Good morning. My name is Travis Clifton. I'm the Chief Medical Officer of Cleety Biotherapeutics. Thank you for joining us today. Today we're going to cover the work we've done in advancing the Redtail platform and CLD 401. We're fortunate to have two members of our SAB here as well to add some context and some of their background and research as well. So without further ado, I'll introduce our first speaker who is one of the members of our Scientific Advisory Board, Dmitry Zamarin. He's a medical oncologist and the head of gynecologic medical oncology at the Mount Sinai. He spent a decade previously as faculty and translational research director in gynecologic medical oncology at Royal Sloan Kettering. He served as the principal investigator and translational chair on multiple institutional and cooperative clinical trials exploring novel immunotherapy combinations in solid tumors, and in particular, gynecologic cancers. He has extensive experience with viral therapies, and so he'll speak to that today. So thank you for being here.
Dr. All right. Thank you so much, Travis, for the introduction. So let me see. Oh, there we go. These are my slides. So I'm going to briefly go over the rationale for intravenous or systemic delivery of viral vectors for cancer. And specifically, I'm going to focus on the viral vector with which we had personally the most experience, which is oncolytic Newcastle disease virus. And I think the whole point for this is really to set the stage to demonstrate that viruses can be used as systemic therapeutic agents. So we all know that we have some efficacy with intratumoral oncolytic viruses. So TVEC, which in the United States remains the only approved oncolytic virus in advanced cancer. This has been improved in 2015 for unresectable malignant melanoma. Now, we have had some recent developments in the field as well with other types of local regionally delivered oncolytic viruses. One of the best known ones is the CG oncology, which is the intravesical CG0070. It's an apnavirus 5. This one has demonstrated good activity in BCG refractory, non-muscle invasive bladder cancer with a 75% complete response rate. So the company is preparing its BLA submission at the moment. Another viral agent to highlight is the CANDEL or CAN2409. This was a study often non-replicating adenovirus which was a trial of it's a phase three study in intermediate high-risk localized prostate cancer there was a disease-free survival benefit so we also anticipate that this company is going to to file with the fda in 2026 and we have all heard about the data with the replimune rp1 which was the ignite trial in patients with the PD-1 refractory or PD-1 resistant malignant melanoma, the study demonstrated close to 30% response rate and they also have had a BLA resubmission actually after the initial filing, but this has been accepted so they have a PDUFA date in April of 2026. So we all know that the efficacy of oncolytic viruses is driven by some tumor lysis, but It's really the induction of the immune response that's probably responsible for the durability and the efficacy of the majority of these agents. But again, there are certain limitations with these intratumoral agents. Most of the patients do not have disease that's directly amenable to your IT administration or intratumoral administration. It requires special scheduling with the interventional radiology, which is not always possible. and the long-term benefit is really highly dependent on abscopal effects and it's it's not always easy to achieve an abscopal effect there's some operator dependent variability so if you're not injecting the right lesion or if you're not able to deliver the sufficient amount of the virus to the lesion you might not get this induction of the immune response that you expect obviously tumors are heterogeneous so one tumor might not be the same than the other but also even the actual distribution of the virus through the tumor might be heterogeneous meaning when we're giving an intratumoral injection it's often actually a peritumoral injection so the virus doesn't diffuse as well as when it comes through the blood vascular or through the vasculature And, again, as I have highlighted, there is costs, risks, and other sort of scheduling factors that make it more challenging for the viruses that are given intratumorally. So systemic administration would, of course, potentially alleviate these issues. The problem is that we have multiple challenges with the delivery of oncolytic viruses. And we've always known that. If you look at this slide, this is a review from 2012, right? So we have been interested in developing systemic oncolytic viruses for a very long time now. But there are some challenges, and one of the key challenges that we always talk about is the viral neutralization. Some of the patients may have preexisting antibodies, neutralizing antibodies that can decrease the amount of virus you can deliver systemically to the tumor. site many of the viruses go to the wrong place like some viruses like adenoviruses