Imunon - Q3 2023

Transcript

Operator (participant)

Good morning. My name is Alan, and I will be your operator today. At this time, I would like to welcome you to the Imunon Third Quarter 2023 Financial Results Conference Call. All lines have been placed on mute to prevent any background noise. Following the speaker's prepared remarks, there will be a question-and-answer session. At that time, you may press star one on your phone to ask a question.

Please keep in mind, if you are using a speakerphone, you must release your mute function to allow the signal to reach our equipment. Again, that's star one to ask a question during the Q&A session. I would like now to turn the call over to Kim Golodetz. Please go ahead.

Kim Golodetz (SVP, Principal)

Thank you, and good morning, everyone. This is Kim Golodetz with LHA. Welcome to Imunon's 2023 third quarter financial results and business update 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, November 14, 2023.

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 Dr. Corinne Le Goff, Imunon's President and Chief Executive Officer. Corinne?

Dr. Corinne Le Goff (President & CEO)

Thank you, Kim, and good morning, everyone. Joining me today is Jeffrey Church, our Chief Financial Officer. In addition, Dr. Khursheed Anwer, our Chief Science Officer, will be available during the Q&A session at the end of our prepared remarks. Imunon's growth and development is dependent on four pillars. Last quarter, I spent the bulk of our time on the development of our vaccine, prophylactic vaccines modality as an out-licensing and partnership opportunity. While I will certainly update you on this modality, and we did have some interesting developments, first, I'd like to highlight IMNN-001, our DNA-based interleukin twelve immunotherapy for the localized first-line treatment of advanced ovarian cancer in combination with the standard of care chemotherapy, and it's currently in phase two clinical development.

Recall that in September 2022, we reached full enrollment of 110 patients, and this year, in September 2023, we reported an additional set of interim, more mature data showing promising progression-free survival and overall survival data. In the intent-to-treat population, we demonstrated a delay in disease progression in the treatment arm of approximately 33% or more than three months benefit. Preliminary overall survival data followed a similar trend, showing an approximate nine-month improvement in the treatment arm over the control arm. The hazard ratio of 0.78 approaches the protocol-defined value of 0.75, set at an 80% confidence interval for the ITT population.

Since OVATION 2 is an exploratory study with a total, so control plus study arms, of only 110 patients, it was not powered to appear inferior to 0.05, and the current trend looks promising. Recall that this study is evaluating the dosing, safety, efficacy, and biological activity of intraperitoneal IMNN-001 in combination with neoadjuvant chemotherapy, or NACT, and this in patients newly diagnosed with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. NACT is designed to shrink the tumors as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three additional cycles of chemotherapy to treat any residual tumor. IMNN-001 is administered weekly during the course of NACT. We also reported for the first time, data on new subset of patients treated with PARP inhibitors.

When we began the OVATION 2 phase 2 trial, the PARP inhibitors were not part of the first-line maintenance treatment in ovarian cancer. Now, they form an important part of the patient's treatment plan. A subgroup analysis of patients who received IMNN-001 and post-chemo maintenance therapy with PARP inhibitors versus PARP inhibitors alone in the control group shows positive impact. The median PFS in the PARP inhibitor plus NACT group was 15.7 months, yet PFS in the PARP inhibitors plus NACT plus IMNN-001 group was 23.7 months or 8 months longer. In addition, the median OS in the PARP inhibitors plus NACT group was 14.6 months, and median OS, overall survival, has not yet been reached in the PARP inhibitor plus NACT plus IMNN-001 group. Although these data are from a small number of patients, they are intriguing.

We also saw continued benefits in secondary endpoints, including a 20% higher R0, tumor resection score, and a doubling of the CRS-3 chemotherapy response score to approximately 30% in treatment arm versus 14% in the control arm. A complete tumor resection, or R zero, is a microscopically margin negative resection in which no growth or microscopic tumor remains in the tumor bed. Chemotherapy response score is considered a good prognostic indicator in ovarian cancer. That's why those endpoints are important to look at. And safety analysis continue to show good tolerability of IMNN-001 in this setting. Now, enrollment in our second phase 2 study, which, if you remember, is done in collaboration with BreakThrough Cancer Foundation, has begun with the first patient treated at MD Anderson Cancer Center last month.

