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

Hello. My name is Rocco, and I will be your operator today. At this time, I would like to welcome you to Imunon's conference call to discuss OVATION 3 Phase III study design. [Operator Instructions]. I would now like to hand the call over to Peter Vozzo of ICR Healthcare, Investor Relations representative for Imunon. Please go ahead.

Thank you, Rocco. Good afternoon, everyone, and welcome to Imunon's Phase III OVATION 3 study design conference call. During today's call, management will be making forward-looking statements regarding Imunon's expectations and projections about future events. In general, forward-looking statements can be identified by words such as expects, anticipates, believes or other similar expressions. These statements are based on current expectations and are subject to a number of risks and uncertainties, including those set forth in the company's periodic filings with the Securities and Exchange Commission. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements. I also caution that the content of this conference call is accurate only as of the date of the live broadcast, March 25, 2025. Imunon undertakes no obligation to revise or update comments made during this call, except as required by law. I would like to now turn the call over to Dr. Stacy Lindborg, Imunon's President and Chief Executive Officer. Tracy?

Thank you, Peter, and good afternoon, everybody. Thank you for joining us on this call to discuss the Phase III trial design of OVATION 3 and the great and timely progress that we've made, resulting in a robust and well-designed trial that now is aligned with FDA to serve as a pivotal registrational trial, and I might add rather expeditiously. We set an internal goal to reach this point in 3 months, which is a monumental undertaking for any company. In fact, 6 months would be more typical time frame for pharma companies. But patients are waiting and with what we know about the potential effect of IMNN-001, we are motivated to move forward with urgency. I'll mention that we will use a few slides later on the call. So if you didn't join the webcast, these slides will be available on our website later today under the Scientific Presentations, which you can access through a direct link from our press release. It will be the same place that we'll have a replay of this call. And on this call, I am joined by Dr. Douglas Faller, Imunon's CMO, Chief Medical Officer; and 2 highly respected guests, Dr. Premal Thaker, the OVATION 2 and OVATION 3 Study Chair. She is also Interim Chief of Gynecological Oncology and Director of the Gynecological Oncology Clinical Research at Washington University School of Medicine; and Dr. L.J. Wei, Professor of Biostatistics at Harvard School Public Health. Douglas, Premal and L.J. will be available for Q&A and each brings a unique and really important expertise that will add to the depth of our discussion today. I want to start by sharing what we're hearing from investors and clinicians. First, we hear that OVATION 2 is a well-designed trial and that the data is strong and warrants a Phase III trial. In fact, we know from just 5 minutes ago, it's so strong that it warrants an oral presentation at ASCO. We've just gotten that notification, and we are delighted and feel it's very deserving and also very unusual for a Phase II trial to receive. We've also hear that we've delivered a clinically meaningful extension in overall survival never before seen in ovarian cancer in the frontline treatment with newly diagnosed patients. IMNN-001 plus standard of care chemotherapy treated neoadjuvantly and then adjuvantly after surgery boosted the median overall survival to 46 months, outpacing the standard of care arm alone by 13 months, which is up 2 months from the prior results of 11 months over the standard of care after 7 additional months of follow-up. We've observed an excellent safety profile that shows no cytokine release syndrome or other serious adverse events. And our confidence in the Phase III trial comes from multiple things, which include the consistency of clinical data that we've observed across endpoints and subgroups and also that the data continues to improve the longer we monitor patients, which I've just spoken about. The current status, as we announced yesterday is that the Phase III protocol is final and ready to go. FDA input has been incorporated with no outstanding concerns. In fact, we're fully aligned, and we had great alignment with FDA throughout the entire review process. And as planned, we're in the final stages of establishing our contracts prior to initiating the first cohort of sites, and then we will begin enrolling patients. Our vendor contracts are final. The required systems needed to start the trial are all in user acceptance testing. And we've done all of this applying multiple RFPs or requests for proposals, which really have delivered incredibly competitive pricing. In fact, we beat our internal targets for the cost of this trial, and we're confident that we're going to be able to stay on budget. And I have to say I'm very proud of the Imunon team and all that they've accomplished. While this is only the beginning, we're starting with an incredible foundation, and I can't imagine a better team within Imunon to operationalize this trial. I also can't imagine a more committed set of principal investigators and partners who will be critical to the trial into the frontline treatment of the women that will be in this trial. I want to move to some comments about our trial design. And similar to OVATION 2, women will