Mink Therapeutics - Q2 2024

Transcript

Operator (participant)

Good day and thank you for standing by. At this time, I would like to welcome everyone to Seres Therapeutics' second quarter 2024 earnings conference call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during that time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press the star one. Thank you. I would now like to turn the conference over to Dr. Carlo Tanzi, Investor Relations. Please go ahead.

Carlo Tanzi (Investor Relations)

Thank you and good morning. Our press release with the company's second quarter 2024 financial results and a business update became available at 7 A.M. Eastern Time this morning and can be found on the Investors and News section of the company's website. The company has also posted an updated corporate presentation to the website. I'd like to remind you that we'll be making forward-looking statements, including related to the financial terms, timing, and completion of the sale of VOWST assets to Nestlé Health Science, the receipt of future payments, and the use of proceeds of the transaction, the timing and results of clinical studies and data readouts, development plans and commercial opportunities, operating plans and our future cash runway, our planned strategic focus and other statements which are not historical fact. Actual results may differ materially.

On today's call with prepared remarks, I'm joined by Eric Shaff, Seres President and CEO, Marella Thorell, CFO, Dr. Lisa von Moltke, Chief Medical Officer, Dr. Matthew Henn, Chief Scientific Officer, and Dr. Terri Young, Chief Commercial and Strategy Officer. With that, I'll pass the call to Eric.

Eric Shaff (President and CEO)

Thank you, Carlo, and good morning, everyone. Last week, we announced our agreement to sell Seres' VOWST assets and commercial rights to Nestlé Health Science in exchange for substantial, immediate, and future financial consideration. We held a call at that time to review the agreements and the deal terms, and to provide a high-level view of our planned corporate strategy to advance our live biotherapeutics, drug candidates, which are a consortia of bacterial strains cultivated from clonal master cell banks and rationally designed and optimized to target disease-relevant pathways. Today's call will focus on our SER-155 program and the clinical data we look forward to obtaining next month and more broadly, our strategy moving forward. Later in the call, we will provide a review of our second quarter financial results.

Jennifer Buell (CEO)

... The continued external financial support to advance our exciting programs. I'll walk you through these developments and illustrate how we're paving the way for main 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 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 only four to 10 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 healthcare 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 (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 treatments 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 (ATS), 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 a critically ill, immunocompromised transplant patient 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%-40% of those patients with severe acute respiratory conditions annually, the burden on our healthcare system is immense. The promising results of 797 underscores potential is an important therapy to contribute to eliminating or mitigating ARDS, and this has broader regulatory and healthcare implications.

MiNK Therapeutics is among a select group of a few 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, and building on the promising findings in 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 U.S. and one in Europe, and represents a critical step in broadening the therapeutic applications of our iNKT cell platform 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're 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 in 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 a Chief of Gastrointestinal Oncology and internationally recognized expert in gastric cancer. Our study is evaluating the potential of 797 in combination with the Agenus next generation checkpoint inhibitors, botensilimab and balstilimab, which have 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 and 10 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. Now, I will turn the call over to Dr. Marc van Dijk, our Chief Scientific Officer, and he'll review our earlier stage programs that are advancing. Marc?

Marc van Dijk (Chief Scientific Officer)

Thank you, Jen. Turning to our preclinical pipeline, we are rapidly advancing MiNK-215 and IL-15-armed 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, 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 in bringing this innovative therapy into the clinical arena, with plans to file an IND in 2025.

We're developing a robust preclinical package that will allow us to identify and enrich a biomarker-based patient population, facilitating more rapid 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's driving our efforts to fully develop MiNK-215 manufacturing in-house. By leveraging our state-of-the-art facilities, we aim to maximize scale and 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 lentiviral 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 the advanced solid tumor malignancies emphasizes the potential for MiNK's iNKT cell therapy to 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. 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 at a key meeting later this year. I'll now turn it back to Jen for some closing remarks. Jen?

Jennifer Buell (CEO)

Thank you very much, Marc. Appreciate it. This is, 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, which you can see, we're also very committed to fiscal conservatism ensuring that we leverage every mechanism available to advance our therapies highly efficiently. Our strategy includes pursuing non-dilutive 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 prefer, or preserve value during this unusual time in biotech.

I want to thank you for your continued support, and I'm going to turn the call over to Christine to review our financials. Christine?

Christine Klaskin (Principal Financial Officer)

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 prior year. Our net loss for the three 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 35 cents per share, for the same periods in 2023. I will now turn the call back to the operator for questions.

Operator (participant)

Thank you. So the floor is now open for your questions. So to ask a question this time, please press star then the number one on your telephone keypad. So for this Q&A, you'll be provided the opportunity to ask one question and one further follow-up question. I'll just pause for just a moment to compile the Q&A roster. Our first question comes from Emily Bodnar from H.C. Wainwright.

