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

Hello, and thank you for standing by. Good morning. My name is Chris, and I will be your operator today. At this time, I would like to welcome you to the Imunon conference call. [Operator Instructions] I would now like to turn the conference call over to Kim Golodetz. Please go ahead.

Thank you, and good morning, everyone. This is Kim Golodetz with LHA. Welcome to Imunon's conference call to discuss top line results from the company's Phase II OVATION 2 study. During today's call, management will be making forward-looking statements within the meaning of the federal securities laws. 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, July 30, 2024. Imunon undertakes no obligation to revise or update comments made during this call except as required by law. With that said, I would like to turn the call over to Michael Tardugno, Executive Chairman. Michael?

Thank you, Kim, and my thanks to everyone for joining us this morning for this important, and I'll say it, not exciting call. I'm going to keep my remarks short because I know you want to hear from our experts and our CEO. But just let me start by saying immunotherapy has been called the holy grail of medicines answer to cancer. The goal has been to recruit a patient's own immune system to secure a persistent fight in neutralizing mutated cells and tumor masses. We know that checkpoint inhibitors have shown us the potential of this approach in many solid tumor indications. And cell therapy has done the same in many hematologic cancers. Unfortunately, and in spite of many efforts, ovarian cancer has shown itself to be a disease too difficult for immunotherapy until now. Earlier this morning, we reported top line results from our large randomized Phase II OVATION 2 study of IMNN-001 to treat women newly diagnosed with ovarian cancer. I am pleased to reaffirm that our novel gene-mediated IL-12 immunotherapy has demonstrated its potential to provide a significant improvement in overall survival in this population who have a very poor prognosis. Equally important, IMNN-001 appears to do so with a highly encouraging safety profile and tolerability. Among the findings we're announcing today is that women treated with IMNN-001 in combination with the standard of care had a median overall survival of more than 11 months. That's almost a year, more than those in the control arm specifically. The median survival for women in the IMNN-001 arm was 40 months, whereas the median for women in the standard of care arm was 29 months, and 29 months was what we expected in the control arm. This outcome is confirmed in our Phase III pivotal trial may change the standard of care for treating this devastating disease. And before turning it over to our CEO, I'd just like to say it's been an enormous amount of work to this point. Our many thanks to the staff and scientists at Imunon and to our shareholders who have had the patience to see us through to this place. So joining me this morning to discuss these and other findings is Imunon's President and CEO, Stacy Lindborg, who will review our results in more detail in our next steps. Stacy?

