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spk03: Good morning and welcome to Mink Therapeutics' third quarter 2023 conference call and webcast. All participants will be in a listen-only mode until the question and answer session. Please note, this event is being recorded. If anyone has any objections, you may now disconnect at this time. I will now turn the call over to Zach Arman, Head of Investor Relations at Mink.
spk09: Thank you, Operator, and thank you all for joining us today. Today's call is being webcasted and will be available on our website for replay. I'd like to remind you that this call will contain forward-looking statements, including statements regarding our clinical development, regulatory, and commercial plans, as well as timelines for data release and partnership opportunities. These statements are subject to risks and uncertainties, and we refer you to our SEC filings for more details on these risks. Joining me today on the call are Dr. Jennifer Buell, President and Chief Executive Officer, Dr. Mark Van Dyke, Chief Scientific Officer, and Christine Klaskin, Principal Financial and Accounting Officer. Now, I'd like to turn the call over to Dr. Buell to highlight our progress in 2023 and plans for the year ahead.
spk10: Thank you, Jack. It's a pleasure to have you all with us for Mink's Third Quarter Earnings Call 2023. I'm excited to report on the excellent headway we've made this quarter, particularly with our proprietary IMKT cell technology and pipeline program. A pinnacle of this progress was presenting compelling new data on our flagship product, HS797, as the recent Society for Immune Therapy of Cancer, or CITC, annual meeting that took place last week. To reiterate, 797 is an allogeneic INKT cell therapy. It's distinguished by its scalability, robust immune modulatory properties, and its administration without the need for toxic preconditioning regimens, a testament to the versatility and promise of these cells. The findings we reported at CIPSE included first-of-kind data highlighting many of these unique benefits of INKTs. particularly related to the lengthy persistence of the cells without liquid depletion or toxic preconditioning. Mark's going to tell you a bit more about that shortly. So last Friday, we reported an update on the durable clinical benefits from HM797 across a diverse set of tumor types in patients who have exhausted all other treatment options. Notably, in late-stage metastatic cancer, we observed long-term durable disease stabilization and biomarker responses in more than 30% of the patients treated. And these are patients with non-small cell lung cancer, refractory to prior therapies, testicular cancer, and appendiceal cancers that were refractory to prior chemo and or commonly used immune therapies like anti-PD-1. Additionally, the durable responses in a patient observed with second-line metastatic gastric cancer continued. This patient was unresponsive to prior chemotherapy, as well as prior chemotherapy combined with anti-PD-1 therapy. This is an exciting continued finding for us, and these data provide continued evidence of the potential that Agent 797 holds in patients with solid tumor cancers. Our data presentations also underscore the benefits of INKT cells beyond cancer, including in infections, inflammatory diseases, and autoimmunity. Just earlier this year, at the end of May, we presented data at the American Thoracic Society meeting, the International Lung Meeting, and we showed an improved survival of more than 75% when patients were treated with HF797 compared to in-hospital controls that ranged anywhere from 10 to 30% in survival rates. And these include patients who were on the most severe form of life support, patients on VV ECMO, where their blood was being oxygenated externally. That's a step past mechanical ventilation. And we had reported earlier in patients with viral ARDS on mechanical ventilation also showed a survival exceeding 75% compared to in-hospital controls of 10% to 22% at that same time point. We continue plans to expand this program through externally financed platforms. These data, along with the others presented earlier this year at AACR, continue to demonstrate that Agent 797 is well-tolerated up to a billion cells alone, as well as in combination with some of the most widely used immune therapies, And these cells also promote clinical benefits in a range of solid tumor cancers. Another important finding from these data are the new translational insights that we've generated into IMKT cells, their immune-modulating mechanisms, and their long-term persistence. Our data demonstrated that 797's ability to persist, amplify, and accelerate immune responses, and promote tumor infiltration beyond what has been observed with any other cell therapy today.
spk05: I'm going to turn the call over to Dr. Mark Van Dyke, our Chief Scientific Officer at Maine, to discuss more about these discoveries.