be randomized we'll pull up the first slide, will be randomized 1:1 to IMUNON plus standard of care versus standard of care alone, and we're using the same dose as in OVATION 2, which was 100 milligrams per meter squared. Maintenance therapy will be given using FDA-approved PARP inhibitor. This will be specified in the protocol so that we will have consistent treatment, maintenance treatment across the treatment arms. Patients will be stratified using 2 different dimensions. The first being the stage of cancer at diagnosis. We're including Stage IIIC and Stage IV in the protocol. We would like those to be evenly balanced across both treatment arms. The second dimension that we will stratify by will be based on key biomarker data from the central lab related to each patient's HR deficiency status. Both of these are really included to focus on the interpretability of the data at the end of the trial as we know these can influence the outcomes of patients. The inclusion criteria are listed on the slide in blue, but we are looking for patients eligible for neoadjuvant treatment, and you can see other key criteria here. We have a statistical design that is expected to support a broad indication statement of women newly diagnosed with ovarian cancer, who are eligible to receive neoadjuvant therapy. And we have a design that supports an indication in an HRD-positive subgroup. Either one of these could result in a regulatory approval. We're implementing an innovative statistical design with 2 planned interim analyses. The goal is to minimize risk and allow for early stopping for success and then submission to the FDA for regulatory approval. The FDA is supportive of this strategy, the overall protocol and the statistical plan. And while the design itself is innovative, and it's referred to in the literature as a group sequential trial design, it has been implemented in other trials and the properties are well understood such that they will not bring regulatory risk. The primary endpoint is overall survival. Secondary endpoints include surgical response score, chemotherapy response score, clinical response and time to second-line treatment. We didn't list exploratory endpoints, but we do have additional endpoints, including quality of life, translational endpoints, serological response and time to subsequent lines of treatment. I want to talk a little bit about financing and money. We've been transparent about the need for financing. And specifically, I want to give you an idea of how we'll proceed to contain costs and to put forward the greatest chance for a successful trial. We shared in our recent 10-K filing and in our earnings call that the current cash runway takes us to late June 2025, and we have a solid plan to bring capital into the company, including some potential nondilutive strategies. We know that the market is a tough environment right now, and we are confident we have strategies to add money to the balance sheet and to do so in a timely fashion. As always, we will seek to fund this trial in the most investor-friendly way possible. We've designed a Phase III trial. In fact, we've engineered it to look at the highest subgroup that has the highest probability of success. The power with this subgroup, which really gives you an estimate of the likelihood that we'll be successful, is 99%. And we estimate that we have a greater than 90% chance of being successful in this subgroup at one of the interim analyses. I want to talk about our operational plan and really, this statistical design brings operational flexibility. And the protocol that has been reviewed by the FDA allows for a 500-patient trial in an all-comers population of newly diagnosed women, and it also allows for an ability to focus on a 250-patient subgroup defined by a well-established biomarker. Both are strong options, both are shots on goal that have statistical power as the trial is designed at 95% or higher, both also are capable of supporting an FDA regulatory approval for IMNN-001. So we find ourselves with options. And we've made a decision that we will focus initially on an HRD-positive subgroup. This strategy allows us to target an enrollment of 250 patients, half of the study size with an opportunity to achieve an enrollment and a readout sooner with an investment that allows us to bring more sites up to speed, but a smaller overall investment required. We expect the study budget for this initial focus would be 40% lower than the full study budget. And we could, again, with the more rapid initiation of trial sites could see a readout pulled forward even as fully as 2 years earlier. This population represents half of the ovarian cancer market and would be an important advancement for patients. Importantly, what we've heard from many of you is that this is a financeable study. So it is an appropriate place to start with our operating assumptions. We're committed to understanding the full effect in a broader population, but this would need to come at a time frame when we have an ability to broaden and to trigger that decision based on budget or positive results. With this initial strategy, we will focus on conserving cash, targeting the highest probability subgroup and delivering results as quickly as possible. So in summary, this strategy addresses 2 key dimensions that have been raised by investors that we've been meeting with. It allows us to decrease the initial investment required, decrease the time line to positive readout, and we have an ability then to be more aggressive with our site engagement to do so. With that, I'd like to open your call for questions. Operator?

