INKT - NASDAQ

Good morning, and welcome to MiNK Therapeutics First Quarter 2024 Conference Call and Webcast. [Operator Instructions] Please note, this event is being recorded. [Operator Instructions] I would now like to turn the conference 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 include forward-looking statements, including statements regarding our clinical development, regulatory and commercial plans and timelines, as well as timelines for data release and partnership opportunities, among other updates. These statements are subject to risks and uncertainties, and we refer you to our SEC filings, available on our website for more details on these risks. Joining me today are Dr. Jennifer Buell, President and Chief Executive Officer; Dr. Marc 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 from this quarter.

Thank you,

Thank you, Jen. Good morning, everyone. I'm Marc van Dijk, and I will provide some further insight into the unique properties and promising potential of our iNKT cell-based cancer therapies, which are uniquely designed to maximize efficacy on solid tumors to two key differentiators -- actually three: targeted tissue homing, relief of immune suppression, and the avoidance of lymphodepletion, and the latter is very, very important for the overall outcome of cancer treatment in our opinion. Our clinical data covering 80 patients across cancer and severe pulmonary disease, indicates that our lead iNKT T cell therapy, agenT-797, rapidly translocate from the bloodstream to essential tissues such as the liver and the lungs. Importantly, these cells remain active and detectable for up to 6 months, post infusion. This prolonged presence is elemental as it significantly amplifies the body's own immune response, enhancing the potential for durable therapeutic effects in cancer and other immune-related diseases. Turning to our latest advancements, I'd like to focus on MiNK-215, the subject of our news this week and differentiated first-class armored CAR-iNKT therapy, targeting fibroblast activating protein, or FAP for short. This therapy is specifically engineered to counteract the challenging immunosuppressive environment found in epithelial origin tumors, including colorectal and non-small cell lung cancer. In preclinical models, we've previously reported that MiNK-215 showed robust efficacy in small cell lung cancer models, resulting in substantial tumor elimination in the lung and improved survival compared to T cell alone. These findings were commensurate with restoring the killing capacity of partially exhausted T cells and increasing T cell infiltration, which is consistent with the natural properties of native iNKT cells. We further reported that MiNK-215 specifically targeted and eliminated type expressing cancer-associated fibroblasts, thereby disrupting the tumor promoting stromal network, and reducing immune suppression in the local tumor microenvironment. We've recently expanded upon this data at recent AACR Meeting, as Jen already alluded to, in April of this year, where we showcased MiNK-215's effectiveness in an advanced preclinical organoid model for colorectal cancer and liver metastases. Liver metastases are notorious for limiting the success of traditional immunotherapies in patients with microsatellite stable colorectal cancer. These tumor metastases typically creates an immune excluded environment, characterized by a lack of T cells and an abundance of immunosuppressive cells, which conventional treatments struggle to overcome. MiNK-215, an IL-15 armored CAR-iNKT cell therapy targeted FAP, is designed to overcome these challenges. It not only remolds the tumor stroma to facilitate deeper T cell infiltration, but also enhances the immune system's ability overall, to fight cancer more effectively. Our preclinical results have shown that MiNK-215 can trigger significant tumor reduction, and even a relocation in this treatment-resistant model of liver metastases. And as Jen already alluded, it showed that it can deplete sort of FAP expressing stellate cells, which is a key immunosuppressive component of these liver metastases. And this provides a new hope for patients who clearly have very limited options. Our team is committed to advancing this innovative therapy to the clinical stage. And with the recently announced financial backing and the relentless efforts of our research and development teams, we're on track to accelerate IND filing to early 2025 and aim to produce clinical-grade material as early as this year. This underscores our commitment to not just advance in size, but also to bring potentially life-saving treatments to patients as quickly as possible. I will now turn the call over to Christine to go over our financials. Christine?

