Immuneering Corporation (IMRX) Earnings Call Transcript & Summary

Welcome to the Immuneering conference call to discuss the positive 12-month overall survival update from the company's ongoing Phase IIa trial of atebemetinib in first-line pancreatic cancer patients. [Operator Instructions] As a reminder, this call is being recorded today, Wednesday, January 7, 2026. I would now like to turn the conference over to Courtney Dugan, Vice President, Head of Investor Relations. Please go ahead.

Thank you, operator. Joining us on the call today from Immuneering are Co-Founder and Chief Executive Officer, Ben Zeskind; Chief Scientific Officer, Brett Hall; Chief Medical Officer, Igor Matushansky; Chief Accounting Officer and Treasurer, Mallory Morales; and E.B Brakewood, our Chief Business Officer. Please turn to Slide 2. During this call, management will make forward-looking statements, including statements related to its Phase IIa trial of atebemetinib as well as the timing of additional data from the study and the company's development plans. Our actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of risks and uncertainties. Factors that could cause these results to be different from these statements include factors the company describes in its securities filings, including its annual report on Form 10-K and quarterly reports on Form 10-Q. Immuneering undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events or changes in its expectations. With that, I will now turn the call over to Ben Zeskind, our Chief Executive Officer. Ben?

Thank you, Courtney. Good afternoon, everyone. We're excited to discuss our 12-month overall survival data for atebemetinib plus modified gemcitabine/nab-paclitaxel in first-line pancreatic cancer patients. Please turn to Slide 3. This is a truly unique late-stage opportunity both in pancreatic cancer and beyond. Our deep cyclic inhibitors shrink tumors differently with exceptional durability and tolerability. And I think that's reflected in our clinical data to date and the clinical data we're sharing today. There are 4 key topics we'll cover on today's call. First, we will review the extraordinary overall survival data we continue to see in our ongoing Phase IIa study of atebemetinib plus chemotherapy in first-line pancreatic cancer. Next, you will hear about the dramatic improvements in quality of life we are seeing in certain patients treated with atebemetinib. On our November earnings call, you heard about 2 such patients. And today, you'll hear an equally compelling case study from Dr. Meredith Pelster at the Sarah Cannon Research Institute, describing a patient who experienced such a dramatic improvement in quality of life that she was able to regain meaningful independence in her day-to-day life, something that unfortunately is rare in this disease. We will then discuss our planned pivotal Phase III clinical trial where dosing is expected to begin in the middle of this year in first-line pancreatic cancer patients. Lastly, we will review our broader pipeline and upcoming near-term milestones. With a strong financial foundation from our financing in September and cash runway into 2029, we are well funded to support multiple value-creating catalysts ahead, including the anticipated Phase III data readout, additional pancreatic cancer data, Phase II combination studies in lung cancer starting in 2026 as well as continued progress across our preclinical deep cyclic inhibitor platform. Please turn to Slide 4. Let's now dive into our 12-month data, starting with the most important endpoint, overall survival. What matters most to patients is how long they live and overall survival remains the gold standard in oncology. We first shared impressive 6-month overall survival data in June and that was gratifying. It was even more exciting to report 9-month data in September, which continued to look extraordinary. Today, we are thrilled to report that this exceptional benefit continues at the 12-month mark and beyond. At 12 months, overall survival is 64% in first-line pancreatic cancer patients treated with atebemetinib plus chemotherapy. That is an extraordinary result. Importantly, median overall survival still has not been reached. Please turn to Slide 5. When compared with historical benchmarks for standard of care gemcitabine plus nab-paclitaxel, or GnP, the separation is dramatic. In the pivotal MPACT study, 12-month overall survival for standard of care was approximately 35%. In our study, it is 64%, representing a 29-point absolute separation. Put another way, the probability of a patient being alive after 12 months in that landmark study was only about 1/3, while in our trial it is almost 2/3. Moreover, median overall survival with standard of care was approximately 8.5 months, while our median has still not been