Emily Bodnar (Analyst)

Hi, good morning. Thanks for taking the questions. First one, 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're seeing early signs of activity in the gastric cancer study, can you provide any more context to what you're kind of seeing and how that might compare to just standard of care chemo alone? Thanks.

Jennifer Buell (CEO)

Thank you very much for your questions, Emily. Your first for the GvHD program, yes, this will be supported by external funding to advance the program. And secondly, in gastric, now I'm given that Dr. Janjigian is planning to present these results at a major conference, I'm hesitant to say any more than, at least in the cohort, that we have now observed and fully enrolled. It'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 ram/tax 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 what that arm, how it will perform, and we're seeing performance far beyond that at this point in the trial.

Emily Bodnar (Analyst)

Okay, great. Thank you. That's helpful.

Operator (participant)

Our next question comes from Jack Allen from Baird.

Jack Allen (Analyst)

Great! 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 wanna make too many comments ahead of the scientific presentation, but could you just remind us about the different cohorts in this 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 get underway. I just wanted to see if you had any more comments as it relates to the size of that study and when we could expect initial data from that trial.

Jennifer Buell (CEO)

Certainly. Thanks. Thanks for that, Jack, for your questions. On the gastric program, this was, this is a program in which we have a very heavy translational component as well as clinical component. So looking at very traditional endpoints, response rates, tumor reduction, overall survival in this population, as well as some of the translational markers. And to do so, what we have embarked on is a trial that allows us to interrogate iNKTs as an induction and, and iNKTs on top of standard of care chemo, ram/tax, as well as iNKTs in combination with bot/bal and chemo. And 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.

GvHD, so this is a program that we are as excited as you are, Jack, to get this underway. This is. Our preclinical data has really supported the importance of iNKTs in this particular disease setting. And what we've observed is that preclinically, we know that iNKTs 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. And we believe that these cells can deliver benefit both in adult patients as well as in pediatric patients. And you may know that there is a mesenchymal stem cell approved in Europe, and not yet in the U.S., that has demonstrated some important benefit, particularly in pediatric populations, specifically where GvHD is organ-based.

We think that our cells may even be able to expand benefit beyond the observations today, certainly beyond ruxolitinib, as well as 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 in this, with response rates and 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.

Jack Allen (Analyst)

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 non-dilutive sources of capital, I just wanted to hear any comments you have around appetite for partnerships and things of that nature.

Jennifer Buell (CEO)

Yes. Partnering is actually really core to our strategy, and, it will be important not only to expand our, 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, the bandwidth to do, to 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.

Jack Allen (Analyst)

Got it.

Jennifer Buell (CEO)

Thank you, Jack.

Jack Allen (Analyst)

Thanks so much, and congratulations again on the progress.

Jennifer Buell (CEO)

Thank you.

Operator (participant)

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

Mayank Mamtani (Analyst)

Good morning, team. Thanks for taking our questions, and congrats on the progress. So, in regards to the 797 combination work with bot/bal, sort of informing also your future combination work you may pursue with T-cell engagers, could you, could you maybe just talk a little bit more about that? And if there are any specific tumor surface antigens, you know, modalities, T-cell engagers that you have in mind? And then the second question about the 215 IND filing plans escalated to, you know, early 2025. Would love to hear, you know, the initial phase one 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 might you be thinking of manufacturing, given, you know, you've invested a ton in-house in developing this modality?

Jennifer Buell (CEO)

Excellent. Okay, Mayank, I'm gonna start with the second question, and then I'll turn it over to Marc. And we also have Dr. Joy Zhou here on manufacturing for MiNK-215. So on the latter, the 215, this is a 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're 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 – that's really 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 as it's continued to build and evolve, and what we've most recently demonstrated is that the 215 program not only can benefit in organoid models, colorectal cancer, but also 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. Now, we will be somewhat in a phase one trial, somewhat inclusive, to identify exploratory signals, but we will be really focused in order to identify patients where we believe that we can measure some of the biomarkers, elimination of the FAP-expressing tumor cells, and the immune-enhancing potential of this therapy to really deliver the benefit that 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, analytic development work is actively underway for release spec, criterion, and that, we're just now in the process of finalizing some of the work that's necessary for the transduction, and then we'll be transferring it in-house to produce the material. Importantly, we have been delivering 797 in our own hands, and we've optimized the protocol to be able to deliver really robust billions of cells per donor. We are able to scale the cells, and we've publicly talked about this, where we can scale the cells without exhaustion, really capitalizing on the possibility. We will plan to leverage that platform in order to now deliver our engineered CAR-iNKT platform. So that's the 215 program.