spk01: Thank you, Jen. As we continue to deepen our understanding of the INKT cells' unique mechanisms in the clinic, we're more and more encouraged by the potential of what they can do for patients with cancer, used alone or in combination with other agents. So durable responses in cancer patients require an active and vigilant immune system to prevent the tumor from escaping and going back again. A key finding in our cancer trial is that we have observed clear signatures of activation of the patient's immune system upon infusion of Agent 797. The clearest signals of this, the systemic immune activation, are changes in cytokine levels. We see these changes both systemically in the blood as well as locally within the tumors in the patients we treated in this trial. One such signal is interferon gamma. This is a key immune activating cytokine and a hallmark of INKT activation. And interferon gamma spikes in the blood of all patients 24 hours post-infusion of agent 797, potentially indicative of tumor INKT activation. The spike in serum interferon gamma correlates with dose. And interestingly, patients treated in combination with anti-PD1, demonstrate elevated baseline levels of interferon gamma and show an enhanced post-infusion spike of interferon gamma, potentially indicating elevated immune system activity when combining anti-PD-1 with agent 797. Now, to retain control of the tumor, the patient's immune system needs to remain vigilant. In that respect, it's important that the anti-cancer activation state of the patient's immune system is persistent. And our data showed first-of-a-kind persistence of an allogeneic by NKT cell therapy in cancer. Here we used a very specific independent method based on high sensitivity donor-specific SNP analysis by duplex sequencing of peripheral blood mononuclear cells. We found that Agent 797 persists for at least six months. And in addition to showing such low persistence, we also saw that Agent 797 levels in blood of patients appears to correlate with response. They appear higher in patients with partial response and stable disease. So for a telegenic cell product to stay around for six months is remarkable, even more so when it is administered without lymphodipletion, which is a toxic pretreatment used for the majority of cell therapies in clinical use today. Even more remarkable was our finding that Agent 797 persistence was apparently independent of HLA matching. Traditional knowledge has it that the higher the degree of HLA matching is between donor tissue and the patient, the longer the donor tissue will be tolerated and stay functional. Our finding that allogeneic IgG T-cells persist in our responding gastric cancer patient for at least six months, even when there is only one out of 12 HLA match, provides further support for the unique nature of invariant natural killer T-cells and underpins the great potential for therapy to use in cancer and in other immune-mediated disorders.
spk07: Over to you, Jen.
spk10: Mark, thank you. This is really profound work. and unique set of findings that are quite different than what we observed with the other available cell types. And witnessing, observing the theoretical advantages of INKT cells actually comes to fruition in clinical practice as well as in translational data observations is a true testament to our team's dedication and innovation. Appreciate your overview, Mark. As we reflect on our scientific advancement, it's also really important to acknowledge our attention and financial prudence that it truly underpins our journey. Our disciplines demonstrated by our contained cash flow with our clinical progress in which we launched three clinical programs. We studied INKT cells, allogeneic off-the-shelf cells in patients with virally induced acute respiratory distress and presented those data at four different conferences. We launched a trial of INKT cells alone and in combination with commercially approved anti-PD-1 therapies, nivolumab and pembrolizumab. And we've presented those data most recently now at CITSE, but also earlier this year at AACR and also last year as well. The most pronounced observations were the findings of long-term durable clinical benefit correlating with the translational insights that Mark just presented. And we've done this with a contained cash outflow, and it's been carefully managed to support the completion of these programs and internalization of our manufacturing process and scale-up. Looking ahead, we anticipate a meaningful reduction in our quarterly cash burn rate, buoyed by the external financing of our clinical programs, and importantly, The progress that we've made in manufacturing has included our ability to have an FDA-cleared process that is now automated, closed, and fully internalized, highly scalable, now beyond 5,000 doses per donor and beyond thousands of doses per year. So we have the process now to support the development needs going forward. Now, importantly, advancing our clinical programs has been critical for us. and we're continuing to do so in a few different ways. First, our Phase II clinical trial in second-line gastric cancer, led by Dr. Yelena Dzantzigi, in chief of Gastrointestinal Oncology at Memorial Sloan Kettering Cancer Center, is on track to launch this quarter. This trial will include the combination of the cells on top of standard care chemotherapy, as well as the combination of cells on top of standard care chemotherapy and combination with botanosilamab and valosilamab. This is an optimized, multifunctional T-cell engaging technology that also binds anti-CCLA-4 from our collaborators at Agenis and valosilamab and anti-PD-1 therapy from Agenis as well. Next. We are advancing our HF797 in opportunistic disease settings in infectious respiratory distress and autoimmunity, specifically GVHD. These externally funded trials will be designed to build on the exciting survival data we've reported in patients with virally induced respiratory distress. This is an unmet need where there are currently no approved therapies. And finally, acute GVHD remains a severe and often fatal complication in more than half of the patients undergoing hematopoietic stem cell transplantation. INKTs have demonstrated the natural capability to not only improve engraftment success in these patients, but also to mitigate GVHD. Given our robust tolerability data, we are advancing an externally funded trial to address this important unmet need. We believe that a small and effective trial can generate data to support this opportunistic indication where rapid development pathways are available. You will hear more on all three of these programs later this year. And parallel to our clinical endeavors, our team is advancing our CMP manufacturing capabilities and continuing to scale our INKT cell production, as I mentioned earlier. We're continuing to ensure that we can meet the therapeutic needs of patients battling cancer and other immune-related diseases. Our progress has advanced with effective financial prudence. We've judiciously allocated resources, emphasized data generation, scalability, and advanced our innovative platform. Our existing infrastructure has been leveraged to its fullest, allowing for the full internalization of our manufacturing process. which underscores our commitment to cost effectiveness and operational efficiency. Additionally, to strengthen our balance sheet, we're in discussions with strategic partners on regional partnerships, research and development collaborations, and manufacturing services, all of which are focused on accelerating our development speed, advancing our innovation more rapidly, and leveraging our core capabilities in non-dilutive ways to continue to fund our business effectively.
