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spk02: Good morning and welcome to Mink Therapeutics' first quarter 2024 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 disconnect at this time. I would now like to turn the conference over to Zach Arman from Mink's Investor Relations. Zach, please go ahead.
spk06: 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. 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 from this quarter.
spk00: Thank you, Zach. It's a privilege to connect with all of you this morning to discuss our achievements in the first quarter and the milestones that advance our long-term strategic goals. Today, I will highlight our latest clinical advancements, notably in our leading programs, Agent 797 and Mink 215. I will also discuss our strength in financial foundation and outline our plans for sustained innovation and growth. Let's start by our progress in streamlining operations and our financials. This quarter, we focus on advancing our pipeline, improving our operational efficiency, and fortifying our financial health. Since this time last year, we have successfully reduced our operating expenses by over 45% through improved manufacturing efficiency, strategic infrastructure alignment, and most critically, the external non-dilutive financing to support our ongoing phase two trial and second line gastric cancer. This financial prudence has enabled us to allocate resources more effectively towards accelerating our key clinical programs. Importantly, yesterday we announced an investment of $5.8 million at a 25% premium from a new investor committed to our vision. This funding will be dedicated to support the rapid advancement of MINK215, our innovative CAR-INKT cell therapy targeting fibroblast activation proteins. or FAP in solid tumors. MINK215 is our lead program from our discovery pipeline that we are particularly excited about. And this investment underscores the unique potential of the program. We've previously presented data at the American Society of Cell and Gene Therapy showing exciting preclinical activity of MINK215 and FAP expressing non-small cell lung cancer tumors. More recently, as a matter of fact, just this past month at the American Association of Cancer Research, or AACR, annual meeting, our scientists presented compelling data demonstrating 215's ability to eradicate tumors in human organoid models of colorectal cancer with liver mets. These recent advancements build on our prior findings and position 215 as an important component in addressing the urgent need for effective treatments in colorectal cancer. This is now the leading cause of death in men under 50 and the second in women in that same age category. Our findings show that administration of MINK215 not only improves immune-mediated tumor destruction, but also targets and depletes immune-suppressive FAP-expressing stellate cells, thereby enabling increased immune infiltration or CD8 T-cell infiltration into the tumor. More simply, this mechanism enhances the body's ability to mount a robust T-cell response against liver mets, which can be further amplified by the combination with immune checkpoint inhibitors. While Mark is going to go through this in more detail, our scientists demonstrated this benefit with a combination of MINK215 and a Genesis late-stage antibody, botanfilumab, a multifunctional T-cell activator. and Balsilumab, a PD-1 antagonist, which are advancing in late-stage clinical trials. These were the data that were presented at AACR, and Mark will highlight these in just a few moments. Now, I will turn to our lead program, 797, and as a reminder, this is our allogeneic, unmodified IMKT cell therapy advancing in Phase II clinical trials. In February, we achieved a significant milestone for this program with the launch of the Phase II investigator-sponsored study, an externally funded program in second-line gastric cancer. This pivotal trial is evaluating a combination of 797 with botanosilumab and valosilumab. And this combination is on top of standard of care chemotherapy. The study is led by Dr. Yelena Genjigian. She's the chief of gastrointestinal oncology at Memorial Sloan Kettering Cancer Center. And the program is supported and funded by Stand Up to Cancer, an organization dedicated to funding and developing the most innovative and promising cancer research. Enrollment in the trial is actively underway. We eagerly anticipate initial data from the trial, which we expect later this year. Beyond cancer, we've also continued to advance 797 and pulmonary diseases, specifically in severe respiratory distress. This is a condition affecting over 600,000 individuals annually in the US alone. Most recently, the full data set from our Phase 1 clinical trial was published in Nature's Communications just a couple of months ago. These data highlighted the clinical activity and important role that INKT cells play in this disease. There are currently no effective or active or approved therapies for patients with severe respiratory distress. We are excited to share additional updates from 797 at the upcoming American Thoracic Society 2024 Annual Meeting, or the APS meeting in San Diego, California on May 21st. Dr. Therese Hammond, a critical care and pulmonology expert, will present the data from the continued dosing of patients with severe respiratory distress through our compassionate and expanded access mechanisms. Her latest case is a patient following renal transplant who was diagnosed with severe acute respiratory distress and treated with 797 under emergency use. While the data have not yet been disclosed and will be disclosed at the conference, this presentation further supports our previously published data and underscores a significant unmet need and severe respiratory distress. We're excited about the potential of INKT cells to make a meaningful difference in the lives of these patients, and we expect further updates on this program in the months ahead. Overall, the progress we've made this quarter positioned us to accelerate the development of our INKP cell platform and programs, and these include programs that are actively advancing in the clinic as well as our lead discovery programs. We'll also expand and continue our in-house manufacturing of INKP cells, setting the stage for an exciting year in 2024 with 797 and pulmonary respiratory distress, and the advancement of our Phase II trial in gastric cancer. We continue to be unwavering in our commitment to improving patient outcomes, and we deeply appreciate your continued support. I'm now going to turn the call over to Dr. Mark Van Dyke to provide deeper insights into the MINK 215 program. Mark?
