Imunon, Inc. (IMNN) Earnings Call Transcript & Summary

Good morning, everybody. I'm Stacy Lindborg, President and CEO of Imunon. And I'm very grateful to welcome you to the 2026 R&D Day. It's great to see a full room here, and we have a really strong registration and online participation. So we're excited by what we're going to share with you and the opportunity to spend real time thinking about frontline ovarian care treatment. We've got a wonderful set of speakers very experienced and with a unique perspective that I know they will [ in part ] to you. So we, this morning, we'll be focusing a lot on the data that we've accumulated. We have a Phase II trial that's completed with overall survival data, which is a critical. Our product is built around IL-12, a cytokine that was tried by the industry for more than 2 decades, and then was largely abandoned. And by the end of this session, my hope is that you leave with 3 things. Number one, an insight into why IL-12 historically failed; number two, why immunon01 is different; and number three, what the next few years will be and why Ovation 3 is a value-defining chapter for Imunon. So the problem. We'll start with the patient. We always have to remain focused on the patient. We have chosen to study newly diagnosed women with ovarian cancer. This is what we call front-line treatment. It follows in the same frontline treatment with maintenance therapy, but we are focusing on women who have just been diagnosed and are seeking the initial treatment. So they're treatment naive. We know that the way it's been treated at its core hasn't changed for multiple decades. Platinum and taxane chemotherapy plus surgery have been the backbone of treatment. They have saved lives. But we also know when we look to future patients, this is -- the really has plateaued in terms of the treatment, the treatment paradigm. There have been many well-run trials with combination treatments and they have failed to deliver overall survival benefits. Physicians will tell you they will use a drug that has small PFS improvement and no overall survival benefit. So for example, bevacizumab, which is frequently used. And this really tells you how much there is need and where the bar really should be as we reach the end of our Phase III trial, and we're seeking to be integrated into the frontline standard of care. Ovarian cancer remains one of the most deadly gynecologic malicancies Women are diagnosed very late, too many women are diagnosed in an advanced stage, too many relapse and too many never get the extra years that all of us take for granted as we have milestones in life that we want to see unfold. So IL-12 is not a new idea. We're all aware of that. But we also know it's one of the most potent cytokines that exist and is a powerful weapon against cancer, if we want to use that term. It activates cytotoxic T cells and natural killer cells, and it works directly through interferon gamma. In preclinical models, the antitumor activity is profound, nothing short of profound. We've studied many different tumor types, and we're excited as we ultimately look at our first up, which is ovarian cancer. We know that this is also the excitement and really the potential of IL-12 is why many large companies, including AstraZeneca and many others, went after IL-12, and they were approaching this with administering recombinant IL-12 systemically, so directly into the bloodstream. These programs did not fail for a lack of biology, they failed because they could not get to a therapeutic dosing window and also because these when delivered systemically, produced dose-limiting toxicity. So there was no therapeutic [indiscernible] they had cytokine release syndrome and other injury -- immune-related injuries that close the door in the field, frankly, moved on. The field does what the field will do. You see a complication and a side effect that is -- that really is stopping development of an asset and IL-12 effectively became a cautionary tale for products. Imunon chose to not move on, and we've changed the delivery problem. We found a way around the complications of before, and we developed a novel proprietary treatment. So IMNN-001 is not a recombinant IL-12 injected into the bloodstream. It's administered as an IL-12 encoded DNA [ plasmid ] that's carried in our proprietary delivery system in a nanoparticle, and it's administered locally. So instead of systemically going around the body, it's actually delivered directly where the cancer resides. It's designed to protect the DNA from degradation, allow it to go into the nucleus of cells and allow those cells that are within each of these women's bodies to become factories that are naturally through the immune system producing IL-12 interferon gamma in a whole cascade of effects. It drives sustained levels. So in our trial as you'll see, we are giving them weekly infusions up to 17 weekly doses. And yet you'll see that the data that we're presenting is out in the years out to some women living and still in the trial being observed for more than 5 years. So sustained delivery of a local IL-12 at the tumor site and using each women's immune system to naturally fight the cancer. So the hypothesis simple, put the cytokine where the cancer is, not where the rest of the body has to absorb the cost. And we have been able to show in 112 patient trial that was randomized against the standard of care that we have been able to avoid these historic safety barriers and concerns. We're studying IMUNON in combination with the standard of care, which is treated -- women are treated in new adjuvant chemotherapy and then adjuvant chemotherapy with surgery. And the final overall survival data from the trial resulted in a median survival in [ IMNN-001 in ] 45 months and in the control arm of 30 months. So a 14.7 month improvement with immunontreatment. We saw with women who receive PARP inhibitors in maintenance therapy, a 24-month improvement over the standard of care, so 56 months versus 41. So again, I can't emphasize this enough. The historic IL-12 safety barriers overcome with our audit. It did not exist in the trial. Our largest trial, 112 women, half on the experimental arm, no cytokine release syndrome, no serious immune-related adverse events. And while we've explored dosing and we actually never hit a dose-limiting toxicity. So we're very confident with the dose that we're taking and used in Phase II and we're replicating in Phase III. And from an oncology standpoint, the IL-12 has been managed by design. So put these results in context carefully, very carefully. If Phase III is confirmed, if we've confirmed the Phase II findings, IMNN-001 would be the first investigational therapy in this setting, so in the front line ovarian space to deliver a clinically meaningful overall survival [indiscernible] in these women that are newly diagnosed this is in combination with the standard of care that has been used for more than a couple of decades. And in a randomized well-controlled trial. So we have multiple randomized controlled trials. It would also be a first-in-class IL-12 DNA mediated immunotherapy in any cancer. And it would be the first late-stage IL-12 program to pair a very favorable safety profile with the median of survival that I've described. To our knowledge now that other investigational agent has produced an overall survival signal this set the front line setting. So this is the opportunity, and I would even say it becomes the responsibility for us to see through, and it's why we are working incredibly hard with partners that are on the front line, but to ensure that we're running a high-quality study. It's a pivotal trial with OS as the primary endpoint. We have 2 planned interim analyses. We have Fast Track designation and orphan drug designation and the FDA aligned with our plans, which includes vertical and the statistical analysis plan and all the accompanying documents that go with registration studies. We had an independent DMC, Data Monitoring Committee recently that recommended the study continue without modification. So as I end my concluding remarks, I want to really focus on where, as a company, we have to live, which is with the patient. If OVATION 3 confirms what we've already seen IMNN-001 holds a promise of giving women more time. Time to go to a wedding time to spend time with grandchildren and for many other memories. It's time that the current standard of care that has not been able to provide in for a new generation. And this is why the morning is built the way it is, we will have Dr. Faller starting, he is our Chief Medical Officer of IMUNON and will be focusing on IL-12 biology. Why the field walked away and health AirPlus and intraperitoneal delivery changed the safety equation. We'll have Dr. Amir Jazaeri from UT MD Anderson Cancer Center, talking about translational work and biomarker data, including preliminary findings from patients under his care in the MRD, minimal residual disease trial that's ongoing. He'll report some early clinical findings, MRD status relating tumor DNA and ultimately, evidence that the tumor microenvironment is being remodeled. And then we'll have Dr. Premal Thaker from Washington University, who has treated women with IMNN-001 for more than 15 years. She has an immense set of experience with our product, our experimental product but more broadly across the field. She will share that experience and data from OVATION 2 and what the survival signal looks like. From her perspective of physician in the OR and also in the clinic. And then lastly, we'll hear from a woman who is treated with IMNN-001. So I'll come back at the end and provide the investment thesis and the catalyst and we're asking of you, but thank you for the opportunity to give these opening remarks. And I would say let's begin. I'll introduce our first speaker, Dr. Douglas Faller. He's IMUNON's Chief Medical Officer. He's a medical oncologist and scientist. He has spent his career treating patients and stepping in gap between patient need and providing drugs that you can give in the clinic. He will introduce the powerful potential of IL-12 from first principles. So why the cytokine to the entire industry looked unbeatable from the bench. Why systemic programs could not be delivered. And then he'll walk you through TheraPlas, the intraperitoneal delivery that we are administering our product through and why historic IL-12 toxicities are not what we're seeing with IMNN-001. Douglas?