spk06: I will now turn the call over to Christine to go over our financials.
spk11: Thank you, Jen. We ended the third quarter with a cash balance of $6.4 million as compared to $10.6 million at June 30, 2023, and $19.6 million at December 31, 2022. Cash used in operations for the three and nine months ended September 30, 2023, was $4.2 million and $12.7 million, respectively. This is a decrease when compared to $5.6 million and $14.4 million for the same period in 2022, reflecting our financial prudence that Jen just described. Net loss for the nine months ended September 30, 2023, with $17 million, or 50 cents per share. compared to net loss for the same period in 2022 of $20.2 million or 60 cents per share. I will now turn the call back to the operator for questions.
spk03: The floor is now open for your questions. To ask a question this time, please press star then the number one on your telephone keypad.
spk06: We'll pause for just a moment to compile the Q&A roster.
spk05: Your first question comes from Emily Bodner from HC Wainwright.
spk12: Hi, good morning, and thanks for taking the questions. Maybe firstly, if you can put into context some of the data that you presented at CIDC. I know you talked about the six-month persistence. Maybe you can discuss what the typical persistence is for cell therapies in the autologous setting. And you also had a median PFS of six months in combination. So maybe just discuss what you would expect the PFS to be with use of checkpoint inhibitors alone in a similar patient population. Thank you.
spk10: Emily, thank you so much for the question. And I have Mark with me. I'm going to have him give you an overview of the translational data presented at CITC And I would say with respect to the median PFS, which as you pointed out is really quite compelling, this is a patient population who have failed all prior lines of therapy in their disease setting and they were really quite sick. It's a heterogeneous phase one population. We observed that in some cases we've had patients of course with refractory cervical cancer, non-small cell lung cancer who had failed prior chemo, Pembro, we had patients with testicular cancer who had failed four prior lines of therapy. The median prior lines of therapy exceeded four for this population. Their typical PFS, as you can imagine in this particular setting, on the currently available therapy would have been far less than that, closer to about 1.8 to two months, depending on the tumor type. So that's just for framing. We are seeing and we're continuing to follow patients now for progression-free, disease-free survival as well as overall survival. The translational data, I'll turn it over to Mark to give you a sense of the reference of what we would expect, what we have seen as we've gone through the data over time, what we've seen in comparative cell types. and what we believe that this may mean for the development of the product. Mark?
spk01: So the fact that, you know, we see six-month persistence in an allogeneic non-HLA-matched therapy without any preconditioning is, I haven't seen that anywhere yet. You know, in autologous CAR T-cell trials, patients are heavily pretreated with lymphoid depletion to make room for the new T-cells coming in, and those T-cells are from the patient itself, which is a full HLA-matched And they are, you know, they spike and then they go away. And in some cases, like pediatric cases, the autologous T cells have been detected for decades. But that's in a full HLA-matched setting by the patient's own T cells. In any other allogeneic setting that I've seen reported on, I haven't seen any persistence reported on longer than a month. And that's also with patients that have received quite toxic, heavy preconditioning lymphodepletion to tone down the immune system of the patient and extend the persistence that way. We don't do that. So we have no pretreatments, and we have no HLA match, and we still see six-month persistence. And I haven't seen that reported anywhere else or any other cell type in this setting. So that's what we think, fairly unique, and we think a special property of these INKT cells.
