INKT - NASDAQ

Ladies and gentlemen, thank you for standing by. Welcome to the MiNK Therapeutics’ First Quarter 2023 Financial Results Call. I would now like to turn the call over to

Thank you, operator, and thank you all for joining us today. Today’s call is being webcast 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. Marc Van Dijk, Chief Scientific Officer; Dr. Joy

Thank you very much,

Thank you, Jen. We’re quite excited about the observations at the AACR of clinical benefit in patients with heavily pretreated metastatic cancers. These patients are the ones who inspire our work as we leverage our iNKT platform to expand the clinical benefit observed with the two therapies and develop innovations to address areas where current therapies actually fall short. So our technologies which you will hear more about at our annual shareholder meeting includes the ability to generate armored-CAR-iNKTs, develop iNKT engagers, cell engagers and advance novel TCR therapies. In addition to our native clinical-stage agenT-797 program, our most advanced preclinical programs includes armored-allogeneic FAP-CAR-iNKT and a next-generation armored-BCMA-iNKT. So our lead program, agenT-797 is designed to expand clinical benefit observed with approved therapies. And our data at AACR is the first glimpse of the possibility of these cells to deliver on these benefits. It’s a well-known phenomenon that anti-PD-1 therapies are effective at countering tumor immune suppression. However, chronic use of these therapies leads to immune exhaustion. So we’ve previously shown that agenT-797 can improve the anti-tumor activity of immune cells that are present in the tumor microenvironment. Specifically, we’ve shown that iNKT cells can activate dendritic cells, preferentially kill M2 macrophages and restore killing capacity of exhausted T cells. So in data, ascertain from our clinical trial of agenT-797 we showed that agenT-797 induced pro-inflammatory cytokine responses including significant increases in interferon gamma, a hallmark of iNKT activation and potentially indicative of tumor iNKT activation, which is paramount to tumor – control tumor destruction. Importantly, iNKT cells are naturally tissue homing, so in preclinical data previously presented, we’ve demonstrated that iNKT’s could be administered without lymphodepletion. They have rapidly traffic out of the circulation, but in days of administration and into tissues, including bone marrow, the liver and lung, where they remain in some cases exceeding 35 days. So in our clinical trials we reported the similar pattern of rapid translocation out of the circulation, while they remain at detectable limits and persists for approximately eight weeks. In our patients with durable response beyond nine months, we also showed that iNKTs drive clonal T-cell expansion in cancers with a high neoantigen burden, immunogenicity really triggering the expansion of these cancer-fighting T cells. While we plan to report more detailed information of iNKTs in the tumor microenvironment at a later update this year. Currently, our data demonstrate the mechanism of iNKT cells to enable T cells and NK cells traffic in two tumors, reinvigorate partially exhausted CD8 T cells and improve factor functions within the tumor microenvironment, which is exemplified in these patients with clinical or biomarker response after a single dose of agenT-797. As we continue to expand the potential of iNKTs in solid cancer, we have advanced our next-generation iNKT programs, including our novel IL-15-armored FAP-CAR-iNKT MiNK-215. Cancer-associated fibroblasts, which are targeted with this therapy are key tumor supportive components of the immune suppressive tumor microenvironment in several cancers, including non-small cell lung cancer. This adverse tumor microenvironment can be addressed by our fibroblast targeting or FAP-CAR-iNKT therapy, which naturally homes to tissue such as the law. In preclinical models, we reported very exciting data showing the potential of MiNK-215, which demonstrated robust efficacy in non-small cell lung cancer preclinical models, eliminating tumor burden in the lungs and enhancing tumor-specific CD8 T cell infiltration through stromal remodeling. This is a program we’re actually very excited about, and Dr. Shannon Boi one of our lead scientists at MiNK, will be presenting new data at the American Society of Gene and Cell Therapy Annual Meeting on May 19th. I will now turn the call over to Jen for closing comments.

Thank you, Marc. Well, I get more and more enthusiastic about the data that we’re advancing the technology and the science behind these very powerful cells. And in conclusion, I’m really happy to share with you the progress that we’ve made in advancing this platform. And as Marc just mentioned, not only addressing and expanding the benefit from available therapies for patients today about what they will need tomorrow. This process, of course, is made possible by the incredible advancements of Dr. Joy

Thank you, Jen. We ended the first quarter of 2023 with a cash balance of $14.9 million as compared to $19.6 million at December 31, 2022. Our cash used in operations for the first quarter was $4.4 million, which compares to $4.2 million for the same period in 2022. Net loss for the quarter ended March 31 was $5.7 million or $0.17 per share compared to a net loss for the first quarter of 2022 of $7.8 million or $0.23 per share. Thank you. And we’ll now turn the call back to the operator for questions.