Thanks, Stacy. So Stacy went through the agenda already, and we'll move right into. Stacy also had this slide as part of her presentation and covered this. So as Stacy said, what we're going to be focusing on for the next few minutes are the power of interleukin the problems with its development and how has really completely overcome the barriers to harnessing interleukin 12 as a therapeutic. And also, as Stacy mentioned, this is really the first and only treatment in decades to demonstrate an impact on overall survival and newly diagnosed advanced ovarian cancer. There's been a long, long period of time in which people have tried to improve on the simple Carbo/Taxol regimen that was developed 30 years ago. but all of the additions that have been try failed to demonstrate an improvement in survival. IMNN-001 has the potential to transform the frontline care -- standard of care for ovarian cancer patients. And I'll emphasize again that this is frontline treatment. You may have heard about other drugs being developed in the second line plus areas, there's some advancement here. This is woeful news for patients. But frontline is the opportunity to potentially cure patients, long, long, long survivals. Anything after frontline in many solid tumors is just giving patients more time but diminishing returns. This therapy is not giving interleukin-12 protein, but rather causing interleukin-12 protein to be expressed by the immune cells. So a very different approach than what's been used in the past to try to use interleukin-12 as a therapeutic. So we're activating the immune system from within the immune system itself. It's a unique mechanism of action. It's one of the few, if any, anti-tumor cytokines stimulates both arms of the antitumor immune system, both the innate and the adaptive and we'll talk more about that in just a moment. But this is a two-pronged approach. Other cytokines that you're familiar with like Interleukin-2, which was developed -- discovered and developed around the same time, only stimulates the adaptive, the cytotoxic T cells, stimulating the innate arm of the immune system, NK cells, macrophages, monocytes, is an additional advantage of interleukin-12. Interleukin-12 is able to turn the tumor micro environment from cold to hot Ovarian cancer is one of the coldest immunological tumors by the time it's diagnosed. And we'll talk about what cold to hot means. I'll also mention to you very experienced investors and analysts, people have been talking about turning cold to hot as long as the tumor immune system has been being developed. We're not just talking about it. I'll show you data that we do it in patients. And importantly, stimulating the immune system is not a one-shot deal. Once you stimulate it, the immune system can continue to recognize and kill tumor cells over years. Finally, we talked about local expression, local delivery. We're delivering interleukin-12 essentially, not the protein but the gene to the site of the tumor where the expression of interleukin-12 would be most important. We're not delivering it peripherally, and so we're not seeing the kind of toxicities that have hampered its development, really more than hampered, blocked its development 2 decades. Why interleukin-12, I mentioned already that a pointer here. Maybe I sort of have a pointer, but it doesn't work. That's fine. Interleukin-12 normally in the body, plays a central role in developing antitumor activity. it's present at low levels generally. It's made by monocytes, macrophages and neutrophils so myeloid cells down at the bottom of the slide. These produce interleukin-12 when they're stimulated by tumor or by some of the other agents that stimulate interleukin-12 pathogens. Interleukin-12 then does a number of things. And I'll just mention before we move up to the top that one of the mechanisms of action of interleukin-12 is to stimulate the production of neutrophils and platelets. And I mentioned this because cytotoxic therapies knock down platelets, they knock down neutrophils. That's a limiting side effect for most cytotoxic drugs. And it's not just drugs like [ Carbo ] and [ Taxol ], ADCs, which have, as part of their mechanism of action, incorporated cytotoxic drugs into the molecule. These also caused suppression of neutrophils and platelets. And as a result, we can combine interleukin-12 with chemotherapy without exacerbating cytopenias, which is something that many other agents are not able to do. Interleukin-12 in turn, stimulates the production of interferon gamma. Interferon gamma is an incredibly potent antitumor agent, does a number of things, and we'll talk about that on the next slide. But the fact that we can stimulate both innate immunity and acquired immunity really puts interleukin-12 and IMNN-001 in a unique spot in terms of therapeutics. So interferon gamma Interferon gamma is an incredibly potent, as I said, cytokine. I took part in trying to develop it as a therapeutic many, many years ago. the toxicity of using it systemically is so great that there's no therapeutic window whatsoever. However, expressing it locally is what we do with IMNN-001 makes all the difference. What does interferon gamma do? Now interferon gamma is just one of the downstream effectors. There are other downstream effectors that interleukin 12 activates including TNF alpha, which is a strong antitumor agent. But I'm just going to talk about the most potent of the downstream effectors of interleukin-12. Interferon has a direct effect on inhibiting metastasis on increasing the dormancy of tumors, so slowing their growth. It causes tumor senescence. It inhibits angiogenesis. And it also, and very importantly, down regulates the cold aspect of the ovarian cancer tumor cells. The -- it reverses really the fact that the T regulatory cells that [indiscernible] press ourselves this entire suppressive microenvironment interferon has the capacity to reverse that. And finally, it changes the cells around the tumor to -- instead of a pro tumor helpful -- tumor helpful phenotype to an antitumor phenotype. And one example is macrophages. There are multiple types of macrophages, but in ovarian cancer, the macrophage is a M2 phenotype, and this macrophage actually supports the tumor. And Dr. Jazaeri will also be talking about tumor-associated fibroblast and stromal cells. What interferon gamma does is it can reverse the phenotype from M2 to M1 and M1 monocytes and macrophages are antitumor. This has all been developed in animal models, very convincing data, pleiotropic effects. So when interleukin-12 was discovered, in the early '90s with the activity that was able to show in mice, it was rapidly tried to be developed by a number of pharmaceutical companies. And the results were, unfortunately, a great deal of toxicity. When trying to give the recombinant protein systemically, patients had a serious major vital organ damage, hypotension, collection of fluids to such an extent that 2 patients even perish from getting systemic interleukin-12. Trials in the U.S. were halted, resumed and then halted again because of the toxicity. At the time, this was called cytokine storm. Now days, we might refer to it as cytokine release syndrome. But it was really an insurmountable barrier. Subsequently, other people tried different ways of administering it throughout the -- up until about 2014. Lower doses, periodic dosing, none of these could develop a therapeutic window for the drug. Currently, there are a few early-stage programs, which I'll mention a little bit later. Which are in to develop local delivery, for example, injecting the tumors directly. This is a fraud approach. As you can imagine, cancer and advanced cancer is not 1 tumor. And trying to inject multiple tumors is really a losing proposition in the long run. What really changed for the entire area of interleukin-12 and delivery and ovarian cancer occurred with the OVATION 1 trial. And this was IMNN-001 with chemotherapy with standard of care chemotherapy, the kind of chemotherapy that every patient with newly diagnosed ovarian cancer gets. And there were encouraging clinical responses with this really dose-ranging trial. There were complete responses. There were excellent surgical responses in the majority of patients. It looked very promising. OVATION 2, a randomized controlled trial, which you'll hear more about from Dr. Thaker in a few minutes, gave us a very strong signal, a very encouraging signal and really the first sign that we could improve overall survival meaningfully in a frontline ovarian cancer. And lastly, we have ovarian 3, which is built on -- OVATION 2, which is built on OVATION 2 to, which is currently underway and enrolling well. And we'll talk -- Dr. Thaker will talk about OVATION 3 also. So to lay out the problems people have -- are still working at early stages on trying to develop IL-2 -- I'm sorry, I'm trying to develop Interleukin-12. The -- some of them are using intratumoral injection of either lipid nanoparticles containing interleukin-12 or interleukin-12 mRNA. But again, the intratumoral approach has the disadvantages I talked about earlier. People have been trying, especially at NCI to link interleukin-12 to an antibody and then have the antibody direct interleukin-12 to the tumor site, in some cases, focusing on debris, tumor debris that the antibody recognizes. And there are also viral vectors that have been used engineered cells, which express interleukin-12 to make them more active. Viral vectors have the problem that you can usually not give them more than once. Because the immune reaction to them is such that the patient will generate antibodies and giving the viral vector a second time, the vector is destroyed before any therapeutic effect