INmune Bio Inc. (INMB) Earnings Call Transcript & Summary

All right. I appreciate everybody joining us this morning. We are very delighted to have this webinar to share with you INKmune in metastatic castration-resistant prostate cancer. I'll remind everybody that we're a public company. And as a result of forward-looking statements, the statements that we make may change, and I encourage you to review our most recent filings with the SEC and our risk factors and disclosures. With that, we have a very distinguished panel here today. We're delighted to talk about this program. We're fairly excited about it internally as a company. And I'd like to pass the call over to Dr. RJ Tesi, Co-Founder and CEO of INmune Bio. RJ?

Yes. Thank you, David. I just want to echo David's sentiment that we are quite excited about this entry into the solid tumor arena for NK cell-based therapeutics. We think that is the future, and we think INKmune is a very important part of that future, and this is the first step we hope of demonstrating that to you. So we'll be talking about INKmune primed memory-like NK cell therapy in metastatic castrate-resistant prostate cancer. Matt Rettig, Professor of Medicine and Urology and the Medical Director of the Prostate Cancer Program, David Geffen School of Medicine at UCLA and a member of the Jonsson Comprehensive Cancer Center at UCLA is the PI of this program. He is a consultant to the company in this arena, and he is very, very experienced and seasoned, and we look forward to his comments. Many of you have heard Mark Lowdell speak before. As David said, he's our CSO, Founder, and he is the inventor of the INKmune technology. So with that, the agenda is relatively straightforward. Professor Rettig will talk about current therapeutic options for men with metastatic castrate-resistant prostate cancer, including the history and the frustrations of immunotherapy in this space. Mark will talk about the mechanism of action of INKmune, and why this is a great strategy for prostate cancer therapeutics. And then I will highlight some of the unique aspects of the clinical trial design, which we think is appropriate, and we should facilitate us learning more about this quickly. So with that, I'll turn it over to Matt.

Thank you. I would have figured this out after several years of using Zoom, but I'm slow to new technology here. Okay. So as a way of background, it's important to recognize that prostate cancer is a major source of morbidity and mortality for men in the U.S. and actually globally. Prostate cancer is the second leading cause of cancer-related mortality in the United States with lung cancer being #1. And what we've seen with prostate cancer is that both the incidence and mortality of the disease has been increasing year-over-year. And what you can see at the top here is a table that illustrates this observation. So first of all, mortality has increased by, on average, about 1,000 deaths per year so that in 2018, there were about 29,500 deaths. And in 2022, we're expecting 34,500. Importantly, the incidence has also increased. And in 2023, in the graph at the bottom, what you can see, assuming that the incidence trends continue, is that 2023 will be the first year that the incidence of prostate cancer exceeds that of breast cancer. So prostate cancer is really a common problem that leads to significant morbidity and mortality. Now the mortality related to prostate cancer is almost all attributable to the metastatic castration-resistant prostate cancer space. And there have been a lot of therapies that have been developed over the last several years. Next slide, please. And this graphic illustrates a time line of the approval of drugs in metastatic castration-resistant prostate cancer that have extended overall survival. So the first drug to have been shown to improve albeit modestly, overall survival for mCRPC patients was in 2004 with docetaxel. And then there was a several-year drought until we had the approvals of sipuleucel-T, a cellular vaccine and cabazitaxel, a closely related taxane to docetaxel. And then you can see, there were several other approvals, including the novel second-generation angioreceptor-signaling inhibitors. We have Radium-223, a calcium mimetic that emits an alpha particle; and then checkpoint inhibitor, pembrolizumab, but that was restricted to patients with mismatch repair deficiency. So pembrolizumab was the first therapy that the FDA had approved agnostic to the tumor type. So the approval is actually for advanced malignancies with mismatch repair deficiency. And in prostate cancer, only about 3% to 5% of patients have mismatch repair deficiency. And then more recently, we have the approval of PARP inhibitors, olaparib and rucaparib. And finally, and most recently, is the approval of PSMA radioligand therapy that is just coming online. So lots of therapies, but some issue with these therapies is illustrated on the next slide. So next slide, please. Thanks. So this is a slide that illustrates the median overall survival benefit of the aforementioned agents for mCRPC based on the registration studies. And what you can see is that the median overall survival benefit is fairly modest, basically 2.5 to about 5 months. So there's a lot of room for improvement. Importantly, immunotherapies have shown great promise in many, many cancers. And I think what's so striking about immunotherapy is not only the ability to induce responses, but the subset of patients who have a complete remission that can be quite durable. And I think this is the exciting aspect of immunotherapy. And unfortunately, in prostate cancer, we have not really reaped the benefits of immunotherapy for really most any state of the disease, but especially metastatic castration-resistant prostate cancer. So I think there's a great opportunity to develop novel approaches to the management of metastatic castration-resistant prostate cancer. And in my view, immunotherapy, if we can leverage it correctly for advanced prostate cancer, would be an ideal approach that has the potential for deep and durable remissions with relatively minimal toxicity as you'll hear. So with that said, I think -- what I'd like to do is turn it over to Mark, who can describe the NK cell approach to immunotherapy for metastatic CRPC, so thank you. Mark?