We're looking forward to getting that into the clinic. We're going to be wrapping up some of the preclinical data that will allow us to get there at a dose that we think will be quite impactful and 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, and we're seeing that in the landscape. I think we may have a very important recipe for success here for T cell engagers, and I'm gonna turn it over to Marc van Dijk to tell you a bit more.

Marc van Dijk (Chief Scientific Officer)

Yeah, thanks, Jen. Engagers are interesting. I mean, there's quite a lot of development in the cell engager space, more and more so also in the solid tumor space. We've seen some success with one approval, and I think we can increase the efficacy specifically, you know, enormously by adding an allogeneic cell therapy component in the form of iNKT cells. And I say this specifically because engagers are so they induce the local central immune response, and they need to pull T cells into the tumor, but there's a lot of resistance in the tumor. And iNKT cells are very good at entering sites where T cells cannot easily go, as well as overcoming local immune suppression. That's the reason to build MiNK-215.

That's the reason why 797 has shown activity in gastric cancer. And we believe that combining bispecific cell engagers for solid tumors with agenT-797 or later with 215 really starts to add those two efficacy mechanisms together to have a much higher impact than either one or cell engagers alone can actually achieve. And the other really differentiating component is that 797 is applied without lymphodepletion, and that's essential for maximizing the immune response of the patient's own immune system. So that combination, no lymphodepleting iNKT cells plus cell engagers, we believe, has an enormous potential for solid tumor treatment. So that's why we're exploring with both our own cell engager program, but also looking at cell engagers that are out there.

We have, you know, quite a lot of preclinical data that we hope to share at a conference later this year.

Mayank Mamtani (Analyst)

Got it. Thank you for that comprehensive answer. And then just, if I could squeeze one more in, Jen, on the couple of options for non-dilutive financing, are you able to talk to, you know, the scale and scope, and in terms of what remains, you know, to kind of get that through the finish line? That would be helpful, and thanks again for taking our questions.

Jennifer Buell (CEO)

Thanks, Mayank. With respect... As you're seeing with some of the non-dilutive grant funding support that we have been able to garner, to support our trials in immune-related diseases as well as in oncology, you can see how the excitement of these cells and their potential is shared with a number of groups, a diverse set of, of groups who are very intrigued by advancing the technology. That has allowed us to continue to really prioritize the development of data that will help us to continue to advance some of the discussions that are actively underway.

So I hesitate to give any additional color, except to say that the interest of what these cells can do have been coming inbound from pharma groups who are interested in expanding the footprint of their cell therapy programs, as well as those looking to get into the space. There's quite a bit of interest in the autoimmunity, the GvHD data, as well as on the engineered portfolio with the preponderance of additional interest in respiratory diseases coming from a very focused group of pharma companies. So I'm going to leave it at that, just to simply say, for us, the most important thing is regional infrastructure and global footprint that can allow us to accelerate the development of these important therapies, and that's been driving our prioritization of the conversations that we're having now, and some of which we'll expand on in the next couple of weeks. And, ideally, we will be able to have some of these advanced far enough by the end of this year or early next year.

Mayank Mamtani (Analyst)

Understood. Thank you.

Operator (participant)

Our next question comes from Matthew Phipps of William Blair.

Matthew Phipps (Analyst)

Hi. Thanks for taking my questions, Jen. 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, the dosing schemes?

Jennifer Buell (CEO)

Yeah, thanks so much, Matt. And on the dosing scheme, at this point, we have been able to administer the cells on and beyond one dose, and we are very pleased that we can do so tolerably in populations of patients that we wanted to monitor really quite closely. So we can administer the cells. We do not see any enhanced cellular reactivity or rejection in administering beyond one dose. We would look at this from a target dosing standpoint. We've generated quite a bit of data now beyond 80 patients in dose finding, and I think we have quite a bit of confidence that a billion cells is our target dose. We wouldn't want to start very much lower than that. We may do a step-down dose in the GvHD trial.

However, we may not need to. So we're negotiating that currently, and we would look at about 1 billion cells. We would do a single dose, as well as we would explore if a second dose or a third dose is necessary. I'm not sure that it will be. We will be open, and we're finalizing those design elements right now with some regulatory interactions. We are open to other lines of therapy.

We want to be sure to have the right reference, so that in our trial, which even in the phase I, we may contemplate, we're contemplating right now a reference group that would allow us to accelerate the development by demonstrating, you know, if we're looking at 40%-50% or higher in response rates compared to what we're seeing is 30%, with some of the available therapeutic approaches. We want to keep the prior lines of therapy relatively clear, so that we have a homogeneous population, even in a phase I setting, that will allow us to advance very quickly into a randomized phase II.

Matthew Phipps (Analyst)

Okay, great. Thank you.

Operator (participant)

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

Jennifer Buell (CEO)

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

Operator (participant)

Concludes today's call. You may now disconnect.