reached with a median follow-up time many months beyond that point at 13.4 months. Please turn to Slide 6. This separation has been remarkably consistent over time. At 6 months, we observed a 27-point separation versus standard of care. At 9 months, a 36-point separation and now at 12 months, a 29-point separation. This consistency reflects the durability we designed atebemetinib to achieve, and it adds further robustness to the data. Importantly, overall survival remains 64% out to the median follow-up time of 13.4 months, which underscores the depth and durability of the benefit we're seeing, nearly double what would be expected with chemotherapy alone. Please turn to Slide 7. Now while gemcitabine plus nab-paclitaxel is the most appropriate benchmark here as it is the most commonly used global standard of care and the comparator in our upcoming Phase III trial, there are 2 other approved first-line regimens, FOLFIRINOX/NALIRIFOX combinations, which are generally reserved for younger, fitter patients due to their increased toxicity. Yet even when compared cross-trial against those regimens, atebemetinib continues to show a striking advantage. At 12 months, overall survival with FOLFIRINOX is approximately 48% and with NALIRIFOX, it's approximately 45% compared with 64% with atebemetinib plus chemotherapy in our study. Please turn to Slide 8. Turning to safety and tolerability. This has remained an important differentiator for atebemetinib. We designed this therapy to achieve both durability and tolerability and the data continues to show very few harsh side effects. Only 2 categories of Grade 3 adverse events occurred in more than 10% of our patients, anemia and neutropenia. Both are well-known side effects of chemotherapy alone and importantly, have not been observed with atebemetinib monotherapy. We are very pleased with the continued favorable safety and tolerability profile of atebemetinib, which we believe is a key differentiator in the competitive landscape. Please turn to Slide 9. While overall survival is the primary endpoint in our Phase III study and the ultimate gold standard endpoint in oncology, the robustness of our data is further supported by strong separation from the pivotal MPACT study of standard of care GnP on secondary endpoints. We observed median progression-free survival of 8.5 months, the standard of care benchmark of MPACT was only 5.5 months. We observed an overall response rate of 39%, the standard of care benchmark was 23%. And we observed a disease control rate of 81%, the standard of care benchmark was only 48%. Please turn to Slide 10. Baseline demographics also support the strength of these findings. Patients in our study were generally well matched to those in prior pivotal trials with one notable difference. Our population was meaningfully older. In our trial, the median age was 69 compared to the low to mid-60s in historical studies. Moreover, more than 2/3 of our patients were over age 65. As such, demonstrating this degree of survival benefit in an older population further reinforces the significance of our results. Please turn to Slide 11. Now we started with this original cohort of 34 first-line pancreatic cancer patients treated with atebemetinib plus modified gemcitabine/nab-paclitaxel. And later, we decided to enroll an expanded cohort that includes these 34 patients and additional enrolled patients who are approaching sufficient median follow-up time. We plan to report overall survival in this expanded cohort of over 50 patients in the first half of this year. And I'm thrilled to say that the overall survival in the expanded cohort is trending consistently with overall survival in the original 34 patients. Please turn to Slide 12. Now behind these numbers are real patients experiencing meaningful benefit. On our November earnings call, Dr. Allyson Ocean at Weill Cornell and Dr. Gregory Botta at UC San Diego, both spoke about how well their patients were doing on atebemetinib combination, with Dr. Ocean describing a patient with a complete response who had "never felt better" and Dr. Botta describing a patient who was able to receive surgery with curative intent and had "great quality of life." Today, we are honored to have Dr. Meredith Pelster from Sarah Cannon Research Institute join us on the call. Dr. Pelster will discuss a patient she is treating with atebemetinib plus gemcitabine/nab-paclitaxel, a patient who is also experiencing dramatic improvements in quality of life, including regaining independence that had previously been lost. This patient is part of the expanded cohort that we will be reporting on in the first half, and her experience is representative of what we are also seeing in many other patients treated with atebemetinib. So with that, let me hand the call over to Dr. Meredith Pelster.