Thank you, Matt. That was an excellent introduction to a field which I'm really struggling to get to grips with. So why NK cells and in that space, why INmune in particular? Well, I'm sure you all know that we will require NK cells as part of our immune strategy mechanism or the most essential part of our immune surveillance mechanism for cancers, which are rising all the time. And we know that healthy individuals with low NK function have increased risk of cancer. And as I'll show you, other people have demonstrated in patients with prostate cancer, those with low NK function and have lower overall survival. So one might aim as we're doing here to increase that, to push them into the better survival groups. NK cells is part of the complex immune network that ultimately leads to T cell immunity through interaction with dendritic cells. And so an NK response is not only an immune response, but it has the capacity to potentiate an acquired immune response. That having been said, we rather than an adoptive NK therapy. Well, adoptive NK therapies, like every adoptive therapy, have manufacturing issues, time delay issues and are very expensive. But they also have to get into the tumor. The beauty of INKmune, as we found both preclinically and in patients, is that it activates the patient's own NK cells. And it generates what we call or what are known in the NK field as memory-like NK cells, which we all know as NK biologists, are the most potent NK cells for killing NK-resistant cancer cells. And those can be generated either by ex-vivo activation with a triple cytokine cocktail, which can't obviously be used in-vivo because cytokine cocktails are too toxic or it can be generated by priming with the relevant tumor cell, in this case, INKmune. And as we'll show you, INKmune can be used in vivo. It's very, very specific to NK cells. It doesn't activate T cells, so the side effects are extremely low. And what we find uniquely with INKmune is that it upregulates really important survival signals and nutrient receptors, which we believe is important in maintaining the NK cells in the general microenvironment, and I'll show you some data on that. And as we've seen in the patients treated so far, once these cells are activated, they stay activated for a long time. And even that population expands, and we have some hypothesis behind that. But I guess the real secret to INKmune and the reason why I'm so excited about it is that we've been able to engineer it from get-go, having myself having worked in a hospital all my life, I know how difficult it is to develop and deliver these therapies. And so what we've done is generate a therapy, which is off the shelf. It can be stored in conventional minus 80 freezers in hospitals. Within the pharmacy, travels around the hospital at minus 80 rather than in nitrogen vapor and is injected into the patient in an outpatient setting. And because these cells are inert, the replication competent, and they drive the patient's own immune system, they don't require a conditioning to chemotherapy conditioning. Can we move to the next slide, please, David? So there's a lot of data here, and I apologize for that. But the best -- if we start off on the top left-hand side, this is a paper from a group [indiscernible] from a couple of years ago, looking at the cells that can be found in normal prostate tissue and in cancerous prostate tissue. And what you can see here on the top line, the most increased cell population of all of these T cells, B cells, NK cells, dendritic cells, the most increased population in the tumor relative to the normal tissue are resting NK cells. And there's a small number, not significantly different to the normal tissue, small number of activated NK cells. What you see is that the normal tissue is predominantly infiltrated with normal CD8 T cells. And these are the cells which conventional checkpoint inhibitors target. And as you can see, they're not preferentially present in the tumor tissue of prostate cancer patients. And this might point to why drugs such as pembro have failed. What we can see from the graph below that, from a different publication from [indiscernible] in looking at metastatic cancer -- prostate cancer patients, you can see that those with higher overall survival are those that have a higher proportion of NK cells by this marker NKp30 or NKp46 in their peripheral blood. So the presence of higher numbers of NK cells in the peripheral blood is prognostically important. And what we believe we may be able to do with INKmune has pushed those patients from a lower prosurvival into the higher survival group. So you can see that patients have lots of NK cells in the tumor microenvironment, but they're not activated. And what we do know about INKmune is it's very good at activating resting NK cells. And you can see here that the cartoon in the middle of the slide, resting NK cells are inhibited by signals from the tumor cells and from the tumor microenvironment. And there's inadequate activating signals to allow these resting NK cells to activate and kill the tumor cells. INKmune is a replication-incompetent tumor cell. It provides those signals that the prostate cancer cells and others are not providing. And so what it does, it pushes the resting NK cell to a prime state by providing all of this excess activating signals. And as you can see, these cells then become able to kill NK-resistant tumors. But