Cash balance of $5.8 million. This is prior to the receipt of the funds Jen mentioned earlier. Cash used in operations for the 3 months ended March 31, 2024 was $2.5 million, compared to $4.4 million for the same period in 2023. Net loss for the first quarter of 2024 was $3.8 million or $0.11 per share, compared to a net loss of $5.7 million or $0.17 per share for the first quarter of 2023. I will now turn the call back over to the operator for questions.

[Operator Instructions] And your first question comes from the line of Emily Bodnar with H.C. Wainwright.

A few for me, I guess. So first one, if you can maybe comment on how the enrollment in the Phase II [Gastric cancer trial] has been going so far since you enrolled the first patient in February. And then could you maybe clarify how many patients are expected to be treated with each of the three treatment arms in that study? And then last question is a bit of a financial question. But given your operating expenses have decreased quite a bit this quarter, could you maybe just comment on what your current priorities are pipeline-wise and which indications you're kind of focusing on, and which ones are kind of taking more of a back burner at the moment?

Emily, thank you very much for your question. We'll start with your first question, which is about enrollment into the Phase II gastric cancer trial. So maybe just as a reminder, this trial did not require us to do -- to wait to do essentially a 28-day wait between patients. So we were able to enroll patients very quickly, into the trial and continue to do so. And that allows us to get exposure to patients that will get the cells alone, the cells plus [indiscernible] -- the cells plus [indiscernible] and [ RamTex ] standard of care in second line gastric cancer. We have been able to dose -- we have not specified on publicly yet the number of patients in each cohort. But suffice it to say, we will have a requisite number of patients that will not only allow us to demonstrate safety of each of these products alone and in combination, but also activity so that we could decouple where we see the most pronounced benefit for patients. And essentially, in about a 40-patient study, we will be able to tease out contribution of components to some extent as we start to expand the cohorts and deepen signals in the areas that we see the most profound benefit. We do believe that mechanistically that the combination of [indiscernible] with standard of care, may not only be quite beneficial to patients, but also quite tolerable. And we've been able to demonstrate that so far in the first patients who have been enrolled. We do have patients that have been exposed to all five agents and those patients are tolerating the combinations quite well, and we're pretty excited to share an update on those, which we expect will be the second half of this year. Given the pace of enrollment in the first quarter of this year, we started enrolling in February, we've been able to bring in patients, as I mentioned, really quite quickly. So we'll have some mature data to present at a late year conference, I'll say, second half of this year. And additional information will be elucidated during those presentations. So I think that addressed your enrollment in the Phase II, and the number of patients, while we haven't been discrete about the total number of patients in each one of the arms, we will have exposure of a proportion of patients on each of the arms, with the largest proportion of patients on the multi-combo, which is iNKT cells, agent-797 plus botensilimab and balstilimab. So that's the multifunctional immune activator, that also binds to CTLA-4 from Agenus. Balstilimab is Agenus' PD-1, and then, of course, standard of care RamTex in this patient population. Financially, I'm going to conclude your questions with your financial question, which would be allocation of funds. So our operational efficiency really was in large part -- so the reduction that we saw this year, in particular, at least in the first quarter, is largely driven by the external funding of the Phase II gastric cancer trial. So MiNK had been executing a number of trials -- sponsor-driven trials, Phase I trial in ARDS, also our Phase I trial in solid-tumor cancers, and we had also agenT-797 in the multiple myeloma study. What we have been able to now continue to pursue is expand on the cohorts that we're really most excited about. The Phase III trial in gastric cancer is funded through Stand Up to Cancer's Tory Coast Foundation, which is essentially the designated foundation that is focused on accelerating effective therapies for patients with gastric cancer. Dr. Yelena Janjigian, the Chief of Memorial Sloan Kettering, is the leader of that Dream Team, it's called, and this is the trial where she's been focusing her efforts to expand, treat therapeutic options for patients with second-line gastric cancer. That has resulted in the most significant reduction in our operating expenses to expand that trial and to have it off the cost offset, through non-dilutive external parties. Additionally, our ARDS programs are an area of great interest to us, as I mentioned earlier. And we have not only concluded and published our Phase I study, we're continuing to treat patients under a compassionate access, while we are preparing to launch a randomized Phase II trial, which we will be conducting with nondilutive financing support, as well as some support from our own team. So it will be a joint program largely externally financed, and it will be conducted through a large platform trial. And that will allow us to also continue to control our operating expenses. So our focus will be on really delivering the Phase II gastric cancer study, ascertaining the data this year, and developing a pathway to advance that program as quickly as possible. We also, in parallel, we'll be expanding our signal in acute respiratory distressed severe, and a large randomized clinical trial that will be largely externally financed, high priority for the company. The signals that we observed that we published in Nature Communications showed the true pronounced benefit that we believe these cells can bring to patients that showed rapid [indiscernible], clearance of virus, prevention of secondary infections, and we saw survival rates that exceeded 75% in a population of patients that historically saw a mortality rate that exceeded about 65%. So this is a dramatic improvement over what's been available to patients, which is currently corticosteroids. And that's where we're focusing our effort at this point in the clinic. Additionally, as I mentioned earlier, our discovery programs and our pipeline continue to mature. And during our last call, which was our 2023 Annual Summary, Marc van Dijk presented how we're advancing our TCR portfolio through a partnership with ImmunoScape. We will be, as I just announced today and yesterday morning, we'll be advancing our MINK-215 program through our new investment, which will allow us to accelerate the development of this very promising armored FAP CAR-iNKT, and we're looking to generate clinical grade material, as early as this year and get it into the clinic as quickly as possible with an imperative to try to do so by early 2025. I hope that answers your question.

