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 Zack Armen, Head of Investor Relations at MiNK.

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 time lines 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. Marcus van Dijk, 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.

Thank you, Zack. 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 iNKT cell technology and pipeline programs. A pinnacle of this progress was presenting compelling new data on our flagship product, AgenT-797 at the recent Society for Immunotherapy of Cancer or SITC annual meeting that took place last week. To reiterate, 797 is an allogeneic iNKT cell therapy, it's distinguished by its scalability, robust immunomodulatory properties and its administration without the need for toxic preconditioning regimen, a testament to the versatility and promise of these cells. The findings being reported at SITC included first-of-kind data, highlighting many of these unique benefits of iNKTs, particularly related to the lengthy persistence of the cells without lymphodepletion or toxic preconditioning. Marcus can tell you a bit more about that shortly. So last Friday, we reported an update on the durable clinical benefit from AgenT-797 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. These are patients with non-small cell lung cancer refractory to prior therapy, testicular cancer and appendiceal cancers that were refractory to prior chemo, 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 benefit of iNKT…

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, use alone or in combination with other agents. So durable responses in cancer patients require 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 the systemic immune activation are changes in slightly high 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-PD-1 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 anticancer activation state of the patient's immune system is persistent. And our data showed first-of-a-kind persistence of an allogeneic iNKT 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. So we found that agenT-797 persists for at least 6 months. And in addition to showing such long persistence, we also saw that agenT-797 levels in blood of patients is to correlate with response. They appear higher in patients with partial response and stable disease. So for an allogeneic cell product to stay around for 6 months is remarkable. Even more so when it is administered with ideally for the patient, which is a toxic pretreatment used for the majority of cell therapies in clinical use today. Even more remarkable what we are finding that agenT-797 persistence was apparently independent of HLA matching. Traditional knowledge has is that the higher degree of HLA matching between donor tissue and the patient, the longer the donor tissue will be tolerated and stay functional. Our finding that allogeneic iNKT cells persist in our responding gastric cancer patients for at least 6 months even when there was only 1 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. Over to you, Jen.

Marc, 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, Marc. As we reflect on our scientific advancements, it's also really important to acknowledge our attention and financial prudence that it truly underpins our journey. Our discipline is demonstrated by our continued cash flow with our clinical progress in which we launched 3 clinical programs. We studied iNKT cells allogeneic off-the-shelf cells in patients with virally induced acute respiratory distress and presented those data at 4 different conferences. We launched a trial of iNKT cells alone and in combination with commercially approved anti-PD-1 therapy nivolumab and pembrolizumab. And we've presented those data most recently now at SITC, 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 co correlating with the translational insights that Marc 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, will be 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 1,000 of doses [ per year ]. So we have the process now to support…

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 3 and 9 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 9 months ended September 30, 2023, was $17 million or $0.50 per share compared to net loss for the same period in 2022 of $20.2 million or $0.60 per share. I will now turn the call back to the operator for questions.

The floor is now open for your questions. [Operator Instructions] Your first question comes from Emily Bodnar from H.C. Wainwright.

Maybe firstly, if you can put into context some of the data that you presented at SITC, I know you talked about the 6 month persistence. Maybe you can discuss what the typical persistence is in our cell therapies in those [ algo ] setting. And you also had a median PFS of 6 months in combination. So maybe just discuss what you would expect the PFS to be, what use of checkpoint inhibitors alone in a similar patient population.

And I have Marc with me. I'm going to have him give you an overview of the translational data presented at SITC. 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 has failed all prior lines of therapy in their disease setting and they were really quite sick. It's a heterogeneous [ Phase ] 1 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 4 prior lines of therapy, the median prior lines of therapy exceeded 4 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 2 months, depending on the tumor type. So 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 Marc 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. Marc? I think we may have a little technical glitch from Marc. Can you hear him, Emily?

No, I just hear you.

I think Marc is now unmuted.

Is this better?

Yes. Perfect. You're on.

Okay. Good. Yes, I was already well on my way to answering the question. So the fact that this, we see 6-month persistence in an allogeneic non-HLA matched therapy without any preconditioning is I haven't seen that anywhere yet. In autologous CAR-T cell trials, patients are heavily pretreated with lymphodepletion to make room for the new T cells coming in, and those T cells are from the patients itself, which is a full HLA match. And 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 or by patients' 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 extends the persistence that way. We don't do that. So we have no pretreatment and we have no HLA match, and we still see 6-month persistence. And I haven't seen that reported anyone else or any other cell type in the setting. So that's what we think, fairly unique and we think a special property of these iNKT cells.

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 for the clinic?

Emily, great question. We absolutely are. We've got our FAP-CAR-iNKT and our BCMA-CAR-iNKT both armored, the second of which the BCMA-CAR-iNKT we've highlighted in prior calls, we've shown potential best-in-class activity with this preclinically, and we've completed effectively the ID-enabling packet. I have mentioned that as we have contemplated advancing our programs forward, BCMA 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 FAP-CAR-iNKT was most recently presented updated preclinical data this year, and I'll have Marc highlight some of the key features of that program. We are planning our IND. We're still on track of our 2024 submission.

Yes. Just on the data. I mean, we're actually quite excited about this whole our FAP-CAR-iNKT program because it has even more impact on the tumor microenvironment that 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 immunosuppressive stroma. And that's what FAP-CAR-iNKTs 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 on in vitro data that we hope to actually publish pretty soon. So full speed ahead for this program for us.

Your next question comes from Jack Allen from Baird.