The study is evaluating IMNN-001 in combination with bevacizumab. All in, the study is expected to enroll 50 patients with stage 3/4 ovarian cancer at several sites, including Memorial Sloan Kettering and Dana-Farber. The trial's primary endpoint is detection of minimal residual disease, or MRD, by second-look laparoscopy, and the secondary endpoint is PFS. Initial second-look laparoscopy data are expected within one year following the completion of enrollment, and final PFS data are expected approximately three years following enrollment completion. This trial will include a wealth of translational endpoints aimed at understanding the clonal evolution and immunogenomic features of the MRD phase of ovarian cancer that is currently undetectable by imaging or tumor markers. We will keep you updated as sites are added, and as a reminder, much of this trial is being funded by Break Through Cancer.

So we are now six-seven months away from seeing the final readout data of our OVATION 2 program, and this is an incredibly exciting time for Imunon. If positive, this data would be transformational to the field and would confirm our hypothesis of IL-12 being a potent immunomodulator for cold solid tumors. We will consult with the FDA on the potential regulatory path forward as small phase 2 is showing promising trends in the ITT population and a strong benefit to standard maintenance PARP inhibitors therapy, which could inform a registration study. PARP inhibitors are known to significantly increase PFS, but the improvement in overall survival is not yet established, and resistance to PARP inhibitor therapy is a concern which warrants novel combination approaches, such as with the immune agent IMNN-001.

Let's now turn to PlaCCine, our proprietary monovalent or multivalent DNA vaccines based on a DNA plasmid that controls the expression of pathogen antigens and a nonviral synthetic DNA delivery system. PlaCCine is currently being evaluated for the development of next-generation vaccines, or as we call them, the vaccines of the future. We continue to bolster our preclinical data set with PlaCCine, which suggests this asset has been de-risked and is performing as anticipated. Our first PlaCCine product is IMNN-101, which is in final stages of preparation for an IND, Investigational New Drug application to the FDA. IMNN-101, which we view as a proof of concept, is designed to protect against SARS-CoV-2 Omicron XBB.1.5 variant, in accordance with the FDA's Vaccines and Related Biological Products Advisory Committee, the VRBPAC committee, announcement that's been made in June 2023, and that established a framework for updated COVID-19 doses.

Imunon is targeting the first quarter of 2024 for submitting the the IND and then enrolling the first subject in a phase 1 trial in April 2024, with rapid advancement into a phase 2 trial by mid-2024. We are excited about the body of preclinical data, and we have been active in presenting this data at various conferences, both in the U.S. and Europe. For example, last month, Dr. Anwer presented at the Third International Vaccines Congress, highlighting immunogenicity data and the development status of IMNN-101. Dr. Anwer's presentation described the multiple advantages of PlaCCine over current commercial vaccine platforms, including modulable antigen expression and T-cell responses versus protein and mRNA vaccines.

In addition, preclinical studies show that PlaCCine elicits better antibody response kinetics, following a single dose, and demonstrates better shelf life of at least 12 months at 4 degrees Celsius, and at least 2 weeks at very high temperatures of 37 degrees Celsius. These characteristics suggest superior commercial handling and distribution properties compared with mRNA vaccines, as well as greater manufacturing flexibility. Compared with viral or other DNA vaccines or protein vaccines, PlaCCine vaccines have advantages in T-cell responses, safety, compliance, and manufacturing flexibility. Dr. Anwer's presentation also describes the versatility of the PlaCCine modality, demonstrating activity against Marburg and influenza viruses, in collaboration with the Wistar Institute, and activity against Lassa virus, which is being evaluated at the NIH NIAID.

I remind you that during the third quarter, we entered into a cooperative research and development agreement with the NIAID. This is a three-year agreement under which the NIAID will evaluate the immunogenicity and efficacy of two IMUNON DNA-based Lassa virus vaccine candidates. The agency will assess the efficacy of plasmid DNA constructs against Lassa virus in guinea pig and non-human primate disease models, including both prime and prime boost vaccine strategies. We also announced our collaboration with Wistar in January of this year, and the Wistar Institute Vaccine and Immunotherapy Center is uniquely positioned to advance new vaccine formulations to facilitate further expansion and development of PlaCCine. Collaboration with outside partners, particularly those that will provide some or all of the funding of the research, is a key pillar of our growth strategy.

Now, later today, Jean Boyer, our Vice President of Research and Development, will be presenting at the Vaccine Summit in Boston. Dr. Boyer's presentation describes preclinical T-cell responses and notes that the induced immune response in vaccinated mice were persistent without decay for up to 14 months after vaccination. So as you might think, we are very pleased with the duration of response. We believe that our PlaCCine modality is revealing itself as an important potential option in addressing not only pandemic response, but also a seasonal vaccine option.