Thank you, Ben. My name is Dr. Meredith Pelster, and I am a medical oncologist with a focus on treating patients with gastrointestinal cancers and serve as the Associate Director of Gastrointestinal Cancer Research and Executive Chair of the Gastrointestinal Cancer Research Executive Committee for the Sarah Cannon Research Institute. I am also a Phase I investigator at the Sarah Cannon Research Institute, Nashville Drug Development Unit and an investigator in Immuneering's Phase IIa study of atebemetinib. Over the years, I have treated many patients with pancreatic cancer and have seen firsthand the urgent need for new medicines. The case study I'm about to walk you through comes from the arm studying atebemetinib in combination with gemcitabine/nab-paclitaxel in first-line pancreatic cancer. The patient is from the more recent group of patients after the company reopened the study for enrollment. So she is not one of the original 34 being reported today, but is part of the extended cohort of over 50 patients that the company plans to report on in the first half of this year. The patient is a 64-year-old female with metastatic pancreatic cancer with a KRAS G12V mutation who is being treated with daily atebemetinib plus modified gemcitabine/nab-paclitaxel in the first line. The patient has now been on treatment for approximately 5 months and remains on treatment. The patient started with a substantial 8.8 centimeters of tumor burden across 4 target lesions. 2 located in the liver, 1 in the pancreas and 1 in the peritoneum. By the first scan, both of the liver mets had been rendered undetectable and they have remained undetectable across 2 subsequent scans. The other 2 lesions have essentially been held in check, ebbing and flowing a bit plus or minus 10% of their baseline size. The net result is slightly more than a 30% reduction in the sum of the longest diameters of the target lesions or in technical terms, a partial response as of the most recent restaging. In addition, her levels of CA19-9, which is a blood-based biomarker of pancreatic tumor burden and prognosis, have dropped from 30,000 to well below 5,000. The patient has also gained a substantial amount of weight on study, which is really great to see because pancreatic cancer patients usually deal with substantial weight loss from cachexia. She has been doing well and has few adverse events and has experienced an improvement in quality of life, including an increase from 96 to 141 in the FAACT score, which is the functional assessment of anorexia cachexia therapy, which I've seen firsthand. For example, when the patient initiated the study, she required significant help from family due to pain and weakness. Now she can drive herself independently and has gained back a sense of self-reliance that she desired. Rarely do I see patients have liver lesions completely eliminated and gain weight with so few side effects. When I met her, she was cachectic and weak. Now she looks and feels healthier as a result of her improved appetite and weight gain. It is clear to me that atebemetinib is providing unique benefit to the patient that she would be unlikely to see with chemotherapy alone. My colleagues and I have treated several patients in various arms of the atebemetinib trial, and we are excited that the Phase III study will begin dosing patients with this combination by midyear. Atebemetinib has potential to improve long-term outcomes and quality of life for patients with pancreatic cancer. With that, let me hand the call back to Ben.

Thank you, Dr. Pelster. We are thrilled to hear how well this patient is doing on the trial. Please turn to Slide 14. Now let's turn to an overview of our planned pivotal Phase III clinical trial, MAPKeeper 301. This will be a global randomized trial in metastatic first-line pancreatic cancer. The study will enroll approximately 510 patients randomized to atebemetinib plus modified gemcitabine/nab-paclitaxel versus standard gemcitabine/nab-paclitaxel alone. Overall survival will be the primary endpoint. We aligned with both the FDA and EMA on the trial design in the fourth quarter of 2025, and we anticipate dosing our first patient in the middle of the year with top line results anticipated in mid-2028. Please turn to Slide 15. In closing, we believe these data represent an extraordinary advantage in pancreatic cancer, a notoriously difficult-to-treat cancer, achieving 64% overall survival at 12 months, nearly double the historical benchmark with excellent tolerability and meaningful improvements in quality of life is something rarely seen in this disease. Our goal is not simply to shrink tumors but to do so durably, safely and in a way that allows patients to live much longer and have much better quality of life. In other words, quality and quantity. We have multiple near-term upcoming milestones, including sharing circulating tumor DNA analyses and updated survival from more than 50 patients, dosing the first patient in our Phase III trial and the start of our Phase II combination studies in non-small cell lung cancer. Importantly, our cash runway extends into 2029, funding us through the pivotal data readout and through the initiation of additional trials in new combinations in cancers where we expect atebemetinib to perform well. The results we have shown to date are extraordinary, and we strongly believe atebemetinib represents a unique late-stage opportunity in pancreatic cancer and beyond. And with that, we're happy to take questions. Operator?

