MiNK Therapeutics, Inc. Q2 FY2024 Earnings Call

Good morning and welcome to the MiNK Therapeutics Second Quarter 2024 Conference Call and Webcast. All participants will be in listen-only mode until the question-and-answer session. Please note this event is being recorded. If anyone has any objections, you may disconnect now. I would now like to turn the call over to Zack Armen from Investor Relations.

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 our discussion includes 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. Jen Buell, President and Chief Executive Officer; Dr. Marc Van Dijk, Chief Scientific Officer; Dr. Joy Zhou, Head of CMC, and Christine Klaskin, Principal Financial and Accounting Officer. Now I'd like to turn the call over to Dr. Buell to highlight our progress this quarter.

Thank you, Zach. Good morning, and thanks for joining us today. I'm excited to share the strides we've made in the first half of 2024 as we continue to align our achievements with our long-term strategic goals. For those of you new to the story at MiNK, our mission is focused on delivering the immune potential of invariant natural killer T cells to tackle diseases of the immune system and cancer. Today I'll be highlighting our latest clinical developments, particularly in our lead programs, AgenT-797. These are native, unmodified iNKT cells, and MiNK-215, our armored FAP CAR-iNKT. Additionally, I'll discuss how we've fortified our financial foundation, setting the stage for sustained innovation and growth. We've made substantial progress in streamlining our operations to optimize our financials in this market. In this quarter, we continue to generate critical data from our ongoing clinical programs. We continue to advance our R&D efforts and ensure efficient in-house manufacturing, all the while appreciating further reductions to our operating burn. Now reduced more than 50% from this time last year, mainly from the internalization of key activities. These reductions have been a result of the internalization of our efforts and continued external financial support to advance our exciting programs. I'll walk you through these developments and illustrate how we're taking the way remains success. We'll begin with our operational and financial progress. Our lead program, 797, is an allogeneic unmodified iNKT cell therapy currently advancing in a Phase II trial for second-line gastric cancer and acute respiratory distress syndrome, or ARDS. On gastric cancer, second-line gastric cancer is a challenging condition with a poor prognosis and a high mortality rate. Patients undergoing second-line therapy for advanced gastric or gastroesophageal junction cancer typically have a median overall survival of only four to ten months, depending on factors such as performance status and treatment regimen. In parallel, 797 is also being evaluated for ARDS. This is a rapidly progressive and life-threatening condition with a mortality rate of approximately 40%. Our commitment to addressing these critical unmet medical needs underscores the potential of 797 to provide meaningful therapeutic benefit in both oncology and respiratory care. Let me begin with our program in ARDS. This is a rapidly progressive form of respiratory failure with alarmingly high mortality rates. The prevalence of ARDS has been growing, particularly in younger populations, and this is likely exacerbated by the aftermath of the COVID-19 pandemic. This condition represents a significant burden on health care systems globally given its high incidence and severe outcomes. The urgency to address ARDS has been underscored by the most recent announcement from the Biomedical Advanced Research and Development Authority, or BARDA, which has committed almost $120 million to a randomized Phase II program focused on critical outcomes such as survival and ventilator-free days. This substantial investment highlights the critical need for innovative and effective treatment in this challenging disease setting. The BARDA program is expected to evaluate three therapeutic options, two of which are monoclonal antibodies and have already been disclosed with the third agent not yet announced. Our published data from the Phase I/II trial of 797 demonstrates a 75% survival rate and significant improvement in ventilator-free days for patients with ARDS, suggesting that iNKT cells could play a pivotal role in ARDS management. These promising results indicate that 797 can be seamlessly incorporated into standard treatment protocols and provide potential for substantial clinical benefit. At the recent American Thoracic Society Annual Meeting, we presented additional compelling data. This is from our expanded access program, building on our findings from our Phase I and II clinical trials, showing the clinical efficacy of 797 in critically ill immunocompromised transplant patients with severe COVID-19-induced respiratory distress. Following a single administration of 797, similar to the dosing in our clinical trial, this patient experienced a rapid reduction in inflammatory cytokines, leading to successful extubation and rapid discharge from the hospital. With nearly 600,000 individuals in the United States alone affected by acute respiratory distress, about 30% to 40% of those patients with severe respiratory conditions, annually the burden on our health care system is unmet. The promising results of 797's growth potential is an important therapy to contribute to eliminating or mitigating ARDS, and this has broader regulatory and health care implications. MiNK Therapeutics is part of a select group of companies advancing therapies in this challenging disease setting, and our early data suggests that 797 could be one of the most promising candidates in the field. Now I'm going to be transitioning to another disease setting that we feel is a significant priority for us and for patients, building on the promising findings and immune optimization with our therapy. We're excited to announce the upcoming launch of a Phase I trial in steroid-refractory acute graft versus host disease and improved outcomes in allogeneic hematopoietic stem cell transplantation. Our investigator-sponsored trial will include two leading hematology centers, one in the US and one in Europe, and represents a critical step in broadening the therapeutic applications of our iNKT subplatform in regions where patients have limited effective treatment options. GvHD is a serious and potentially life-threatening complication of bone marrow transplants, where donor immune cells attack the recipient's body. Our iNKT cell therapy is designed to modulate this immune response, aiming to reduce the incidence and severity of GvHD while preserving the graft versus tumor or disease effect. The trial will also explore other important endpoints such as disease recurrence, infections, and improved engraftment which iNKT cells may positively influence. We are currently collaborating with our partnering institutions and investigators to finalize the study design with plans to activate the sites to readiness this year with first dosing by late year or very early in 2025. Now another important initiative we have ongoing in oncology is our program of 797 advancing in a Phase II trial in second-line gastric cancer. This trial is currently underway at Memorial Sloan Kettering Cancer Center under the leadership of Dr. Yelena Janjigian. She's Chief of Gastrointestinal Oncology and an internationally recognized expert in gastric cancer. Our study is evaluating the potential of 797 in combination with the Genesis next-generation checkpoint inhibitors, botensilimab and balstilimab, which has shown very promising antitumor responses in a number of disease settings. Our collaboration represents a critical opportunity to explore the synergistic benefit of iNKT cell therapy with advanced checkpoint inhibitors, potentially offering a powerful new treatment modality for patients with advanced gastric cancer. This is a condition with historically limited therapeutic options, and as I mentioned earlier, survival between four months and ten months in these patients. Enrollment is actively underway, and the first cohort of patients are now exceeding three to six months of follow-up in the trial and showing very exciting signals of clinical activity, where the majority of patients have already demonstrated some semblance of benefit in this population. We're very optimistic about the balance of clinical activity and tolerability of these combinations. We expect to see data presentation at a major oncology conference this year or very early in 2025.