occurs. So the translational challenges from these platform approaches. We already mentioned that systemic recombinant interleukin 12 is just not viable. The therapeutic index is far too low. Intratumoral injection needs accessible lesions and very few advanced cancers are [ tumors ]. There's also the issue of off-target expression even with linking the interleukin-12 to an antibody. There's also target expression and toxicity. And there are other repeat dose consents with viral vectors, as I mentioned. So how does IMNN-001 overcome this? We do regional delivery, which is exactly where the tumor is. We're not using viruses. We're using assets, which do not generate an immune response against the plasma. And we're covering the parent meal space. We're not trying to inject individual tumors. We're putting a liquid [indiscernible] of these nanoparticles into the peritoneum where they can reach all of the tumor within the peritoneal space. I'll mention here that the effects of the interleukin-12 exposure, not the interleukin-12 but the effects of stimulating the immune system reach far beyond the perineal space, however. I'll come back to that in a moment. but very important to realize, we're delivering the drug systemically, but the immune antitumor effects are systemic. Thank you, Stacy. So IMUNON is a regional repeatable nonviral approach for peritoneal ovarian cancer, but the Xtend far beyond, we get systemic antitumor activity. And we're the only late-stage program working with IL-12. Is the intra paritoneal delivery and issue? Is this a problem? Does this make the drug potentially less applicable for patients. In this situation, not at all, because gynecologic oncologists have been doing intraperitoneal chemotherapy administration for over 20 years. These physicians are experienced in the delivery of the drug. When I talk to physicians as we open new sites, they're very excited about having an intraperitoneal approach again. And they're even new excitement about intraperitoneal delivery of chemotherapy with a program called [ IPEC ] and things like that. So this is a very well accepted and appreciated approach to delivering therapies. I'm just going to go up 1 level and mention that IMNN-001 is part of a platform we can develop this platform to express other immune agents very easily because the plasmid is easily changed to put any -- really any protein that you want to express the gene for that in the plasmid. Very simple construction. The development and synthesis of the nanoparticles is also proprietary but straightforward. And in fact we manufacture this drug ourselves. IMUNON does the drug manufacturer. So this is a platform that IMNN-001 is just proof of principle for. We have many ideas about how to develop this further. We've talked about this, and this is just an example again of what we are hoping to achieve. We talked about the expression system. We talked about interferon being able to activate very potent antitumor responses, both arms of the immune system, but also inhibit the suppressive aspects of the immune system in the tumor and the tumor micro environment. We've talked about this. We've talked about animal models. Let me show you that we can actually do this. So the first is we designed this molecule -- sorry, we've designed this agent to deliver interleukin-12 locally. And let's just show you that in patients, we've been able to demonstrate that. And the top boxes on the left, interleukin-12 levels and right next to it interferon gamma levels. The teal bars are Ascites and the darker blue or purple are the levels in blood. And when we look across on the left side, different doses of IMNN-001 in patients sampled from the peritoneal fluid and the blood after treatment with the different doses, 36 ranging up to 100, we're able to show multifold 25-fold induction of interleukin-12 and next to it interferon gamma in the ascites in the place where the tumor is but not in the blood. The blood levels barely change, often don't change at all. So clearly, local delivery of interleukin-12. And this is why we see the safety profile that we've been talking about. Also, innovation 2 and Innovation 1, we've been able to take tumor from patients at the time of diagnosis. And then at the interval debulking surgery. And look at the immune response to the tumor in those tissues. So this is not mouse model, this is actual what happens in patients when they get IMNN-001. We've presented some of the data shown on the right at a number of meetings recently, and we're going to be presenting at the Society for Immunotherapy and Cancer a month from now. The translational data, the biomarker data. I won't go through these because I'm running out of time. But I've just mentioned that we're showing truly cleaning a hot tumor micro environment. We're increasing the recruitment of cytotoxic T cells, myeloid dendritic cells, the M1 macrophages, the ones that I told you are anticancer in most of the paired samples in both the tumor and the stromal cells, the tumor micro environment. We're able to show decreases in the immunosuppressive markers, exhausted T cells, T regulatory cells, M2 macrophages. And people have shown that these favorable ratios of antitumor activity, tumor suppressive activity are associated in patients with improved patient outcomes. What about safety? This is published data from the OVATION 2 study. Most of the serious treatment emergent adverse events and the other treatment emergent adverse events in addition to the serious ones, related to gastrointestinal and cytopenias. And we'll talk about both of these. The cytopenia has turned out to be a red herring. I mentioned earlier that if anything, interleukin-12 should be stimulating neutrophils and platelets. It turns out that our participating investigators pointed out to us that the cytopenias were an artifact of the way in which we were looking at and sampling patients. We were seeing patients every week. For the immunonarm, but we were seeing patients only every 3 weeks for the chemotherapy-only arm. And therefore, we were seeing in the immunonarm the chemotherapy-induced cytopenias. So cytopenias are not really an issue with respect to IMUNON treatment or addition to standard of care. Gastrointestinal, we've seen nausea and vomiting in some patients. This is manageable. And also hard to dissociate in some cases from -- with the chemotherapy that's being given at the same time that the immuno is being given. Our treatment-emergent adverse events of special interest are abdominal pain and cytokine release syndrome. We have not seen cytokine release syndrome consistent with everything I've told you earlier about where we're getting expression of interleukin-12. Abdominal pain though is something that was more common in patients who were getting the infusion. We think that this is mechanical and not due to the drug, but nonetheless, pain is pain, discomfort is discomfort. And abdominal pain was the most common cause for us to reduce IMNN-001 doses in OVATION 2, but only 3% of patients discontinued treatment. However, we wanted to do better. In the course of OVATION 3, we instituted a prophylactic pain regimen so that ideally, women would not even experienced comfort the first time. They would already have medicines to prophylax against abdominal discomfort. And this has been very effective. Abdominal pain has been a very minor issue in terms of numbers of patients affected in Dr. Jazaeri MRD study in OVATION 2 and innovation. So safety, no cytokine release syndrome, no serious systemic toxicity, no immune-related adverse events. Most of the TEAEs were gastrointestinal. We have a very consistent safety profile across multiple studies. And truly, we have overcome the historical safety and efficacy barriers associated with developing interleukin-12 as an immunotherapy. As Stacy mentioned, our independent safety review committees met in May for OVATION 3. There were no safety concerns, continue the trial without modification. And Dr. Jazaeri's MRD study, the committee met very recently in August, a different independent committee. No safety concerns continue the trial. So, we believe that IMNN-001 is really defining the modern era of interleukin-12 in cancer immunotherapy. It's making it available to patients for the first time. We've got a reliable system for expression of interleukin-12, a flexible and scaling manufacturing system. We've got a stable product unlike recombinant proteins. These nanoparticles are extremely stable. We can induce the immune response. We've been able to show that in patients. We have direct access of the drug to the tumor microenvironment as well as the tumor and we have very limited systemic exposure, potentially no systemic exposure. IMNN-001 has great mental in tumors beyond ovarian cancer including gastric, pancreatic, colorectal, glioblastoma, mesothelioma, we have preclinical data for all of these, and I'm very pleased to say that we are actually in the process of starting trials in collaboration with the National Cancer Institute. They've asked to partner with us in developing IMNN-001 in the indications I just mentioned. Newly diagnosed ovarian cancer with checkpoint inhibitors, colorectal cancer, pancreatic cancer, glioblastoma and also not listed here, mesothelioma. So I'll conclude just by saying I think you can sense my excitement about this therapeutic. This is -- this novelty, this ability to treat frontline patients to change the course of their disease to enhance their lives. This is what drove me to join as Chief Medical Officer, IMUNON. And I think you'll hear from our next speakers that we are really meaningfully affecting patients' lives, and we'll continue to do so with OVATION 3. Thank you.