Its stability at regular refrigerator temperatures of 12 months, room temperature stability of at least one month, and stability at high temperatures for at least two weeks, plus the immune response duration and the plug-and-play model, using the plasmid DNA backbone, has shown excellent preclinical results, that are so important to a commercial vaccine product. And this is particularly important as many pathogens, such as Lassa virus, may arise in geographies where there are challenges with refrigeration, storage, and distribution networks.

In addition, our ability to rapidly switch out antigens and load multiple antigens into the same vaccine should be instrumental in addressing the spread of disease. So in addition, our plasmid modality uses a DNA plasmid and a nonviral synthetic DNA delivery technology for the expression of pathogen antigens.

Our DNA-based vaccines can be administered using a standard syringe and IM injection, and are independent of viruses or specialized devices for delivery, like incorporation. Last quarter, I touched on our work to develop two more modalities as logical extensions of our prophylactic vaccine modality. FixPlas concerns the application of our DNA technology to produce universal cancer vaccines, also called tumor-associated antigen cancer vaccines. We have initiated preclinical work to develop a Trp2 and NY-ESO-1 tumor-associated antigen cancer vaccine in melanoma, which we call IMNN-201. This work is in a very early stage, and I look forward to updating you as it progresses. We are also in early discovery of our fourth modality, IndiPlas, for personalized neoantigen cancer vaccines.

We plan to enter into new collaborations that focus on developing AI-powered computational approaches and state-of-the-art cell sequencing technologies to identify tumor antigens in patient samples and create the next generation of personalized cancer vaccines. And as with Six Flags, we'll update you as our development work progresses. Importantly, recall that we manufacture our vaccines at our own cGMP facility in Alabama, and our decision to manufacture in-house offers us many strategic benefits, but notably, the control on costs, quality, and timelines. Now I will turn the call over to Jeff Church, who will discuss our financial results. Then I'll come back and provide a review of upcoming milestones and activities. Jeff?

Jeffrey Church (Interim CFO)

Thank you, Corinne. Details of Imunon's third quarter 2023 financial results were included in the press release we issued this morning and in our Form 10-Q, which we filed today before the market opened. Imunon ended the quarter with $19.5 million in cash and investments. Our net cash usage for operating activities was $4.5 million for the third quarter of 2023, down slightly from $4.6 million for the comparable prior year period. Cash provided by financing activities of $100,000 resulted from equity sales under our at-the-market facility. If we combine the $1.8 million of planned future sales of Imunon's State of New Jersey NOLs, we believe we have sufficient resources to fund operations at least 12 months from the filing date of our 10-Q, which we just filed.

Let me now turn to a review of our financial results. Imunon reported a net loss for the third quarter of 2023 of $3.5 million or 37 cents per share. This compares with a net loss of $6.1 million, or 87 cents for the third quarter of 2022. Operating expenses were six point... I'm sorry, $3.9 million in the current quarter, down 38% from the $6.3 million in the third quarter of 2022. Breaking down these items by line item. Research and development expenses were $2 million, a decrease of $400,000 from the prior year's third quarter. More specifically, R&D costs associated with development of our PlaCCine DNA vaccine modality increased to $800,000 from $500,000 a year ago.

Clinical costs decreased to $400,000 from $1 million in the third quarter of last year, as a result of completing enrollment of the OVATION 2 study last September, which Corinne mentioned in her earlier comments. Other preclinical development costs were $300,000, compared with $600,000 in the prior year. Our CMC costs increased to $500,000 from $300,000 a year ago. This reflects the development of the in-house pilot manufacturing capabilities for DNA plasmid and nanoparticle delivery systems, and the manufacture of supplies for IND enabling studies, as well as the phase 1/2 clinical trial for our COVID vaccine. General administrative expenses were $1.9 million in the third quarter of 2023, compared to $3.9 million in the comparable prior year period.

This $2 million decrease was due to lower non-cash stock compensation expense, professional fees, primarily legal costs, employee-related costs and insurance. Other non-operating expenses were $400,000 in the third quarter of this year, compared to $26,000 for the prior year. This increase was due to higher interest income from the company's short-term investments. I'll just briefly touch on our financial results for the first quarter... I'm sorry, for the first nine months of the year. For the nine months ended September 30, 2023, we've reported a loss of $14.6 million, or $1.64 per share. This compares with a net loss of $22.7 million, or $3.42 for the same nine-month period of 2022.

Operating expenses were $15.1 million in the first nine months of 2023, an 18% decrease from $18.4 million for the same period of 2022. Cash used for operating activities was a little over $15 million for the first nine months of 2023. This compared to $18.1 million for the same period of 2022. The decrease was primarily due to a one-time payment of $4.5 million in interest expense resulting from the sale and subsequent redemption of $30 million of Series A, B convertible redeemable preferred stock in the year ago period. Cash used by financing activities of $3.7 million during the first nine months of 2023 resulted from the early repayment of the company's loan facility with Silicon Valley Bank.