Thank you, Michael. Joining this call is Dr. Premal Thaker of Washington University School of Medicine and the OVATION 2 Study Chair. In a moment, she will be speaking about her impressions of the data and where IMNN-001 might fit in the ovarian cancer treatment landscape. We also have our Chief Scientific Officer, Dr. Khursheed Anwer; and our Chief Medical Officer, Dr. Dr. Sebastien Hazard available for Q&A. Before we discuss the results, I'd like to remind you of the trial design. OVATION 2 is a Phase Ib -- Phase II study that evaluated the dosing, safety, efficacy and biological activity of the intraperitoneal administration of IMNN-001, in combination with neoadjuvant chemotherapy or NACT, which is paclitaxel and carboplatin. We were studying patients newly diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. Treatment in the neoadjuvant period is designed to shrink the tumors as much as possible for optimal surgery removal after 3 cycles of chemotherapy. Following NACT, patients undergo an interval debulking surgery, which has been followed by 3 additional cycles of adjuvant chemotherapy to treat any residual tumor. This open-label study enrolled 112 patients who were randomized 1:1 and were evaluated for safety and efficacy to compare NACT plus IMNN-001, administered weekly versus standard of care alone. Patients randomized to the IMNN-001 treatment arm received up to 17 doses of 100 milligrams per meter squared of our drug in addition to NACT. So let's get right into the data, which I hope you will agree are very, very encouraging. I'm going to be using a few common acronyms. So just to be clear, OS is overall survival. PFS is progression-free survival and ITT is intent to treat. So the key findings from the trial include the following: an 11.1-month improvement in overall survival, or OS, with IMNN-001 in the ITT population, with a hazard ratio translating to a 35% improvement in OS. This is by all standards or measures a clinically meaningful improvement in a difficult-to-treat disease. Number two, a 15.7 month improvement in OS among patients who received at least 20% of the protocol-specified treatment in both arms, which is over 90% of the intent-to-treat population, demonstrating a greater benefit achieved with higher dose exposure. The third, the potential for a remarkable improvement in overall survival benefit by IMNN-001 in patients exposed to standard of care PARP inhibitor therapy, which was 38% of the ITT population. Treatment with IMNN-001 also improved progression-free survival in the ITT population. This benefit in PFS is qualitatively consistent with the overall survival data. Consistent with OS improvement, similar PFS improvement was seen in patients receiving at least 20% of the protocol-specified treatment along with evidence of a progression-free survival improvement in first-line PARP inhibitor therapy with an 11.7-month improvement in the median PFS. To underscore 1 of these findings, the data get even better for the approximately 90% of trial participants who received at least 20% of specified treatments per protocol in both study arms. Patients in the IMNN-001 arm had a 15.7 month increase in overall survival, representing a further extension of life with a hazard ratio of 0.64 or a 56% improvement in survival. This clearly showed a greater benefit was achieved with repeat exposure to our drug. While these data are quite strong and very encouraging, we saw an even more compelling effect with IMNN-001 in combination with NACT and PARP inhibitors. It's important to note that when the OVATION 2 study began, PARP inhibitors had not yet been approved for first-line maintenance treatment in our study population. Since then, for patients with certain genetic characteristics, PARP inhibitors form an important part of the treatment plan. A subgroup analysis of patients who received PARP inhibitor maintenance therapy with IMNN-001 suggest an even greater clinical benefit, one that improved further since the most recent reporting of interim data last year. Importantly, 38% of ITT population were treated with a PARP inhibitor, which is a higher number than we had originally anticipated. For this group, the hazard ratio dropped to 0.41 in the median overall survival in the IMNN-001 treatment arm had not yet been reached at the time of data lock, which compares with the median overall survival of 37.1 months in the standard of care treatment arm. Our conclusion from OVATION 2 is that IMNN-001 meaningfully improves overall survival in patients exposed to standard of care PARP inhibitor therapy. Now turning to progression-free survival, which was the trial's primary endpoint. The OVATION 2 trial, PFS data support the overall survival results we just reviewed. And these are the following data points that are critical. A 3-month improvement in PFS compared with standard of care alone in the ITT population, with a hazard ratio of 0.79, indicating a 27% improvement in PFS for the IMNN-001 treatment arm. The benefits in PFS are qualitatively consistent with the OS data, and data from OVATION 2 are consistent with the literature, which show greater protective effects with immunotherapies with overall survival compared to PFS. Also consistent with OS data, similar PFS improvements were seen in patients receiving at least 20% of protocol-specified treatments along with evidence of a PFS improvement in first-line PARP inhibitor therapy, where an 11.7-month improvement in median PFS was observed. It's important to note that as a Phase II study, Ovation 2 wasn't powered for statistical significance, rather it was designed to determine trends and inform the pivotal Phase III trial protocol. The bottom line is that patients who received IMNN-001 in the trial lived substantially longer than those in the control arm. If they received a PARP inhibitor or if they had at least 20% of the treatment per the protocol, they fared even better. These Phase II results are promising and if confirmed in an adequately powered Phase III trial, they would likely change the standard of care. Now I'd like to turn the call over to Dr. Premal Thaker, our study chair and principal investigator, who will provide her thoughts on the trial and where IMNN-001 might be included in the treatment regimen for advanced ovarian cancer. Then I'll come back and talk to you about next steps. Premal?