have a high receptor expression in the liver so they could be sequestered in the liver or other organs without actually getting to the tumor and some of the viruses just you know stay in the circulation without actually accessing the tumor site and there are multiple factors that can prevent the virus from infection of the tumor cells one being the tumor micro environment being exclusive sort of exclusive and not allow the permeabilization nevertheless there are some studies in the literature that have demonstrated that systemic delivery of oncolytic viruses can achieve therapeutic efficacy this is a study with Newcastle disease virus which is the virus strain that I work with it's called PV701 so this is an avian paramyxovirus it's a receptor for entry sialic acid which is present on virtually every cell in the body but this company called ProVirus was initially developing this virus I would say about 25 years ago or something so this was a naturally adapted strain to replicate in the tumor cells and And they performed this initial dose escalation study until they were able to achieve the type of infusion protocol that the patients were able to tolerate. And in the latest study that they performed, out of 18 patients that they have dosed, there was a close to 30 percent response rate, including one CR in a cervical cancer patient, three partial responses in CRC and melanoma, and some patients that had reduction of the tumor burden and prolonged disease stabilization. So certainly this is a study that demonstrates that the viruses can be given systemically. There was a recent sort of reignited interest in oncolytic virus or specifically Newcastle disease virus. This is a study that was just published in Cell several months ago, so in 2025. Essentially, this was a recombinant Newcastle disease virus into which the investigators engineered this porcine alpha-1,3 glutamine transferase. So this is essentially an enzyme that's normally not present in the human bodies. the goal of this is really to generate a rapid antibody response to this sugar so they enrolled 20 patients with widely metastatic refractory disease various types of cancers in this study that initially actually did it in monkeys and then went into the patients and were able to dose very high doses of the virus from the 10 to the 10 to 10 to the 11 and there were a number of responses that they have seen including cervical hepatocellular and ovarian cancers and many of those were quite durable as well so again just another study highlighting that this that systemically delivered viruses can be utilized and in the united states astrazeneca has also picked up on newcastle disease virus and have engineered one that's expressing gmcsf this was a study we've actually run over the past few years and this was published in JITSI last year demonstrating that we can achieve some responses in these patients and some of these responses were durable and again most of these patients have failed prior anti-PD-1 therapy but you know the response rate in this study was 10.3 percent and partly because this virus was a poorly replicating virus strain so uh so you required the very high doses. Nevertheless again this is a proof of concept that these kinds of agents can actually make it to the tumor. So some of the key things we have learned from systemic NDV therapy is that you know using very high doses could potentially overcome some of these challenges that I have highlighted with the systemic administration but there are certain challenges that we have with Newcastle disease virus because we do believe that even with systemic administration we need to have a virus with a higher replicative potential because like I mentioned we can't fully overcome many of these challenges with just increasing the dose of the virus and and specifically for Newcastle disease virus because it is a birth pathogen USDA has certain restriction on a highly replicating NDV strains which prevents us from using the viruses that are probably most lytic and most replicative so so essentially and for an ideal platform for systemic delivery for any oncolytic virus you need to have a virus that's shielded from immune clearance essentially you don't have to dose as high but the virus is still able to make it to the tumor. You want the virus that has a tropism to tumor tissue over normal tissue that doesn't go to to normal organs like liver, spleen or lungs and the viruses that express certain payloads that could be used to alter the tumor microenvironment. We know that not all oncolytic viruses can be engineered so would you need the platform of the viruses where we can incorporate additional agents and further modify the virus to make it potentially more effective and immunogenic and uh and i think that's the end
of my slide jack thank you dimitri next i'm going to introduce antonio centindrian our chief scientific officer and he's going to talk about the development of the red tail platform and CLD 401 sort of how we've gone about it to address the issues that Dr. Zamarin mentioned.