equally important and perhaps more important is this element of what's called trogocytosis. So you can see in the photo micrograph below that the INKmune cell, in this case, it's labeled as [ NB16 ], which is the parent cell of INKmune. We've membrane di-labeled that. And when it incubates with the -- or interacts with the resting NK cell and the NK cell becomes a tumor-primed NK cell, it actually -- the NK cell rips out of the membrane of the INKmune big lipid routes and carries with it the activating ligand from INKmune. And what we've been able to show is that those primed NK cells then interact with resting NK cells and pass on that priming signal. And we've done that both at resting and dynamic modeling settings. So we believe this is why these patients end up having been treated once with INKmune, end up with a long-standing activated NK -- memory-like NK population in their peripheral blood and hopefully, in the tumor. Next slide, please, David. So what does this do? Well, if you look here on the graph on the left-hand side, these are a number of different tumor cell lines from lymphomas, myelomas and indeed prostate cancer. And if you look at the resting NK cell ability to kill these in the first column of each selection, you can see these cells -- these tumor cells are very, very resistant to NK killing. But when we prime them with INKmune, in all cases, lymphoma, myeloma but particularly in prostate, we got a dramatic enhancement in killing. Now here, these are our data and they're in a single prostate cancer cell line, but others have published using PC3, for example, the same outcome. And indeed, in both DU145 and PC3, the NK function after priming with INKmune is far greater than after priming with cytokines such as IL-2. And this, I think, is the question. The problem that we've seen in the past with NK therapy trials is that a single cytokine is being used to either sustain these NK cells or indeed trying to activate them in vivo. And NK cells don't live in an environment of single cytokine signaling. What INKmune does here is in fact there's what we call a pseudokine. It gives all of the signals that combination of IL-12, IL-15 and IL-18 give in the generation of cytokine-induced memory-like NK cells. So what we end up then with, if you look at the graph on the right-hand side, here, we're looking at the ability of NK cells activated either with R15 or with INKmune and seeing how they behave in a hypoxic tumor microenvironment. So in case it's very good at killing in normoxia. But of course, the tumor is hypoxic. What we've demonstrated here is that INKmune increases the ability of the NK cells to function in a hypoxic environment, whereas IL-15 doesn't. If anything, it decreases it slightly. This assay is an interesting assay because it ran for 48 hours, and we were able to show that the peak activity was at 24 hours. And by 48 hours, the tumor cell is actually all being killed, which is why it falls back at 48 hours. So these cells are very, very potent. Can we pass next slide, please? Great. So what else do we know? Why do we -- what evidence we've got that these NK cells really are better after they've been primed with INKmune? And this, on the left-hand side, is a proteomics plot, looking at over 9,000 proteins. And you can see here that NK cell is activated with IL-15 and Lac15, blue circle, they don't generate these proteins that are on the top right-hand side that are generated by INKmune. Indeed, even the cytokine combination to make cytokine memory NK cells doesn't generate that population. When we look deeply into what those proteins are, you can see on the right-hand side that they are largely or at least a good combination -- a good number of them are involved in mitochondrial survival. We know that NK cells and indeed, T cells in the tumor microenvironment, end up with mitochondrial insufficiency and they die. And that's been published by a number of groups, not just our own. And what we can show here is that the red dots, those NK cells treated with INKmune and becoming tumor-primed NK cells substantially, and this is a log scale on the left-hand side, substantially upregulate mitochondrial survival proteins, which are not upregulated by cytokine-induced memory-like NK cells or indeed by IL-15 alone. We believe this is critical to their survival in vivo and may indeed point to why in our patients who have been treated, they've shown sustained presence of primed NK cells, even 100 days after the last dosing. The other thing that we believe is critically important here is that mitochondria mustn't just upregulate their survival proteins, but they must function better. And of course, respiration is critical to mitochondrial function. That's why we breathe up oxygen, of course. And if you look at these tumor-primed NK cells, the maximum mitochondrial respiration in the middle there is slightly higher, albeit not significantly higher than cytokine-induced NK cells. But most importantly is the spare respiratory capacity. So after the NK cells have been maximally activated and maximally stimulated, the tumor-primed NK cells retain spare capacity to continue to be mitochondria active. Whereas the cytokine-induced NK cells have lost that spare capacity, and this is almost certainly due to the upregulation of the mitochondria-survival proteins as far as we understand it. Next slide, please, David. RJ, I'll hand over to you.