That totaled $6.4 million, which was offset by $2.8 million of sales of equity under our at-the-market facility. We also received net proceeds of $1.6 million from the sale of unused New Jersey NOLs in the first quarter of 2023. As I mentioned earlier, we have an additional $1.8 million of NOL sales that we anticipate this year and next. Our projected cash utilization for the balance of 2023 is approximately $4 million for the fourth quarter. The majority of expenses are related to the development of our PlaCCine modality, including the development of in-house pilot manufacturing capabilities mentioned earlier. I'll now turn the call back to Corinne.

Dr. Corinne Le Goff (President & CEO)

Thank you, Jeff. Imunon is tightly focused on harnessing the power of the immune system. Our goal is to provide more potent and durable immunity for millions of people with cancer or infectious diseases, while creating significant value for our shareholders. Collaborations are a key component of our strategy, and we are committed to ensuring that Imunon has the most talented advisors available to help us achieve our goal. To that end, we are delighted to expand our scientific advisory board with the additions of Dr. Patrick Ott, Clinical Director of the Melanoma Disease Center, and the Director, Clinical Sciences at the Center for Immuno-Oncology at the Dana-Farber Cancer Institute, and Dr. Sachet Shukla, Assistant Professor in the Department of Immunology, Division of Basic Science Research at MD Anderson, where he also serves as Director, Computational Biology, ECLIPSE, or Evolution of Cancer, Leukemia and Immunity Project.

The third quarter and recent weeks were exceptionally busy and full of achievements, with more expected milestones to come. Among them, we reported compelling interim data with IMNN-001 in the OVATION 2 study in advanced ovarian cancer, particularly in a subset of patients taking PARP inhibitors in combination with chemotherapy and IMNN-001. Our next milestone from this study is to report top-line data in mid-2024. We de-risked our PlaCCine modality across several pathogens of interest by demonstrating the immunogenicity and safety of our vaccines. We generated compelling data in SARS-CoV-2 and IMNN-101, our next generation COVID-19 seasonal booster, will be in the clinic in April, with human clinical data expected in the second quarter of 2024. And we also generated excellent immunological response against pathogens of concerns, specifically monkeypox, flu, Lassa virus and Marburg virus.

We unveiled a state-of-the-art manufacturing site in Huntsville, Alabama to reduce our reliance on others, which is intended to give us control not only on quantities of material, but also quality and cost. We entered into collaborations to advance our technology with more to come and to build capabilities for the development of cancer vaccines. Before we take your questions, I want to mention that we will be available for one-on-one meetings with the investment community the week of January eighth in San Francisco, concurrent with the annual JP Morgan Healthcare Conference. So please contact our investor relations firm, LHA, if you would like to schedule a meeting. With that, I open up the call to your questions. Operator?

Operator (participant)

We will now begin the question and answer session. To ask a question, you may press star, then one on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star, then two. At this time, we will pause momentarily to assemble our roster. The first question comes from Emily Bodnar of H.C. Wainwright. Please go ahead.

Emily Bodnar (Biotech Equity Research Analyst)

Hi, good morning, and thanks for taking the questions. I wanted to ask on OVATION 2 to the recent data that you had. Obviously you talked about the benefit you had with PARP inhibitors and assuming also benefit in BRCA positive patients. But you had a previous interim data readout where you mentioned that you had a benefit in BRCA negative patients. So curious if you can maybe speak to why you think you might be seeing the switch there, and why you think there is synergy with PARP inhibitors, and then just discuss how you're thinking about next steps, whether you're planning to evaluate IMNN-001 broadly or specifically a combination with PARP inhibitors. Thanks.

Dr. Corinne Le Goff (President & CEO)

Thank you very much, Emily. So I will start and maybe I'll let also Krish ask answer your questions. You're absolutely correct. If you remember last year, we did a preliminary data cut, which with very immature data, and we show benefits in the BRCA negative population. Now that we have more patients and more events, so this data cut was with 70 events across both arms. We are showing a benefit in the ITT population, and we specifically decide to look at patients treated with PARP inhibitors because the molecular signature with BRCA doesn't give the full answer. As you know, you know, patients receive PARP inhibitors if they are BRCA positive.

