MiNK Therapeutics, Inc. Q1 FY2024 Earnings Call

Good morning, and welcome to MiNK Therapeutics First Quarter 2024 Conference Call and Webcast. Please note, this event is being recorded. I would now like to turn the conference over to Zack Armen from MiNK's Investor Relations. Zack, please go ahead.

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, Zack. 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 and financial foundation and outline our plans for sustained innovation and growth. Let's start with our progress in streamlining operations and our financials. This quarter, we focused 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 II trial in 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 MiNK-215, our innovative CAR-iNKT cell therapy, targeting fibroblast activation protein, or FAP, in solid tumors. MiNK-215 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 previously presented data at the American Society of Cell and Gene Therapy showing exciting preclinical activity of MiNK-215 in FAP expressing non-small cell lung cancer tumors. More recently, just this past month at the American Association of Cancer Research, or AACR, Annual Meeting, our scientists presented compelling data demonstrating MiNK-215's ability to eradicate tumors in human organoid models of colorectal cancer with liver metastases. These recent advancements build on our prior findings and position MiNK-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 MiNK-215 not only improves immune-mediated tumor destruction, but also targets and depletes immune-suppressive FAP-expressing stellate cells, thereby enabling increased immuno-filtration 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 metastases, which can be further amplified by the combination with immune checkpoint inhibitors. While Marc will go through this in more detail, our scientists demonstrated this benefit with the combination of MiNK-215 in a late-stage antibodies, botensilimab, a multifunctional T-cell activator, and balstilimab, a PD-1 antagonist, which are advancing in late-stage clinical trials. These were the data that were presented at AACR, and Marc will highlight these in just a few moments. Now I will turn to our lead program, 797. As a reminder, this is our allogeneic unmodified iNKT 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 the combination of 797 with botensilimab and balstilimab, and this combination is on top of standard of care chemotherapy. The study is led by Dr. Yelena Janjigian, 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 in pulmonary diseases, specifically in severe respiratory distress, a condition affecting over 600,000 individuals annually in the U.S. alone. Most recently, the full data set from our Phase I clinical trial was published in Nature Communications just a couple of months ago. These data highlighted the clinical activity and the important role that iNKT cells play in this disease. There are currently no effective 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 in San Diego, California, on May 21. Dr. Trace Hammon, 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 is 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 in 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 positions us to accelerate the development of our iNKT cell platform and programs. 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 iNKT cells, setting the stage for an exciting year in 2024 with 797 in 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. Marc van Dijk to provide deeper insight into the MiNK-215 program. Marc?

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 designed to maximize efficacy on solid tumors through three key differentiators: targeted tissue homing, relief of immune suppression, and the avoidance of lymphodepletion, which we believe is crucial for the overall outcome of cancer treatment. Our clinical data covering 80 patients across cancer and severe pulmonary disease indicates that our lead iNKT T 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 critical as it significantly enhances the body's own immune response, improving 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 a differentiated armored CAR-iNKT therapy targeting fibroblast activating protein, or FAP for short. This therapy is specifically engineered to address the challenging immunosuppressive environment found in epithelial origin tumors, including colorectal and non-small cell lung cancer. In preclinical models, we 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 cells alone. These findings were consistent with restoring the killing capacity of partially exhausted T cells and increasing T cell infiltration, which aligns with the natural properties of native iNKT cells. We also reported that MiNK-215 specifically targeted and eliminated FAP-expressing cancer-associated fibroblasts, disrupting the tumor-promoting stromal network and reducing immune suppression in the local tumor microenvironment. We recently expanded upon this data at the AACR Meeting 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 create 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, as an IL-15 armored CAR-iNKT cell therapy targeting FAP, is designed to tackle these challenges. It not only remodels the tumor stroma to enable deeper T cell infiltration but also enhances the immune system's overall capability to fight cancer more effectively. Our preclinical results have shown that MiNK-215 can trigger significant tumor reduction and even relocation in this treatment-resistant model of liver metastases. Additionally, it can deplete FAP-expressing stellate cells, which are a key immunosuppressive component of these liver metastases, providing new hope for patients who have very limited options. Our team is committed to advancing this innovative therapy to the clinical stage. 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 highlights our commitment to not just grow in size, but also to bring potentially life-saving treatments to patients as quickly as possible.

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, 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.

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?