Thank you, Jen. Turning to our preclinical pipeline. We are rapidly advancing MiNK-215 and IL-15 armored FAP-targeting CAR invariant natural killer T cell therapy, that's a mouthful, but it's targeting tumor stroma. This therapy has demonstrated very promising preclinical activity against solid tumors, including microsatellite stable colorectal cancer and liver metastases and non-small cell lung cancer. The strategic focus on targeting FAP-expressing tumors stems from the overexpression of FAP in the tumor microenvironment, which plays a key role in supporting tumor growth and suppressing immune responses. By disrupting this environment, MiNK-215 is designed to enhance immune-mediated tumor destruction, offering a novel approach to combating these resistant cancers. Our team is dedicated to bringing this innovative therapy into the clinical arena, with plans to file an IND in 2025. We are developing a robust preclinical package that will allow us to identify and enrich a biomarker-based patient population, facilitating more rapid signals and signal detection and development. The potential for MiNK-215 to disrupt the treatment landscape in solid tumors is significant, particularly as we continue to see breakthroughs in CAR T therapies. Our manufacturing is led by Joy Zhou, who is driving our efforts to fully develop MiNK-215 manufacturing in-house. By leveraging our state-of-the-art facilities, we aim to maximize scaling performance, ensuring the efficient production of high-quality allogeneic cell therapies. Our partnership with a leading lentiviral-vector producer, utilizing their novel technology, ensures a seamless and efficient production process for our antiviral vectors, critical for the development of MiNK-215. The recent approval of an allogeneic cell therapy in solid cancer marks a significant milestone in the field and serves as a relevant benchmark for MiNK. This approval highlights the growing acceptance and potential of allogeneic therapies, reinforcing our confidence in the regulatory pathway for MiNK-215. Additionally, the anticipated success in CAR-T treatments for solid tumor malignancies emphasizes the potential from MiNK's iNKT cell therapy that contribute to significant treatment advances. Our research and development teams continue to push forward our pipeline of next-generation cell therapies. These include T cell receptor-based therapies and bispecific cell engagers, which have the potential to address gaps in traditional therapies and can be combined with more advanced assets such as AgenT-797. Our partnership with ImmunoScape is now well underway and centers around the discovery and development of T cell receptors to a specific class of pan-tumor neoantigens. We believe that our invariant NKT cells are ideal allogeneic hosts for these pan-tumor neoantigen TCRs and offer the potential to develop cost-effective, off-the-shelf allogeneic TCR-based cell therapies. In parallel, we are continuing to advance our proprietary PRAME TCR-iNKT program. We've also investigated combining AgenT-797 with bispecific cell engagers. AgenT-797 is administered without lymphodepletion, has shown activity in solid tumor settings, and we have detected circulating AgenT-797 in non-HLA-matched patients for up to six months. We have compelling in vitro data on the combination of AgenT-797 with cell engagers, our own as well as third-party engagers. And we believe that the combination of AgenT-797 and cell engagers, specifically in absence of lymphodepletion, will significantly enhance tumor penetration, counteract local immune suppression, and improve overall efficacy. We plan to present preclinical data from some of these programs as a key meeting later this year.