Thank you, Stacy. And it's my pleasure to be joining you today. Let me start by stating that it was my honor to serve as the study chair for the OVATION 2 study. This was a rigorous Phase II trial, and I was joined by a team colleagues at 22 additional institutions, including some of the most prominent in treating ovarian cancer patients. As a rigorous study, the data we're discussing today is clinical and scientific integrity of utmost importance. The women we enrolled in the study all had advanced ovarian cancer, which is a deadly disease. And this population and an increase in survival of 6 months would be clinically meaningful. As mentioned, women treated with IMNN-001 had an increase in survival of 11.1 months in the entire population, which clearly is in the realm of being clinically meaningful to me as a physician as well as to patients. And I can tell you that adding nearly a year of life to the women I treat would be a very big deal for them and their families. The impact of experimental treatment in the trial can be further assessed and importantly, confidence in the data strengthened by a 24% higher improvement in R0 surgical response in women treated with IMNN-001 compared with the control arm. And what that really means is that we're getting patients down to no gross residual disease that we can see, which we know is a very critical way to impact patients. As you are likely aware, an R0 surgical response is associated with a higher survival rate and lower recurrence and the response rate was 65% with the IMNN-001 arm versus 52% in the control arm. As mentioned, PARP inhibitors became a new component of standard of care for advanced ovarian cancer after the OVATION 2 study had already started. For various reasons, we did not go back to revise the protocol to include PARP inhibitor but a sizable number of women in both study arms were treated with them. Here's where the data becomes the most interesting. As Stacy described, IMNN-001 remarkably improved the overall survival and progression-free survival in patients exposed to standard of care PARP inhibitor therapy. We do not yet know the length of that extension because the median overall survival has not been reached in the IMNN-001 arm. I'm aware of the ongoing scientific work at Imunon that supports the synergy between IMNN-001 and a PARP inhibitor and a mouse model of BRCA mutation, and the follow-up mechanistic studies to understand the synergy. It is anticipated that the OVATION 2 findings should increase patients' motivation for participation, a potential win-win for all. We look forward to seeing Imunon advance the product into a later stage of development and is confirmed in a Phase III study, IMNN-001 could reset the standard yet again. From a practical perspective, throughout the OVATION 2 study, adding IMNN-001 into the treatment plan was quite straightforward and presented no barrier to its use for me or for other investigators. Of critical importance, IMNN-001 was not to be safe. Medical science has known for years that IL-12 is a powerful anticancer agent by causing NK cell activation, T cell activation, anti-angiogenesis and T-regulatory suppression. Until now, we have not also known that it has high systemic toxicity and administered as a recombinant protein, harnessing that power while reducing or eliminating the toxicity is the beauty of IMNN-001. Now I'll turn it back to Stacy.

Thank you, Dr. Thaker, both for joining us on today's call and for your leadership in OVATION 2. Immunotherapies have not been active in ovarian cancer, thus far. The novel mechanism of action of IMNN-001 and its ability to deliver safe and durable levels of IL-12 in addition to other important cytokines that are useful to fight cancer could usher in the first immune-based therapy for ovarian cancer. For historical context, the evidence for the current NACT standard-of-care being equivalent to upfront surgery for first-line treatment of ovarian cancer comes from the pivotal study, EORTC-55971, which was published by Dr. Vergote in the New England Journal of Medicine in 2010. The use of NACT chemotherapy for advanced ovarian cancer continues to rise with estimates being close to 50% of these cases receiving NACT. Therefore, with the addition of IMNN-001 to NACT, we at Imunon helped to change the outcome for these women. So what's next for IMNN-001? Our immediate plan is to ask the FDA for an end of Phase II meeting as soon as possible. An agenda item will be the discussion of our plans for a pivotal trial. Our expectation is that our next study will include a subgroup evaluation of IMNN-001 in combination with PARP inhibitors. Our review of the OVATION 2 data is ongoing. There's still a number of implants to be evaluated, including the chemotherapy response score, genetic information and surgical results, all of which are intended to inform the Phase III trial. Meanwhile, we're submitting a late-breaking abstract to an upcoming major medical conference, and we'll submit the full OVATION 2 results for publication in a peer-reviewed medical journal. This additional awareness should also support trial enrollment. I want to remind you that a second study of IMNN-001 in advanced ovarian cancer is ongoing, principally funded by the Breakthrough Care Foundation, MD Anderson Cancer Center at the University of Texas is the lead clinical site. The trial is expected to enroll 50 patients with stage 3 and 4 ovarian cancer. Patients indicated for frontline neoadjuvant therapy will be randomized 1:1 to receive chemotherapy plus Avastin or chemotherapy plus Avastin and IMNN-001. The primary endpoint is minimal residual disease by second laparoscopy and progression-free survival. Both of these studies are very good news for the 300,000 women diagnosed worldwide with ovarian cancer. We are grateful that our work appears to be paying off and has the potential to provide a very important solution for these patients. Let me close by saying we believe the IMNN-001 will be the first immunotherapy that's proven effective for the treatment of advanced ovarian cancer and will demonstrate that our TheraPlas platform may have a place in medicine to treat range of intraperitoneal cancers. I want to thank the patients who so bravely participated in the study as well as their families and caregivers and the dedicated physicians and scientists who are committed to providing a safe and efficacious treatment for this deadly disease. That concludes our prepared remarks. Thank you for your attention, and we're now ready to take questions. Operator?

