Hello, everyone, and welcome to Oppenheimer's 36th Annual Healthcare Life Sciences Conference. I'm Jay Olson, one of the biotech analysts here at Oppenheimer, and it's a pleasure to welcome you to our discussion with Immuneering, and it's an honor to introduce Ben Zeskind, CEO and Co-founder of Immuneering. Thank you so much, Ben, for joining us here today. I'll turn it over to you.
Great. Thank you, Jay. I wanna thank you and the entire Oppenheimer team for having us today, thank everyone for joining. I'm Ben Zeskind, Co-Founder and CEO of Immuneering, today I'm gonna talk about our work on improving survival in first-line pancreatic cancer and beyond. I'll be making forward-looking statements today, please see our disclosures for more information. We're working on improving survival in first-line pancreatic cancer and beyond, starting with atebimetinib. Atebimetinib is the first in a new category of oral drug candidates called Deep Cyclic Inhibitors that are designed to improve overall survival by three mechanisms. It's really encouraging what we're seeing so far. In January, we reported 64% overall survival at 12 months in our ongoing P IIa study of atebimetinib plus modified gemcitabine nab-paclitaxel in first-line pancreatic cancer patients.
You can compare that to a 35% benchmark for standard of care gemcitabine/nab-paclitaxel. For P III , we're aligned with FDA and EMA and fully funded to move forward in first-line pancreatic cancer, the MAPKeepeR-301 study. This is gonna be a global randomized pivotal trial of atebimetinib plus mGnP versus standard of care gem/nab, with overall survival as the primary endpoint, 510 patients, and we expect to dose the first patient in mid-2026, mid this year. As I mentioned, atebimetinib has three mechanisms that are each well-established to improve survival: shrinking tumors durably with less resistance, preserving body mass, which involves counteracting cachexia, and minimizing side effects to maximize combinability and performance status. Atebimetinib and our pipeline, more generally, has broad potential.
Atebimetinib targets MEK, it's applicable to a broad range of RAS, RAF, and other MAPK-driven cancers, about half of all tumors. We have a P II trial of atebimetinib in combination with Libtayo in lung cancer. We expect to dose the first patient in the second half of this year, we have other combinations to follow, as well as a preclinical pipeline of Deep Cyclic Inhibitors. How does atebimetinib fit in to the broader landscape? We believe it has a differentiated profile as compared to both RAS inhibitors and other MEK inhibitors. If you look at atebimetinib, it shrinks tumors in both RAS and RAF-driven tumors. It also preserves body mass, it counters cachexia, and it minimizes side effects.
When you look at RAS inhibitors, they typically do a great job of shrinking RAS-driven tumors, but they can't really do much for RAF-driven tumors. They can't really do much to preserve body mass, and I don't think anyone would call the side effects minimal. The same is true of other MEK inhibitors, kind of the first generation or legacy MEK inhibitors that are out there. They've generally not been used in RAS mutant disease. They are used in RAF-driven disease. They do preserve body mass, counteract cachexia, but again, I don't think anyone would say that they minimize side effects. What makes atebimetinib unique is its ability to shrink a broad range of tumors while preserving body mass and minimizing side effects, all of which promotes overall survival.
I think this is a really important point, 'cause I, you know, I think sometimes people think about minimizing side effects or preserving body mass, and they kind of think, "Oh, that's a nice to have, that. You know, that's just sort of, that's qualitative, that's warm and fuzzy." These are actually quantitative mechanisms that have been shown to directly promote overall survival. Just to emphasize that, on the next page, you know, just to kind of summarize some of the clinical evidence for atebimetinib plus modified gem/nab, in first-line pancreatic cancer patients, clearly shrinking tumors with a disease control rate of 81%, clearly preserving body mass, 84% of patients have stable or gain weight.