[Operator Instructions]. Today's first question comes from Emily Bodnar with H.C. Wainwright.

Congrats on all the progress. Just I guess, 2 quick ones for me. Since in OVATION 2, the median overall survival was almost 4 years. I'm curious what potential endpoints or interim analysis you're planning to do to potentially get an approval quicker than that? I know you mentioned 2 interim analyses ahead of time and also the HRD population might kind of reduce the time frame by 2 years. So maybe just frame that a bit more. And then if you're able to comment on the split in alpha for the HRD population that you're assuming in the statistical analysis today?

Emily, thank you very much for the question. So -- we used the experience and really the detailed level of information that we have from OVATION 2 to plan this trial. And we have conducted really some quite extensive and spanning many months of simulations and really, ultimately, when you generate different assumption sets, different sample sizes, you're simulating these trials, basically, you're taking individual trials, you're simulating hundreds and thousands of them. It allows you to really break down what you think is likely in a broader setting and then what you might see with any one trial because at the end of the day, when we conduct trials, we only do one. But we run lots of them in simulation to really help inform us. So those simulations helped us pick the timing of the 2 interim analyses. These are endpoint-driven interim analyses. And so we got to really choose what would be optimal and where the very first interim would allow us to have a pretty good chance of being successful. So with this trial design, for example, we know that at the first interim analysis in the HRD population, there's a greater than 60% chance of being successful at that time. The second interim is then based on another set of HRD events, and it then goes above -- well above 90%. So the work to really ensure that we are -- that we're designing a trial that really will come forward with a very significant positive outcome, goes back to patient level data and properties that we want to fully understand before going into this trial. And of course, it drove the estimates of the size and the power and everything else that goes along with a well-designed trial. So let me take a stab at the second one, and then I'll see if anybody wants to add to the discussion. But we're using well-known control of the type 1 error rate. The way that the trial is designed, it's a hierarchical testing. And so you have an ability to test at the first interim, if it is not mature enough to hit, then you would move to the second interim and then the final. And it has a way of controlling the type 1 error appropriately, which was detailed in great -- many pages of detail in the statistical analysis plan, which the FDA has accepted without comment. But it also then allows a hierarchical testing across your endpoints. So it lets you basically control the testing and to make sure your type 1 error rate is controlled.

And our next question comes from David Bautz with Zacks Small-Cap Research.

So Stacy, I just want to make sure that I understand the logistics of how the study is going to run. So are you only going to be enrolling HRD patients initially?

That is exactly what we're communicating today. We think that it is a very important decision to bring clarity. We're incredibly close to getting the trial started. We want to make sure that we are confident that we have the funding that we're able to move forward very quickly with the trial. And then the protocol would allow a trigger for a broader population, but we're really listening very closely to the conversations we've been having, including with investors that we're still actively talking to. And this is the strategy that we believe is appropriate for the company at this time and that we will then consider as we look at our ability to finance and what will be right really from an investment perspective of then the right time to consider to consider a broadening of the all patients all-comers study. I mean you'll know, David, from the overall trial that we see an effect in all patients. This is something we're very passionate about, but we're wanting to sequence and make very good decisions that allow us to operate within the budget we have and within the framework that we have right now.