Thank you for your question, Emily. To address your first inquiry regarding enrollment in the Phase II gastric cancer trial, it's important to note that this trial did not require us to implement a 28-day wait between patients, enabling us to enroll them rapidly. This approach helps us gather insights from patients receiving the cells on their own, in combination with other agents, and alongside standard care for second-line gastric cancer. While we have not disclosed the exact number of patients in each group, we anticipate having a sufficient number to evaluate the safety of these products both individually and in combination, as well as their effectiveness, allowing us to identify the most significant benefits for patients. In this approximately 40-patient study, we can analyze the contributions of various components as we expand the groups and refine our understanding of the most pronounced benefits. We believe that combining our treatments with standard care can be very beneficial and well-tolerated, which has been evidenced by the initial patients enrolled. Some patients have received all five agents, and their tolerance of these combinations has been promising, prompting us to look forward to sharing updates in the latter half of this year. Since starting enrollment in February, we've been able to bring in patients efficiently, which should allow us to present some mature data at an upcoming late-year conference. Additional insights will be shared during those presentations. This addresses your question about Phase II enrollment. Although we haven't specified the total number of patients in each arm, we will have a proportionate number of patients across each arm, with the greatest concentration in the multi-combination arm that includes iNKT cells, agent-797, botensilimab, and balstilimab. Regarding your financial question about fund allocation, our operational efficiency has mainly stemmed from external funding for the Phase II gastric cancer trial. MiNK has been conducting several sponsor-driven trials, including Phase I studies in ARDS, solid tumors, and the agenT-797 study in multiple myeloma. We're focusing on expanding the cohorts that interest us the most. The Phase III trial in gastric cancer is funded through Stand Up to Cancer's Tory Coast Foundation, which is dedicated to accelerating effective therapies for gastric cancer patients, led by Dr. Yelena Janjigian from Memorial Sloan Kettering. This collaboration has significantly reduced our operating expenses, allowing the trial to be funded through non-dilutive external sources. Additionally, our ARDS programs are of great interest, and having completed and published our Phase I study, we are continuing to treat patients through compassionate access while preparing for a randomized Phase II trial, which will have non-dilutive financing support along with contributions from our team. This will be a collaborative program primarily financed externally, helping us manage our operating costs. Our priority remains on delivering the Phase II gastric cancer study and confirming the data this year, while also working to advance the program as swiftly as possible. Concurrently, we are expanding our efforts in acute respiratory distress syndrome, with a large randomized clinical trial funded largely externally being a top priority. The encouraging signals published in Nature Communications showed a significant benefit, with our cells potentially enabling rapid viral clearance and reducing secondary infections, resulting in survival rates exceeding 75% in a population that historically faced a 65% mortality rate. This marks a substantial improvement over existing treatment options like corticosteroids. This is where we are concentrating our clinical efforts. Furthermore, our discovery programs and pipeline are continuing to grow. In our last call, our 2023 Annual Summary, Marc van Dijk discussed how we're advancing our TCR portfolio through a partnership with ImmunoScape. We plan to move forward with our MiNK-215 program using a new investment to speed up the development of the promising armored FAP CAR-iNKT. Our goal is to produce clinical-grade material as soon as this year and to get it into clinical trials as quickly as possible, ideally by early 2025. I hope this clarifies your questions.

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 the 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 on FAP expressing colorectal cancers. This is an area of high unmet need. We know that the disease is growing in prevalence among a younger population, and there's an urgent need to move therapy forward as quickly as possible. 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.

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 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 are making final modifications regarding the budget allocation over time. We expect to wrap that up sometime, even as early as the end of this week, with an announcement shortly thereafter. On graft versus host disease, we are pursuing an investigator-sponsored trial. This area represents unmet need, and Jack, you did a brilliant job summarizing the potential of the cells in this indication. We've also deepened our scientific insights into how these molecules and cells may have a profound effect in not only mitigating but preventing graft versus host disease in patients undergoing hematopoietic stem cell transplantation. We have not yet announced the launch of that program. So we have designed the program but have not yet secured the financing necessary to launch it. During this time, we are being quite prudent about our focused efforts in the clinical programs that we're advancing. We will continue to find ways to advance graft versus host disease, and this is a priority for us to do so, but at this very moment, we cannot allocate capital for it.

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 TCR directed T cells. And just curious how you think of the 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, whether we should really think about this being combined with other therapies.

Matt, this is an excellent question. We've invited a couple of special guests onto the call today, who are leading up this effort that includes the interrogation of MiNK-215 as a monotherapy and the kind of efficacy we're observing with the molecule in that capacity, which would be a critical milestone for us to demonstrate monotherapy activity. If we need to expand that and confront other tumor escape mechanisms, we're exploring where those optimal combinations may lie. We have Dr. Dan Chen, the Head of Discovery at Agenus, one of the inventors of botensilimab. Dr. Nils Rudqvist, who joined us from MD Anderson Cancer Center, and Eleni, our Head of Discovery at our Cambridge U.K. site for MiNK Therapeutics. This team has been working to address exactly your question. I'm going to turn it to Dan to give you a quick review of how we're thinking about this. Our goal will be to launch and interrogate monotherapy activity, particularly in FAP expressing tumors, which would give us the quickest development path forward, and identify areas where we want to expand efficacy with combinations. I'll turn it over to Dan for deeper insight.

Thank you for the question. To the first part, we do expect monotherapy activity with MiNK-215, and there are several reasons based on the preclinical data. First, in preclinical models, we observed direct tumor killing of FAP expressing cells, including FAP expressing cancer-associated fibroblasts and tumor cells. In turn, we've observed a significant infiltration of T cells within the tumor microenvironment, particularly evident in cold tumors like liver metastases or other tumor models we've tested. We do expect monotherapy activity, given the ability to promote T cell infiltration, and we've modeled the tumor microenvironment to enhance T-cell responsiveness. We expect this to be an ideal combination partner with checkpoint inhibitors, particularly in areas where we've seen non-responsiveness to PD-1 and CTLA-4, which includes both the liver metastases model and pancreatic models. In situations where the tumors are refractory to checkpoint therapy, adding iNKTs, including MiNK-215, can open up a response and 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 delivering innovative medicines to patients with cancer and other immune-mediated diseases. I appreciate your time today.

Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.