In terms of minimizing side effects, only two categories of Grade 3 or higher adverse events were seen in more than 10% of the patients. Just to hammer home the point that each of these is a separate mechanism that's linked to survival, if you look at prior literature, published studies, of course, overall survival is well correlated with disease control rate. 0.74 is the correlation coefficient, highly significant, so we know disease control rate is well associated with overall survival. Is preserving body mass. Published studies have shown when patients have weight loss in pancreatic cancer, the hazard ratio is 1.55, a substantial increase in the risk of death when patients have weight loss.
In fact, a third of pancreatic cancer patients die from complications of cachexia, sadly. In terms of minimizing side effects, look, when a patient declines to ECOG 2 performance status, the hazard ratio for death increase is 1.48, about a 50% increase. Similarly, when a patient, because of side effects, cannot go on to second-line treatment, it's a similar hazard ratio, about 1.51. The point I wanna make here is that there are three distinct mechanisms, each of which contributes to overall survival. That's shrinking tumors, preserving body mass, and minimizing side effects. It's really each of those mechanisms together that enables atezolizumab to uniquely promote survival, and that's what we're seeing.
Here's the survival that we ann ounced in January, from our study of atebimetinib in first-line pancreatic cancer patients. What we're seeing is 64% overall survival at 12 months, with the median not yet reached, and that's all with a median follow-up time of 13.4 months. This data is very encouraging, and in fact, it's particularly encouraging when you view it in the context of the standard of care benchmarks currently available for first-line pancreatic cancer. Here we're plotting the cross-trial comparison between the data from our study and the data from the pivotal study of standard of care gemcitabine/nab-paclitaxel, the P III IMPACT study. Take it with a grain of salt, as you would any cross-trial comparison. What we're seeing is really a striking difference.
Whether you look at six months, at nine months, or at 12 months, you see a very consistent separation in sort of the high 20s to 30s, in terms of the separation between the survival you would expect for standard of care and what we're seeing. In fact, you know, because we have 13.4 months of median follow-up time, you can kinda look out to that point, where the overall survival in our study stays at 64%, whereas the benchmark for standard of care declines actually to 31%. We're actually more than double the benchmark for standard of care at our median follow-up time. This is very encouraging, and it certainly, we think, robustly justifies the P III that we'll soon be dosing patients in.
you know, I think even if you wanna take the most pessimistic view of the data that's statistically defensible, you could take the bottom end of our 95% confidence intervals. Even if you wanna be that skeptic and take that lower number, at six months,nine months, and 12 months, those numbers are each well separated with the standard of care benchmarks. Again, our median overall survival is not yet reached with a median follow-up time of 13.4 months, whereas in the pivotal study, the standard of care benchmark, it was eight and a half months overall survival. We believe this data is very encouraging and certainly well justifies the randomized P III that we're getting ready to run.
gemcitabine nab-paclitaxel is the most relevant benchmark because it's the most common global standard of care. It's the one we're combining with. It's the one that's gonna be the control arm in our P III study, and it's the one that's typically given to the kinda older, lower fitness patients, like the ones we had in our study. There are two other approved standard of care treatments in first-line pancreatic cancer, and I think it's important to compare our survival against all three of them to really put that into context.
Here we're plotting the cross-trial comparison, so again, take them with a grain of salt, between our overall survival data and the pivotal data for not only gem/nab, but also FOLFIRINOX in the green and NALIRIFOX in the red, all three standard of care treatments in first-line pancreatic cancer. You can see why, even though FOLFIRINOX and NALIRIFOX generally have harsher side effects than gem/nab, some of the younger, higher fitness patients generally get them 'cause you know, there is a survival benefit. You can see the red and green curves are a bit better than the orange. That said, you know, what we're seeing so far with atezolizumab plus modified gem/nab is kinda head and shoulders above all of them. We certainly...
we think that's very encouraging to see this kind of separation not only from gem/nab, but from all three of the standard of care benchmarks in first-line pancreatic cancer. Overall survival is the most important thing. It's the primary endpoint in our P III study. It's the thing that matters most to patients. It's the thing that, pancreatic cancer drugs are approved based on. There are secondary endpoints, and it's important to look at them because I, you know, I think that adds robustness when you see a good separation from standard of care. Fortunately, we do on each of those secondary endpoints.