Okay. And actually, I think that's a pretty good segue into my next question to follow up. So if you're successful in one of these interim analyses with the HRD population, I guess, it sounds like that's going to be the trigger to turn it over to an all-comers. And then do you approach the FDA at that point for approval in HRD while the trial continues?

Yes. So what I would say is there are business decisions around this. And if we have the ability to fund something larger, it would not necessitate waiting. But really, the intent would be positive news would allow us to then to trigger a broader setting. But again, we're going to be making decisions that are right for patients that allow us to get as cleanly as possible to answers. And so I don't want to pull forward a discussion, but what I can say is that we're going after the strategy that would get us the fastest to a positive signal and then to allow us to look more broadly at the full trial population.

Could I add though, to your specific question? Yes, the intention would be to go for approval in the HRD population, absolutely. That's always been the trial design.

Okay. Understood. And do you have any estimation at this point about time frame for enrollment?

Yes. Would you like to touch on that? Would you like me to take that?

Well, we're actively as Stacy has said, we're actively initiating sites at this point in time and will start enrollment. And we'll accelerate enrollment as financing allows. We plan on opening 20 sites in this year and expanding to 50 sites at the beginning of next year.

And our next question today comes from James Molloy at Alliance Global Partners.

This is Laura Suriel on for Jim Molloy. So as mentioned, this trial will first focus on the HRD-positive patients to be treated with PARP inhibitors as well in the IMNN-001 combo. And if I remember correctly, in Phase II, the survival outcome [ patient population ] was seemed to be a bit greater. So I'm just wondering, do you anticipate similar results to be conducted as well in Phase III for this patient population in particular?

You broke up a little bit. I hope I am answering the question you asked. But yes, the patient population, HRD used to be a population of patients who did poorly. But with the innovation of using PARP inhibitors in maintenance, as not exactly part of frontline, but maintenance following frontline, the survival of these patients has benefited from this. In fact, the survival data are still reading out from the PARP inhibitor studies. Yes, we would expect this patient population to do well with PARP inhibitors, but our findings in OVATION 2, as I'm sure you know, have been that this population benefited exceptionally well with the addition of IMNN-001 in the front line. And so we would certainly expect to see that in the OVATION 3.

I want to see if Dr. Thaker has anything she wants to add about what we expect or what we observed from OVATION 2 in patients that were treated with PARP inhibitors. Premal, do you have anything you want to add?

Sure. So this is Premal Thaker. I think in HRD, we do know that those patients benefit from -- it's actually not just PARP alone. It's PARP with Avastin or bevacizumab in comparison because if you look at the data with niraparib, there is a benefit. But as we also know, there was not an overall survival benefit when it just read out at ESMO. So it's really encouraging to see the overall survival benefit that we see in these patients. So there is probably a hypothesis that the OVATION molecule because it's an IL-12 given intraperitoneally is changing the tumor microenvironment that probably is allowing the PARP to even, in my mind, have a better chance of controlling the disease in HRD patients. So I do think we would expect to see similar results in the Phase III and also save these patients from taking dual maintenance, which is an oral drug and an intravenous, which if you treat patients like I do, it is also a little more inconvenient for patients to have to come back and get these infusions and has another set of side effects as well.

All right. And also just looking ahead to the potential approval of IMNN-001, given that the current standard of care is currently surgery and chemotherapy, do you think there's going to be any challenges in physicians integrating an immunotherapy option like IMNN-001 into like a patient's treatment regimen? And how do you think IMNN-001 fits within the overall ovarian cancer treatment space?

I am going to have you start and then maybe, Douglas, you could add to that. Sure. I could start.

Sure. I could start.

Did you hear the question? Yes, great.

I did. Yes. So I think that's a great question. I would take you back that intraperitoneal chemotherapy was actually thought -- had an NCI mandate done in the early 2000s of an improvement in overall survival. So GYN oncologists for a long time have given intraperitoneal chemotherapies to patients with ovarian cancer. So I do think even though currently, it is not standardly given at most centers, but it's still at some that it is definitely something that would be accepted. And a lot of times, these ports can be put in surgically by a GYN oncologist like myself or even with interventional radiology, so it does open up a mechanism for medical oncologists to even give this drug ultimately when we get approval. So it would be no different than sort of like a dialysis catheter that's given for peritoneal dialysis for patients. So it's not a hard issue for patients, especially when they see the benefit that it can give them, hopefully, for their actual survival because that's really what patients want is survival. So I hope that answers your question.