Thank you, Mark. That was a great review, and I'm sure we'll have a few questions on this really interesting biology. My goal for the next couple of slides is really just to kind of give an overview of the clinical trial protocol. And really to talk a little bit about really some of the interesting design elements that we had to design into the program to meet the FDA concerns as well as to make sure we reached our goals, in determining whether INKmune was going to be an effective therapy and an effective immunotherapy for patients with metastatic castrate-resistant prostate cancer. So the FDA must-haves for the trial design was a little more stringent than for a small molecule in -- or even a traditional immunotherapy in man, they were really, really curious and interested in both short- and long-term safety most of the time with either small molecules or biologics. They're interested in the Phase I at least for short term. But I think as their interest because it's cell therapy, because of the techniques that Mark used to make these cell replication incompetent, they wanted to make sure that long-term safety was going to be appropriate for the target population, that has meant who -- I don't know, I'll ask Matt to comment, but I imagine the average age of these patients is in the -- as well in the 60s. For INmune Bio, our must-haves, of course, were safety in the target population, but we also wanted to show what we call proof of biology. Now in an open-label trial with small, you can't have statistical evidence of improved of antitumor efficacy, but we can use biomarkers to determine if we're having any antitumor effect. And that is a must-have for us to make the decision to move into a blinded, randomized trial, which would potentially be a pivotal trial. And then the FDA, as I said, wanted us to understand what the dose needed to be, and our interest in the dose was really a practical interest because one of the unspoken secrets of cell therapy is the cost of therapy. And it's -- you can have a great therapy, but if the cost becomes inappropriate for the patient group that you're treating, you really haven't moved the ball forward. And one of the things that Mark has prided himself from the very beginning is making sure we had a manufacturing strategy that was rational for the disease that we're going after. And I think that he's reached that with INKmune. But obviously, we want the smallest dose that's practical because that makes it easier to make. Kind of the unique problem, I think, that we have treating solid tumors with a cell therapy is that measuring what's going on in the blood, measuring NK function in the blood with our various assays may not predict to correlate with the NK activity in the tumor microenvironment. Now Mark showed you that the blood compartment does predict survival, but we predict that actually it will be less robust of a predictor than actually some of the biomarkers that we have correlated with activity in the TME. So our solution was to use this modified BOIN12 trial design. BOIN is a Bayesian optimal interval Phase I/II trial design really aimed at finding both safety and utility dosing. So it's a perfect setup. And it allows for basically continuous safety monitoring and dose evaluation. So at the end of the -- in this case, about 30 patients, we will have a very clear understanding of both the safety and the dose -- optimal dose for the future. David, next slide, please? So it's really a 2-step trial. The first step is kind of a Phase I, a step that's the small end, the modified part of the BOIN12. And basically, it's a typical 3x3 run-in with short-term safety, which is 28 days and what we call short-term immunologic efficacy. And what we're looking for is how INKmune has increased the number of resting NK cells in the patient's blood to memory-like NK cells and that those memory-like NK cells actually kill tumors. The step 2 is where it becomes interesting because we simultaneously test doses, either 2 or 3 doses. That runs out for 6 months. By the way, the patients in the step 1 become part of the step 2. In other words, they're carried out for 6 months. And during that step 2, we can demonstrate proof of biology, which is the antitumor effects. And for that, we're looking at blood PSA, the tried-and-true measure in prostate cancer, circulating tumor DNA and PSMA PET scan as a measure of tumor burden. Ultimately, one of the more interesting aspects is quantifying long-term immunologic efficacy is the term I have termed, which is equivalent to what we think of as persistence. In other words, one of the most difficult aspects of NK cell therapeutics is the effects of your NK activation seems to be short-lived, 7 to 14 days, what Mark showed in the Laurel trial was even after 120 days, we had high levels of circulating memory-like NK cells in the blood, which is very encouraging. We'll need to see if that happens in men, and it should, we think, correlate with efficacy of the therapy. The desired outcome is pretty simple. We want clear safety data. We want to understand the dose that we need to use to get the proof of biology, and that will help us as a company and help the clinical team make a decision about moving into a blinded, randomized trial. Next slide. So this is what it looks like from a pick-to-world point of view. You can see there the first step past this dose escalation part. The FDA did ask us to have 28 days between the first and second and the second and third patient in each dosing cohort. So that will allow a careful evaluation of safety. And then we can move as many as 3 of the doses forward in step 2, and those get enrolled simultaneously. And then there's a confirmatory group once we choose the dose that we want to move forward with, that will complete. So this will end up being about 30 patients. There is some information on the bottom that you can look at on the slides. But the main issue is we get the information we're looking for, which is short- and long-term safety data, we get short-term and long-term immunological efficacy data and we get evidence of antitumor effects or hopefully control of those tumors. So we're quite -- this trial is really well designed for our needs. So with that, anything you want to summarize, Matt Rettig, before we move to Q&A?