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

Hi. Good morning and thanks for taking the question. Is there anything you can share about details for the non-small cell lung cancer expansion study? And then also, I believe you previously said that you were going to also do an expansion in testicular cancer. So is that also still the plan? And then at this point, do you think you’re just focusing on combination approaches? Or do you still think there’s a role for monotherapy in your view? Maybe just discuss plans for multiple dosing. Thank you.

Thank you very much. So to your first question on small cell lung cancer and testicular cancer indications in which we have observed some specific benefits and non-small cell lung cancer, we are advancing our Phase 1 into a Phase 1b, and we’re able to enrich a little bit more clearly in lung cancer, the more prevalent tumor non-small cell lung cancer in patients who are refractory. There’s really nothing toward those patients and very low response rates. We believe that when patients fail on anti-PD-1 therapy, they have a profile where iNKTs may benefit, as Marc mentioned just a bit ago. And adding on to what’s available standard of care, these actually allows us to take a monotherapy approach to development, just taking standard of care – patients who are on standard of care, when it’s not active for those patients adding on to that – gives us an opportunity for rapid development. So while we do see a path for iNKTs alone, and we’ve seen benefit, as you can see what the data presented at AACR, we do see benefit with iNKT-797 specifically without other therapies both long-term disease stabilization and biomarker responses. We see more robust activity and a very clear path to rapid test for registration when we can add on to available therapy and expand the benefit or reinvigorate a patient’s immune system and reactivate it to respond to what’s currently available. We will be doing multiple doses in our study. While the cells are persisting for about eight weeks, we do plan to do with – and we’ll share more about these trials as we launch them, but we will be dosing more than one dose, and we’ll probably be dosing consistent with some of the most commonly used therapies at week six or eight that will take advantage of the pharmacology that we’re seeing as well as make the treatment burden as light as possible for our patients. With respect to testicular cancer, that is also a study that will also continue to interrogate signals with that indication, it’s a bit rarer. And so we are just currently enrolling some more patients to deepen our understanding the biology of patients who fail prior therapies with testicular cancer. But that’s an area that we do see benefit and want to continue to explore that. I think I covered all of your questions.

Yes. Thank you.

Our next question comes from the line of Jack Allen from Baird. Your line is open.

Great. Thank you so much for taking questions and congratulations to the team on the progress made throughout the quarter. I wanted to ask on the updates on COVID. I think in the press release, you outlined that there will be some data presented in late May here. I’d love to hear what we should expect ahead of that data set. And any comments you have around – I think there were some ongoing negotiations with DARPA around potential funding for some of these viral diseases, I guess, response programs. I’d love to hear any updates there. Thank you so much.