Thank you very much, Marc. I appreciate it. As you can see, we have an incredibly efficient platform in which we've been able to not only advance clinical programs but also some highly innovative next-generation technologies. As we advance these programs, we are also very committed to fiscal conservatism, ensuring that we leverage every mechanism available to advance our therapies highly efficiently. Our strategy includes pursuing nondilutive funding sources, and these include some of the grant funding programs that are currently underway, as well as strategic partnerships to maintain our financial health while bringing these deserving therapies to the forefront of treatment options. Our approach will not only accelerate the development of iNKT cell therapies but also preserve value during this unusual time in biotech. So I want to thank you for your continued support. And I'm going to turn the call over to Christine to review our financials.

Thank you, Jen. We ended the quarter with a cash balance of $9.3 million, which reflects cash used in operations for the quarter of $2.3 million. This is a reduction from the $2.6 million used for the first quarter of this year. And as Jen mentioned earlier, an almost 50% reduction from the prior year. Our net loss for the three months and six months ended June 30, 2024 was $2.7 million or $0.07 per share and $6.5 million or $0.18 per share. This compares to $6.2 million or $0.18 per share and $11.9 million or $0.35 per share for the same period in 2023. I will now turn the call back to the operator for questions.

Thank you. The floor is now open for your questions. Our first question comes from Emily Bodnar from HC Wainwright.

Hi, good morning. Thanks for taking my questions. Jen, just to confirm, so the GvHD study that you're planning to initiate, it sounds like that's going to be funded with external capital. Is that correct? And then second question, when you say you are seeing early signs of activity in the gastric cancer study, can you provide any more insight on what you're kind of seeing and how that might compare to just standard of care chemotherapy alone? Thanks.

Thank you very much for your questions, Emily. Your first question on the GvHD program, yes this will be supported by external funding to advance the program. And secondly, in gastric, given that Dr. Janjigian is planning to present these results at a conference, I'm hesitant to say any more than that at least in the cohort that we have now observed and fully enrolled that's beyond three to six months of follow-up, we are seeing some very exciting signals of clinical benefit that do exceed what our expectations are with RAMTAX on its own. And as you can imagine, given the number of patients, thousands of patients have been dosed with the chemotherapy, we have a strong sense of how that arm will perform. And we're seeing performance far beyond that at this point in the trial.

Okay great. Thank you. That’s helpful.

Our next question comes from Jack Allen from Baird.

