancer as our first indication to go after? Well, number one, if you look in the literature, you'll see that immunotherapy has always, those who develop it and from a market standpoint, looked to epithelial ovarian cancer as a really highly valued target because the disease itself is immunologically cold. When we reflect on ovarian cancer, effectively, it's evading our immune system, so the natural defense that we have. And therefore, if you can tap into the immune system and alter the tumor microenvironment, you would have the ability to then harness the immune system, therefore making an immunotherapy very attractive.
SL: Our product is an IL-12 DNA-based plasmid. It is encoded with IL-12. We're not administering IL-12, we're administering a product that basically is carried through a synthetic nanoparticle, a lipopolymer, that allows our novel therapy to go directly... It's administered directly into the peritoneal cavity, which is exactly where the tumor is residing. Then the cells in the peritoneal cavity uptake the novel product, and these cells start producing IL-12. We're not delivering IL-12; we're effectively delivering a recipe, and the body is then able to take over and produce this naturally occurring cytokine that is very effective and very well understood. IL-12 and immunotherapy, the IL-12 that we are producing, what we call IMNN-001, really is renewing this promise for ovarian cancer survival.
SL: In fact, when we reflect on the approaches, this has been such an incredibly sought-after and really highly thought-of in terms of being able to really revolutionize the standard of care. Why do we believe IMNN-001 will result in a different approach? And I would say for multiple reasons. Number one, when we look back over the last 25 years, the reasons products have not been successful in going forward is they were administering IL-12, recombinant IL-12, directly intravenously, so IV, which resulted in safety side effects. And those safety side effects, in some instances, didn't allow them to actually titrate up to effective doses. What is very different again about IMNN-001 is that it's going directly into the peritoneal cavity. And I'll show you data that conclusively show that the product that is stimulating higher levels of IL-12 is not systemically being distributed, staying in the peritoneal cavity.
SL: We have an ability, and we know that the dose is effective because when we look at our clinical data, we see something that no product – not just relying on immunotherapies – but there's been no product that's ever been able to show an overall survival benefit. We have an unprecedented clinical effect. We have the ability to look at our biological response, which I'll show you in just a second. And we can also measure levels systemically being distributed, and we see that we do not have an elevation. Fundamentally, we've overcome the challenges that stopped previous attempts, and we've been able to generate evidence that shows that this is an incredibly strong platform that we have incredibly high hopes and, I would say, estimates from a probability standpoint of this being an effective treatment that we want to deliver in Phase 3 for approval.
SL: I mentioned before that ovarian cancer is the first indication that we chose to go after. We've done actually quite a bit of animal research and discovery work in other indications. This is actually a very small representation of the studies that we've done, but it's meant to really illustrate that there are very attractive targets, including pancreatic cancer, colorectal cancer, bladder cancer, and glioblastoma. You can see there are different routes of delivery that we could consider. And even your note on here, in combination with immune checkpoint inhibitors. This is something that gains a lot of interest in our conversations. We know that immune checkpoint inhibitors have been very effective in other cancers, yet have failed in ovarian cancer. And the effect that we are having in the tumor microenvironment may, in fact, allow for a bigger effect and a synergistic effect with a combination therapy. That is definitely an area that would be of interest for future research.
SL: We know that unmet need is high. This is, again, with no change to the standard of care in over three decades. And we also know that the concern with this specific cancer is that in women, the symptoms are so nondescript that 80% of diagnoses in women who have ovarian cancer don't come until the cancer is already in late stage, so Stage 3 or 4. That really stacks the cards against these treating physicians and the women who are fighting this disease and, unfortunately, means that we see that only 40% or less will make it to five years after their diagnosis. And we know that even in cases in the US, there's about 20,000 new cases every year, very consistently, 13,000 deaths.
SL: We know that even of those that respond to chemotherapy, to the frontline chemotherapy and have the best response possible, almost 70% will recur. It really is critical that we're making advances, and this really puts IMNN-001 in a very, very important role and a place where we would expect, if we replicate what we've shown in a large Phase 2 trial in Phase 3, we would expect to revolutionize the standard of care.
SL: This just goes into a little bit of the data that I'll be showing you. Again, no frontline cancer trial has been able to show an overall survival improvement until our Phase 2 trial, which I'll show you. We're up now, the final readout of our OVATION 2 study showed almost 15 months over the standard of care. The median was prolonged, and we're talking well over a year; women were living longer than those who only received chemotherapy. The ability for this to truly transform the standard of care, I think, is very well understood. You can see in the third strike here, the third bar, the 14.7 months, and I'll show you this data in just a minute.
SL: And of course, the knowledge that we are actively enrolling in our Phase 3 trial. FDA is fully aligned with our plans, and in fact, we're continuing to beat the enrollment projections in our forecast internally. We're on track, with each passing month, to be getting closer to the end of the trial. It's very important that we continue with this acceleration, but a big part of this is really being driven by the fact of the magnitude of the effect that we've observed. This is carrying an enormous, an enormous response by the medical community.