spk01: Thank you, Jen. Good morning, everyone. I'm Mark Van Dyke, and I will provide some further insight into the unique properties and promising potential of INKT cell-based cancer therapies, which are uniquely designed to maximize efficacy of 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 cell therapy, agent 797, rapidly translocates from the bloodstream to essential tissues such as the liver and the lungs. Importantly, these cells remain active and detectable for up to six 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 MIG215, the subject of our news this week, and differentiate it. First class armored CAR-IKT 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 NYNC215 showed robust efficacy in small cell lung cancer models, resulting in substantial tumor elimination in the lung and improved survival compared to T cells 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 RNK T cells. We further reported that NYNC215 specifically targeted and eliminated fat-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 a recent AACR meeting, as Jan already alluded to, in April of this year, where we showcased NINC215's effectiveness in an advanced preclinical organoid model for colorectal cancer liver metastases. Liver metastases are notorious for limiting the success of traditional immunotherapies in patients with microsatellite-stable colorectal cancer. These tumor metastases typically create an immune-excluded environment characterized by a lack of T-cells and an abundance of immune-suppressive cells, which conventional treatments struggle to overcome. MING-205, an IL-15-armored CAR-IKT cell therapy targeting FAB, 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 NINX15 can trigger significant tumor reduction and even eradication in this treatment-resistant model of liver metastases. And as Jen already alluded, it showed that it can deplete have sort of fat-expressing phthalate cells, which is a key immunosuppressive component of these liver metastases. And this provides 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 IND5 into early 2025 and aim to produce clinical-grade material as early as this year. This underscores our commitment to not just involvement in science, 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?
spk03: A cash balance of $5.8 million. This is prior to the receipt of the funds Jen mentioned earlier. Cash used in operations for the three months ended March 31, 2024, is $2.5 million compared to $4.5 for the same period in 2023. Net loss for the first quarter of 2024 was $3.8 million, or 11 cents per share, compared to a net loss of $5.7 million, or 17 cents per share, for the first quarter of 2023. I will now turn the call back over to the operator for questions.
spk02: Thank you. We'll now begin the question and answer session. If you have dialed in and would like to ask a question, please press star 1 on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star 1 again. If you are called upon to ask your question and are listening via loudspeaker on your device, please pick up your handset and ensure that your phone is not on mute when asking your question. Again, press star 1 to join the queue. And your first question comes from the line of Emily Bodner with HC Wainwright. Please go ahead.
spk04: Hi, good morning. Thanks for taking the questions. A few for me, I guess. So first one, if you can maybe comment on how the enrollment in the phase two gastric study 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? Thank you.