Yes. Thanks, RJ, for that great description of the clinical trial and outcomes that we're expecting. So I think this trial gives us an opportunity to use an off-the-shelf cellular therapy. I think that's critical that it's off the shelf. I don't have to go through the process of making a patient-specific treatment, which can markedly increase cost and time to deliver therapy. So that's a key aspect, in my view, of this NK cell approach. I think it also offers the potential. I think this is a real opportunity here based upon some of the preclinical data that Mark described, of developing a therapy that is not only effective but can actually lead to deep and durable responses. So I think those are some of the keys here is that we need better therapies. There's an opportunity in prostate cancer, which is so common. There is great room for improvement on our existing treatment options, and a cellular therapy that's off the shelf like this NK cell approach represents a treatment that has the potential to meet these goals. So I think it's really a great opportunity. I personally, as an investigator who's been doing lots of prostate cancer clinical research over the last couple of decades, really feels that this is exciting. And I'm personally excited about this, probably more so than any other treatment that I have brought to the clinic.

Thank you, Matt. Thank you. And a few questions. And by the way, if there's any questions, please do feel free to type them into the chat and we'll read them. Two questions, really two parts. Number one, for Mark. What about -- and you did mention this earlier, typically, when you see a lot of immunotherapy-type therapies, there's a CRS issue, and I know that's more of an adaptive issue, but what can you talk about with CRS related to INKmune?