In terms of median progression-free survival, we're at eight and a half months, which is a full three-month separation from the standard of care benchmark at five and a half months. Very happy with that. In terms of overall response rate, we're at 39%, substantially higher than the 23% benchmark from standard of care in the IMPACT study. Then disease control rate, we're at 81%, as I mentioned earlier, again, a nice separation from the standard of care GNP at 48%. Really encouraged to see that the secondary endpoints also show strong separation from the standard of care benchmarks, and I think this adds robustness to the overall survival result that we're seeing. What about tolerability? As we mentioned earlier, you know, side effects drive performance status.
They drive combinability, they really have a direct relationship with overall survival. As I alluded to earlier, what we're seeing really quite encouraging in this combination. There are only two categories of adverse events that we see at the Grade 3 level in more than 10% of the patients, neutropenia and anemia. Both of these side effects are associated with the gemcitabine nab-paclitaxel chemotherapy that we're combining with.... neither of which do we see in the monotherapy setting with atezolizumab alone. It's really not clear that atezolizumab is adding much, if anything, in the way of harsh side effects on top of what you would expect for the chemotherapy alone.
That's so important to help patients maintain their performance status and enables us to really do this combination at full dose. Let me emphasize that we're using 320 milligrams of atebimetinib, the full dose, in combination with chemotherapy. That's not something others can say. I think that's really important. Again, to help patients maintain their performance status and, you know, go on to subsequent lines of therapy if needed. Really encouraging to see this kind of tolerability.
When you look at these kind of cross-trial comparisons, and I, you know, I mentioned earlier, take them with a grain of salt, really the way to gut check them, make sure that it's, you know, it's a reasonable comparison, is to look at the baseline demographics of the patients. When you compare the baseline demographics of the patients in our study against the three pivotal standard of care studies in first-line pancreatic cancer that we've been talking about, our patients are pretty well matched, with the exception of age. We had a meaningfully older population, median age 69 versus low to mid-sixties in the pivotal studies. More than two-thirds of our patients were over the age of 65, whereas it was half or less in the pivotal studies.
The fact that we're seeing 64% overall survival at 12 months, you know, so well separated from the benchmarks for standard of care in a meaningfully older population, I think just lends further robustness to the, you know, to the results that we're seeing, and just lends further justification to the randomized P III study that we're excited to start dosing in mid-year. Again, just to summarize, we have 64% overall survival at 12 months in this cohort. What we've guided to as the next data catalyst is in the first half of 2026, we plan to report overall survival data from an expanded cohort of over 50 first-line pancreatic cancer patients treated with atebimetinib, plus Modified Gemcitabine Nab-Paclitaxel.
You know, our original goal for this arm was to enroll 30 patients. We enrolled 34. There was so much demand from our site, so much interest in getting more patients onto the study, based on what they were seeing, that we reopened the study and took another 20 or so patients. The full cohort of over 50, you know, that because those patients started later, it pulls the median follow-up time earlier. It's approaching sufficient median follow-up time, and, you know, we're looking forward and excited to share an update on this in the first half of 2026.
You know, what we said in January is that the overall survival in the expanded cohort is trending consistently with the overall survival in the original 34 patients, and I think that's important. Now, on our call in January, Dr. Pelster from Sarah Cannon, joined us to share a really remarkable case study of one of the patients in that expanded cohort. I encourage you all to listen to the replay, if you haven't heard it. She tells it quite well in her own words. Essentially, this is a patient, who, after about five months of treatment, as of the data cutoff, had two of her lesions, the two liver lesions rendered completely undetectable, improved quality of life, gained weight.
Look at that, 33 pounds of weight gain. