Hello, everyone, and thank you for joining us at our H.C. Wainwright's 26th Annual Global Investment Conference, taking place from September nine through eleven. My name is Emily Bodnar, and I'm an equity research analyst at H.C. Wainwright. I'm pleased to introduce Jennifer Buell, who's the Chief Executive Officer and President of MiNK Therapeutics, which is a company focused on creating innovative invariant natural killer T cell therapies. Maybe to start, for those who are newer to the story, can you walk us through the key MiNK pipeline programs and where you are in development? Of course, Emily, thank you, and we're so glad to be here, and it's wonderful to have your continued support. So for those newer to the story, at MiNK Therapeutics, we're focusing on developing invariant natural killer T cell therapies that are off the shelf, and these are a very unique class of immune cells that bridge both innate and adaptive arms of immunity. This enables them to rapidly orchestrate a broad anti-tumor, and as we're seeing, an anti-pathogen immune response. The cells have a very unique receptor, so they're essentially naturally engineered, which makes them unique from conventional T cells, as well as unique from NK cells. Importantly, these iNKTs are actually T cells, and I'll talk more about that, I think, later in our discussion. But essentially, the engineering of these cells, the natural, invariant TCR arm, allows the cells to go to work without engineering, and we've taken advantage of this feature, to build a pipeline, and this includes cells in their native form. These are donor-derived, allogeneic, off-the-shelf cells, as well as in their engineered form, and we'll talk a little bit more about that. We're a clinical stage company. We're in phase two, and our leading program is agenT-797, and this is an allogeneic, unmodified, invariant natural killer T cell therapy, and it's advancing in a phase two trial in patients with second-line gastric cancer, as well as in acute respiratory distress and pulmonary disorders. These are diseases currently where there are no effective approved therapy, and importantly, in gastric cancer, the median overall survival is about four to ten months on conventional therapies, chemotherapy. And in ARDS, similarly, this is a rapidly progressive and life-threatening condition with a mortality rate approaching around 40%. So developing in these areas enable us not only to advance very quickly in areas of critical unmet need, our goal is to really provide a meaningful therapeutic benefit in these disease settings. So those are our native cells, and those cells are in phase II development. On our engineering platform, so we take the cells, and we're able to actually transfect them and generate CARs. We also have shown that we can generate high-quality, reproducible TCRs, and we have T cell engagers. Some of these are in a collaboration that we can speak about, but effectively, we've been able to accelerate the development of a very important CAR-iNKT therapy, and this is MiNK-215. This is in preclinical development. We're planning to file the IND in early twenty twenty-five and start the clinical trial just thereafter. MiNK-215 is an IL-15 armored FAP-targeting CAR-iNKT cell, and what we've been able to demonstrate at some presentations at AACR and SITC is the therapy has shown really promising preclinical activity in tumors that are generally overexpressing this particular FAP protein, and that's non-small cell lung cancer, colorectal cancer, and a host of other solid tumors. What we've been able to show is in models of microsatellite stable colorectal cancer with metastatic disease to the liver, and that's the majority of these cases, FAP MiNK -215 or FAP CAR-iNKT has actually been able to deliver some very important, and in some cases, curative benefit in these preclinical models. So we're excited to get that into the clinic, and we have a new investor through GKCC, who's partnered with us to finance the advancement of this program, and we've accelerated the advancement. So we're looking forward to telling you more about that program in the course of the upcoming months. Great. Definitely a very extensive pipeline. You mentioned some of the benefits of iNKT cell therapies already, but maybe can you discuss a bit more about the differences between iNKTs versus natural killer cells or T cells, and what makes iNKTs better suited for treating solid tumors? Great question. I guess I'll start with, for an effective cell therapy, something that's accessible and scalable, you need a cell type that has disease-fighting properties, we're talking about in and of itself, and also can be manufactured at large scale, and this is a rare combination, but one that invariant natural killer T cells have in spades, and we've been able to really capitalize on this, and I'll talk about this specifically. So NKT cells, as I mentioned, are T cells. They express a unique invariant T cell receptor, and this invariant receptor straddles the interface between innate, which is NK cell, and adaptive T cell immunity. So this innate, this NK, or natural killer, component of their name refers to their ability to really rapidly respond, properties that they share with NK cells, of course. This allows them to identify abnormal and stressed cells, and they get to move much more quickly than conventional T cells do. As part of their response, they secrete a high level of cytokines, specifically interferon gamma. I think that they're the highest producer of interferon gamma, which is really important, and they can directly influence their immune environment in ways that conventional T cells cannot. For instance, in tumors, through the attraction and activation of T and NK cells, through this chemokine signaling pathway that they induce upon moving towards CD1d. The T cell part that I've mentioned before is this invariant T cell receptor, and it gives them some additional unique properties. Functionally, this TCR does not recognize peptides presented in MHC class I molecules like conventional T cells do, but specifically responds to glycolipids, and these are glycolipids that are presented on CD1d, and this is a specialized MHC molecule. This specifically responds to glycolipids generated through altered metabolism that you see in infections, in infected cells, as well as in cancer cells. We also believe that these are quite active in other metabolically altered states, such as senescence, and this is a very important component of our development considerations, and one that's of quite a bit of interest to some of our potential partners. Through the additive effect of the natural killer early response, and then the invariant T cell receptor response to CD1d glycoproteins, glycolipids, iNKT cells really have some broad and far-reaching effects. They can kill metabolically altered and stressed cells directly, and through cytokine secretion, they modulate the immune system and amplify the response beyond what conventional T cells and NK cells can do. So they're really quite different. I, you know, it's... Many people will mistake that these cells, because of their name, are NK cells, but they're so much broader because they do have the rapid response, but they also really have the durable memory response that's associated with conventional T cells, and that's really important. They like to home to tissue, so they're predominantly tissue-resident, for instance, in very hostile places like in metastatic disease to the liver, and this is what we've shown preclinically, these are notoriously hard to treat with conventional chemo or even quite active checkpoint modulating antibodies. The invariant nature of these T cell receptors allows these cells to actually home to these hostile areas and modulate activity there. Importantly, we all share the same T cell receptor, and this is a really important component of this particular therapy and its differentiation as well. This invariant, common, ubiquitous T cell receptor allows us to use donor iNKT cells in unrelated patients. So I can take iNKT cells from you, and I can give them to another patient without having to worry about graft versus host disease, and that's really unlike conventional T cells. So we don't have to genetically engineer the cells; we don't have to knock out the T cell receptor. It's just not necessary for iNKT cells, and that's an enormous advantage. It brings me to the other critical advantage of these cells. They're really quite scalable. They're iNKTs are rare in our blood. They're one of the most highly conserved and potent cells in immunity, and they are also one of the rarest cells. As little as 0.1% of our T cells are invariant natural killer T cells. We have a unique proprietary antibody that allows us to isolate these cells from a donor, and these are, you know, any donors. We can take healthy donors. We can isolate the invariant natural killer T cells with a proprietary antibody technology, as well as some proprietary manufacturing steps with quite high fidelity. Once we isolate them, and when we isolate them in such purity, we're over 99.6% pure, we can get hundreds of billions of cells from a single donor. That allows us to scale, and these cells don't lose function. They don't get exhausted in our manufacturing process, and we could demonstrate that through a series of functional assays and release assays. So far beyond what we've seen with conventional T cells or NK cells, iNKTs can achieve this kind of scalability that allows us to have a very efficient and scalable manufacturing process that enables these cells to be really quite accessible across a host of different diseases, so this allows these cells to be cryopreserved without loss of functionality, and that also enables us to ship these all over the country. We've had clinical trials ongoing in Brazil, in different parts of Eastern and Western Europe, and all over the United States, so these are some features that, in some cases, are really quite comparable to what you might consider with an antibody-type therapy, that level of scalability and distribution ability. Logistically, we have really nailed it when it comes to what these cells can do and how we can create medicines from them. Yeah, I think those are all very interesting points, especially considering the cell therapy issues we've seen, where a lot of companies are struggling to manufacture and keep up with demand. Maybe shifting to agenT-797, you touched on the phase II gastric study that you have running now. Maybe remind us of the design of that study and just discuss how enrollment's been going. Sure. Yeah, yeah. This is a critical initiative for us. We've got the pleasure and the honor to be working with Dr. Yelena Janjigian, she's the chief of gastrointestinal oncology at Memorial Sloan Kettering, and she's the lead investigator on the trial, and also the trial is being sponsored by Stand Up to Cancer. It's a wonderful endorsement, and the trial is designed as essentially a randomized phase II trial with an induction period with the cells, followed by a multi-combination in one of the arms. That combination are INKT cells plus a standard chemotherapy, which is approved in second-line gastric ramucirumab and essentially RamTaxol. In that combination, we have the cells plus chemo, and then we have the opportunity, which we're taking advantage of right now in the second part of the study, which is the cells on top of a Agenus very active botensilimab, which is an Fc-engineered, the engineered molecule. The Fc region of the antibody, anti-CTLA-4 antibody, is engineered, and it's actually created a multifunctional T-cell engager from this antibody design. So it binds CTLA-4, but it does a lot of other things, and it's shown remarkable activity in colorectal cancer. We've taken that molecule in combination with PD-1, the cells, and we're testing this in this setting on top of standard of care chemotherapy. So the trial launched in February. It's. There are about 40 patients planned to enroll. Enrollment's actively underway, and in the first couple of cohorts of patients, where we now have a minimum of three and exceeding six months of follow-up on some of those patients, we're seeing some exciting signals of activity, and we're really quite optimistic about the balance of the clinical activity as well as tolerability. Now, this is a multi-drug combo in one of those arms, in which we have essentially standard of care chemo on top of two antibodies, a PD-1 plus botensilimab, and the cells. So in this particular disease setting, it warrants that level of combination to get around the really difficult and aggressive disease setting in the second-line setting, and these are patients who have failed prior first-line nivo and FOLFOX and really only have RamTax as follow-on therapy. We're looking to get the data presented at a major oncology conference, and that'll be either this year, the H2 of this year, or very early in 2025. We're working with Dr. Janjigi an on the timing of that presentation, and it's up to her discretion to do so. That is something that we can look quite a bit forward to. Maybe taking a step back to focus on the phase I study, where you had the gastric cancer patient who had the partial response. What was the background of that patient, and how confident are you that the response was driven by agenT-797? That's a great question, and by the way, that phase I study, what we did observe in a number of different solid tumor cancers, including testicular, appendiceal, gastric, as you've mentioned, pancreatic, and lung, we've seen really durable disease stabilization as well as the response that you've mentioned, which was pretty pronounced, a tumor shrinkage of over 42%, which was durable beyond 10 months, and the patient has continued to be followed in the trial as quite a long-term survival. This was a patient who had failed prior chemo first-line, and that was FOLFOX, FOLFOX and nivo. And so the patient had been exposed to PD-1, had failed PD-1. Best response was stable disease, short-term stable disease, approaching 12 weeks, and then the disease progressed pretty rapidly. The patient went on the trial, and we saw the tumor shrinkage of over 42%, and when we added the cells on top of nivolumab in this particular setting, and we saw that durability that had not been observed with this particular patient. We've done quite a bit of genomic and translational data analysis on this patient, and we published the patient in Oncogene, which profiles the preclinical and translational data. That foundational information was really necessary and essential to get the level of enthusiasm that we've now observed with Yelena and a number of other KOLs in gastric cancer. We're confident, particularly that this was a response that was attributed to the addition of the cells for a few reasons. This patient was a PD-L1 positive, HER2 negative, MSI high adenocarcinoma with a mutational burden approaching the eighties, and prior treatments included single-agent PD-1, that was pembrolizumab, failed to elicit a response, prompting a combination with chemotherapy, FOLFOX and nivo. And even that combination was proved ineffective. The best response was stabilization, as I mentioned, and then progression. And then the patient went on the treatment with the cells, were added on to continued nivolumab, and that's actually where we saw an increase in immune cell infiltration, and we also saw proliferation of immune cells in within the intratumor environment, and that correlated with the radiologic partial response that you brought up at the part of the call. So we're pretty enthusiastic about this, but it would... You know, we're taking our excitement really from the experts in the field who have even published that this is unlikely to have been related to anything but the addition of the cells and sparked the ongoing phase II trial that's underway. How should we think about the standard of care efficacy in the second-line gastric cancer setting, and what's the typical response rate that the patients have? Response rates under 30% in most of the studies that have been done, under 22%, and median overall survival is really only four to 10 months, depending on factors such as performance status and treatment regimen, so really best fit patients, we could see a survival of up to 10 months, but really predominantly between four to 10 months, so for us, this is a trial that we will have a very good sense of the clinical activity and the observations that we're seeing in a short period of time. ... Can you discuss why you're evaluating the combination with botensilimab as well as agenT-797, and how you kind of think about potential synergy between these different assets? Yeah, so, maybe just very brief background is that Bot/Bal has been tested now in over 1,100 patients, and, in the studies that have been done to date, we're seeing really quite a bit of activity in about 10 different solid tumor cancers. And specifically in patients with microsatellite stable colorectal cancer, which is predominantly immune unresponsive, so it does not respond to standard of care, nor immune checkpoint inhibitors. It's uniformly fatal, even with the available therapies today. TKIs are available for patients, chemotherapies, and they don't respond. When we saw the level of activity exceeding 25% tumor shrinkage and more than a doubling of overall survival in microsatellite stable colorectal cancer, we started to interrogate the potential clinical activity in other GI cancers, pancreatic, gastric, et cetera. There are features in which botensilimab works really quite well in patients without metastatic disease to the liver. When we started to have our early observations from our phase I study with the cells, we saw that there were some patients with metastatic disease to the liver, with cancer of the lung, of the liver, of the GI tract, and we saw quite a bit of activity in reduction, in modulation of disease within the liver. In gastric cancer, we do see that the disease does spread to the liver, and we see that those patients have the poorest prognosis. The potential to actually bring the benefit of Botbal on top of INKTs could allow us to really benefit patients with widespread disease, with very active immune checkpoint inhibitors, that show features of immune modulation that have not been seen with other immune checkpoint antibodies, and then you take the myeloid features and the tumor microenvironment modulation of INKT cells, and you think this could be a perfect recipe to really bolster the immune response, address disease in the liver, and truly generate a memory response that could be potentially curative for patients, so for us, it was an obvious combination to proceed with, and certainly, the activity that we had the ability to observe with Botbal, and we were able to get an inside view into really the depth of the responses and the translational data associated with those responses. It seemed to us to be. Let's try to really make a difference in second-line gastric cancer, where there's nothing that works for these patients. It's a rapid disease. It takes lives very, very quickly, and generally, it extensively spreads, so bringing these therapies together gives us, we believe, the best shot at eliminating the disease for these patients. Are you evaluating a single dose of agenT-797 in the gastric study, or is it multiple doses? And how do you kind of think about the best or ideal dosing strategy? Currently, we're dosing as a single dose at a billion cells. What we've been able to demonstrate is these cells appear to persist peripherally for beyond six months. And as I mentioned earlier, these cells are really heavily localized, so we may not necessarily know how long they're persisting for because they're tissue-resident, but we are able to measure them in the periphery to about six months. And we previously presented some of these data of the cells, their persistence previously, but we've also presented data of the iNKT therapy in combination with Botbal in preclinical models, showing robust tumor clearance in non-small cell lung cancer, as well as in metastatic microsatellite stable colorectal cancer models. What we are able to see in some of the data presentations that we've had is that these cells actually enhance the activation and the function of T cells, and it appears to really amplify the immune response. They, you know, in addition to their localization, they recruit and activate a variety of cells, so their work continues, I should say, after a single dose. They just really amplify the response. The response persists, and then the response brings in other NK cells and T cells that actually continues to build on that memory response. So I think, you know, when you take CTLA-4, PD-1, particularly the Fc enhanced CTLA-4, from our observations, it appears to amplify the immune response by preventing the tumor from dampening this immune response. That ensures that the iNKT-activated T cells remain effective in a single dose, appears to actually be able to do that really quite well. I'd like to spend a few minutes on the other indications you're evaluating with agenT-797, including ARDS and GVHD. So maybe just touch on those programs a bit, what the status is, and how we should think about next steps for those indications. You know, absolutely. I've been on the front lines to really personally see how acute respiratory distress can complicate patients. And we had an active phase one trial we published in Nature Communications, showing that a single dose of agenT-797 unmodified iNKTs, administered in patients with acute respiratory distress syndrome, secondary to a virus, and that could be influenza, COVID, et cetera, demonstrated a remarkable survival benefit in those patients. And ARDS is a rapidly progressive. It's a life-threatening condition [that] has a high mortality rate. About 40% of patients succumb to the disease and die. And in this, it appears that the prevalence and incidence of respiratory distress is growing in a post-COVID era, where we seem to see something that is a compromised lung function. It presents like bronchiectasis or a scarring of the lung tissue. So patients who previously had optimal lung function now are unable to combat influenza, pneumonia as effectively. The cells appear to bridge that gap, which is a very important part of the development pathway for this. So our commitment is to address this unmet need and this growing unmet need with agenT-797 to actually really aid in this care. One of our lead investigators, Dr. Therese Hammond, had said that this therapy, which she's able to administer with great ease in the ICU, has brought more flexible and dynamic responses more quickly than anything that she has available in her hands at this time in the ICU. So what we have. Our published data from the phase I/2 trial showed a 75% survival rate. This compares to an in-hospital control rate of around 10% survival, so it was a marked improvement and we also showed a significant improvement in ventilator-free days, so these are patients coming off ventilator quickly and being able to independently breathe, and it suggests that these cells could play a real pivotal role in ARDS management, so we are planning to launch and publicly disclose a randomized phase II trial of the cells compared to standard of care corticosteroids, and we're looking to do so through a large platform trial. I think I mentioned publicly a couple of weeks ago that most recently the BARDA arm of the government has launched a substantial program, which is a 600 patient study with three different agents. Two are monoclonal antibodies. The third molecule has not yet been announced, and they're fully externally funding this program to the tune of about $117 million, showing not only the importance of addressing respiratory distress and the urgency in doing so, but also the opportunity to do so pretty quickly using platform trials. That was one example of a platform trial, and there's another one not yet publicly disclosed, either of which we are working very aggressively to participate in in order to bring these therapies forward quickly. Now, GVHD, I've mentioned this, you know, now, and I'm thrilled that we're able to currently advance this program. We were focused on gastric cancer second line, which is now off and running and enrolling, with data readouts and pending. Our respiratory distress program, which we read out quite successfully, published and are now moving forward and with the randomized phase two imminently. We are able to announce the launch of a phase one trial, and it'll be essentially a phase one two trial in patients who are really at risk for GVHD, and those are either steroid refractory acute graft versus host disease patients who are diagnosed essentially in the first line or in the refractory setting. This particular program will be announced in much more detail once we formally announce our partnership on the program. But effectively, iNKT cells naturally suppress graft versus host disease and also naturally enable engraftment. These data have been published by our scientific advisors and are really important in allowing patients who are undergoing hematopoietic stem cell transplantation, of which about half of whom succumb to graft versus host disease, which complicates their ability to demonstrate a curative benefit from the stem cells, so this launch, which is an investigator-sponsored trial, will include two leading hematology centers, one in the U.S., one in Europe, and it's a critical step in broadening the therapeutic applications of iNKTs in a high area of unmet need, which is really... We are going to be able to develop this really quite rapidly. The readouts are twenty-eight and ninety days, so upon enrollment, we'll know very quickly about the activity of these cells and the potential benefit to patients with GVHD. Great. I think we are at time now. So thank you very much, Jen. It sounds like you obviously have a lot going on. I'm very eager to see the updates for the rest of the year and into the next year. Thanks everyone for tuning in. Hope you have a good rest of your day. Thank you again, Emily. I really appreciate your time.