SL: On the safety front, it's always important to talk about the benefit-risk. I've been talking about efficacy, but the benefit-risk is incredibly favorable, with a very highly favorable benefit-risk profile. And if we talk about the largest study that we've done, the comments I'll make are cumulative across all of our exposures, all of our treatments; we have not seen systemic dose-limiting toxicities. And we were watching very closely for the side effects that were seen through IV administration of IL-12; they weren't observed. An adverse event of special interest that we were monitoring for, cytokine release syndrome, did not occur with IMNN-001. We've not had an elevation of immune-related adverse events. And really, the common treatment adverse events you see here are managed, and our principal investigators are very accustomed to them, as many of these are associated with the chemotherapy that's been given in combination with IMNN-001.
SL: Getting into first the biological response, because when you ultimately look at clinical data, it's really, I think, helpful to step back and say, okay, what's happening in the tumor microenvironment, and do we know what's actually causing this extension in overall survival? In our case, we do. We see that the product is working exactly as intended. And you'll note that, really, as we go across a couple of slides, and these are published data, so we have more extensive data, but you'll see that we really are fundamentally altering the tumor microenvironment. When we start to look at individual biomarkers that are of interest and are very important, we can see that IMNN-001 is not simply resulting in a high level of IL-12, and that certainly is happening.
SL: I'm going to go to the next slide, so you can see that as we look across on the right, we see the doses from 36 up to 100. It's very clear we have an exponentially increasing level, fold change of IL-12 at the highest dose, which is what we are studying in Phase 3, compared to the lower dose. What is exciting, though, if this were a simplistic response of IL-12, we would not see movements that really are showing that we are having a cascade of effects and that our product is actually having an influence on both of the major arms of the immune system, both the innate and adaptive immunity. We see this fundamental decrease in immunosuppressive biomarkers, which, as I said before, is a hallmark of the cancer itself. It's one of the problems why our bodies are constrained from being able to appropriately attack this cancer on its own. And again, I've already spoken about the potential for this in a future set of studies. This could open up combination therapy that really could be very fruitful as we look down the path for patients fighting this disease.
SL: But there are two other points I want to make on this slide. Number one, interferon-gamma is the potency assay that the FDA has already approved that we could use in the commercial domain. If the product's approved, interferon-gamma would be our potency assay. And you can see that we have the same really high elevation. At 100 milligrams, we're above a 60-fold change from baseline. We have this substantial effect, and interferon-gamma on its own is critical. But one of the things I want you to look at in both of these graphs are, we're focusing on the teal bars, but if you look at the dark blue bars, this is the critical point from a safety standpoint, that as we were increasing dose, you can see that the systemic distribution, so if we measure IL-12 and interferon-gamma and many other molecules, we would be able to see that in fact, it is being contained to the peritoneal cavity. The drug is actually in the compartment where the cancer is. That's exactly where we want it. The safety profile that we see, we really do believe, is largely driven by the fact that there is no systemic distribution. This is a very effective result, and in fact, it shows that the product, what is actually causing the clinical data that we're very excited by.
SL: I described before a 15-month, 14.7 to be precise, difference in the median overall survival. You'll remember, if you've followed us for a while, if you're new to it, when we first looked at the data from this study, we had an 11-month difference in the medians. We continued to monitor and observe overall survival, and we have now closed the trial, and we've ended with, again, an unprecedented but even larger effect of close to 15 months. You can see how we get to that. So, for women who were treated with the standard of care plus Imunon, the median overall survival was 45 months. For those only receiving chemotherapy, it was 30 months. We're talking over a year, a substantial amount of life that these women get to experience, and ultimately, from a very short treatment course. What we're studying is consistent with Phase 2, and we're excited, ultimately, down the path to be able to explore what further and longer treatments would be. But this is the course that we would go after for a registration trial, and you can see the effect in all comers.
SL: The next slide goes through women who received PARP inhibitors. On both treatment arms, we know that women were receiving the treatments that they were randomized to, and then this shows whether they received PARP treatment on top of that. And you can see that previously we had not yet reached the medians, so that meant that in both treatment arms, we still had more than half of the women still alive in the trial. We have now reached a mature study endpoint for this subgroup, and you can see that we have a 24-month difference. Women with Imunon treatment are living on average two years longer.
SL: This is one metric of how excited the medical community was. Last year at ASCO, we were invited to give a platform presentation, and we had the simultaneous publication of the results in the preeminent journal, Gynecologic Oncology, which has open access. I'll wrap up fairly quickly, because I want to allow time for Q&A, but this plot is in our manuscript. And what's really important, we don't have time to go through all the secondary endpoints and other subgroups, but you can actually see that across every single endpoint and every single subgroup, we observed an Imunon treatment effect in OVATION 2.
SL: This is an amazing consistency going back to the biomarker data: what we know is actually happening in the tumor microenvironment, and then ultimately what is coming downstream. This is revolutionary, certainly for ovarian cancer, even more so for immunotherapy. And so we have a Phase 3 trial ongoing. We can talk about it if you want me to go into further detail, but this is really a very similar, it's a confirmatory trial. We're implementing a trial that's very consistent with our Phase 2 trial design.