[Operator Instructions] We'll take our first question from Allison Bratzel at Piper Sandler.

Congrats from me on this data. Maybe a question on the Phase III design. Now that you finalized that with FDA, could you just kind of help us understand assumptions on median OS for the control arm? Is it 8.5 months we've seen for standard of care a good assumption? Or just any color there would be helpful. And then as a follow-up question, I think we all recognize how important safety and tolerability is to patients, and this is just such a big differentiator for atebemetinib. So it does look like you're including QOL measures as a secondary endpoint in the Phase III. Can you just kind of talk some more to that, what PROs will use? And then how that can affect positioning of when it comes to market?

Yes. Thanks, Allison. Appreciate the questions. And yes, we couldn't be more excited for the Phase III study, MAPKeeper 301. I think with OS as the primary endpoint, I think we're thrilled to be able to go with 64% overall survival that we've seen and reported today at 12 months just really sets us up very nicely going into this study, and we're excited to dose the first patient midyear. So you're absolutely right, we are going to include quality of life metrics as part of the study. And I think that's so important because as you heard from Dr. Pelster, we really are seeing just remarkable improvements in quality of life in these patients. I mean to be able to drive again just that kind of independence, regaining independence is really remarkable. So it's important to us to have those quality of life metrics as part of the trial. And certainly, we believe the trial is extremely well powered to detect really just the dramatic differences that we're seeing between the survival that you would expect from standard of care gemcitabine/nab-paclitaxel and really what we're seeing with atebemetinib. I mean to nearly double the overall survival at 12 months is just remarkable. So we're really excited for the trial.

We'll move next to Ami Fadia at Needham.

Thanks for the data update today. I had 2 questions. Firstly, can you talk about particularly in PDAC, how much can one rely on median PFS to predict median OS? And if you could sort of tie that up with the mechanism for atebemetinib and how that could translate into durability as we see that data mature? And maybe just sort of put in context for us, how important is quality of life in terms of maybe treatment choices for this patient population?

Ami, thanks for the questions. Well, look, overall survival is the gold standard, right? I mean this is our sole primary endpoint. This is what matters most to patients is how long they live. And that's why we're thrilled to have 64% overall survival at 12 months, nearly double the benchmark for standard of care, which is 35%. But that being said, progression-free survival is a surrogate endpoint, right? It's something that is helpful to kind of assess the robustness of the overall survival result that you're seeing. And that's why we're thrilled to see such a strong separation between our median overall survival at 8.5 months and the benchmarks from standard of care, 5.5 months is the benchmark for GnP. So that full 3-month separation in terms of median PFS, we think just adds further robustness to the strong overall survival results that we're seeing. So we're thrilled to see that kind of separation on progression-free survival. And I think ultimately, it speaks to the durability that we've built into this treatment, right? The deep cyclic inhibitors are designed to not drive resistance in quite the same way. And just to be clear, the median PFS is 8.5 months. I may have misspoken a minute ago, but the median progression-free survival we're seeing is 8.5 months versus 5.5 for the standard of care benchmark. So just a really remarkable gap there, which again, I think, lends robustness to the overall survival advantage that we're seeing so clearly with 64% OS at 12 months. Now you asked about how important quality of life is, and I think it's incredibly important. Again, I think Dr. Pelster's case study really brings that home, right? I mean this matters to patients, right? Patients don't just want more time. They want time and they can enjoy, right? To be able to drive independently, to be able to have an appetite and gain weight, not have to deal with harsh side effects to the same extent as other treatments. This is really -- we mean it when we say quality and quantity, right? I think too often with harsh cancer treatments, patients are forced to make this trade-off to essentially accept debilitating toxicity, whether it's nausea, vomiting, diarrhea, rashes, just terrible sacrifices on quality of life to gain quantity, to gain survival. And it doesn't have to be that way. It doesn't have to be that way. We believe it's possible to have great quality of life and great overall survival. And I think the data we're showing today and the kind of reports you're hearing from Dr. Pelster today and that you heard from Dr. Ocean and Dr. Botta on our call in November, all show that it's possible with atebemetinib with deep cyclic inhibitors for patients to have great quality of life and to have great quantity, great overall survival. And we're thrilled to be able to present that new option for patients, and we think it's going to be remarkable. So thank you for the question, Ami.