So we'll hold questions and take them at the end. Thank you, Dr. Faller. So it's my pleasure to introduce Dr. Amir Jazaeri. He is Vice Chair for Clinical Research -- and oh, gosh, this is -- these are Premal's slides. They've been -- they'll be pulled up. Let me finish my introduction while they are pulling up. Dr. Jazaeri does not want to add live and get Premal's stock. Although I'm sure he'd be very capable. So Dr. Jazaeri is Vice Chair for Clinical Research and Director of Gynecologic Cancer Immunotherapy Program at MD Anderson Cancer Center. He's still lead principal investigator for our ongoing Phase II MRD study. And he's here because our confidence in IMNN-001, as Dr. Faller just -- evidence goes well beyond the overall survival curves in the clinical data. He will show evidence the mechanism of action having achieved and is being achieved by IMNN-001, and we'll take up the critical question of his product actually remodeling residual disease. So welcome.

Thank you so much. It is indeed a pleasure to be part of the immune on Science Day. Before I get started with my talk, I just want to provide a little bit of context for our study, which is really complementary to a lot of other cool clinical and transitional information you're going to get today. As you can see, this is a study that's jointly supported by IMUNON and Break Through Cancer. Now Break Through Cancer is a philanthropic organization that started about 5 years ago with the idea of using the COVID model of urgency to really attack the cancer problem. And they decided to reach out to 5 premier cancer institutions: MD Anderson, Dana-Farber, Sloan Kettering, MIT and Johns Hopkins University to get investigators from these top-notch cancer institutions to really address the issue of cancer. And so they requested proposals about different projects. And One of the proposals that later became our project was how do we deal with the problem of ovarian cancer minimal residual disease. Now what we mean by minimal residual disease and ovarian cancer is microscopic cancer cells that remain after frontline treatment. So many of you might know that ovarian cancer's frontline treatment is a combination of interval debulking and surgery. But the problem with ovarian cancer traditional treatment has been that many patients -- most patients cancers come back. And when we say cancer comes back, that's really a misnomer, right? So cancer doesn't really come back. It never leaves the body. So it's this issue of cancer becoming undetectable going under the radar and that under the radar phase is what we refer to as MRD or minimal residual disease. But now we've become better at picking up the under the radar. We can do that 2 ways. We can do it using surgery. So a second surgery where we go in there, do multiple biopsies and identify cancer surgically that would be missed based on scans and blood's tumor markers. And then there are new class of tumor markers called circulating tumor DNA, or ctDNA. So that's another way of capturing this clandestine portion of cancer. And so we proposed this project and the flagship aspect of our multi-institutional project was the IMUNON MRD study. And the idea here was we wanted to take standard chemotherapy, but add to it the most cutting-edge, the most likely effective treatment possible and that, of course, is the IMUNON platform for multiple reasons. Not only that -- as you heard, this platform has solved the issue of IL-12 being difficult to give administer so the deliverability issue. But also, as you heard, the platform is incredibly versatile that there plus you can imagine that there can be multiple immunologic sort of products that can be delivered through the same platform. And with really very little risk because you've already shown that the delivery platform is safe and effective. So I just wanted to offer that little bit of background. And what I'm going to share with you is our study, which is also ongoing. So this study has not completed, but I'm going to share with you some of the preliminary findings because I think they will complement and add to what you already heard from Dr. Faller. And so the why of it why -- why do we want to do this? As you heard, a frontline treatment is the best chance to offer a cure. So patients who have recurrent disease are largely basically accepted to having curable disease. You heard about IL-12 boosting both innate and adaptive immunity, but the adaptive immunity is what gives you long-term protection against cancer. Sometimes use the example of, you get chicken pox and the chicken box virus stays in your body, but your immune system can control it long term, so it doesn't cause effects. Of course, as I mentioned, this platform also lends itself very well to additional future modifications of the immune system as we learn what makes this work and what are avenues where cancer cells might become resistant. And so the better understanding of the mechanism of action is going to be fundamental future development of this platform. So this is just the schema of our study, and I'll take you through it. So on the left-hand side, you'll see that patients that are eligible for this trial are patients that have advanced stage disease. And in fact, they have a disease distribution and volume that makes them candidates for neoadjuvant chemotherapy. Neoadjuvant chemotherapy means that there's too much cancer to start with surgery. So we're going to start with chemotherapy to shrink the tumor, use surgery in the middle and then in a sandwich manner, give additional chemotherapy afterwards. As you can see, this is also a randomized study. Patients undergo initial diagnostic laparoscopy so we can document and sample areas of tumor before starting treatment and then they're randomized to either neoadjuvant chemotherapy on the [indiscernible] the control arm is neoadjuvant chemotherapy plus Avastin or bevacizumab for 4 cycles and the experimental arm, patients have an intraperitoneal port place. This is the way we give IMNN-001 directly into the abdominal cavity, and they get the same treatment plus the weekly treatment with IMNN-001. All patients are considered interval surgery after 4 treatments. And then under surgery and recovery, then all patients get adjuvant chemotherapy. So that's treatment after surgery. Again, the control arm gets to control treatment, experimental arm gets the IMNN-001. And as I mentioned, we wanted to look specifically as accurately as possible to see who still has residual disease after treatment or not. One of the limitations of current clinical trials in this space is that we have to follow patients until recurrence. As you might imagine, that has a time line of years. What if we could tell right after treatment, whether there's still residual disease or not. And so one of the goals of this study is to see how does determination of minimal residual disease at the end of treatment correlate with long-term outcomes. So obviously, the patients are still going to be followed by for long-term outcomes. And then many of you may be aware that there is a maintenance phase for most patients with ovarian cancer, and that's determined based on the molecular subtype of ovarian cancer. Roughly half of ovarian cancers are a molecular subtype that's called HRD positive or homologous recombination deficient. Those patients go on and get PARP inhibitors and in this study, they get olaparib plus bevacizumab, and those that are HRD-negative or homologous recombination proficient then in the maintenance phase in the standard arm are going to get just Avastin, that's the currently used maintenance for this patient population. But in the experimental arm, we had the opportunity to demonstrate safety of IMNN-001 in this maintenance setting for future studies that and we may want to extend the administration. And in this setting, patients again get IMNN-001 intra-abdominally, but instead of once a week, they had once every 3 weeks in conjunction with Avastin. So that's -- 2 things that kind of stand out in this study is, one, that patients have determination of residual disease with a second surgery, so-called second look laparoscopy, that's what SLL stands for. And then the second thing is that the study also adds a maintenance phase that may be important for future development. And so I'm going to share with you some of the clinical updates. This just sort of demographics. Again, it's a randomized trial. So it's always good to show the control and experimental arms are roughly the same. And I won't go through the [indiscernible] but it's sort of enough to say that there is -- the populations are roughly equivalent in both arms. And then this is the outcomes. These are swimmer plots where the green shows patients that are in the experimental arm. The blue shows the control arm. And I think the kind of the key information is summarized in the box on the right side. If we look at MRD positivity rate, in the control arm, you can see that 6 out of 9 patients still had ritual disease after finishing line treatment, so 66.7%. The MRD positivity rate in the experimental arm was numerically smaller, 4 out of -- only 4 out of 9 patients that have made it to that second surgery had residual disease. So again, an improvement in residual tumor at that time point. And again, as I mentioned, another way of capturing this minimal residual disease is looking at tumor DNA in the bloodstream. That's called circulating tumor DNA. And when we look at the rates of that circulating tumor DNA becoming undetectable, you can see that in the control arm, 62% of patients became undetectable, while in the experimental 87.5% of patients became undetectable. So again, kind of these are small numbers, but favoring the experimental arm. And then this is again some clinical information. One of the things that I want to draw your attention to is chemotherapy response score. So this is a pathologist examining tissue that's removed at that middle surgery. Remember that middle surgery is performed after 4 cycles of neoadjuvant chemotherapy, and they look at how much the tumor cells appear to be affected by the treatment. So chemotherapy response score of 1 means that the tumor cells are hardly affected. As you might imagine, 2 and 3 means that the chemo has had a greater effect on the tumor cells. And so as you can see, again, in the experimental arm, there is a preferential effect by the chemo plus, of course, IMNN-001 in that arm. The second sort of emerging clinical observation is, if we look at, again, the second look laparoscopy positivity rate, I already went through in the previous slide. But also if we look at just regular way of looking at who doesn't have any disease, which is currently with CAT scan and CA-125. You can see that of the patients that were NED or no evidence of disease only 5 out of the 9 patients in the control arm, but all 9 of the 9 patients on the experimental arm reached NED. So sort of suggesting that favorable effect for the experimental arm. These are progression-free survival curves. Again, this is immature. As you can see, the numbers are small, but you can see the trend is in favor of the green line, which is the experimental arm with medium recurrence-free survival of 26 months in the experimental arm and only 12 months in the control arm. I think another sort of opportunity from our study is this ability to look at tumor at multiple [ endpoints ] so that diagnostic laparoscopy allows us to look tumor before treatment starts. The interval surgery after 4 cycles allows us kind of a middle view. And then those patients that are second positive or have MRD tell us sort of what's going on in the cancer cells that are remaining after the end of chemotherapy phase. And so this is just a sort of a diagram. So again, as I mentioned, patients undergo screening and diagnostic laparoscopy in the beginning they're randomized to a incremental arm or a control arm for the neoadjuvant phase. They all undergo a second book -- or sorry, interval cytoreductive surgery that ICS is that interval surgery. And then all patients undergo a second look laparoscopy after adjuvant chemotherapy. And there's sort of -- I won't get too technical, but there are newer ways of looking at the cancer environment where we can look at individual cancer cells and look at what's going on inside the individual cancer cells. And this is often referred to as spatial studies or spatial transcriptomics. We also performed a single cell RNA and TCRs that tells us about clonality of immune cells and then whole genome sequencing to look at clonal evolution. This is just -- this is just a plot of the different types of cells in the tumor microenvironment that we can detect using these cutting-edge transitional methods. So you can see the tumor cells, the big cluster on the right side, but you can see various different types of immune cells that are able to be identified using these technologies. And this is how we identify them. We identified these different cell types based on their gene expression signature. So the yellow bars are genes that are preferentially expressed and on the Y axis, you can see the different types of immune cells. And so this is how we know different immune cells that are present in the tumor microenvironment. This graph shows looking at proportion of cells that change. So the colors and -- on the bottom is categories of patients in the experimental arm in the red colors and the control arm in the blue colors at the 3 different time points. So the diagnostic laparoscopy or DL before any treatment [indiscernible] surgery is at the middle and then second local laparoscopy is at the end. And you can see that in the experimental arm, there is significant increase in macrophatages, is a type of immune cell that's part of the innate immunity. You heard talk about how IMNN-001 stimulates innate immunity. And then importantly, we see an immunosuppressive populations that are called myeloid cancer associated fibroblasts. And you can see that their proportion goes down in the experimental arm compared to the control arm on the right-hand side. And then here is really kind of the crux of the matter. So here we're showing that only in the experimental arm the macrophages are expressing the genes for IL-12 A and B. So that's what's programmed in that plasmid. So we're showing direct mechanism of action with expression of IL-12A and IL-12B in macrophages, which are normally an immunosuppressive population. So Douglas mentioned turning a cold tumor into hot. This is showing you precisely how that happens that we're taking a major [ immunodepressed ] population and macrophages and cancer associated fibroblasts, and we're turning them into inflammatory cancer-associated fibroblast. And of course, you see this only happening in the incremental arm and not in the control arm. This is just kind of showing you visibly. Again, we're looking at all the different cells in the tumor microenvironment. The white shows you the tumor cells, the blue shows T-cells and B-cells and then various other immune subtypes are also shown -- and if we sort of look at this and look at where is IL-12 being produced. So this is kind of taking the same topography. So if we go back, you can see the macrophages here and myeloid cells are shown in shades of green. So if you focus on where the green areas are, these are samples from 3 different patients at the time of their interval cytoreductive surgery. Here the peaks correlate with where the green is. So again, this is a different way of showing in the tumor microenvironment. We're actually showing the macrophages are expressing IL-12. And then sort of another way to look at that is, again, looking at IL-12 sort of -- and the surrounding radius of cells that are exposed to IL-12 and you can see a much, much greater number of radius or spatial field associated with IL-12 in the patients that are on the experimental arm. And again, visually, that -- this is the graph of it, but visually, you can see IL-12 here shown in this heat map as areas that are red. And so if we look at the red areas and we look at what's going on in terms of cell populations and then move away from the red area. So like if you have a bomb that goes on you expect the cancer cells that are killed to be in the immediate vicinity. But as you go farther and farther away, there's going to be less effect. So on the right-hand side, you can see the proportion of cells that are seen within the field, and then you see the radius as you go gradually farther and farther away. So you see macrophages are concentrated because they are the cells that are picking up the IL-12. And then you can see the -- again, the cancer cells are in the vicinity and get more as you get farther away. And this shows the same thing sort of in a different way. And then if we look at what's happening over time in the experimental arm and in the control arm with regards to immune cell clonality. So one way to think about clonality is that if immunotherapy is working, then our immune cells are keying in on specific targets on the cancer cells, and so there should be less random immune cells. There should be more production of those cancer cells that are recognizing -- sorry, those immune cells that are recognized into cancer cells. So the higher the clonality, the more specifically our immune cell is recognized in cancer. And you can see that in the experimental arm, regardless of whether they were MRD positive or MRD negative, you see a much higher clonality compared to the control arm, again, showing that not only is IL-12 being produced but it's impacting the immune system on recognition and attacking the cancer cells. Okay. Thank you. So in summary, while preliminary, our data demonstrates a MRD positive rates, higher chemotherapy response score and lower NED positive rates and progression-free -- higher -- better progression-free survival in patients that received IMNN-001. IMNN-001 made drop the expansion of macrophages and reduction in the immunosuppressive myeloid cancer associated fiberblast. Macrophages are the major cell population that pick up IL-12 as part of the platform and to a lesser extent, also cancer-associated fibroblast. And IMUNON treatment drives TCR clonal expansion, suggesting induction of antitumor community. In terms of future directions, -- of course, we plan to complete enrollment on the MRD study and to hopefully show the first abstract of the completed results in 2027. And -- there is integration of a lot of the transitional stuff that I just touched upon looking at both protein and RNA expression and then also looking at how tumor evolution in the control arm and in the experimental arm differs. And then we also are interested in looking at the microbiome, the gut microbiome sees collected in patients on both arms, and we look forward to analyzing those samples as well. And I'm happy to -- I know we're going to wait for questions until the end. But Happy to chat with anybody either during the Q&A or after. So thank you so much.