spk12: Very helpful. And then maybe if you could just provide an update on your CAR-INKT cell therapies and if you're still advancing those toward the clinic.
spk10: Great question. We absolutely are. We've got our SAP-CAR-INKT and our BCMA-CAR-INKT both armored. The second of which, the BCMA-CAR-INKT, we've highlighted an prior calls, we've shown potential best-in-class activity with this pre-clinically, and we've completed effectively the IUD-enabling packet. I have mentioned that as we have contemplated advancing our programs forward, DCMA is something that we have been in deep discussions with partnerships and see as opportunistic as a next-generation therapy for companies who are actively developing this program. with a broader footprint than mink. So that is something that continues to be advancing. The FAPCAR INKT was most recently presented, updated preclinical data this year, and I'll have Mark highlight some of the key features of that program. We are planning our IND. We're still on track for a 2024 submission.
spk01: Yeah, just all the data. I mean, we're actually quite excited about this whole, our FAPCAR INKT program, because it has even more impact on the tumor microenvironment than we've seen with the native INKT cells. And specifically for highly resistant solid tumors, we think that that is a benefit. We see that it really potentiates the immune system to go in and change the tumor microenvironment from cold to hot. And we think that that's going to really help extend the reach of native INKT cells in cancer. It's one of the fundamental mechanisms to tackle tumor suppression is by attacking the sort of immune-suppressive stroma. And that's what FAPCAR and KTs have shown to do very, very well, both in vivo systems that we've actually reported in a couple of conferences this year, as well as all in vitro data that we hope to actually publish pretty soon.
spk06: So full speed ahead for this program for us. Awesome. Thanks so much.
spk05: Thank you. Your next question comes from Jack Allen from Baird.
spk08: Great. Thanks so much for taking the questions, and congratulations on the progress made throughout the quarter.
spk02: Maybe my first one on the translational data, Mark, you spoke a bit about the persistence, but could you elaborate a little bit more on the expansion of these cells and what you're seeing in the acute dosing as it relates to translational data from the 797 program?
spk01: Yeah, so that's a good question. So what we see is typically the moment we infuse these cells, they're quite rare in the normal blood, but we infuse a billion cells at the time of dosing, which at the time of infusion is about 15% to 20% of your total white blood cell count, which is a bolus. And that, we think, is one of the reasons why you get a systemic effect of immune activation on the whole immune system. Beyond that, what we see is that these cells continue to be detected in blood for over six months. Now, we don't have definite evidence that which part of the tissues they go from clinical data. Preclinically, they go to lung, liver, bone marrow. So we expect that in patients themselves, this would also be the case. And we expect them to go to tumors. And some evidence of that we do see. We can't currently say how much of that is driven by expansion and active division of IKT cells. The detection level in blood over the six months remains relatively stable, although in responding patients we see a sort of cycling. And the cycling may mean two things. One, they're actually actively dividing. Two, they're actually trafficking between the compartments in the body. And we can't currently distinguish between those two, but they do stay around for much longer than we had thought they would be able to stay around, given that they're not HLA-matched.
spk02: Got it. Got it. Great. And then you made some comments on the call as it relates to partnership discussions. Can you elaborate a little bit more about what kind of partnerships you're contemplating? Would these be indication-specific or product-specific? How are you thinking about that path moving forward?