We'll take our next question from Jay Olson at Oppenheimer.

Congrats on all the progress you're making on behalf of patients. We're curious about how Dr. Pelster would compare the profile of atebe versus other emerging therapies for PDAC, especially based on atebe's impressive OS results so far, along with its clean safety and tolerability profile. We're wondering what would Dr. Pelster consider to be the ideal patient population for atebe?

Jay, thanks for the question. So we did let Dr. Pelster get back to treating her patients. But I think you heard from her really her excitement about the pivotal study, the Phase III study. And I think it's easy to see why, given the -- just the incredible dramatic improvement in quality of life that she's seeing in the patient that she described. And look, we're -- we've been so focused on the quality of life, but that patient's tumors are shrinking, too. I mean to have 2 liver mets rendered completely undetectable -- I mean liver mets are supposed to be the challenging ones in pancreatic cancer and not for atebemetinib. We just cut those 2 down to being rendered undetectable, which you heard Dr. Pelster say is really not something she commonly sees. So I think that's great to see. I think you heard it from Dr. Ocean and Dr. Botta on the call in November, right, to have a complete response as Dr. Ocean described on the call in November, with a patient who's never felt better, to quote Dr. Ocean. And by the way, we have an update in the appendix of our slide deck that complete response, which was unconfirmed at the time of the call in November has now confirmed. You can see that update on Slide 24. So confirmed complete response in that patient. So just this remarkable combination of shrinking tumors, but doing it differently, doing it in a way with durability, with quality of life. You heard it from Dr. Botta as well with his patient that was able to get this surgical resection, the Whipple procedure and I think that's -- and again, but to feel -- to have great quality of life together with that. So it's this combination of quality and quantity, right, great quality of life, great survival. And we think this is why there's just so much excitement for the Phase III. You heard it from Dr. Pelster. You saw it in the quote in our press release in December from Dr. O'Reilly at Sloan Kettering excited for the Phase III. You heard it from both Dr. Ocean and Dr. Botta. Everyone is excited for this Phase III because they're seeing the benefits. They're seeing the tumor shrink. They're seeing the overall survival and they're seeing the quality of life. And it's really just a remarkable combination we believe atebemetinib is going to be fantastic for these patients.

We'll go next to Graig Suvannavejh at Mizuho.

Happy New Year. A couple of questions for me. One, I was curious, I know overall survival is your primary endpoint. It's the gold standard. You did share some median PFS data in this 12-month update. I was wondering if you could maybe comment on what you might think the PFS rate might look like? And what are the gating factors to be able to share that readout or that number? Secondly, just maybe a clarification from me. You've got a data update in the first half on your expanded enrollment of additional patients. I think you mentioned the update would include data from about 50 patients. Maybe just to clarify, is that an extra 16 on top of the 34? Or is that an incremental 50 on top of the original 34? And just on that, what should we be thinking in terms of the follow-up -- treatment follow-up period when you share that data set from those 50?