Your next question comes from the line of Jack Allen with Baird.

I guess the first question I had was on the 215 program. As you just look to advance that asset into the clinic, what sort of solid tumors do you expect to study that? And how do you think about the clinical development there? And then I have a few follow-ups on both the ARDS program and then also a question about where you think you sit in graft versus host disease as well?

Excellent. Well, Jack, let's start with the first, which is 215. Now, as we approach the clinic, we've been able to interrogate a lot of preclinical functionality of the molecule and determine where we believe this could be best fit and most impactful in the clinic. Obviously, FAP expressing tumors would be our area of great interest. We will explore the asset more broadly, but with an emphasis and FAP expressing colorectal cancers. This is an area of high unmet need. We know that the disease is really growing in prevalence and incidents in a younger population, and there's an urgent need to move therapy forward as quickly as possible. And the preclinical data we presented at AACR, really demonstrates the potential of this molecule in FAP expressing colorectal cancer. Similarly, we shared some very exciting data in a FAP expressing non-small cell lung cancer, preclinical models. Those are some very obvious unmet areas of need where we believe there's not only a development opportunity, but we have a molecule that can actually biologically address the gap that we're currently observing in patients with FAP expressing tumors in lung as well as in colorectal. So that's where we're starting. Of course, we will interrogate the molecule and a couple of other disease indications, expressing FAP sarcoma represents another one. But this is an opportunity for us to pursue and even optimize and accelerate development by the identification of patients with FAP expressing tumors with a large emphasis in non-small cell lung cancer and colorectal cancer.

Got it. That's great color. And then as it relates to ARDS, where do you think it fits as it relates to securing that external funding, what are the potential aspects that need to be buttoned out there before you have that funding? And then on graft versus host disease, I believe there was also a previous discussion of an external program there. I'd love to hear any updates, as it relates to that getting off the ground as well.