[Operator Instructions] And today's first question comes from Emily Bodnar with H.C. Wainright.

Congrats on the very positive data. I guess first one for me is kind of like a clarifying question. So I understand the study was not powered for statistical significance. I believe that you've said the protocol hazard ratio for PFS was 0.75. It looks like it ends up being 0.79. So did this study technically meet its primary endpoint? And how is 0.75 determined? Maybe just give some context on how you view the PFS results.

Yes. Thank you, Emily, for the question. Our view is that we really view it as very consistent with the overall survival data and the summary that we provided. One thing that we did not appreciate as a company at the time that we designed the trial was really this understanding of PFS and the strength and ability for PFS to really measure and assess the effect of a treatment. So there have been publications including 2018 meta-analysis of 10 studies, thousands of patients, 8 different cancer indications that consistently show that PFS really underestimates the treatment effect across immunotherapies. So this was not appreciated at the time, it's a very important finding. And in fact, we observed very consistent with all of these other trials. The overall survival is showing an incredibly meaningful effect we can -- I think we can easily agree to the strength of evidence in terms of prolonging life. So really, what's important for this trial is that it gives us great clarity. It reinforces that we're consistent with the literature in terms of the importance of these endpoints, and it really gives great direction for Phase III to focus on overall survival, which will be our intent. So we're extremely pleased. And I think just going back to the root of your question, when we look at a 3-month extension on progression-free survival, we're also very encouraged with the consistency of conclusions.

Great. That's helpful context. Maybe just a follow-up question. For the 20% of patients who -- or sorry, the 10% of patients who didn't get the 20% specified treatments, what were like the key driving reasons for that? And is that something that you think you could potentially account for in a Phase III design?

Yes. Let me start by just giving you a little bit of context of why we included this in our analysis before we locked this data, we were aware that there were some women that had medical complications that prevented them from getting -- including one person that didn't get any Imunon exposure. We had a woman that was in the NACT arm that only received 1 dose of chemotherapy. So we knew there were cases that for reasons unrelated to therapy were really getting under treated from the protocol regimen. And because of that, we really wanted just to see, if you took out these outliers, right, from a dosing standpoint, what would the robustness of the overall study results be. So that was really the sentiment and why it was important for us to include, it wasn't that there was something magical with 20%. But since there were only 6 cycles of chemotherapy, 1 or more really ends up being 20%. And so we wanted to use a similar threshold. So that's a little bit of the background. I do think that we've learned a lot about this study and management of our product, and we'll incorporate all the learnings going forward. And I think we'll certainly delve more into that in future calls at the medical meeting that we'll present the data.

The next question comes from James F. Molloy with Alliance Global Partners.

Congratulations on the excellent early data or final data in the study. I'd love to get your thoughts on the Phase III trial design and the inclusion of the PARP inhibitor in the Phase III. And what do you think -- I know it's early days yet, but you still do at the end of Phase II. I mean with the FDA, but how do you think you'll progress or present that the PARP inhibitor arm into the Phase III trial? And then maybe as well the -- I imagine, given the remarkable results, an interim look here and potential early stoppage, wouldn't be out of the question should these results repeat, correct?