spk10: Thanks so much, Jeff. So this is such an important part of our strategy, and maybe just as a reminder, Mark and I have have both together shared leadership roles at our parent company, Agenis, where we were incredibly successful and prolific at establishing partnerships that not only expand our discovery engine and capability, but also speed the development of agents. So our discovery capability is incredibly prolific here at Mink with Mark and his team, producing discovery targets and particularly in engineering them all in-house. And I'm going to have Mark speak a little bit about the unique capability for our team at MAPE to be able to not only isolate novel targets, but then engineer them into INKTs for cars, for TCRs, for engagers. And those activities are very actively underway. In order for us to fully leverage that engine, We are in active discussions at this time with companies who need innovation and who are very interested with quite a large appetite to be able to take on some of our discovery items. So could we help a partner in that regard? And those are one of the types of discussions we're talking to partners about would be, supporting the discovery engine through a research and development collaboration. In addition, the opportunity for us to take 797, the clinical data that has been generated to date, and fully exploit its benefit, and that is in optimal combinations and expanding benefit. And we've seen in our own hands that these cells can be incredibly powerful in the clinic in combination, of course, with widely used chemotherapies as well as most commonly used immunotherapies like anti-PD1, Keytruda, Opdivo. In addition to that, we've demonstrated preclinically that these cells can expand the benefit of what we observe with engagers in the clinic, as well as some other more novel technologies. So we are also contemplating the strategic collaborations that would enable us to provide access to 797 to expand the benefit in optimal combinations for patients with cancer. And those are both global discussions as well as regional partnership discussions that are actively underway. There are some parts of the world where mink does not have a footprint, and being able to leverage experts regionally will also help us to expand our footprint and hasten our development speed in different parts of the world. So certainly the research and development capabilities, leveraging those capabilities and supporting the acceleration of bringing some of these technologies to the clinic more rapidly, as well as leveraging the clinical data from 797 to support expanded benefit for patients with cancer through really optimal combinations. And the soonest to start, of course, would be our combination in the clinic with second-line gastric cancer. The INKT cells will be in a randomized study, the cells on top of standard of care chemotherapy, and then the cells on top of standard of care chemotherapy plus the really exciting products, botansilumab and valstilumab from Agenis. And that trial, as I've mentioned earlier during the call, will be run through Yelena Jigian and externally financed. Trials like that are being actively pursued in our discussions through collaborators at this time.
spk02: Got it. Great. And if I may, just a couple more. On autoimmune diseases, it's good to see that on the slide here as it relates to the pipeline. As I read the slide, it mentions a 2023 IND potentially in a phase one study initiation. Should we expect that in the coming months here? And then just briefly, as it relates to innovative programs, I see that you've added a PRAME program to your early discovery aspect of your pipeline. I'd love to hear any thoughts you have around the PRAME target and its potential across multiple solid tumors.
spk10: Excellent. On the first question, which is with respect to advancing a clinical program with INK T-cell 797 in patients with acute graft-versus-host disease, that is something that we plan to launch this year into the clinic, effectively amending the IND with our new study program that's very close to getting into the clinic at this time. So we believe we'll be announcing that this year. We're on track. to do so or certainly planning to do so. With respect to the PRAME TCR, I'll have Mark say a few words about that.
spk01: Yeah, that's a pretty exciting program for us, actually, because we've actually been working on TCRs for quite a long time now. We have several of them generated, including what we believe is a very, very good TCR for PRAME. And PRAME, as you know, has actually already started to show some really good benefit in solid tumors with a T-cell approach to this. And Given the sort of properties of INK T-cells in actually getting into difficult places in the tumor, even suppressive tumor microenvironments, and then enhancing them with a PRAME-TCR, we believe will probably extend or has the potential to extend clinical benefit beyond what T-cells could do with PRAME. And that's what we're hoping to exemplify. And currently, it's in preclinical stage. And this will be one of the programs that we will progress following the FAPCAR program that we are currently speeding to an IND phase. Well, we're quite excited about that. And also the specific thing of this is these INK T cells now express two TCRs, the brain TCR as well as the invariant TCR from INK T cells, and they're both useful and they're both active in the tumor microenvironment. So that's, I think, a unique aspect of combining TCR expression with INK T cells, and then specifically the brain program as a frontrunner, I think is a very valuable program for us.
spk08: Great. Thanks so much for taking all the questions, and congratulations again on the progress.
spk05: Thanks so much, Seth. Thanks. Your next question comes from Mayan Kamantami from B. Riley.
spk04: Hi, this is Brandon Kanyan from Mayan. Thanks for taking our questions. Just, I guess, first, regarding the landscape in gastric cancer, we saw Dr. Jinjibian give a presentation on Tuesday, and I think there was another presentation on, or that was on TIGIT, and I think there was another presentation on ADC. in gastric and I was just wondering how you think the cells fit in the emerging landscape, you know, given the digit in the ABCs.
spk05: Absolutely.