Thank you so much Jack for your question. I am incredibly excited about the data – an upcoming data presentation at the pulmonary conference. It’s an international conference of infectious disease and pulmonary science. The largest of its kind of about 30,000 participants. It’s created in Washington, D.C. this year, and our presentation is slated to be presented by Dr. Terese Hammond, who was the lead investigator in our Phase 1 trial, a pioneer in delivering cell therapy to patients with infectious disease and the presentation is on Sunday, the 21st. And we’ll share a bit more about that data as the release of it. What we see is the opportunity here now and very importantly, we had a number of key observations with these cells. Never one, we could administer these cells. They were at the site in emergency settings when the patients needed them, and they were able to be administered very easily within the standard practice in an emergency room and an ICU setting. So that set us up for addressing and confirming that these cells are logistically feasible. They can be cryopreserved, they could be administered in the hands of non-oncology experts. These are ICU experts and emergency group critical care physicians who don’t have as much experience with cell therapy products, and we were able to deliver benefits to some patients that we reported pronounced benefit in our cohort that showed survival rates in patients who are elderly, mechanically ventilated and we saw survival benefits of over 70% alive after a single administration of 797. We also showed that these cells could be dosed in that severe critically ill population – they could be dosed tolerably to 1 billion cells. And we also show that these data compared so favorably when in-hospital control that had a survival rate of less than 22% and the CDC data, which was really comparable with in-hospital controls at the time of our enrollment. We’ve also demonstrated that we could administer these cells not only tolerably we saw no cytokine release in the population. But we also show that these cells could be administered in patients who are so severely sick that they need a supportive – essentially ECMO procedure. This is a procedure that requires heavy intervention. It’s very difficult. It’s recirculating the patient’s, less supply, and we were able to administer the cells in that setting and see benefit as well. You’ll see a deep dive into that data set at the ATS – upcoming ATS Conference. You will also hear about some exceptional cases where we’ve administered the cells and saw some remarkable benefit in patients who have cleared COVID but had secondary infections and that were resistant to all available antibiotic therapy. And the cells actually promoted some really exciting data in that setting. So you’ll hear all about the data sets there. In advancing this program, we do believe that the data we’re serving is really far too good to turn away from, yet our focus and our prioritization has really been advancing the cells in solid tumor cancers. While we have our negotiations are with non-dilutive government-sponsored sources and clinical trial platforms that allow us to very rapidly expand the potential benefit of these cells in patients with acute respiratory distressed syndrome secondary to viruses, and this could go beyond COVID-19. Those discussions are very actively underway, and we will certainly be making some public announcements about the collaborations in the upcoming near-term.

Great. Thank you so much for that comprehensive answer. And then just one brief follow-up on the CAR-iNKTs and very much looking forward to that presentation as well at the upcoming ASGCT meeting. I’d love to hear a little bit more though about your development strategy as it relates to the CAR-iNKTs. Are these assets that you look to bring forward on your own? Or would you look to partner these assets? I’d love to hear how you’re thinking about that. Thank you so much.

Jack, thank you. I want to make one last comment that I can make about the cells and ATS, and then I’m going to come to the CAR-iNKTs. We also will report some very important translational data that shows what these cells can do biologically. In cancer, we saw that these cells can helm to tumors and generate a pro-inflammatory phenotype, which is what we really need in that setting. What we see in infections, particularly in acute ARDS, is it the cells actually induced an anti-inflammatory phenotype, which is really powerful and it showcases how these cells can modulate immunity based on the disease setting that they’re in, which makes them a really remarkable candidate and also underscores the next steps in our platform. On the FAP-CAR-iNKT and partnering, partnering is absolutely core to our strategy. As you know, we’ve been in an incredibly aggressive team. Marc and I have worked together with the Agenus Group, and we allowed the access to our remarkably fast and innovative discovery research and finance the business in parallel. So through nearly $1 billion in partnerships, we were able to continue to finance our innovative pipeline at Agenus. And at MiNK, Marc and his research team have continued that pace of discovery and innovation. And what – our ability to get the science into as many hands and out to as many patients as possible, partnering will be necessary for that. That includes local, national U.S.-based pharma partners who may be seeking that have the capabilities that will allow us to expand quickly, but also regional partners where we don’t yet have the infrastructure or bandwidth. You will be hearing more about that also in the near-term and our strategy and access to advancing FAP-CAR-iNKT very quickly. Suffice it to say though, today, we are well positioned to advance FAP-CAR-iNKT through the IND enabling and into the clinic, and that’s a very high priority for our company.

Great. Thank you so much.

Our next question comes from the line of Matthew Phipps from William Blair. Your line is open.

Thanks for taking my question. Jen, I’m wondering if you guys think – what could be special about that gastric cancer patient that had such a strong response. They had an MSI high tumor, but obviously didn’t respond to two prior rounds of checkpoint inhibiters. Do you think MSI patients, in general, might be more prone to iNKT selectivity? Do they have more CD1d expression or anything like that?

That’s a great question, and I’m going to turn it over to Marc just after a couple of words. This is – there are a few points that I’d like to have, Marc also expand on that we observed, which included the tumor microenvironment modulation that I’ll have Marc to sort of further expand on. But a very important part of that modulation included increased TCR clonality and diversity. And some of the drivers of that are continuing to be under investigation. But I think what I do see is that MSI-high tumors are quite responsive to PD-1 for a period of time and then no longer. And in this case, we saw absolutely no response on pembro mono not on nivo combo and not until we added the cells. And there are a couple of features that we presented and Marc will go into that may help us better understand the disease modifying benefit in this particular data set. To the extent that it is translatable across MSI tumors, we will explore and are actively doing so. Our clinical trial with Dr Janjigian will allow us to answer this question as well. Marc, I’ll open it to you to say a few words.