Dr. Zamarin Zamarin Thank you so much. Thank you, Dimitri, for the great presentation. So, actually, I really would like to say thank you for everybody being here today. I'm very, very honored to show you the work that we are doing with the Red Tail platform to actually overcome these challenges in the field. I think we succeeded, and actually, again, I'm very proud to show in the data how we build this platform today. So, Calidi has been working on this challenge for almost a decade, and we feel that, again, the solution will be to build viruses resistant, not to the quick elimination by the immune system, but also we need that virus with that tumor tropism, No, they actually will avoid the normal tissue and accumulate directly into the tumors, not a tumortropic virus. But also we need a tumor now that is able to target those viruses, but those tumors without the need of a very specific receptor. So it could be more of a tumor agnostic and more generally used to accumulate on the tumors. So we built this platform that we call Red Tail, and it's based on a vaccinia virus. So, on the right side, you're going to see just a schematic representation is very abstract, you know, but the circle on the right represents a vaccinia virus that is self-amplifying. So, vaccinia virus has been chosen because it's that, you know, it offers a solution for many of these challenges. First, it's tumortropic, doesn't have a specific receptor that is required to infect the tumor cells, has also a very potent and rapid lighted cycle and replicates only in the cytoplasm. It doesn't integrate into the human genome. Vaccinia virus also has a very large capacity for genetic payloads. Vaccinia virus has a very interesting viral cycle, now actually represented on the bottom left of the figure. So it has a form that is intracellular and a form that is extracellular. During infection, the majority, 99% of the viruses are intracellular, with only one layer of a membrane. Is the virus that is being secreted, there has a double membrane. But the majority of the strains, that secretion occurs only in 1% of the viral particles. Calivi has selected a strain, a genetically engineered that strain, where we have a very high levels of production of this envelope or extracellular envelope, because at the end is that envelope that offers the resistance to the complement and to the neutralization of that virus. That envelope is coming from the cell line that is used to manufacture, and that means that those properties on the envelope are gonna be linked to the cell line that we are gonna choose to manufacture that virus. Here we can see a representation on how two different viruses may spread based on these characteristics. On the left, it's a virus that don't produce that much level of EEBs or extracellular envelope viruses. And the virus is spread as a ball, just creating these balls or spheres because it moves cell to cell. On the contrary, a virus that has these high levels of secretion with an extra membrane will jump and create very long tails and spread very far away. That's also a characteristic that we want on these viruses, to spread as much as we want we can on the tumor. This virus, the red tail, produces these long red tails in the plate, and this is actually the origin of the name of this virus. Obviously, once we have now a virus that is able to survive systemic, we want to be sure that we have a safety profile that is appropriate for systemic delivery. For that reason, we have genetically engineered near this virus with multiple knockouts to be sure that we have a very tumor selective amplification of this virus. So in this graph, this is an ex vivo signal of how the virus is able to replicate in multiple tissues. We have multiple generations of the virus, but you can see on the right, the triple knockout that we selected is able to only preferentially amplify on the tumor tissues. This is the reptile background that has a knockout on TK, A46R, and BGF to generate this tumor selective virus. This reptile has a broad tumor cytotoxic characteristic. We have tested the cytotoxicity capacity of this virus in more than 60 different tumor cell lines. The virus has a preference for the majority of the solid tumors with almost no difference between the different tumor types, And this is also, as I was mentioning before, one of the main characteristics of vaccinia So vaccinia virus, now triple knockout, with that extra envelope represented as a black line around this circle, it offers a good level of protection. However, we want to go farther than that. We have genetically engineered the virus so that virus overexpresses a molecule, a receptor or called CD55 on the surface of this envelope. That high levels of expression of CD55 will further inhibit the complement inducing activation of the virus. That initial inhibition of the virus will be further protected. And again, that's, with all these modifications and engineers together is what we build the Red Tail platform that is the basis for our first lead candidate, CLD-401. Before going to explain what is CLD-401, I want to show you some data of how this overexpression of CD55 makes a huge difference. So on the left, we can see three different forms of the virus. The first one on the top is the virus, vaccinia virus that has only the single envelope. This is the majority of manufacturing processes and focus on purifying this virus. This virus, the IMB, has a very low rate of survival when it's incubated with human serum. The second one