spk10: So, I'm familiar with that presentation and we agree, we actually have discussed this with Yelena and right now, as you can see, there's a very significant and relatively urgent need for patients in the second line setting after REM tax failure. And being able to expand the benefit of what's currently being available to patients in a rapid way is quite opportunistic. And in addition to that, we believe that based on the observations we've seen in GI cancers overall with botanostilumab and valastilumab, and this is in patients now over 741 patients treated, in which the products are quite active both in the disease setting in CRC but also more broadly outside of CRC in lung cancer, ovarian, endometrial, and we see activity not only at the disease sites but also at metastatic sites that have largely escaped attack by other available therapies like metastatic lesions of the bone, the peritoneum, and liver. Given the preponderance of evidence that we've seen here and the data observations, we do believe that the cells in combination not only will expand benefit with what's currently available, which is quite a rapid path for us with the cells on top of chemo, but also the cells on top of chemo with expanded benefit from bowel combination, we believe could be immensely beneficial to patients in quite potentially a potential best-in-class approach for patients with gastric cancer. In addition to that, we've also had some preclinical observations and observations from others that the cells combine really quite effectively and tolerably with other agents, and those include engagers as well as ADC technology. So I think that when we look at these cells, and I'll have Mark say a few words specifically immunologically about what's happening when we administer these cells. So not only we're administering without HLA matching, without lymphodepletion, no toxic preconditioning, the cells are tolerable to over a billion cells now per dose. And we see that these cells appear to modulate the tumor microenvironment in ways that eliminate tumor escape mechanisms that we do observe with technologies, approved therapies today, as well as some of the developing technologies that are not yet approved. And therefore, I see a place in which these cells, just like I mentioned earlier with the expansion of benefit from our observations with engagers, we also see expansion of benefit with some of these other more novel technologies. And Mark, to give you a little bit of additional insights expanding on the observations we presented at CISI today in that regard.
spk01: Yeah, and I think, I mean, So a lot of the IO failures that we see today we think are due to, at least in large part, resistance within the tumor microenvironment. And a big part of that, for instance, is myeloid cells, macrophages and myeloid-derived suppressor cells. And one of the unique features of IKT cells is that through their invariant TCR, they target CD1D, which is universally expressed on all myeloid cells. And we've also seen that they can actually modulate M2 macrophages or kill M2 macrophages specifically, for instance. So that's an additive effect beyond what is possible with checkpoints. And we think that together with checkpoints, they can start really changing the microenvironment in a way that would potentiate a much better immune response to the tumor. So that's why we think INKT cells on top of, for instance, both bowel and gastric cancer or chemo or standard of care that changes the way the tumor sort of operates. really helps augment the overall clinical response that we think is possible because it starts to address non-overlapping immune suppressive mechanisms in the tumor itself. And also, of course, the fact that we now add these cells to patients without lymphodepletion, we don't attack their immune system. If you lymphodeplete patients, you actually diminish their immune system quite significantly. We don't do that. We don't do that because we don't need it, but we also don't do that because we think it diminishes the overall effect of the infusion of INK T cells on conjunction with, for instance, what checkpoints can be, uh, can achieve in, uh, in a given clinical setting. So that's, that's a pretty key reason why we think INK T cells are a great additive to, um, pretty much all the IO therapies out there at the moment. Does that answer your question?
spk04: Yeah. Yeah, yeah, no, that's helpful. Um, And I guess maybe just to follow up on the trend that you mentioned between responses and critical levels of 797, I'm just wondering if you think there's enough data there right now to give you confidence in that trend and what we can expect to see from that going forward?
spk01: You mean on the persistence? Yeah, we continue to follow that actually quite actively because, you know, to be honest, it surprises us. And also in light of our thinking about how to redose, if we should redose and when to redose, This is key data for us to help us decide when it makes sense to redose and why we would do this or in what patients, for instance. So we'll be collecting a lot more data on this phenomenon of persistence and also how it relates to responses in patients because we have some early indications that the levels of INK T cells we detect are higher in patients that have either stable disease or partial response. And we try to understand why that is and what's happening there. Got it, got it.
spk04: And then lastly, I guess I wanted to ask on the testicular patient that dropped out. I'm just wondering if you could give us any details on the reasoning behind that and, you know, if there's any update on the other testicular cancer patient that was presented in AACR. And also, I think that the CITSE poster mentioned an expansion cohort for testicular. Can you give us any details on that?