Yes, it's a great question. And James, thank you for it. It's a very thoughtful question. In this trial, PARP inhibitors weren't combined with chemotherapy for toxicity reasons, which still remains the case. And so I think that the trial design, our early design and really sketching out the core tenets of the design, have PARP inhibitor as a central part of maintenance therapy. And I think we'll have to decide if that is changed on OVATION 3 compared to OVATION 2, where it really was in the treating position, the principal investigators up to them of the appropriate maintenance treatment. It certainly will be a critical part of the maintenance therapy. And given the results that we have. It's a point that we will discuss carefully with our medical advisers and the PIs who will be intimately involved in running the study.

Great. And then what's -- maybe just a quick question on timing. When do you think you should be able to start -- again, I know you still dealing with the FDA, of course, when do you anticipate to starting the Phase III and when could an outsider looking in expect to potential early cut off or early look in interim data for a potential action event.

Yes. So we've been planning for success for a long time as a company. We're intending to start the Phase III trial in the first quarter of next year. And you'll have to wait for a definitive answer on early look, but I think we're thinking probably 2 years out from start.

Okay. Great. Maybe final question, Dr. Thaker. I think it was Dr. Thaker, I apologize if I misheard the name. Can you walk through how this would change, again if these results rolled up in the Phase III, how this would change the treatment paradigm?

Dr. Thaker?

I'm on Stacy. Yes, I am. I'm juggling my real clinical life too, so I apologize. It would change a lot because we know that 50% of women now get neoadjuvant chemotherapy. So there's a huge rise in the number of patients who actually get neoadjuvant because of the surgical bar to get women down to know growth residual is quite hard in the upfront setting. And this is a nice way to also see how patients respond to therapy because surgery is not in and of itself the only therapy for these women. So I do feel the applicability will be quite large for the patient population as we see such an increase neoadjuvant, and this is the only trial even though I know it's a Phase II that shows OS approval -- improvement, excuse me, because if you look at the EORTC trial that Stacy mentioned along with the CHORUS trial, which are both neoadjuvant trials, which are randomized Phase III, there was no difference in overall survival for patients. And actually, their survival in terms of months was far inferior to what we're reporting today. So I do find this very encouraging because we do feel that immunotherapy should benefit our ovarian cancer patients based on the biology, we just haven't been able to harness the right immunotherapy. So I think we're really on to something, the right immunotherapy to help these women gain meaningful and quality of life.

[Operator Instructions] The next question comes from David Bautz with Zacks Research.

My first question is about whether you are going to be reporting data on either IL-12 levels, T cell activation or other type of immunological parameters?

David, we do not have that data available at this time. We do have a set of samples that we will analyze in the future, and we'll certainly bring forward for not only ongoing learning of IMNN-001, but also advancing the scientific understanding of this disease.

Okay. And what were the most common adverse effect for the patients that received IMNN-001 in the study?

So let me check if Dr. Dr. Sebastien Hazard has been able to join?

Yes. Can you hear me -- can you hear me?

We can, Sebastien.

So yes, to answer your question, and this is something we saw already in the Phase I study. The most frequent adverse event were gastrointestinal toxicity, so mainly transitory abdominal pain, nausea, vomiting. So these are things that we often see with chemotherapy that can be managed.

Yes. I'd like to just add to that, that safety was monitored by DSMB throughout this study and that profile was consistently deemed very tolerable and managed as Dr. Hazard just walked through.

And the next question comes from [ Alex H with Neuro Garman ].

With significant outcome in the Phase II study, do you believe that this qualify for a breakthrough designation by the FDA or a de novo as the first in line?

So I think that we are -- we love your way of thinking. We're certainly thinking very appropriately and aggressively in terms of what these women are going through. And we will discuss with FDA, anything that allows us to get access to this drug more quickly. So those are very important discussions that we look forward to having very soon.

And at this time, we are showing no further questioners in the queue, and this does conclude our question-and-answer session. I would now like to turn the conference back over to Stacy Lindborg for any closing remarks.

Yes. Thank you. So I want to thank everyone for participating in this call and for the questions. I really want to underscore the potential of our proprietary technologies in immuno-oncology. We are looking forward to keeping you appraised of next steps, including the release of additional trial data and the progress with advancing towards our pivotal program. So enjoy the rest of your day.