Thank you, Amir. So I'm delighted to welcome Dr. Permal Thaker to the podium. She is the David & Lynn Mutch distinguished professor at Washington University. She's Chief of Gynecologic Oncology and Director of Gynecologic Oncology Research at Washington University. She was the lead investigator for OVATION 2 and is also the lead investigator for OVATION 3. And as I mentioned in my opening remarks, she's been associated within on development and has really had a very influential role in the development of IMNN-001 across the 15-plus years that she's been involved. And she's going to take you through her view into IMNN-001, our clinical data and offering remarks that really impress upon why advancing Phase III and getting the trial enrolled needs urgency. So welcome, Premal.

Well, thank you so much for having me. I'm going to actually bring you back to the clinic, which is really why we're here, right? We care about talking about patients. It's great to show data about how we are changing that tumor microenvironment because it's very important for a proof of principle. But when I'm in the clinic every day, how am I going to translate this to a patient? And how do I describe it to that? So I have been involved. I do a lot of drug development. So this is obviously one that's very dear to my heart. I've been there for a long time. I've developed lots of drugs in the platinum-resistant space, platinum-sensitive space. So I'm very active in clinical trial development, but this is the first time we can really maybe affect a cure, which I think is a big word that we don't get to use often enough for our patients. So just to bring it back into perspective, about 21,000 patients will be diagnosed with ovarian cancer, and we'll lose approximately 12,500 patients. And we do have a 5-year survival rate of about 51%, and it's pretty dismal because the fact is as we diagnose these women way too late because we don't have a good screening test. So we diagnose these women, they're stage 3, stage 4. So as has been alluded to, they have disease that's widespread. They're very malnourished when they come to us. They have been misdiagnosed, even before they come to us. So it becomes a real issue. And so because of that, we really don't use the word cure as often because the fact is, as we know that most of these women will recur and how do we really change and break that paradigm. So only about 20% of our cases are found localized as a Stage 1 or 2, and that's just usually by being very lucky because you went in for some other CAT scan for a kidney stone and got found out that you had a mass and you might have gotten diagnosed early. So it really is important for us to try to say how do we break this sort of paradigm and improve this for our patients that sit in front of us every day. So it's a very difficult disease because, as I said, it's -- we diagnose it late. We don't have a screening tool. We actually have these patients that more and more are getting neoadjuvant chemotherapy. So if you look over, there's been a huge paradigm shift because we know that sort of more and more women get neoadjuvant to treat nowadays, it might be as high as 60% to 70% because we know that we can't surgically go in and remove all this disease. So we really have shifted from being like, [ going to be ] surgeons and just cut it out to knowing that we really need to be able to give them treatments to hopefully sort of chemically reduce the disease, have more successful outcomes. And recurrence is very common as we have talked to. And really, the way is for us not to have to [indiscernible] the women that you're going to get palliative treatment because you've recurred. How do we really try it, as I said, to keep breaking this cycle. And really, we're desperate need because the joke in medical oncology is which you give patients who have gynecologic ovarian cancer is you can have Taxol/Carbo is for 40 years, we haven't changed that paradigm. We really have added Avastin or bevacizumab, and we did that with only a progression-free survival difference of 3 months, but no overall survival benefit. So yes, it's something that we can add, but it's not really changing our upfront paradigm, which is when you talk to a patient or you really want to know what's gold standard is, are you really changing overall survival? Not that incremental. If I looked at any one of us and you all are in the finance world, saying, it's a quarter, you wouldn't be like that's amazing. I get an extra quarter of life. It's really something not meaningful to a patient. So how did we end up doing this? And what has been so important is really, we've been very thoughtful of how we have brought this drug to patients. And so really, ovations to schema was we wanted to build on the localized IL-12 safety. We wanted to say, can we actually change the tumor microenvironment? The MRD study has taken of course a lot step further in the biology, but the initial sort of studies we're looking at, and it was in OVATION 2, it really was trying to say what we knew at that time because remember, trials are always what we knew best at that time was that surgery was our best option. So if we knew that we could get [indiscernible] more to a no gross residual component at their time after chemotherapy that we would be hopefully affecting their survival. And how do we actually start helping the immune system learn how to control a disease. And we actually are learning that in a lot of diseases, that's sometimes giving it while the tumor is present, can actually educate the immune system much better than actually after we resected and then giving immunotherapy. So we're learning that in quite a few diseases. I mean, it's pretty novel that in like colon cancer, if you're mismatch repair deficient, you might get your immunotherapy upfront with the cancer being there and not even need surgery potentially because they are disappearing. So this is a concept that makes a lot of sense and is also being seen in other disease sites as well that we need to get the immune system involved earlier. And so we've had a lot of an eloquent talk about MRD and how we're seeing more CTDNA clearance how the macrophage is really in the peritoneum are taking up the IMNN-001. And really, we're asking these women to take this treatment upfront. So these are patients that which diagnose them, we ask them to take it upfront. So very different than the Phase III trials that you all talk about for maintenance because in order to get a maintenance drug, you have to have responded. You have to have had either stable disease or a complete or partial response, really complete or partial response. These are women, we don't know how they're going to respond. We're taking them right from the get-go. So it's a harder to treat population because when you look at those other Phase IIIs you don't ever see those women who could not were not eligible because they were not eligible for a trial because they did not respond. So here, we are giving these women intraperitoneal therapy. We're giving it to them weekly. If you talk to breast cancer patients, they get weekly treatments all of the time. So it is not something that's overly burdensome to a patient, and there's a finite date to be done with treatment. Yes, if they have an HRD signature, they could potentially go on to a maintenance treatment, but they actually, if they don't, they stop on this trial. So when you want to think about ringing the bell, being done, having a goal, setting a goal, you can actually time it out for yourself, too. So why am I so passionate about this is [ because really ] OVATION 2 gave us the first signal of an overall survival benefit. We have not seen that. We have tried so many different ways. We've tried different combinations of chemotherapy. We've tried different combinations, as I mentioned, with antigenic like bevacizumab, all with the hope that we would affect overall survival. We have never been able to do that. So this trial is for all comers we made a difference of 14.7 months with a cutoff in December of 2025. That is something I can go and talk to a patient very meaningful about because [indiscernible], she stole my line. It's another set of birthdays. It's another set of weddings. It's being a grandparent. It's just another year of life, which is huge in a disease that we're trying to make it that they have fully never recur, but if not, talking about that type of gain is really something substantial for patients. Additionally, when myself and Amir, we both train together at MD Anderson. So we're [ compadres ], we were always taught that like patients who have a Bracutation or an HRD signature will always do better we've also learned from our maintenance trials, these patients actually recur to. But you can see when you have that subset population, when you add IMNN-001 to the PARP inhibitor, they do significantly better as well. So we're even making transformational changes for patients who are thought to do well. And we can make it even better. And that is also important because patients recur, and we want to try to prevent that breaking that cycle. So this is the graph that you saw earlier with Dr. Faller who did not get as much time to go through it, but it's really trying to just a perspective we keep talking about how we're trying to make this cold tumor into a hot tumor so that we really can affect it. And people always ask all the time because they're like we've used checkpoint inhibitors, and we've actually had lots of patients take those medications and concurrent with chemotherapy, they've not been successful. Thousands of patients have been on those trials. And it's mainly because you're not affecting the immune system on both the innate and the adaptive portions and also affecting all the other cells. There's nothing that's a singularity about the immune system. We don't just say your only T cells, your only macrophages, your only NK cells. Your everything, your lymphocytes. And that's what we're looking at is showing that we can really affect that portion of the immune system, which is a very much broader [ "BOM" ] to help the immune system really attack and make the women's own immune system augmented to do this and in the area where the disease is located, intraperitoneally. That's where the disease is. So it's very important, we're not getting those systemic side effects, which is also very critical. So patients can tolerate this and get it very successfully, and we've even shown proof of concept that the more you get, the better you do because not every woman every week, they might miss the cycle for whatever reason. And so we're actually very impressed how much -- even with some patients who've got fewer doses are still seeing robust responses. So with the mitigation strategies of like giving for abdominal pain, we hope that we'll be able to give less learned in order to