No, that's a great question, David. And it's something that the FDA obviously asked about as well. I started my career in NK cell therapies giving IL-2 to patients in parts in London when [ Malcolm Brendan ] was doing it in my current hospital friend in London, and we killed a lot of patients with IL-2 because of CRS. So CRS is something I take extremely seriously. And I still work one day a week as a full professor in University College London, and we have a big CAR-T program here, and we see a lot of CRS. So we've been very, very keen from the get-go to look at whether INKmune, not only activating NK cells, but could lead to primary or secondary activation of T cells and get the IL-6-driven CRS problem. We can't do it in vitro. We've never been able to do it in vitro. All of our in vitro assay show that it doesn't activate T cells, it only activate NK cells. And so I was really, really heartened when we treated our first patient a couple of years ago in the U.K. and the Laurel trial that RJ alluded to, a patient with triple with trilineage myelodysplasia and saw no CRS at all. Moreover, when we looked at the cytokines in his peripheral blood, not only whether it was a no IL-6 subregulation, but there were -- there was upregulation of critical cytokines involved in NK function, and they mirrored the cytokines that we see increased in vitro. So real evidence in vivo, we were modeling the in vitro study. We've now treated 5 patients, none of them have shown any signs of cytokine release syndrome or indeed any signs of detectable increase in IL-2 or IL-6 in the peripheral blood. So I'm very confident that we won't see CRS in these patients. And NK cells have been given as therapies as direct adoptive therapies for many, many years now, and there's never been an instance of CRS. And indeed, our original trials before INmune Bio was created, where we used INKmune to activate a HLA-mismatched NK cells from donors and gave them to patients, we saw no cytokine release syndrome there even in the presence of engraft itself. So I'm very confident that it's not going to be something we see here.

That's great, Mark. Thank you. And we had a couple of questions come in, so we'll try and go through them all live. Matt, obviously, you were pretty clear in your presentation that you see a lot of patients with this disease, and there's not a lot of good options. In terms of recruiting for the trial, what's your feel for being able to get enough patients for the trial, number one? And then that kind of relates to an investor question, which either I think RJ can jump in as well after you've spoken, Matt, is what -- how are we going to communicate results of the Phase I trial to investors? Obviously, it's an open-label trial and kind of what the thought process is with INmune about communicating results?

Yes. So I think the nature of this therapy will make it relatively easy, smooth sailing, to accrue patients quickly and get the trial done in a short time frame. And that's because, one, it's off-the-shelf therapy. We don't have to make patient-specific immunotherapy. Two, it's very well tolerated. And three, there is a short overall treatment course. And four, it's immunotherapy. And in my experience, patients really like the idea of immune therapy using their own body, if you will, their own immune system to target and eradicate tumor cells. mCRPC patients are many in number, and they're always looking for novel approaches. So there's really, I think, no issue with getting patients enrolled in this study and getting to completion of accrual in a relatively short time frame. I really feel that, that will come to fruition.

Super. Thank you, Matt. The second part for you...

If I could jump in, in a second, Dave, yes, just to make sure we manage some expectations here. Remember the slide is up, the FDA did ask us to go slow in step 1. So the first 9 patients will take 6 months to complete. So the natural break of kind of communicating at least some top line data of what's going on with safety is obviously after step 1, which will be about 6 months after we enrolled that first patient. Hopefully, by then, we'll have a bunch of patients teed up and then step 2, which we'll enroll at least 12, maybe as many of 18 patients, will actually move with some dispatch because you could really admit or treat multiple patients on any given day. So obviously, at the end of step 2 would be a natural break for some top line results. Ultimately, our goal and we would hope that Matt would be the mouthpiece here, will be to present this at one of the major oncology meetings, AACR, SITC, ASCO, ASCO GU, I mean there's a lot of options. I think you know how it is. We make a difference in these men's lives. People would want to hear about it, and we'll make sure that information comes out. David?