Yes. Thanks, Jen. It’s an interesting question. And we’ve been, of course, scrutinizing this deeply. And it’s the case that in tumors that actually have an infiltrate of T cells or that are high in tumor mutational burden. There is a T cell response. But clearly, with this patient having gone through two rounds of PD-1 directed therapy, this isn’t enough to actually either get into the tumors progressively and actually start doing something. And what happened after iNKT infusion is that somehow that got unlocked and these T cells started to do what they were actually generated for is attack the tumor cells. So what we see in preclinical models is that iNKT cells are more resistant to quite a few of the immune suppressive mechanisms that tumors employ to keep T cells down. And what we see in, for instance, our FAP-CAR model, but also in some of our 797 preclinical models is that these tumor suppressive – of these immune suppressive mechanisms actually get neutralized or countered by iNKT cells. If you could think about the local TGF-beta or actually the cells of secrete TGF-beta, CXCL12 that keeps the T cells out all of those actually and specifically the myeloid component, all of those get translated, transformed into pro-inflammatory nonimmune-suppressive environment. And that actually brings the T cells in and also reinvigorate the T cells. We’ve also seen that, for instance, supernatant that we get from activated iNKT cells is able to rescue partially exhausted T cells. So all of those mechanisms, I think, contribute as a whole as a package. It’s not a one-trick pony to activating the T cells that are there in the gastric cancer patient, but obviously, you are not able to do anything. And I think that very well fits what we see in our preclinical models as well and is one of the key features that we think is going to build the platform for iNKT cells in solid tumors.

Great. Thanks, Marc.

Our next question comes from the line of Kalpit Patel from B. Riley Securities. Your line is open.

Good morning. This is Andy on for Kalpit. Thank you for taking our questions. Starting off, what should we anticipate next from agenT-797 in solid tumors? Is there any dose escalation work still remaining?

Andy, thank you. We will continue to interrogate dose frequency and optimization that I should say to you that I feel based on the pharmacology data that we’ve generated and the signals of activity that we’ve identified and the tolerability profile, where we feel very close and confident with our dose, but it will be important just to strengthen in our data package for future regulatory interactions to continue to deepen our scientific exploration of dose and dose frequency. The next phase for us will be multiple doses, and that will be happening near immediately.

Great. And then maybe one additional follow-up. With your upcoming presentation on MiNK-215, is it fair to say that you’re prioritizing this program ahead of 413. And maybe give us a sense of the time lines of when we should anticipate these programs to enter the clinic?

Sure, sure. So I’ll answer the second question, which is on 413. I personally believe and our key opinion leaders have continued to emphasize this point that there is a critical need for an accessible, affordable product that targets BCMA that expands the duration, the durability and really eliminate the continued antigenic profile, the BCMA targeted. What we do see today with autologous products as they work well, high response rates, they are not as durable as they need to be and when patients progress, about 2/3 of them are still revealing the antigen BCMA. So I do think that there’s a major opportunity to advance an allogeneic off-the-shelf armored-BCMA that shows superior qualities as a next-generation therapy for patients. For MiNK to do so, given the competitive landscape, we would be – an intensive effort and one that we are deprioritizing to FAP, which is novel engineered and within our solid tumor strategy. So our BCMA program has continued to advance. We’ve continued to deliver the manufacturability and the scalability, and we’re interrogating it and getting it ready for a Phase 1 clinical trial, and it’s really quite close. Yes, this would be something that we have advanced some discussion to really expand our footprint and leverage additional external non-dilutive capabilities to advance this program in this competitive setting. That for iNKT is really, we think, an outstanding product. Our preclinical data continues to get stronger. The profile of the molecule is very compelling. The need is great, and there are a host of solid tumor self-expressing cancers that actually we believe we can bring benefit to. And for all of those reasons, we’ve accelerated this novel and differentiated product into the forefront of our trial, and we will be filing an IND in 2024. That will bring us into the clinic very, very quickly. We have a very fast path from IND filing to first in human. So those would be tied together really quite quickly towards the middle to second half of 2024.