improve our administration as well, which we're doing much better on the OVATION 3 trial. And as we made that amendment in OVATION 2, we also got much improved administration of immuno. And I think one of the other things, everyone gets the CFS plot, and I know the OVATION 2 trial is not statistically powered for all of this, but it's very consistent in that it's always favoring the IMNN-001 sort of factors that we look at, patients overall survival, you're looking at progression-free survival, were they HRD-positive, not positive. And so this is very much telling to us that OVATION 3, if it can hit the same marks, which we very strongly feel it will based on this data that we will be able to show that we can really move the needle and maybe make the first breakthrough in ovarian cancer. We don't have the side effects of cytokine release syndrome. For some of you who may or may not be aware of that, that's very severe. It says if your body has like a sepsis. So it requires you to be in an intensive care unit. It is -- you have the neurological checks, you need intensive care. So it's not something that's minute because people ask about CAR T therapy, other therapies and those have these adverse side effects. And so trying to also think of a treatment that we can not only give -- not only in academia, but we'll be able to give broad spread into your rural areas or community areas. That's also important. I love academia, that's where I am, but not every patient can come to us nor do they have that sort of care team to take care of them. And a lot of people are going to shy away from giving those therapies because they just can't do it. So this is a therapy that I also want you to realize can be widespread given because we're not talking about something esoteric, which is a key thing. So why is this important to me as a physician, I think you hear me, the patients are the sickest of the sick. We're taking them when we don't know how they're going to respond and seeing responses. And then the translational components, which really confirm what we have been saw preclinically. We're [indiscernible] in our clinical specimens. We're seeing them durable. And if you look at a lot of immunotherapy, you see overall survival benefits because it takes a while for our immune system to be revved up and to give us those incremental gains. And then importantly, this is a treatment for all patients, not just the patient who's HRD. It's for every patient who walks in because I said this sort of yesterday, it's very hard for a patient to accept that their tumor microenvironment doesn't have the signature that they wanted in order to think ahead because all of these women are on logs and talking with their social networks or care teams. And they know that if I have an HRD signature or I have a BRCA mutation, I'm going to get a PARP inhibitor, and that's going to maintain my response, and I'm going to do better. But think about the other flip of the coin who comes in who does not have that. This is a way that we can overcome this. And from a patient's perspective, what do they want? They want hope and they want to know that there's going to be active treatment. That is the reason there's people like myself and Dr. Jazaeri , you could keep pounding the pavement year after year, trying to figure out newer treatments. So we can honestly make a difference to those patients. So we won't be just saying you're going to get tax all carbo and maybe bevacizumab. We'll be able to hopefully say you're going to get IMNN-001 with Taxol/Carbo and Dr. Jazaeri's study gives us also the benefit that we can add bevacizumab, if necessary. The treatment is time limited. I'm not -- I'm happy for my patients who can get on maintenance therapies, but there's a lot of them who don't also realize the side effects that they get from their maintenance therapies until they're really off the treatments that are oral. The fatigue, the nausea as well as we're not even talking about the financial toxicity to families because one of the parts of cancer treatment is also thinking about what are the ramifications after treatment. These women lose work. They may have to take extra time off, affects families, affects their finances, and we're starting to appreciate that. So I'm putting that in a perspective because if you think about it from a patient's perspective, this all is in their sort of head what's going on and how to get this to become a reality that they can overcome their disease. And quality of life is really important. And in OVATION 3, we will be collecting that data. But talking to patients and having treated them, their quality of life is much improved because the fact is they're living their life. And that is the key because patients are willing to take side effects as long as they know they're going to get benefit at the end or a benefit from the treatments they take. And as I said, we had learned to help them with the abdominal pain, with nausea try to help them get through these medications and also giving better education. I think a lot of it is once you educate patients and they know what to expect. They're much more able and capable to take the medications too. And this is not uncommon. If we look at antibody drug conjugates. We're all on a learning curve. We all became now pulmonologists ocular specialists. So it's just a matter of learning. So I'm going to take you through a case study of actually my own patient who was diagnosed with stage IV disease, and she's 45, so young, young kids, not even in college, just in sort of great school. And comes in, gets randomized because she was on trial to 6 doses of [ carboplatin ] and [ paclitaxol ]. She did the 3 cycles adjuvantly and 3 adjuvantly and she ended up taking 15 weekly doses of immuno-001, 88% dose intensity. She took 8 in the presurgery and then 9 afterwards. And then she had an R2 resection. So what does that mean is that we had to leave some disease behind. So it was not the R0 that we always hope that we could remove everything. So that really would make you think like, "Oh, she's not going to have as good a response," but she ended up having a good chemotherapy response score pathologically of 2. And she had a complete response that she mean for remained on for 2 years and normalized for [ CA125 ] quickly because that used to be one of the markers we used to utilize to say if you have an elimination of your CA125 quickly that you have a better response as well. So she ended up on [ olaparib ] maintenance because she's a BRCA mutation carrier. And so she was able to maintain her response but progressed at 34 months and then passed away at 70 months, which is much better than the curves that you actually typically see when a patient recurs. So she got to get to see her kids graduate high school. She even saw one of them actually get married. So these are the differences that make. Because we get to see these patients. So as a gynecologic oncologist, we take them through diagnosis and hopefully to cure. That's what we're here for today, but we do take them through end of life as well. So we get to know these women really well in and out. And so even though we don't have a quality of life that was measured on OVATION 2, she did get quality and she got quantity. It's never enough, and that's what I tell every patient. And that's why we're here today to hopefully make that difference. So what is OVATION 3? It's building really on OVATION 2. So the schema is going to look very much the same. It's just a larger randomized trial. OVATION 2 had 112 patients. This is going to randomize 500 patients Stage IIIb or higher. All of them have to get neoadjuvant chemotherapy. They'll get their diagnostic laparoscopy, they randomized 1:1 to receive frontline chemotherapy versus frontline chemotherapy with IMNN-001 and then afterwards undergoing interval debulking and then get their adjuvant treatment. And then at the end of treatment visit if they are HRD or BRCA mutated, they will end up on a PARP inhibitor. And then really, we're going for the gold standard. We're going -- this is a trial that's looking at overall survival. And that is the actual FDA recommended gold standard. We rarely get it. So that's why we don't -- where was there like surrogates of duration of response, progression-free. But really, we're going for the gold standard because we really feel that based on OVATION 2, we will hit that mark. And it's really important because we also have those interval looks at our data because we do feel that we will heated earlier as well. And so these are ways to try to get these treatments to patients as early and as safely as possible. So what is really the importance is that we also are accruing quite well. We actually have activated quicker than a standard pharma trial. We're getting patients to enroll overall at a faster clip. We anticipate that we'll have complete enrollment in quarter 1 of 2029. We are looking at clinical as well as more importantly, biomarkers. So we'll have much more data to substantiate what we have presented today. And then we have the preplanned interim analysis, which will also be very helpful because, as I mentioned, we're hoping to get this to patients sooner. So why if this would become the next global standard of care is that we would really be giving patients a huge benefit and opportunity to get a chance for a better tomorrow. And so the mechanism of IL-12 interferon gamma, I think we've talked about it all the time. It's really the first drug that has been able to prove that we can affect this critical cytokines, and we are changing the tumor environment. We all talk about it theoretically and hypothetically, but we really are doing it as you've seen from the presentations that were eloquently ahead of me, and we're giving it without the systemic toxicities. So we are able to -- we're able to actually expand this to other disease sites. And more importantly, I can say for sure that it has been a very consistent safety profile because I've done it in platinum-resistant ovarian cancer. I've done it in the early Phase I, all the way now to Phase III. So you can give it to your patients very safely. We've never seen this type of benefit in overall survival. And I think having that consistency, we have the opportunity to really change the standard of care, which is not something we can ever really say. And this is really very exciting to me as a clinician and also, more importantly, to the patients that I serve. So in closing, we're targeting ovarian cancer where it is in the intraperitoneal cavity. We're giving a frontline immune therapy that's effective. We're giving a way to give this repetitively to patients in order to change the trajectory of their clinical course. And ultimately, we want to transform our patients so that they are getting cutting-edge newer therapies and longer lives. With that, I thank you.