Even BRCA negative patients get PARP inhibitors, as it has been demonstrated that it is, you know, it can increase progression-free survival in HRD positive patients. Right? And so we wanted to be a bit more accurate in our description, in designing the subgroup of patients we wanted to look at. As you know, HRD, which is homologous recombination deficiency, is very common. 50% of women with advanced ovarian cancer have tumors that test positive for HRD, and only half of these are BRCA mutations, you know?

So, it's very interesting to look at, you know, patients treated with PARPs regardless of their BRCA status and then to get the granularity, and we'll get this data as we get to the top line data. So, what is our assumption here in terms of what's happening with the PARP inhibitors? So, we call that the PARP inhibitors are administered after the chemotherapy. We discussed this with our advisors, and their hypothesis is that IL-12, so IMNN-001, kind of sensitizes the tumor for the PARP inhibitors.

That's what they are thinking, which makes sense if you want and because our hypothesis is that IL-12 has as being a very potent immunomodulator agent can turn a cold tumor into a hot tumor. So as we progress, of course, we'll talk to the regulators. We want to discuss with them the regulatory path, and we'll should do this sooner than later, in anticipation of the top-line results in June. Maybe Krish, if you'd like to add to what I have said?

Khursheed Anwer (Chief Scientific Officer)

Yeah. I mean, I think you covered pretty much Corinne, but I just wanted to start with Emily's last part of the question, which you just kind of addressed that potential mechanisms. So, Emily, as you know, back in phase 1 study, we did report change in the tumor microenvironment from the treatment... where we saw increase in CD8 positive cells to immunosuppressive marker ratio. That suggests that the environment was transitioned from immunosuppressive to immunostimulatory. That itself, as Corinne said, you have this environment now before PARP come in, your tumor environment has changed to be more fighting for, you know, against tumor. That could be one potential mechanism. In other words, you know, you sensitize the tumor for PARP.

As you know, PARP causes cell death, you know, DNA repair doesn't happen, and that releases antigen. And if you have a good immune stimulatory environment, that released antigen will potentiate the immune response. So that's a potential mechanism. We're not saying that's it, but I think that's potentially, theoretically, it makes sense. Now, first part of your question was about BRCA negative, and Corinne did eloquently point that out as well, that that was early data. But also the molecular signature-wise, it's a lot more to learn in ovarian cancer. Initially, we defined it as BRCA positive, BRCA negative. That's more of a somatic, but in tumor also, you have this homologous recombination deficiency, and there's a lot of variability, variety there. There's several enzymes. Some are deficient in some patients, some are not deficient in other patients.

We're also trying to look into the database to better understand the molecular signature, not just BRCA positive, BRCA negative, but further subtype as to really what's the extent of deficiency and see if we can make some correlate. If you do that, then you really lower the sample size because you already have about 70, and now you're going to further break down. But I think that's what we're trying to look into further understand these results, understand the mechanism, maybe through some preclinical studies. But also what's next type of broad application you ask, or maybe more limited to, I think PARP combination certainly direct us towards specific type of application. But as you learn more about molecular signature from this ongoing study, more data come in, perhaps that will shape up our future direction strategy.

Emily Bodnar (Biotech Equity Research Analyst)

That is very helpful. Thank you.

Khursheed Anwer (Chief Scientific Officer)

Thank you.

Operator (participant)

Our next question comes from James Molloy of Alliance Global Partners. Please go ahead.

James Molloy (Managing Director & Senior Biotechnology and Specialty Pharmaceuticals Equity Research Analyst)

Hey, guys. Thank you for taking my questions. I just want to get your thoughts on, you know, the OVATION002 data coming out here mid-next year. Can you walk through what the potential phase 3, I know much will depend on how the data looks, what a potential phase 3 or phase 2b trial design or next steps on trial design might be from that? And then on the Avastin trial, the phase 1/2 Avastin trial, the interim data coming up here, what should we be anticipating here in the second quarter for that, the interim look?

Dr. Corinne Le Goff (President & CEO)

Thank you, James. As I mentioned, for the OVATION 2 program, we'll be discussing with the FDA on a potential regulatory pathway. We notably would be very interested in a breakthrough designation that could shorten considerably the development timelines. So that's something that we are working on. And you can imagine that what we have in mind is, you know, we could continue enrolling in the current phase 2. As we mentioned, you know, this phase 2 program is only exploratory, right? So, with 110 patients, we would need to increase the number of patients including in the trial. And certainly, you know, we would look at the subpopulation of treated with PARP inhibitor.

That's what we have in mind right now. Now, but unless we speak with the regulators, you know, we have—we don't have... Until we speak with the regulators, we have not confirmed any development plan at this stage. And, Khursh, do you want to comment on this point before I address the MRD study?