SL: And then I'll close basically with this slide, which is a summary of what I've gone through. Consistency with the FDA, full alignment on our plans, which include the CMC plans and the treatment in the trial, which is coming from our labs. The confidence in this product ultimately comes from clinical data, the consistency of the data, and the ability to enroll it. We have set forecasts that I've talked about openly on our earnings calls. We expect to be at 60 patients by the end of the year, 80 by the end of Q1, and we are 100% on track to meet that. With that, I'll pause and entertain questions.
David Bautz: All right, thanks, Stacy. That was a great overview. There are a couple of points that I want to drill down a little bit if we can, the first of which is the use of IL-12. Some of the feedback that I've heard is that investors are a little bit skeptical, maybe, or nervous about IL-12 given past issues with toxicity with systemic IL-12 treatments. Maybe you can walk us through what are really the big differences between IMNN-001 and those previous IL-12 therapies that led to those toxicity concerns.
SL: It's a great question, David, and it's an important point. I'd say there really are twofold. Number one, the route of administration is radically different. All of the historic attempts were administered directly into a vein, so IV, which then allowed it to distribute systemically throughout the body. We're taking a catheter that is implanted just under the skin of women, right in the abdomen. And it allows for direct injections into that catheter over the course of our trial. And it stays, as we showed, our product is actually delivered exactly where we want it. The route of administration is number one.
SL: The side effects that were coming because of the systemic distribution didn't allow some products to even titrate up to effective doses. They also had significant safety findings. So again, the route of administration is at the heart of it. But we're fundamentally also different in that we're not delivering IL-12. Our vials do not contain IL-12. They contain, effectively, a recipe that allows our body to produce the cytokine, which all of us have, this protein that we all have. And as you see, there's an incredibly effective cascade. It's igniting the immune system, and it's working very well.
DB: All right, thanks for that. The other thing I wanted to drill down into is the interim analyses that you talked about that are planned in the OVATION 3 trial. What exactly will those interim analyses be looking at, and then what are the potential outcomes of those interim analyses?
SL: The way the protocol was designed and aligned with the FDA, we ultimately look at this as a fatal illness for which we've seen an enormous unmet need and no change to the standard of care. Companies like Imunon always have an urgency. If we have an effective treatment, we want to move beyond treating women in the trial as quickly as we can get it into the hands of women who are fighting for their lives. The strategy with the interim analyses was to allow for an early read on the primary endpoint, fully specified, fully alpha-controlled, and fully blessed by the FDA, such that, if we were to hit positively, then we would have the ability to file the data at that time for full approval while we continue to monitor and allow the trial. The treatments are going to be long done, we would be just basically observing overall survival. So we set up two, and we will, as I've talked about in the past, you choose kind of the earliest time point where you could really have an effect, but obviously, the later you wait, the more likely it is that you hit.
SL: We're using a method that is very well understood, and therefore the FDA didn't have any concerns with the methodology. It's called a group sequential trial. We appropriately adjust for Type I error rate. It's actually a very small hit. There's enormous upside. If it hits, you then immediately file, and we would have our application ready such that it would be a very short timeframe from looking at the data monitoring committee looking at the data, triggering an early submission, and then the filing. But if the first interim is not successful and there's more time that's needed, at the end of the day, we've designed a trial to be very effectively powered. We would continue with the timing of the second interim. The timing of those is based around events or deaths, so they're event-driven.
SL: And then if we have success at that second, the same thing would happen that I described before. If we're not, then we would go to the end of the trial. And what we see through—we've done lots of clinical trial simulations—is that basically, with each passing time, of course, the probability of success is going up. It's a very well-thought-out design, but it gives us confidence that if we see a bigger effect than we are conservatively assuming, then we will be able to act on it.
DB: Okay, we've got a couple of questions from attendees about partners. As the Phase 3 trial has been progressing, have you seen any more interest from Big Pharma or larger oncology partners? And how are you thinking about partnering, say, in the US versus ex-US?
SL: We are, and we'll always be, open to partnerships that will further our goals, which are to bring forward a transformative treatment starting with ovarian cancer, and that's in the best interest of our shareholders. We approach conversations from a very open perspective, and we are agnostic as to the geography. In fact, we do have ongoing discussions with a company that is outside the US, and we continue to turn, as information requests for information come in, we turn things around quickly, and I hope it's something that I have an opportunity to give a formal update on in the future. But we'll continue to engage in discussions and have had and will continue to have conversations with bigger pharma. But right now, I have nothing formal to announce other than we remain engaged and look for opportunities that can propel the company forward.
DB: Okay. Well, Stacy, thanks for the overview today. We really appreciate it. Thanks for tuning in.
SL: I appreciate the opportunity to present this and really appreciate everybody who has joined the presentation. For the Q&A, we'll make sure we capture it and have a way that we can respond to questions, and I look forward to giving updates in the near future. Thank you very much.
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