is the envelope form with this orange envelope. Now then we can increase that survival to 40 to 50%. But it's only when we have that high levels of overexpression of the CD55 molecule on the surface where we can achieve remarkable survival in the presence of human serum, making now the platform a realistic approach for systemic delivery. Redtail, as a platform, now is able not only to kill those tumors and to prime those tumors to the immune system, but also can be used as a genetic medicine. It can be used as a vector to deliver a massive payload. Vaccinia virus is a virus of more than around 200 kilovases with a cargo capacity of 25 to 40 kilovases, it depends on the amount of promoters that you add. This enables the insertion of multiple and large therapeutic genes. Vaccinia virus also have their own transcription machine, meaning that doesn't depend on the human cell that is infecting to express those proteins. For that reason, vaccinia virus is one of the more potent viral vectors to express genetic medicines into the target tissue. CLD-401, the first lead of our platform. So it's designed for systemic administration, is protected now with this extra envelope and the expression of the CD55, target the tumor cells, and is able to prime these tumors to enhance the activation of the anti-tumor immunity but the first payload that I would like to present to you on the CLD 401 is that we are going to be able to deliver IL-15 super agonist and the virus is designed to target those tumors and transform the tumor into a factory of IL-15 super agonist locally. That will induce also a massive innate and adaptive response against the tumor that would follow the initial activation that was done by the virus. With that, we designed the virus to achieve and maximize the therapeutic efficacy to achieve complete responses with this platform. I'm going to show you only one slide of data. After me, Dr. Wango is going to be explaining more about the IL-15 super agonist. But I wanted to show you how different preclinical animal experiments. On the left of the graph, we have animals with two or multiple tumors that are subcutaneous that there's triple negative breast cancer tumors in multiple locations of the animal. You can see how the tumors grow in a very high and exponential way. The reptile alone, empty vector, no IL-15, is able to infect those tumors and control the growth of these tumors in the first two weeks. That is the moment where the tumors are prime, and we are actually, we achieve a 10 percent, one out of ten of complete responses. On the right, that is the CLD 401, the red tail overexpressing IL-15 super agonist. When the virus genetically transformed those tumors to express IL-15 super agonist, we are able with one single dose achieve around 80 percent of complete responses. So I'm very proud again to show you the development on this platform. We are, we feel that we have in our hands for the first time a true systemic platform that is able to target the virus. Thank you so much for being here today.
Thank you, Antonio. Next, we're going to, I'm going to introduce John Rangel. He's a thoracic oncologist and an associate professor of hematology and oncology at the Medical University of South Carolina. He has an extensive experience using systemic IL-15, perhaps the most in the world, in the clinic, and so he's going to talk about that aspect of the value of IL-15 as a genetic payload. In addition, he also has a translational lab that focuses on delivery of genetic payloads via viral therapy as well. So we're lucky to have him.
Male Speaker 1 So thank you for having me. As Travis mentioned, I'm here to sort of talk mainly about the experience with IL-15 superagonists as opposed to virotherapy. The IL-15 superagonist that I have a tremendous amount of experience with is formerly known as ALT803, then N803, and now commercially branded as Anctiva. So IL-15 is a potent cytokine that activates both NK cells and CD8 cells, and that's significant because it's both adaptive and innate immunity. It's a member of the common gamma chain family of cytokines. The most famous constituent of is IL-2. The important distinction between IL-2 and IL-15 is that while both activate NK and CD8 cells, IL-15 does not directly activate regulatory T cells. We have not observed capillary leak, CRS, significant hypotension. We don't observe activation-induced cell death of lymphocytes, and IL-15 is still capable of generating this long-lived central and memory effect, capable of generating durable tumor surveillance. IL-15 superagonist is a fusikine. It's a mutine of IL-15 fused to the IL-15 receptor, and that dramatically increases is the activity of this compared to recombinant human IL-15, depending on which study you look at, but somewhere in the neighborhood of 100X more active than recombinant human IL-15. On the left is my investigator-initiated trial combination of ALT803, the IL-15 superagonist, in combination with nivolumab. We published this in 2018. We started this trial right after nivolumab was approved in lung cancer. We were actually anticipating, knowing that the response rates from trials were in the neighborhood of 20 percent and that everybody eventually progresses. We started preparing for this trial literally the month that nivolumab was approved by the FDA, anticipating folks being either never responding to checkpoint inhibitors or responding responding and then progressing, knowing that there was still going to be an ongoing need for immunotherapy