Khursheed Anwer (Chief Scientific Officer)

No, I think you've covered it. I think that's exactly. We're just still in formulating our strategy and perhaps help from agency or, you know, feedback will be important.

Dr. Corinne Le Goff (President & CEO)

On the MRD study, right, so what we expect is like a year from enrollment, you know, we would have already some interesting data. So maybe, Krishna, do you want to comment on this and what we expect from this study, which also has in the protocol design a number of translational data accounted for that, you know, I think would be super informational for us. Do you want to comment on the MRD study, Krishna?

Khursheed Anwer (Chief Scientific Officer)

Yeah, of course. Of course. Thank you. James, yeah, so as you said, maybe second quarter next year, what kind of information is anticipated from MRD study. So the MRD study, this is the first time we will be testing IMNN-001 with Avastin in humans. We have never done that before. So Avastin is now in a neoadjuvant setting. It's been approved. So I think the first lead Phase 1 part of the study is to really look at the safety with Avastin. So that's, I think we want to get that out of the way. We don't anticipate any issue. So that's something I guess will be to move on from its safe combination and then open up the study into that population.

Now, what to anticipate is certainly more enrollment by that time, second quarter. But down the road, as Corinne said, this study is really important because when patients get cytoreductive surgery after three cycles of chemo, tumor burden is surgically removed, and then you get another three cycles of chemo, and then nothing happens to maintenance therapy. But now we'll be looking at the peritoneum again after the surgery and one month after, and we anticipate that by IMNN-001 and Avastin, we have preclinical data to show benefit, would reduce the burden, the residual disease, and lower the residual disease will be anticipated with longer survival. So we expect to see maybe some patients. I can't promise in second quarter we'll have that.

Like I said, safety part has to complete, but what you anticipate down the road will be the second-look laparoscopy, you know, how many patients have we have seen those, you know, residual disease versus what's known, which is about 70% of patients have residual disease minimal, versus we're trying to get it down to about, you know, 35%. So we might see some of that data coming in, but also we are collecting a lot of translational research, you know, understand the tumor biology. That is probably will be done when all the patients have sort of all the samples have been collected. So I think safety plus some maybe update on minimal residual disease and obviously PFS data, our R0 data secondary endpoints.

You know, as with OVATION 2, you know, we have been updating the community over the years or different time periods. So we'll probably some of that. But clearly this study will have a lot of translational component to it to understand the combination.

James Molloy (Managing Director & Senior Biotechnology and Specialty Pharmaceuticals Equity Research Analyst)

Great. Thank you for that. I see, also you guys, signed a cooperative R&D agreement, NIAID, or talking about it here in the third quarter, the Lassa virus. Does Lassa virus, is that a potential, for priority review voucher down the road?

Dr. Corinne Le Goff (President & CEO)

Yeah. Thank you, James. That's a good question. So, you know, as I mentioned, with the development of the PlaCCine modality, you know, we would look at partnerships to develop vaccine candidates, and if NIAID is interested, why not? But maybe, Krishan, do you want to elaborate on this agreement that we have with NIAID?

Khursheed Anwer (Chief Scientific Officer)

Yes, of course. James, initially, of course, I mean, the PlaCCine is a new platform, as you know. The history suggests that we have, you know, just last couple of years, we have kind of embarked on that. So our goal has been to demonstrate proof of concept or application in as many indication or opportunities we can. Some we have facility like biosafety level for some viruses, and we don't. There, you would need some collaborations, and NIAID is looking at Lassa. They have looked at Lassa with different approaches. In the past, they have ground force in West Africa, including Mali, where they have done some clinical trials. So, as commercial potential for the company, as Corinne said, may not be as, as today, you know, it doesn't look very huge, but it's increasing.

There's a report on Lassa come out where there's more incidents coming in South America and perhaps also heading west. So who knows? But certainly in NIAID, if the results are positive in animal studies, then NIAID is interested in pursuing Lassa in West Africa. And that would be another sort of proof of concept approach for our technology to see the different kind of virus. So, as such, company-wise, again, I defer to Corinne on that, but certainly that's not our big sort of commercial aspect, but, you know, through collaboration, proof of concept, and if NIAID want to do that further, why not? Would company be taking a lead role at some point? I think Corinne may comment on that, but right now we're focused on SARS-CoV-2.

James Molloy (Managing Director & Senior Biotechnology and Specialty Pharmaceuticals Equity Research Analyst)

Okay, great. Last question is just for Jeff. If I could, Jeff, OpEx has been kind of trending down last few quarters, you guys are doing a good job, shepherding cash. Is this the level we should anticipate going forward, or we start seeing OpEx perhaps bumping up going through 2024?