Perhaps I could just add that the fact that the investigators on OVATION 2 are eager to participate in OVATION 3 means that these -- the issue of the catheter placement has not been an issue for them.

And our next question today comes from Kemp Dolliver with Brookline Capital Markets.

Great. A number of interrelated questions regarding the simulations and interrelated questions relate to the all-comers versus the subgroup. So how far back in the literature did you go for the simulations first for all comers and then because PARP inhibitors is a relatively recent addition, how far back did you go and look at the HRD population? And can you speak to the heterogeneity in the populations in those studies versus the expected population in OVATION 3.

I will start with this, and then I'll ask L.J. to offer perspective just to the value that simulations, clinical trial simulations bring. And Kemp, it's a great question. We actually did -- we did a lot of work, including even looking at historical neoadjuvant trials that could perhaps be used in more of an informative way in the trial, meaning augmenting, so historical data that augmented the trial. These are accepted in many areas. And again, it's something we explored and ultimately didn't move forward with. Predominantly for one of the points you just made, which is that the emergence of PARP inhibitors came more recently, and they were not available in these earlier trials. So our simulations really are coming from -- they're rooted in what we've observed in the OVATION 2 trial, which as you know, is still ongoing. So it's very contemporary. And what you do then is really take a simulation at its heart is basically you're making assumptions about what truth might be, the effect size, different elements that you want to bring out in the simulation. And then you're looking for how likely is it with a sample of the size of your trial that you're going to find significant results. And so you run different assumptions, you vary assumptions, you look at, well, what if you have a stronger effect, what if you have a less strong effect, what are you then ultimately, what are the properties of your trial, the operating characteristics of your trial that ultimately you fix, right, and run once. So the process itself is really just helps you think through in a very rigorous way and to think about what's likely to happen in that one trial. L.J., I don't know if you want to add to this. And please also anything else that you want to -- you've been waiting for the opportunity to speak to.

Yes. Thank you, Stacy. This is L.J. Wei. I am a professor at Harvard. I've been doing clinical trials for 40 years. So I was reading the protocol OVATION 3 carefully 2 days ago. It is amazing because there's a possibility, there is a delayed treatment effect, as everybody knows, right? It's the phenomenon we observed in immunotherapy. And the sponsor did a great job to simulate the situation. What would happen if my hazard ratio change over time. Instead of conventional wisdom, assuming a fixed hazard ratio and figure out the number of events they needed. But instead of, for example, in the HRD subgroup, they started with a hazard ratio 1 between months 0 and 6 and then reduced 0.9 between 6 months and 12 months and et cetera, until the end, greater than 18 months, the hazard ratio become 0.42. So this is a very interesting phenomenon. That means if you look at the Kaplan-Meier curve, the end of the study, you notice the curve probably grew together in the beginning. Then they slipped. That means the treatment indeed has a so-called long-term benefit. So the sponsor did a great job and simulate the situation and try to figure out how many events they need to get enough power. I think this is very unique because I haven't seen many protocol wing this way. And I'm really glad to -- the sponsor did this way.

Could I follow up on that? So the comment regarding 18 going out 18 months. So should we take -- make any assumptions with regard to the timing of the first interim look?

So we have simulated this very carefully, Kemp. And one thing that we definitely know is that it's dependent on the enrollment rate, right? So again, with all of these ideas, we've done lots of different simulations to ultimately inform us what to expect. The important -- one of the important things that we learned going through this is that it's important to not allow the first interim to occur until after we've been fully enrolled. And we're expecting that, that would be a year or so beyond that point. So it really will depend on the unique trial, the speed at which we enroll and other properties. But again, we've described generally the framework for this trial and what we could expect.