spk00: Emily, thank you very much for your question. We'll start with your first question, which is about enrollment into the phase two 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 CELS plus Botval, the CELS plus Botval and RAM-TAC, standard of care and second line gastric cancer. We have been able to dose, we have not specified 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 BOTVAL INKTs 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 two and the number of patients. While we haven't been discreet 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 botansilumab and valstilumab. So that's the multifunctional immune activator that also binds to CTLA-4 from a genus. Valstilumab is a genus of PD-1. And then, of course, standard of care REM tax 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 on a number of trials sponsor-driven trials, phase one trial in ARDS, also our phase one 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 two trial in gastric cancer is funded through Stand Up to Cancer's Torrey Coast Foundation, which is essentially the designated foundation that is focused on accelerating effective therapies for patients with gastric cancer. Dr. Yelena Jantjigian, the chief at 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 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 ARDS. a randomized phase two trial, which we will be conducting with non-dilutive 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 two gastric cancer study ascertaining the data this year and developing a pathway to advance that program as quickly as possible. We also, in parallel, will be expanding our signal in acute respiratory distress 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 extubation, 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, Mark Van Dyke 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 FAPCAR 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.
spk04: Yes, very helpful. Thank you.
spk02: Your next question comes from the line of Jack Allen with Baird. Please go ahead.
spk07: Great. Thank you so much. I guess the first question I had was on the 215 program. As you look to advance that asset into the clinic, what sorts of solid tumors do you expect to study that in? How do you think about the clinical development there? Then I have a few follow-ups on both the ARDS program and then also a question about where things sit in graft-versus-host disease as well.
spk00: Excellent. Well, Jack, we'll 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. 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 in FAP expressing colorectal cancers. This is an area of high unmet need. We know that the disease is really growing in prevalence and incidence in a younger population, and there's an urgent need to move therapies 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.
spk07: Got it. Got it. That's great color. And then as it relates to ARDS, where do things sit as it relates to, you know, securing that external funding? What are the, you know, potential aspects that need to be buttoned up 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.
spk00: Absolutely. So on the external funding, we have the platform trial identified in the team and that essentially is responsible for the operational execution of that platform trial, 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.
spk07: Got it. That makes a lot of sense. Congratulations again on the progress, and thanks for taking the question.
spk00: Thanks so much, Jack.
spk02: Your next question comes from the line of Matt Pipps with William Blair. Please go ahead.
spk08: You know, on the FAPCAR, I know in a lot of the preclinical work you've all done, you've combined it with other therapies, including other kind of like TCR-directed T-cells. And just curious how you think of a mild therapy activity of this or if it has to be combined. Really, if the IL-15 addition is something that can, you know, drive enough activity or, again, really should think about this being combined with other things.
spk00: 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 a really important milestone 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 Chan. He's the head of discovery at Agenis, one of the inventors on botancilumab, and leading up our discovery and combination efforts at Agenis. Dr. Nils Rubquist, with who you may not have met before. Nils is an accomplished scientist. 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 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, UK 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 would 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 may want to expand efficacy with combinations. And I'll turn it over to Dan to give you some deeper insights, and he could work with Eleni and Nils and give you some more, a deeper response to your question.
spk05: Thank you for the question. So to the first part, we do expect monotherapy activity with MINK215, and for several reasons based on the preclinical data. First, in preclinical models, we observe direct tumor killing of FAP-expressing cells, including FAP-expressing cancerous cell fibroblasts and tumor cells. In turn, we've observed that post, there was a massive infiltration of T cells within the tumor 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 remodel the 2-microenvironment to enhance T cell responsiveness, we expect this to be an ideal combination partner with Bot-Bal, particularly in areas where we have seen non-responsiveness to PD-1 CTLA-4. Data which includes both the liver metastases model as well as pancreatic models, in situations where the tumors are refractory to both bowels, adding INKTs, including MING215, can open up a response to checkpoint therapy and indeed promote monotherapy activity as well.
spk00: Thank you, Dan. Matt, did you have any other questions?
spk08: No, that's it for me. Thank you.
spk00: Thank you.
spk02: Okay. And with that, That concludes our Q&A session. I will now turn the conference back over to Jennifer Buol for closing remarks.
spk00: 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. I appreciate your time today.
spk02: Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.
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