Yes. Thank you, RJ. So what are the plans for manufacturing release of different lots, Mark, this was asked. And is there an accepted NK cell activation assay? Obviously, I know you've done a tremendous amount of work with assays, and that's one of the unique things of our program. And I'd love to hear your thoughts about that.

Yes. So manufacturing is central to my heart. I'm somewhat unusual in that having gone into the immunotherapy space very early on, we had to make our own immunotherapies. So wearing my university hat, I used to run the largest cell and gene therapy manufacturing facility in Europe with over 30 trials of adoptive immunotherapies, both academically and commercially. So I live this stuff, and we're very lucky to have built a team that have really ironed out the problems of manufacturing. So we're at scale, and we're at a very scalable scale. So we're in multi-liter manufacturing facility now, which can easily expand to over 100 liters per batch. So batch manufacturing is nailed, and the FDA were quite rightly, very interested in what our reproducibility was batch to batch. We were able to convince them with a lot of data. I mean, obviously, we've been -- I've been working on this since 2005. So I know a lot about how these cells grow. And we were able to present a lot of data to show that we had to control the manufacturing process, and we have good definition of our product. Part of that product definition, as has been asked, is about potency, how do we know these cells actually do activate an NK cell. And once again, with the fortune of wearing my academic hat, I sit on the MHRA British trial of appeal working party or first cell gene therapy potency assays. So I've been able to leverage what I've learned from other people on those committee as well as my own experience. We're able -- we do have a very well-controlled assay using pooled NK cell donors, healthy donors that we can use to demonstrate each factor does appropriately activate NK cells ex vivo and that shows us homogeneity between batches. So we have enough -- we've got a 2-year shelf life now validated on INKmune. We have a formulation which we know we can deliver and a delivery to the end user in a format that end users -- we spent a lot of time talking to end users, how do you want this drug delivered? Do you want it in a vial, do you want it in a bag? And we've got a formulation and delivery that we know end users would like and they're familiar with. So the real critical point from my perspective was this has to go into hospitals and into physician surgeries even, where it can be delivered without the complexity of a conventional adoptive cell therapy. And I'm very proud -- that's one of the things I'm really proud about, to have brought something which I think can be delivered in the real world.

If I can boast a little bit, as Mark said, he's earned the gray hair that he has because he's been in the space for more than 20 years, but we are really proud to state that he's been invited to give a lecture at the presidential plenary session of the Cell and Gene -- Society of International Cell and Gene Therapy meeting, which is the preeminent cell and gene therapy meeting in June in Paris. And so it's quite an honor for him. He's earned it from his many years of work, and it's an honor for him. for the company because he is one of our founders and partners. So David, another question?

Yes. Very simple question. Would larger trials require a partner?

Let's see the results, okay? There's no question that we would expect, and we have not spoken with the FDA on this, we would expect that a registration trial will require a blinded, randomized trial in some way. Now that's a challenge in cell and gene therapies. But we think that because one of the beauties of the INKmune is, although it's a cell therapy, it's actually more like a biologic. I actually think, and Mark and I have only talked about this briefly. I actually think we would actually be able to do a blinded, randomized trial. And to my knowledge, I have not seen, and I'll let Mark comment on this, whether there's actually been truly a blinded, randomized trial in cell therapies. Most of them use historic controls, which are riddled with problem. So obviously, the size of the trial is dictated by the -- by how well the product works. So at this point, I don't know. But I think that this program, because of its unique characteristics, actually has a much better chance of being approvable in what would be considered somewhat of a standard biologics approach in oncology, which is with a pivotal blinded, randomized drug. Anything you want to add to that, Mark?