That's great. And then my last question relates to group sequential trial design and history of or the precedent of approvals using that. Do you have any sense of the number of approvals that have occurred with that trial design?

Yes. I don't have a number, but what I would say is it's not rare, and we know that we did not get any questions about the application of this from FDA. So there is great comfort with use of this design. L.J., I don't know if you have any broader points you want to make about [ anything ] or Douglas...

That's a good question. In my experience in the past in the cancer trial, we actually have so using a biomarker, right, defined the so-called potentially promising subgroup. And then you have all-comers. So usually, we ask yourself, should we start with all-comers and testing the treatment difference if we can hit this hurdle first, then we go down to subgroup. So this is a trade-off, right? You think about if you're taking the subgroup first, the number of events are probably smaller than the number of events for the all-comers. But on the other hand, your hazard ratio for the subgroup are probably dramatically reduced by the treatment. right? So I think it depends on the recruitment rate, if you go very fast of the recruitment, I agree with you, maybe we should sit down a little bit to say what is the timing of the first look because basically, you're absolutely right. And if we look too early, probably because the hazard ratio probably didn't kick in yet. But I believe the sponsor also consider all kind of scenarios and do the simulation. I believe the interim analysis they choose, I think it's 68 events, first look. The second one is 101 event, total is 135. So I believe they actually did a homework to find out what is the optimal timing to do the first and second interim analysis.

I say, that is -- and you are right. We did do a lot of homework. And I actually want to make one clarifying point, which I may not have presented clearly. So the HRD events that are required, and this is true of the original design, right, that had all 500 patients. This is effectively a trial within a trial that we're pulling out. So even in the context of the 500-patient trial, the interim trigger was based on HRD events, not all events. And so really, the property, it's -- frankly, it's an amazing aspect to have a trial that we can so easily pivot for different reasons to this focus. It is all very well. It's been well vetted by the FDA. We have very -- we have confidence in the operating characteristics. And really what we're choosing right now is to not undertake the fuller nature of the trial, but we understand it extremely well.

I was less concerned about FDA, more just innovation brings risk. And I just want to be sure we understand it.

Yes, you bet.

This concludes our question-and-answer session. I'd like to turn the conference back over to Dr. Stacy Lindborg, President and CEO, for closing remarks.

Thank you, Rocco. So I'll just make a couple of comments. I really do think that we're in an incredibly strong position right now. The strength of evidence of IMNN-001, you've heard Premal describing the importance and the effect that we'll see in this trial. We know that we have a trial that has an unusually high probability of success, I think, amongst Phase III trials because of the strength of evidence that we've observed in OVATION 2. And we expect that this will positively influence patient enrollment. Douglas commented on the PIs who were part of OVATION 2, and we hear this directly from them in our discussions, our planning discussions. And what you're now appreciating is that we're designing and implementing a trial that takes advantage of the highest probability of success, and this is based on what we observed in Phase II. And we're using a design that allows us if there -- if it's warranted to stop early in an interim analysis, then we will allow that to happen. And it's an event-driven trial. So it's well thought out. It's not based on just a size, but it's driven by the number of events that we're expecting to have for the full trial to be well powered and then delineating what would occur at interim 1 and interim 2. And this really -- at the end of the day, what this means is there's this potential for a rapid access for patients that would be outside the trial. So if we have a trigger and we then file, then this would mean faster access broadly in the community. So while we're focusing on this cohort initially, we have highly powered, 99% powered with a more than 90% chance that we'll be successful at one of the interims. I really don't think there could be a stronger position, and we still have the ability to broaden the inclusion criteria as we believe that is warranted and beneficial. We have a solid financing strategy, and we have a long track record as a company of success in keeping our company financed to accomplish our corporate objectives and also effectively showing discipline in cash management, which will continue. So I want to thank you for joining, and I look forward to providing you with updates as we make progress in the future. Have a great day.

Thank you. This concludes today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines, and have a wonderful day.