Graig, thanks for the question and happy New Year. So with regard to progression-free survival, yes, so we're sharing today the median progression-free survival, 8.5 months median progression-free survival, which is just a remarkable advantage or improvement over the benchmark from the standard of care gem/nab, which is only 5.5 months. So we're thrilled to see that really substantial increase in the progression-free survival. And again, that's a surrogate endpoint. That's a predictor, albeit an imperfect one of overall survival. But ultimately, overall survival is the gold standard. It's the primary endpoint, and we're thrilled to see that we're nearly doubling the overall survival at 12 months with 64% versus 35% for the standard of care benchmark. And by the way, our median follow-up time here is 13.4 months. So while we're focused on 12 months because that's kind of the -- that's the landmark that a lot of people look at, I mean, it stays at 64% out to that 13.4-month median follow-up, whereas the standard of care continues to decline. So at 13.4 months, standard of care is only about 31%. So actually more than double the OS of standard of care at that 13.4-month mark. So we're thrilled about that. In terms of your second question, the data that we plan to share in the first half from this expanded cohort, right, it's more than 50 patients. So that includes both the 34 patients we're talking about today, plus an additional 20-or-so patients. So that's the expanded cohort. It's both. It's bringing in those additional patients. And if you'll recall, I mean, we talked about this in June, but we originally intended to enroll 30, enrolled 34. And just the demand to get more patients on to this study was so strong that after a period of time, we essentially reopened it and took another 20-or-so patients. And to your point, those patients have a shorter median follow-up time because they started much later, but it's approaching the point where together, it was at 34. I think that group of 50 is approaching the point that we're ready to talk about really in the first half. And I think it's frankly, it's big news we're sharing today that the OS in that expanded cohort is trending consistently with the OS in the original 34 patients. So for everyone who's been kind of focused specifically on the specific 34 patients that we had here, the fact that adding another 20 patients in and you still see consistent overall survival, I think just adds yet another layer of robustness to the already really robust and remarkable results we're seeing with 64% OS at 12 months. And look, we hope to share those data at an upcoming medical meeting and with dosing the first patient in the Phase III midyear as we expect to do, I think the timing will be really good for that.

And we'll go next to Andrew Berens at Leerink Partners.

This is Emily on for Andy. I guess I was wondering if you could provide any color on patient -- what portion of patients were treated in the second line and third line after the atebe combo? And for those patients that did receive subsequent therapy, what treatments did they get?

Yes. Emily, that's a great question. So we know that about half the patients from our study went on to receive treatment in the second-line setting that we have information about. And of those patients, the vast, vast majority received additional chemotherapy. So there's only one patient that we're aware of out of the entire 34 who went on to an experimental targeted agent. So I'm glad you asked because there's -- it's important to understand that this is not a group of patients that's going on in large numbers to experimental therapy. Again, there's only 1 of the 34 that we're aware of. And so I think the fact that they're only receiving really, if anything, mostly chemotherapy after treatment just lends further robustness to the strength of the overall survival result that we're seeing and the fact that atebemetinib really appears to be helping these patients stay alive much longer. I mean to have essentially nearly a 2/3 chance of being alive at 12 months versus only about 1/3 probability of being alive at 12 months with the standard of care gem/nab is just a really dramatic change for patients and to be able to do that with great quality of life. I mean we're just so excited for atebemetinib. We think it compares so favorably than anything else that's out there in development in the competitive landscape. We believe it will be best-in-class, and we have the prospect to become standard of care with the modified gemcitabine/nab-paclitaxel.

And that concludes our Q&A session. I will now turn the conference back over to Ben Zeskind for closing remarks.

Great. Well, I want to thank everyone for joining our call today. We particularly like to thank all the patients and the investigators involved in our ongoing studies, and we look forward to updating you on further progress in the coming year. Thank you, everyone. Have a good night.

And this concludes today's conference call. Thank you for your participation. You may now disconnect.