despite the sort of massive enthusiasm around PD-1 monoclonal antibodies. The reason why we got into Lancet Oncology with this phase 1b was this was the first ever published report of responses to immunotherapy combinations after checkpoint failure. The IIT safety study progressed into phase two studies where we continued to see responses after checkpoint failure, but also saw really impressive median overall survival statistics in all subsets, but highlighted here PD-L1 greater than 50 percent and then checkpoint relapsed patients with almost 20 months overall survival after checkpoint progression. You can see that that there are there are patients who do just remarkably well it's really important to sort of pay attention to what what the hash marks denote here. One year, two year, three year, four year. That's a pretty incredible swimmer plot when you're when you're looking at at post post-checkpoint survival. Toxicity. I gave a lot of IL-2, high-dose IL-2 in fellowship, and it was a horrible experience. Everybody's on pressors in the unit. IL-15 superagonist can very easily be given in the outpatient setting without consideration of hospitalization and And a very predictable sort of flu-like constellation of symptoms. And the most frequent supportive med given to nurse people through the sort of fevers and flu-like symptoms is Tylenol. This is a very manageable medicine to give systemically, even at the highest doses that we looked at. IL-15 super agonist Anctiva is approved by the FDA in non-muscle invasive bladder cancer. It was approved in April of 2024 in BCG refractory non-muscle invasive. This is where it's really important to talk about like dosing and concentrations. When you're treating non-muscle invasive bladder cancer, that's essentially local disease, so you're able to instill the medicine directly into the bladder. That's intravesicular therapy. And so when you mix 400 micrograms and 500 milliliters, that yields an 80,000 picomolar concentration in that environment. When we give subcutaneous ANGTIVA systemically, that yields about a 2 picomolar systemic concentration. Anctiva in that setting for non-muscle invasive is administered with BCG, and that's an important thing to note when you're comparing the paradigm of CLD-401, is that you're combining IL-15 superagonist therapy with an immune priming reagent. So, Anctiva plus BCG yielded potent and durable efficacy and a 62 percent complete response rate with 58 percent of responders with a greater than one year duration of response. So those are obviously incredible statistics for giving IL-15 super agonist where you're able to sort of achieve this very high IL-15 concentration plus immune priming. So the, just to sort of be very explicit about the comparison of the bladder paradigm with what is hoped for with the CLD-401 paradigm, Anctiva in bladder cancer, you achieve extraordinary levels of IL-15 super agonist in the tumor microenvironment, approximately 80,000 picomolar. BCG is responsible for accomplishing the immune priming mechanism. And then you, of course, get extremely low systemic exposure with IL-15 super agonist. With CLD-401, and I'll show a little bit of Kalidi's data in the next couple of slides to support this, CLD-401 in a syngeneic murine model accomplishes, again, extraordinary levels of IL-15 superagonist in the tumor microenvironment on the order of 60,000 picomolar. The immune priming effect accomplished by the CLD-401 red tail vaccinia virus vector itself, and again, very low systemic IL-15 exposure. So this is Kaliti data in their murine model that this is the data from which those assumptions or those assertions of concentrations are based. Approximately 60,000 picomolar concentrations of IL-15 superagonists manufactured in response to the CLD-401 infection of the murine model. And then concentrations denoted in other columns here for normal tissue. So while you're getting these extraordinary concentrations in the tumor, you're getting low concentrations in the tumor-bearing model. But very interestingly, in the non-tumor-bearing model in the lower rows, you see essentially no IL-15 superagonist. And this means that basically the systemic observation of IL-15 superagonist is essentially leak from this tremendous amount of IL-15 superagonist production within the tumor itself. To reiterate Antonio's data, there is some tumor control achieved by the vector itself, and that belies the sort of immune priming effect of the viral infection itself. But that effect is dramatically enhanced when the virus is armed with the ability to manufacture IL-15 superagonist. So, to sort of reiterate the paradigm here, IL-15 superagonist has activity in non-small cell lung cancer, Anctiva is approved in bladder cancer, where you get extraordinary tumor exposure to IL-15 plus immune priming. IL-15 superagonists can overcome resistance to checkpoint inhibitors. And one of the potential mechanisms there in terms of, you know, potential patient selection is this HLA loss phenomenon that, so if you're presenting tumor neoantigens to the immune system in order to get immune recognition, you can delete your antigen presentation machinery in order to acquire resistance to checkpoint inhibitors. And this is an assayable biomarker sort of potential selection mechanism for patients. But in summary, CLD-401 administered systemically in a metastatic setting can potentially achieve the extraordinary IL-15 superagonist levels observed when administered locally, like in the bladder paradigm, still achieving very low levels of IL-15 super agonist systemically on the order of what I observed in patients and healthy volunteers, side effects controllable with Tylenol. And so the immune priming and extraordinary doses of IL-15 super agonist can hopefully be applied in the metastatic setting using this paradigm. So I'll conclude my remarks there thank you very much thank you john that was great so again my name is travis