Okay. I have the pleasure of introducing you to [ Terry ]. She is a woman who was diagnosed with late-stage ovarian cancer and was treated as part of our OVATION 1 study. She's chosen to tell you in her own words, what her diagnosis and treatment was like and she's joined by Dr. William Bradley, who is Professor and Vice Chair of Clinical Research and the Division of Gynecologic Oncology at the Medical College of Wisconsin. Dr. Bradley has been an investigator in OVATION 1, OVATION 2 and now at OVATION 3 as well. And, Terry, unfortunately, we're not able to be here in person, but sat down recently to reflect on their relationship together across a 10-year span. So we'll play the... [Presentation]

So thank you, Dr. Bradley and Terry. Very difficult to get up and talk after that -- the story brightens our role that I think gives us the hope that we're looking for. So let me take us back to the investment case that you have heard. So this is obviously about people. It's about proving lives, but there is a very meaningful investment opportunity here. And if I can recap what you've heard. So the frontline standard of care has essentially remained frozen for 3 to 4 decades. You've heard why systemic IL-12 could not be delivered and how IMNN-001 has overcome that. You've seen a safety profile that is easily managed and that we can then deliver the kinds of effects that we're observing in the clinic. You've heard the translational signals and the observed biomarker data that's consistent with our mechanism, a colder micro environment turning hotter. You've heard lower MRD rates, higher circulating tumor clearance and early evidence that IMUNON may be able to be given even in a maintenance setting down the path. We're studying that now in the MRD study. And we also know from that trial that as we get to the real world, we know starting out that can be given safely with combination with bevacizumab. You've heard from descriptions from our surgeons that have been treating these women and what it's like for them and directly from Terry to receive this product. And at the end of the day, a 14.7 months overall survival improvement received with this product and our largest and our most recent clinical trial. You've heard from a patient of what it means to be cancer-free in her words and the opportunity that she has to live -- to live life. So here's the thesis, plainly stated IMUNON is developing a first-in-class immunotherapy based on IL-12, a potent cytokine in the randomized Phase II trial, we have seen clinical effects and biomarker data that has not been seen previously. The confirm [indiscernible] trial, the Phase III trial is open, it's enrolling. We're exceeding our forecast and our assumptions from a site perspective. And if Phase III is able to replicate these findings, we will have what we believe is going to be a change to the standard of care. IMNN-001 is fast track designation and orphan drug designation in the U.S. We also have orphan drug status in Europe. And we haven't spent a lot of time talking about it. Douglas mentioned this briefly, but our manufacturing story is also an incredible bright spot. So our plasmid plus the interparticle that is delivered, that really is this novel proprietary delivery we expect to have incredibly attractive margins at the commercial scale. So it is -- we're producing the core active pharmaceutical ingredients in-house, and we're able to track and are preparing readily for the years to come, which will be, we hope, the commercial setting. The platform, as we've referenced, is not only ovarian cancer TheraPlas has an opportunity to be encoded with other proteins. And as we learn and continue to expand in science, and we learn from our partners in academia, we have an opportunity to certainly turn our sights to other cancers and with the announced partnership and the [ CRADA ] grant through National Cancer Institute, we expect to be able to accelerate that. So we're very excited. So what comes next is really going to be about execution. So we have a new leadership team that is here. Douglas attested to the reason he joined IMUNON on, it is the reason it was very easy for me to accept the role of CEO and President, we have an incredible leadership team that is extremely well prepared for the task at hand, which is going to be execution of this trial. We follow the trial design. This is a confirmatory trial, so it follows Phase II with some enhancements that really just give us more confidence as we enter and we think about the pricing and reimbursement discussions that we would have in the future. So as Premal noted, we expected fast enrollment. We did not expect to exceed. At a site level, we set a target, which is far above what we've observed in larger trials from the past in the frontline space. Our target was 0.3 patients per site per month, we're actually observing 0.5 patients per site per month as an average across the trial. So we're doing incredibly well and we think it really is a testament to the effects that we've been able to uncover with a very thoughtfully laid out clinical development plan. So Premal referenced treating patients recurrent setting. These are actually the 2 trials that we have going are seventh and eighth clinical trials in ovarian cancer four of them we're in later lines, we decided with advisers and through multiple sets of the advisory guidance that we would be well served to go after the front line. It was a bold move, and I think we're obviously very pleased, very pleased we did that. Our data monitoring committee will continue to meet across both of these trials, and we're extremely pleased that we continue to see the safety profile that we expect because of the design, which was very intentional to avoid the systemic challenges. So with that, what we have before us, is to continue to activate sites at a pace that allows us to keep with the enrollment that I've committed to. We have publicly advised that we would have the 500-patient trial enrolled in Q1 of 2029. We are working hard. We have phenomenal sites, the quality of our data, the ability to deliver clear signals ultimately comes from the product, but it comes from the clinicians that are ensuring that all of the detailed records that are required to get a registration will follow. We're working to make sure our supply is strong and that we can raise capital to really ensure that the trial continues at a pace, perhaps even accelerate, which is really important. So let me just be direct and clear from a capital standpoint since this is predominantly -- we're speaking to investors and the investment community. We are a clinical stage company with a revenue stream. Therefore, this really becomes a funding business. So we're at our heart, we're scientists. We want to advance this transformational therapy, but we do need to keep the company funded. And as we have disclosed in the past, we had a financing in June that brought in additional capital. We had a financing last December, but to complete the trial, we do need to raise additional capital. And we're working on that right now. The objective, of course, is to keep pace and have far enough frontline with our cash truly be able to accelerate. And -- we've commented before in earnings calls, that leadership has taken a meaningful portion of our compensation, actually, not just leadership. Many of our employees have also volunteered to do this. In equity instead of cash compensation. So this is not a [indiscernible] this is really how we're aligning our burn rate with the time line of the trial, and we're ensuring that we're really leveraging the capital that we have that we steward on behalf of our shareholders as effectively as we possibly can. So here's what I'm asking. I know we'll have clinicians viewing this in the future, help us enroll the right patients, help us do so quickly to get this trial approved, hopefully, approve the drug approved and the trial completed and to do so cleanly because we know that every month that we wait is another month that the field is waiting for a treatment that they can bring to the forefront. And if you're an investor or a potential partner, the data that you've heard this morning, my ask is that you'll diligence -- we have many [indiscernible] here. Our primary publication in gynecological oncology from Phase II. We have other publications that are here, dig in, look at the safety data, look at the data that's been released across other trials, the translational biomarker data and then decide if you believe from all that you've heard that if a first-in-class IL-12 with a randomized clinical study in the Phase III setting or we confirm this overall survival benefit is priced like the value that we believe will come and with the risk that we think we've quantified. We did not come here to claim that we are finished. In fact, we came here because the biology is working. We've shown you evidence of this. And the safety barrier that I think has been looming across many people as they've heard about IL-12 over time that it has been overcome. So I guess, in closing, really confirming that this is the job that we're signing up for and that we are very ready for. And I want to thank everybody for your time. We've gotten a couple of questions online that I'll pull up -- and we will provide microphone at the webcast people can hear questions, but we'll start with questions in the room.