spk10: Absolutely. So what we're looking at here is inpatients who actually have refractory testicular cancer. There's currently nothing available for them. And the observations that we've seen now are somewhat early but really quite compelling. And the patient would continue to see the durable disease stabilization in the patient who's continuing in the trial and we're continuing to follow those patients. And we also continue to follow everyone for survival even if they've made choices to come off the trial just in order to spend more time with family and not necessarily in the clinic. And part of that choice, given that we are administering the cells with a single administration right now in this current trial, we get enough information from the patients now biologically from the per biopsy samples as well as peripheral samples that we collect. So that patient who did discontinue just the follow-up period of the study is still accessible to us and available to us. The other patient is a continued durable disease stabilization, and it's really quite intriguing. So we will expand the trial in our own hands, our phase one trial going into a phase one beam, adding a dose, an additional dose to patients and specifying some deepening our understanding in some specific disease areas where we have seen some very provocative signals of activity in patients who are not responsive to other therapies. And that includes gastric, it includes non-small cell lung cancer, and it includes relapsed refractory testicular cancer. And so those data will continue to develop over time and we'll be sharing updates at upcoming meetings, of course.
spk06: Great. Thanks for taking our questions. Thank you.
spk05: Your next question comes from Matt Phipps from William Blair.
spk07: Hi, Jen. Thanks for taking my question and the update. Given the just outsized effect in that GATS or cancer patient, do you think there's any reason to specifically look at MSI-high cancers?
spk10: Well, that's a very intriguing question. More broadly, there is, first I'll have maybe Mark for the broader group just highlight a couple of the observations that we've seen with respect to microsatellite, MSI high as well as MSS. Some of our patients are microsatellite stable, but there may be a biological rationale to your point, Matt, about expanding our observations more broadly and in a pathologic agnostic way, but using MSI high, particularly in some of the combinations given the observations we're seeing, as well as some germline tumors where we have seen some continued evidence of activity. Maybe Mark?
spk01: Yeah, so MSI high is an interesting tumor type because, you know, you could expect there's more new epitopes there, so there's more intrinsic T cell priming in the patients. And it's one of the indications where Pembrolizumab is approved, which sort of capitalizes on that existing T cell response. So those tumors are not entirely cold. But this particular patient was progressing on, Nivo was progressing on Pembro. So clearly that was not enough. There was still some resistance in the tumor microenvironment that prevented this full response, even though we detected specific cancer, so neoantigen-specific T cells in the tumor. prior to his treatment with INK T cells. So he was progressing even in that state. When we added INK T cells, it appears that some of the blockage that prevented the T cells to activate was removed or diminished because the T cells in the tumor started to expand dramatically. So we saw a lot more CD8 T cells in the tumor post-infusion of INK T cells. And that sort of to me speaks to what we think is happening in the tumor microenvironment is that INK T-cells are able to reduce some of the local suppression in a way that then further potentiates an already existing T-cell response, but that was blocked. So that's what I alluded to earlier, that we think there is overlapping and additional benefit of INK T-cells by reducing suppression that is not tackled by standard IO therapies. And the gastric cancer patient is currently the best example we have of that particular mechanism there. Do we see this also in other tumors? I think it helps if you have an existing T cell response. And of course, having been pretreated with PD-1 and then progressing probably has led to a change in the activation state of T cells. And in many cases, this is still not enough. And can INK T cell then block a further response? Well, a cancer patient indicates that that potentially is possible. So we hope to see more of that.
spk07: Thanks, Mike. Sorry if I missed it, but have you ever said how frequently you are going to test redosing or multidosing given the persistence you've seen?
spk10: Again, Mark, I could ask you to give some insight into this. I'll tell you what we're thinking currently. Our clinical team is thinking at this time is the most important component for us right now is as we continue to separate out the... the inject the administration and the trafficking and the persistence based on where the cells are localizing peripherally locally at the site of the tumor does give us a sense that we could dose probably we don't need to dose any less than six weeks so it gives us an opportunity to dose at around the six week mark which enables us to combine really well and favorably with widely used standard of care therapies at this time particularly in some of the tumor types that we're seeing our most pronounced benefit and in doing that we we may and this will be something that we're going to explore more deeply in our expansion cohorts can we push that persistence out which we're still monitoring in the patients who are on the trial does it change the dynamics within the tumor microenvironment based on the localization and should we explore delaying that to possibly 12 weeks. And we don't know the answer to that at this time. But based on the fact that we have seen very transient alloantibodies, which we presented at CITSE two years ago, we've already established that we believe we could dose safely without any rejection. And six weeks appears to be the time point that is in the sweet spot where we may optimize the benefit and optimize the convenience for patients.
spk06: and undergoing current definitive care. Great. Thank you.
spk05: That was your final question. I now turn it over to Dr. Buell for closing remarks.
spk10: Thank you very much, operator, and thank you all for your time and attention and continued support to me. I appreciate your time.
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