clifton i'm the chief medical officer of kaliti and i'm going to speak a little bit about the clinical development plan for cld 401. so we've heard about challenges with systemic delivery how we've designed the red tail platform to address those challenges to allow systemic delivery and then our choice for IL-15 as a genetic payload in addition to some of the data that underlies that choice and the excitement around that specific cytokine. So as we approach getting closer to the clinic, you know, we're excited about our ability to shield the virus from system and to allow systemic delivery. We're excited about the potentials with vaccinia and then again the payload. When it comes to vaccinia, one of the advantages to it is that it's naturally trophic to a variety of tumor types. So this is again data from the NCI-60 looking at lyticability of our virus and a variety of cancer types. And as you can see, there really are quite a few cancers that have high rates of lytic or high proportion of tumors with lysis when exposure to our virus. Really the only exception in this was some of the leukemia cell lines. So we think we have broad opportunities. And then in addition to that, you know, from a safety standpoint, as Antonio showed, we've really engineered this virus to be very specific for cancer with very little off-target infection or lysis of cells in production of IL-15. So I think it'll be an exciting thing to get into clinic and see the activity behind it, but as we talk about moving forward, you know, where do we want to put our focus with our clinical trial design, and we think there are a few opportunities. For one, we think IL-15 is uniquely suited to target PD-L1 resistance. A major mechanism of resistance to PD-L, to checkpoint inhibitors broadly is loss of HLA. So as John mentioned, And HLA class I molecules are essential for presenting neo-antigens to CD8 lymphocytes. Cancers evolve, especially after resistance, particularly with secondary resistance, to downplay these HLA molecules so that these antigens cannot be presented as CD8 lymphocytes. So that's a mechanism that also viruses use. They down-regulate HLA production to shield from the immune system, and your body has naturally, you know, evolved a way to address that, and that's through natural killer cells. Natural killer cells recognize HLA loss as a cell type that they want to attack in lice. And so we think that the natural ability for IL-15 to stimulate natural killer cells will work really well in PD-L1-resistant types that have loss of HLA. So in order to do that, you know, we will pay special attention to that in our clinical trial. But by enrolling patients who are PD-L1-resistant, which are in any cancer type that that's indicated in, you know, to get into the phase one, they will be PD-L1-resistant, we'll ensure that we have that mechanism represented in our trial population. And then, as we pay attention to that, that's an opportunity for a biomarker-driven patient selection strategy during the course of the clinical development. And this chart on the left just shows the prevalence of different mechanisms for HLA I'd like to point out that beta-2-microglavin loss is represented in a high proportion of cancers, and that's something that we can definitely test for. So as we look forward, you know, there's a couple ways we look at how to leverage the natural ability of vaccinia to infect tumors, as well as the IL-15 mechanism of action to develop a patient selection strategy and a clinical development plan. Again, we think the opportunities are broad, but we want to be able to bring the benefits of immunotherapy and those being the tolerability, but really it's the long-term disease control that we'd like to get that you cannot get as well outside of immunotherapy for tumors that have both primary resistance. So those are patients or tumor types that never respond to checkpoint inhibition. And so therefore it's not typically indicated or if it is, it adds sort of a minor benefit and also acquired resistance. So those are patients that derive a lot of benefit out of a checkpoint inhibitor as a whole for a patient population. However, they may have some element of disease control or response but then go on to progress so some cancer types that were particularly interested with primary resistance so again these are cancer types where a checkpoint inhibitor may be indicated now but we don't think it's the main driver of benefit in those very often it's more heavily on the chemotherapy side those include ovarian cancer gastroesophageal cancers triple negative breast cancer cervical and biliary tract cancers as well as acquired resistance and those are ones where checkpoint inhibitors really do the heavy lifting of therapy in the metastatic setting to include non-small cell lung cancer, head and neck, melanoma, and renal cell carcinoma. So for our clinical trial design itself, it will be an accelerated escalation at low doses and then followed by a Bayesian optimal interval design escalation. Importantly, we will include biomarker backfills. Those serve two