I'm Emily Bodnar from H.C. Wainwright. Thanks for hosting this even and really impactful to hear the different results you've had. Two questions for me maybe. You mentioned the prophylactic regimen in OVATION 3 to lower rates of abdominal pain. Can you mention what specifically you're using that regimen? And also kind of the extent of reduction in abdominal pain you're expecting from that based on kind of what you've seen in the patients you've used it in so far. And then secondly, if you could talk a bit more about the NCI partnership and what the terms of that look like and the plans for colorectal and erratic development.

Sure. So I'll answer the clinical question. So what we realize, and it's very well known that there is somewhat of a distention effect because you're putting this medication into the abdomen directly. So we give them a narcotic such as like oxycodone, which they take or if it's IV, delated and then also give them anti-analytic because the fact is a lot of it is the anticipatory once you do it, if they have had pain. So we're trying to eliminate that. And we saw the reduction go down by over 50%. So probably about 20% to 30% of our patients still have some discomfort, but they're able to go home and take oxycodone at home for about 24 or 48 hours and then it self-resolves. So -- and I think as I also mentioned, education has been a key for us to let the patients know that this is an anticipated just like we sort of when people hear chemotherapy, they anticipate they may have nausea and vomiting, and we want to be

very proactive. And could I just add to that. we've been tracking dose intensity, meaning the intended dose versus the dose the patient receives for immunon. And in both the MRD study and innovation 3 so far, we're about 90% of the intended to 0abdominal discomfort is not limiting our ability to give the drug. Certainly. The opportunity with NCI is one that's extremely exciting to us. I selects a few novel and very promising drug candidates. [Audio Gap]

A and then you will perform the TD assets, -- what additional biomarkers they kind of sort certain will not have a contact for Mahalo? And based on that, what is the treatment plan for that patient in terms of sequentially or not?

Yes. Thank you for that question. So these are -- I'm sorry. These surrogate biomarkers of efficacy, both surgical MRD and ctDNA MRD and clearance have to be tied to standard outcomes such as progression-free and overall survival. So our study is designed to accomplish that and show proof of principle that maybe someday in the future, that early time point can predict what would be the eventual outcome. From a practical standpoint, patients that have evaluation for MRD after finishing that main phase of chemotherapy are still going to undergo maintenance therapy. So we don't stop at that point. regardless of the results of whether they're MRD positive or negative because we feel that at this point, there isn't sufficient data to act on that information. It's prognostic rather than causing an intervention. So every patient, whether they're MRD positive or negative in our trial are going to go on to the maintenance phase and they get the appropriate maintenance therapy if they're HRD positive. They get a PARP inhibitor plus Bev, if they're HRD negative, they either get Bev in the control arm or they get Bevs plus IMNN-001 in the [ experimental ].

Stacy, [indiscernible] from Brookline. Can you discuss in more detail what you think has caused this terrific and unexpected faster pace of enrollment, the 0.5 versus 0.3. Maybe dig just a little deeper on -- and what's causing that?

I think that it really is due to the data that we're able. So when -- and Premal should follow me, but I think that we anticipated -- so we were advised by the CROs that we were interviewing. We did a proper RFP went out to contract research organizations that would be able to come alongside and really help us with a broad trial they advised us to actually go after 0.2 patients per site per month. And we believe that as our -- the clinical team that were on site that they would have data they could share from OVATION 2 that really was differentiated that we might see a higher rate of women that were saying yes to the clinical trial. It's a personal decision. Obviously, there's a lot involved as you're making these decisions, but we believe that evidence would be something that we didn't have innovation 2 and as we ultimately looked at our own experience, how we would set those targets, Premal?

Just to add to that. I think part of it is also patients like the concept of immunotherapy. They see it all the time. They don't understand it like you've gotten told today about innate and adaptive. They see TRUDA, divo, everything immunotherapy changing the world. So patients want it because they understand the concept of what the immune system does. And so I think putting it in combination with chemo is very attractive for patients now. and especially on top of it, we have the data that shows a large trial that shows a huge benefit. So I think we can -- with much more confidence and always having a patient go on a Phase III trial is a lot easier of a conversation than when it's a Phase I, like Terry did because that's really the unknown, right? We don't know if the dose is right, we don't know if it's going to work, but now we're at a Phase III. So I think it's a much easier way to get patients to enroll. And also, patients are savvy. They are looking for trials and they want to live. So I think they're also seeking us out too.

One other aspect that we've focused on extensively is to make sure that enrollment onto our trial does not delay in any way the patient's ability to get therapy because that's paramount in the physician's mind and in the patient's mine. So we've actually made a few changes in the course of OVATION 3 already that have made it very simple for the patient to get enrolled to start treatment and nothing about the enrollment process, the screening process delays the ability of the patient to start the treatment that she needs.

[indiscernible] I guess a few on MRD. You're now having that added to the new adjuvant setting. Is that to in your practice [indiscernible].

Yes. So as you heard, addition of Bev to standard chemotherapy has some PFS improvement of 3 months. So it's a little bit underwhelming. At the same time, we're so limited by what else we can offer patients. And there's some retrospective studies that suggest especially in patients with stage 4 disease or larger volume disease addition of bev might have some incremental benefit. So for our study, we decided everybody would get bev and also I think there is a biological rationale for why inhibiting the VEGF pathway, which bevacizumab accomplishes can be sort of complementary and synergistic with activating the immune system because VEGF is also a very potent immunosuppressive molecule. So there's sort of rationale for that. The second part of your question was whether -- what's the situation with Ovation [indiscernible].