Hi, thanks so much for taking the questions and congratulations on the progress. I wanted to dive a little bit more deeply into the gastric update that we expect. I guess I understand you don't want to make too many comments ahead of the scientific presentation. But can you just remind us about the different cohorts in the study? And any comments on where patients were enrolled as it relates to those cohorts to date? And then on the graft versus host disease trial, very exciting news to see that got underway. I just wanted to see if you had any more comments as it relates to the size of that study and when we can expect initial data from that trial.

Certainly. Thanks, Jack, for your questions. On the gastric program, this is a program in which we have a very heavy translational component as well as clinical components. We are looking at very traditional endpoints: response rate, tumor reduction, overall survival in this population as well as some of the translational markers. To do so, we have embarked on a trial that allows us to interrogate iNKT as an induction and iNKT on top of standard of care chemotherapy, RAMTAX, as well as iNKTs in combination with BOT/BAL and chemotherapy. We have representative patients in each of those treatment considerations. So the data that you will see will give some semblance not only of translational mechanisms that are happening but also clinical outcomes in those populations. As for GvHD, we are as excited as you are, Jack, to get this underway. Our preclinical data has really supported the importance of iNKT in this particular disease setting. What we've observed is that preclinically, we know that iNKT may uniquely transform the landscape that will enable engraftment success and also mitigate and prevent GvHD. This is such a growing problem, impacting over 50% of patients that are undergoing stem cell transplantation. We believe that these cells can deliver benefit both in adult patients as well as in pediatric patients. You may know that there is a mesenchymal stem cell approved in Europe and not yet in the U.S. that has demonstrated important benefits, particularly in the pediatric population, specifically where GvHD is organ-based. We think that we can expand the benefit beyond ruxolitinib, as well as go beyond some of the available cell approaches given the mechanism of action. We will be activating the trial. We're working aggressively to do so this year. Ideally, we will have some patients who can start enrolling in this calendar year; otherwise, it will be very early next year. The endpoints are rapid with response rates and for protection and mitigation within about a 28-day window, so we would expect to have data from the trial in 2025, probably in the second half of the year.

Got it. Great. Thank you so much for that update. And then maybe just one last question, more broad, but as it relates to securing additional nondilutive funds to the capital, I just wanted to hear any comments you have around the appetite of partnerships and things of that nature.

Yes. Partnering is actually really core to our strategy, and it will be important not only to expand our bandwidth but also our global presence. So we continue to have very active interactions with potential partners who share our vision and also have the bandwidth to do deliver in regions of the world where we do not yet have a footprint but also to help us accelerate the development of these cells.

Got it. Thanks so much. Congratulations again on the progress.

Thank you.

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

Hi, good morning team. Thanks for taking our questions. And congrats on the progress. So in regards to the 797 combination work with BOT/BAL, could you maybe just talk a little bit more about that? And if there are any specific tumor surface antigen modalities, T cell engagers that you have in mind? And then the second question about the 215 IND filing plans actually to early 2025. I would love to hear the initial Phase I protocol plan you're looking to submit with your IND filing. And any color on what dose levels you're looking to produce? And how much you be thinking of manufacturing given you've invested in-house in developing this modality?

Excellent. Okay. Mayank, I'm going to start with the second question, and I'll turn it over to Marc, and we also have Dr. Joy Zhou here on manufacturing for 215. So on the 215 program, as you know, we now have a new investor who has joined us and partnered with us to accelerate the development of this program we're doing so actively. We had already generated quite a bit of preclinical work to support our IND filing. We are expanding that to bolster our initial clinical protocol, which will allow us to identify patients most likely to respond and deliver therapy at an effective starting dose. That's our highest priority at this moment in order to accelerate the development of this important therapy. Our preclinical data, which we've now presented publicly in a number of locations, continues to build and evolve. We have demonstrated that the 215 program can benefit in organoid models, colorectal cancer, and penetrate metastatic liver disease in those human-like models. This has increased our imperative for identifying patients most likely to benefit, and those will be very likely to be patients with FAP-expressing tumors. We will be somewhat inclusive in a Phase I trial to identify exploratory signals, but we will be focused in order to identify patients where we believe we can measure some of the biomarkers, elimination of the FAP-expressing tumor cells, and the immune-enhancing potential of this therapy to deliver the benefit we think is possible. We will be manufacturing this program in-house and Dr. Zhou and her team are working very aggressively to do so. Our process development analytics development work is actively underway for release criteria. We are just now in the process of finalizing some of the work that's necessary for the transaction, and we'll be transferring it in-house to produce the material. Importantly, we have been delivering 797 in-house and optimized the protocol to deliver robust billions of cells per donor. We are scaling the cells without exhaustion, capitalizing on the possibilities of the platform to deliver our CAR iNKT platform. So that's the 215 program, and we are looking forward to getting that into the clinic. We are wrapping up some of the preclinical data to allow us to get there at a dose that we think will be quite impactful in a population that we believe will benefit. Now on the engagers, I'm really glad that you asked this. We have done a lot of work in our own hands with engagers with the concept that engagers need more presence in the landscape. We believe we have a very important recipe for success here for T cell engagers, and I'm going to turn it over to Marc van Dijk to tell you a bit more.