purposes. as allows us to get tissue from a higher proportion of patients, but also gives us greater experiences at those higher dose levels where we think are likely to be the therapeutic levels we will ultimately select for our recommended phase two dose. From there, we will transition into dose expansions and particular types, tumor types of interest. On here, I've listed non-small cell lung cancer, head and neck squamous cell carcinoma, melanoma, and triple negative breast cancer. But as we mentioned in the previous slide, there's a variety of tumor types, all of which will be in our initial dose, including our initial dose escalation, where we have the ability to enroll as well based on the responses we've seen with our experiences to date. Importantly, we think we'll be able to see proof of concept fairly early in this trial when we talk about systemically delivered oncolytic viruses compared to an intratumoral injection. With an intratumoral injection, seeing that the virus is in the tumor, seeing that the payload is in the tumor, and also even seeing responses to the injected tumor itself, at some level that's to be expected if you inject a virus into the tumor that virus will be in the tumor however in this case with systemic delivery you know being able to show virus present in the tumor payload in the tumor you know serves as proof of concept that we are able to effectively shield the virus from systemic clearance and that we're able to infect tumor cells and effectively delivered that genetic payload, which is something we think, you know, we can deliver early on in a way that really builds excitement for our platform and will allow us to expand the clinical development into multiple areas. As we move forward, we're confident that we have the ability to get this into quick, quickly into clinic. I say quickly, I mean, obviously with every drug development, there are steps that you have to go through, but we think we have the right team with an experienced executive team as well as board helping guide us. We have experience with successfully applying for IND applications. We certainly have all the relevant expertise both in the deep experience with oncolytic viruses as well as the CMC and manufacturing components of that. We have a new experienced and relevant clinical advisory board with really decades of experience in both IL-15 and oncolytic viruses. And then importantly, the cost of goods thus far, you know, we've been able through our experience with developing oncolytic viruses to have this really comparable to other therapies where we think we can produce this on par with monoclonal antibodies. So the plan now is for IND submission towards the end of 2026 with the first patient in in the first half of 2027. Next to introduce our CEO is Eric Poma.
Thanks, Travis, and thanks to all our speakers. This is our first investor day. We wanted to highlight why we're so excited about the technology. Again, we think that we have a really unique approach here to systemic delivery by creating this engineered, selected form of vaccinia virus that can evade immune surveillance. It's tumor-tropic. It's replication deficient outside of tumor cells. It's potently lytic. It can imprime the immune system. And then, as John's data showed, IL-15 supra-agonist is an excellent payload, and here we're seeing from all our syngenetic animal models that you can get extraordinarily high concentrations patients at metastatic sites, but not systemically. So we're extraordinarily excited about this. We can move this compound into the clinic quickly, as Travis said, and we think we can get proof of concept for this early in the phase one. We wanted to highlight all of that in the investor day, but I think I'd be remiss here if I didn't talk about the public history of the company. So again, Cleety's been around for over a decade working on vaccinia, trying to solve this problem of systemic administration. But in terms of a public stock, the company went public in October of 23 via D-SPAC. It was a huge amount of redemptions after the D-SPAC. The company had struggled with its balance sheet. By virtue of the fact that we went public via D-SPAC, we don't have a strong institutional investor base. We don't have a lot of analyst coverage. But the board made a strong decision earlier this year to really shift the focus of the company to Redtail, brought in a new management team. I'm here as of six months Travis is here as of eight months we have a new chairman of the board as well to really focus on driving red tail into the clinic and really focus on the potential here we've done an excellent job I think on getting debt off the balance sheet here so we're cleaning out all that we've been really focused here on having an efficient capital use system here we've been reducing gna and now we're looking at a spend in 20 in 2026 where 70 percent of spend will be on r d so we're trying to be as lean as efficient as we can and again the entirety here is focused on getting 401 to the clinic as quickly as possible again we believe as travis laid out that if you start to see evidence of response evidence of clinical benefit early in your in year phase one we've proven out systemic delivery we've proven out payload delivery here so we think that there's the potential to really validate much of the platform very very quickly so that I think we can conclude our first but not last investor day thank everyone for their attention and again look forward to speaking more with investors thanks