Congratulations on the progress made throughout the quarter. Maybe my first one on the translational data. Marc, 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?

Yes. So that's a good question. So what we see is typically, when the moment we infuse these cells, they are quite rare in the normal blood, but we infuse 1 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 6 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 iNKT cells. The detection level in blood over the 6 months remains relatively stable, although in responding patients, we see a sort of cycling. And the cycling may mean 2 things. One, they're actually actively dividing; 2, they're actually trafficking between the compartments in the body. And we can't currently distinguish between those 2, 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.

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?

So, it's Jen. This is such an important part of our strategy. And maybe just as in mind, Marc and I have both together shared leadership roles at our parent company Agenus, 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 agenT. So our discovery capability is incredibly prolific here at MiNK with Marc and his team producing discovery targets and particularly in engineering them all in-house. And I'm going to have Marc speak a little bit about the unique capability for our team that make 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 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 this benefit, and that is an 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 immune therapies like anti-PD-1, 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…

Got it. Great. And if I may, just a couple more. On the autoimmune diseases, it's great to see that on the slide here as it relates to the pipeline. As I read the slide, it mentioned the 2023 IND potentially in a Phase 1 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?

Excellent. On the first question, which is with respect to advancing a clinical program, with iNKT 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, we're certainly planning to do so. With respect to the prime PRAME TCR, I'll have Marc say a few words about that.

Yes. Look, 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 iNKT cells and 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 FAP-CAR program that we are currently speeding to an IND. But we're quite excited about that. And also the specific thing of this is these iNKT cells now express 3 TCRs, the PRAME TCR as well as the invariant TCR from iNKT 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 the TCR expression with iNKT cells. And then specifically, the PRAME program as a frontrunner, I think, is a very valuable program for us.

Your next question comes from Mayank Mamtani from B. Riley.

This is Brandon Carney on for Mayank. Just I guess, first, regarding the landscape in gastric cancer. We saw Dr. Janjigian give a presentation on Tuesday, and I think 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 sit in the emerging landscape given the TIGIT and ADCs.

Absolutely. So I'm familiar with that presentation, and 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 [indiscernible] 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 botensilimab and balstilimab, 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 to 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 bot/bal combination, we believe, could be immensely beneficial to patients and 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 combined 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 Marc 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 1 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 Marc to give you a little bit of additional insights expanding on the observations we presented at FITC today in that regard.

Yes. And I think, I mean, 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 myelo-derived suppressor cells. And one of the unique features of iNKT 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 potentially a much better [ immune ] positive tumor. So that's why we think iNKT cells on top of, for instance, bot/bal in the 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 nonoverlapping immunosuppressive mechanisms in the tumor itself. And also, of course, the fact that we know 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 iNKT cells on conjunction with, for instance, what checkpoints can achieve in a given clinical setting. So that's the key reason why we think iNKT cells are a great additive to pretty much all the IO therapies out there at the moment. Does that answer your question?

Yes, yes. No, that's helpful. 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 an update there right now to give you confidence in that trend and what we can expect to see from that going forward?

You mean on the persistence, yes, we continue to follow that actually quite actively because, to be honest, it surprises us. And also in light of our thinking about how to redose if we should redose and when to read those. 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 iNKT cells we detect are higher in patients that have either stable disease or partial response. And we just try to understand why that is and what's happening.

Got it. And then lastly, I guess I wanted to ask on the testicular patient that dropped out. Just wondering if you could give us any details on the reasoning behind that? And if there's any update on the other testicular cancer patient that was presented at AACR. And also, I think that the SITC poster mentioned an expansion cohort for testicular. Can you give us any details on that?

Absolutely. So what we're looking at here is in patients 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 is 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 some 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 [ paired ] 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 1 trial going into a Phase 1b, addingan 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.

Your next question comes from Matt Phipps from William Blair.

Given the just outsized effect in that gastric cancer patient, do you think there's any reason to specifically look at MSI high cancers?

Well, that's a very intriguing question. More broadly, first, I'll have maybe Marc, for the broader group, just highlight a couple of the observations that we've seen with respect to MSI high as well as MSS. Some of our patients are stable or microsatellite stable, but there may be a biologic rationale to your point, Matt, about expanding our observations more broadly 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 Marc...

Yes. So MSI high is an interesting tumor type because 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 the 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 iNKT cells. So he was progressing even in that state. When we added iNKT 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 were starting to expand dramatically. So we see a lot more CD8 T cells in the tumor post infusion of iNKT cells. And that's sort of to me speaks to what we think is happening in the tumor microenvironment is that iNKT cells are able to reduce some of the local suppression in a way that don't further potentiate 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 iNKT cells by reducing suppression that is not tackled by standard IO therapies. And the gastric cancer patient is clearly 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 iNKT cell then block a further response? Well, gastric cancer patient indicates that, that potentially is possible. So we hope to see more of that.

Sorry if I missed it, but have you guys said how frequently you're going to test redosing or multi-dosing given the persistence you've seen?

Again, Marc, I could ask you to give some insight on 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 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 6 weeks. So it gives us an opportunity to dose at around the 6-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 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 wandering 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 a very transient [indiscernible] antibodies, which we presented at the SITC 2 years ago, we've already established that we believe we could dose safely without any rejection. And 6 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 undergoing current standard of care.

That was our final question. I now turn it over to Dr. Buell for closing remarks.

Thank you very much, operator, and thank you all for your time and attention and continued support to MiNK. I appreciate your time.