Yes. Thanks, Jen. So engagers are interesting. There is quite a lot of development in the cell engager space, increasingly so in the solid tumor space. We've seen some success with established approvals. I think we can increase the efficacy enormously by adding an allogeneic cell therapy component in the form of iNKT cells. Engagers induce a central immune response and need to pull T cells into the tumor, but there is a lot of resistance in the tumor. iNKT cells are particularly effective at entering sites where T cells cannot easily go, as well as overcoming local immune suppression. That's the reason to build 215. That's why 797 has shown activity in gastric cancer. We believe that combining bispecific cell engagers for solid tumors with AgenT-797 or later with 215 will lead to enhanced efficacy, providing a much higher impact than either one or cell engagers alone. Importantly, 797 is applied without lymphodepletion, essential for maximizing the immune response of the patient's own immune system. This combination and non-lymphodepleting iNKT cells plus cell engagers has enormous potential for solid tumor treatment. We're exploring this with our own cell engager programs and looking into third-party engagers as well. We have a lot of preclinical data to share at the conference later this year.

Thank you for that comprehensive answer. If I could ask one more question, Jen, regarding the options for non-dilutive financing. Can you discuss the scale and scope and what is needed to finalize that?

Thanks, Mayank. With respect to the non-dilutive grant funding, we have been able to garner support for our trials in immune-related diseases as well as in oncology, showing that the excitement around these cells and their potential is shared among various groups. This has allowed us to prioritize the development of data that helps advance ongoing discussions. I hesitate to give additional color, except to say that interest in what these cells can do has been coming inbound from pharmaceutical groups keen to expand their cell therapy programs, as well as those looking to enter the space. There's significant interest in our autoimmunity, GvHD data, and our engineered portfolio with a focus on respiratory diseases from a targeted group of pharmaceutical companies. For us, most important is regional infrastructure and global presence to accelerate these important therapies. That's been driving our prioritization of conversations, and we hope to advance some of these by the end of this year or early next year.

Hi, thanks for taking my questions. Jen, I'm glad to see the GvHD trial getting started. Just wondering if you could give some details; steroid-refractory, but will you allow for other lines of prior therapy? And is this going to be a single ascending dose, multiple ascending dose? Can you give us any details on the dosing schemes?

Yes. Thanks so much, Matt. On the dosing scheme, we have been able to administer the cells beyond one dose, and we are very pleased with the tolerability in monitored populations. We can administer the cells without seeing enhanced reactivity or rejection with multiple doses. We would look at our target dosing standpoint—with confidence, we have generated data with more than 80 patients in dose finding. Our target is about 1 billion cells, and we may do a step-down dose in the GvHD trial. However, we may not need to. We're discussing that currently and would aim for a single dose, exploring whether a second or third dose is necessary. We will finalize the design elements with regulatory interactions. We are open to other lines of therapy, aiming for a homogeneous population even in a Phase I setting to encourage rapid advancement into a randomized Phase II.

There are no further questions. So I'll turn the call back over to Dr. Jennifer Buell.

Thank you very much, everyone. I want to thank my team as well as for those on the line for your continued support. I appreciate it.

That concludes today's call. You may now disconnect.