Jeffrey Church (Interim CFO)

Yeah, we anticipate our cash realization in the sort of the low $4 million a quarter range, and we'll manage to that. The big driver will be the phase I/II study. But as we mentioned, the OVATION 2 is fully enrolled. We're doing just a follow-up on that. And then the Break Through Cancer program with the Avastin is being funded largely by that foundation. So we're gonna manage to a quarterly cash utilization of four to four and a quarter million.

James Molloy (Managing Director & Senior Biotechnology and Specialty Pharmaceuticals Equity Research Analyst)

Great. Thank you for taking the questions.

Jeffrey Church (Interim CFO)

Mm-hmm.

Operator (participant)

The next question comes from Kemp Dolliver, from Brookline Capital Markets. Please go ahead.

Kemp Dolliver (Director of Research & Senior Analyst)

All right. Thank you, and good morning. So I have a couple of questions about the IMNN-001 trial in combination with Avastin. First, when do you expect to activate Dana-Farber and MSK?

Dr. Corinne Le Goff (President & CEO)

Thank you, Kemp. Yes, very soon. We have not announced it yet, but we're expecting that they'll be, MSK will be on board pretty soon. Khursheed, do you want to give a bit more color to my answer?

Khursheed Anwer (Chief Scientific Officer)

Yes, exactly, Corinne is right. We did a site initiation call with them a couple weeks ago. We did respond to their, you know, IRB question standards, so I think they could be very soon activated. The other one is Johns Hopkins for phase I part, but Dana-Farber had from the very beginning, they would participate from the phase II part of the trial. As Corinne said, MSK should be. There's no unexpected hiccups. We should be making that announcement. They should be coming on board. A lot of paperwork has been completed with them. It's basically setting up the contract, all the, you know, different approvals from their committees. We have made good headway in that direction. So MSK is very likely coming up soon.

Kemp Dolliver (Director of Research & Senior Analyst)

... That's great. Thank you. And, yeah, this trial is using, I believe carboplatin as, in the comparator arm, and, you know, that's been in short supply. How have you been able to manage that in terms of, A, both avail, you know, availability, but then also cost?

Khursheed Anwer (Chief Scientific Officer)

Yeah, I mean, that's a good question. We did run into this issue back in 2012 with Doxil. If you remember, that was a big issue. But no, we haven't... I mean, the centers that we are doing our studies are really big names. So, say, investigators in MD Anderson has not brought that to attention in terms of the cancer center having any deficiency. And you're right, this chemotherapy is carboplatin and paclitaxel. So, we haven't really heard from the sites yet, certainly these big centers having any deficiency issues. Cost-wise, this is standard of care, it's normally given to patients. But cisplatin is another, of course, you know, a platinum-based drug is used.

I'm not forecasting that we may use cisplatin, but I haven't heard anything about any problem with these cancer centers, so I don't anticipate. But, cisplatin is always available there as another platinum drug. I probably don't want to say any more here because you did point out something, and we haven't been really told that would be a concern to these centers. Maybe a lot of small centers, perhaps that could be an issue, as there was with doxil, and we have about 25 sites or so. So I heard about four sites so far and big names. I don't know. I'll look into that. Certainly, we haven't been told by the sites yet any issue down the road, certainly.

Dr. Corinne Le Goff (President & CEO)

Yeah, and the cost of standard of care are, you know, paid by Break Through Cancer.

Kemp Dolliver (Director of Research & Senior Analyst)

Right. You know, two questions. I apologize. The first one is gonna require you to repeat some information, but I just want to be sure I understand, stood for this trial, the timing of anticipated completion of enrollment and availability, you know, the first set of interim data you'll provide. 'Cause that, that... I think the line was breaking up, and it wasn't clear how those line up together.

Dr. Corinne Le Goff (President & CEO)

All right. I will start, and I'll let Krish continue. So, you know, we anticipate that enrollment will be done cautiously for the first phase of the trial, which is the safety analysis of the combination of 001 and Avastin. In case that's what the investigators are telling us. And of course, you know, as more centers come on board, you know, you will see an acceleration in the enrollment. But, Khursh, please, if you could answer the second part of the question, and-

Khursheed Anwer (Chief Scientific Officer)

Right. So I apologize if there was, you know, a signal issue. So what we had said in response to, I believe, James' question, that initial set of the data would be safety, of course, because Avastin has not been combined with GEN-1. So we hope to finish that phase 1 part of the study out. I mean, it all depends on the enrollment. Four sites have been, you know, put into place initially, but we are trying to expand that. And I would think second quarter would be more of a safety clearance that indeed this new combination is safe in patients.