Absolutely. So on the external funding, we have the platform trial identified and the team that essentially is responsible for the operational execution of that platform trial is -- and has already designed the protocol and started activating centers. We have agreed to the terms of the contract, and we're just making some final modifications with respect to the budget allocation over time, which we expect we should wrap up sometime, even as early as by the end of this week. That's our goal to do so, and then we would be announcing it shortly thereafter. On graft versus host disease, we are pursuing an investigator-sponsored trial. This is an area, of course, of unmet need. And Jack, you did a brilliant job in summarizing not only the potential of the cells in this indication, we've also deepened our own scientific insights into how these molecules and these cells may actually have a profound effect, in not only mitigating but then preventing graft versus host disease in patients who are undergoing hematopoietic stem cell transplantation. We have not yet announced the launch of that program. So we have designed the program, but we have not yet accumulated the financing that would be necessary to launch it. So during this time, we are being really quite prudent about our focused efforts in the clinical programs that we're advancing. But we will continue to find ways to get graft versus host advancing. And this is a priority for us to be able to do so, but it's not an area that, at this very moment, we can allocate capital to doing at this time.

Got it. That makes a lot of sense. Congratulations again on the progress.

Your next question comes from the line of Matt Phipps with William Blair.

On the FAP CAR, I know in a lot of the preclinical work you have done, you've combined it with other therapies, including other kind of a TCR directed T cells. And just curious how you think of a monotherapy activity of this or if it isn't and has to be combined, whether the IL-15 addition is something that can drive enough activity or again, really should think about this being combined with other things.

Matt, this is an excellent question. And we have invited a couple of special guests onto the call today, who are leading up this effort that includes the interrogation of 215 as a monotherapy and the kind of efficacy that we're observing with the molecule in that capacity, which would be really important milestones for us, to demonstrate monotherapy activity. And in the case that we may need to expand that and address other tumor escape mechanisms, we are in parallel exploring where those optimal combinations may take. So there are three people on the line, and you'll be familiar with them. And this is Dr. Dan Chen. He's the Head of Discovery at Agenus, one of the inventors on botensilimab and leading up our discovery in combination efforts at Agenus. Dr. Nils Rudqvist, who you may not have met before. Nils is an accomplished scientist who joined us from MD Anderson Cancer Center. He was associate professor there. And prior to that, he was at Weill Cornell working in the Radiation and Oncology Department. And his emphasis is really on optimizing immune biology and determinants of how to modulate the tumor microenvironment and enhance efficacy. Eleni is also our Head of Discovery in our Cambridge U.K. site for MiNK Therapeutics. And this team together has been working to address exactly this question. I'm going to turn it to Dan just to lead in and give you a quick review of how we're thinking about this. And from my perspective, our goal will be to launch, interrogate monotherapy activity, particularly in FAP expressing tumors, which would give us the most rapid development path forward, and identify areas, where we want to expand efficacy with combinations. And I'll turn it over to Dan to give you some deeper insight and he could work with Eleni and Nils and give you a deeper response to your question.

Thank you for the question. So to the first part, we do expect monotherapy activity with MiNK-215 and for several reasons based on the preclinical data. First, in preclinical models, we observed direct tumor killing of FAP expressing cells, including FAP expressing cancer [indiscernible] fibroblast and tumor cells. In turn, we've observed that post -- there was a massive infiltration of T cells within the two microenvironment, which is particularly evident in cold tumors, like liver metastases or other tumor models that we've tested. So we do expect monotherapy activity, given the ability to promote T cell infiltration and we've modeled the two macro environment to enhance T-cell responsiveness, we expect this to be an ideal combination partner with [indiscernible], particularly in areas where we have seen nonresponsiveness to PD-1, CTLA-4, which includes both the liver metastases model as well as pancreatic models, in situations where the tumors are refractory to [indiscernible], adding iNKTs, including MiNK-215, can open up a response to checkpoint therapy and indeed promote monotherapy activity as well.

Thank you, Dan. Matt, did you have any other questions?

No, that's it for me. Thank you.

Okay. And with that, that concludes our Q&A session. I will now turn the conference back over to Jennifer Buell for closing remarks.

Thank you very much, and thank you all for joining us today. We look forward to continuing to keep you updated on our progress and advancements with a real focus on advancing our clinical stage programs, continuing to strengthen our financial foundation, and deliver innovative medicines to patients with cancer and other immune-mediated diseases. And I appreciate your time today.