Then from second quarter on, if we get more sites on board, we can probably get more enrollment and begin to update on the second-look laparoscopy results over time and perhaps maybe in quarterly update or so. But in terms of completing that study, I would say Corinne and even Jeff can chime in here. I would say at least about two years to complete the enrollment and at least with these three sites plus a couple more sites. I think immediate is the safety data and some efficacy data maybe trickle down. We can update this open label study, so I would say within two years, maybe some significant data. But overall survival is a longer endpoint. That will probably take a long time to mature.

But certainly, second-look laparoscopy, we could get within two years some meaningful data, hopefully. Again, this is what we are anticipating, and we'll also get faster with more sites.

Dr. Corinne Le Goff (President & CEO)

Right. Kim, at this stage, you know, we cannot give very, very precise timelines where we're waiting for more centers to enroll. So it's a preliminary assessment, really.

Khursheed Anwer (Chief Scientific Officer)

Correct. Correct.

Kemp Dolliver (Director of Research & Senior Analyst)

No, that's super. Yeah, thank you. And just the last question is for Jeff, and it relates to the trial and the Break Through Cancer reimbursement. Will those essentially, the, the reimbursements just net against your R&D expense, or will those show up as, you know, grant revenue?

Jeffrey Church (Interim CFO)

It'll be the former, as we anticipate. We'll just treat what we're gonna be paying as R&D expense.

Kemp Dolliver (Director of Research & Senior Analyst)

Fabulous. Thank you very much.

Operator (participant)

The next question comes from David Bautz from Zacks Small Cap Research. Please go ahead.

David Bautz (Senior Analyst)

Hey, good morning, everyone. Thanks for the update this morning. I just have a question on the COVID seasonal booster vaccine plan for the phase 1/2 trial. So I'm assuming that the phase 1 trial is gonna be a safety study in healthy volunteers, but then will you look to do an efficacy study in phase 2?

Dr. Corinne Le Goff (President & CEO)

... David, thank you for your question. Yeah, so, in vaccine development in phase one already, we will have, immune response data, right? So you have the neutralizing antibody data that you get quite rapidly, you know, after, the injection of the vaccine. So the phase one will already give us that data, and that's why in the design of our program, we are looking for phase 1/2. We'll simply continue enrolling in a phase two program with the chosen dose.

Emily Bodnar (Biotech Equity Research Analyst)

Okay. And then will the phase two have an efficacy outcome?

Dr. Corinne Le Goff (President & CEO)

Of course, the phase 2 will have efficacy and yeah, efficacy outcome and immunogenicity, reactogenicity as well.

Khursheed Anwer (Chief Scientific Officer)

Yeah.

Emily Bodnar (Biotech Equity Research Analyst)

Okay.

Khursheed Anwer (Chief Scientific Officer)

As you know, vaccine trials efficacy is really not challenging human being, right? So it's really the titers of the antibodies, neutralizing antibody, really, that's what you look at above baseline. I think that's essentially maybe what you're probably referring to, efficacy part. So in phase two, we'll be looking at that, that how much of the titers, from baseline have gone up, against this particular, variant that we are targeting and the variant of the, you know, concern at that time. Basically, neutralizing antibody titers above the, above the baseline. That's the measure of efficacy, you know, in vaccine studies, typically, as opposed to a therapeutic marker, right, in cancer. So yeah, we will be looking at that in phase two.

Emily Bodnar (Biotech Equity Research Analyst)

Okay, great. Thanks for taking the question.

Khursheed Anwer (Chief Scientific Officer)

You're welcome.

Dr. Corinne Le Goff (President & CEO)

Thank you, David.

Operator (participant)

This concludes our question and answer session. I would like to turn the conference back over to management for any closing remarks.

Dr. Corinne Le Goff (President & CEO)

Thank you. We believe that our technology holds excellent promise in immuno-oncology as our work in providing options to, women with ovarian cancer looks very interesting, and we are excited about reporting phase 2 data, around next spring, next summer. We've also been using the phrase, vaccine of the future, to describe our work, and that's exactly what our vision is: to be the provider of safe and effective vaccines that are superior to current vaccines in terms of, durability and breadth of protection, are stable at workable temperatures, can be manufactured rapidly to respond to evolving pathogens, and offer better compliance for mass immunization, with no need for a device or a virus. We very much look forward to keeping you informed of our progress. Have a very nice afternoon.

Operator (participant)

The conference has now concluded. Thank you for attending today's presentation.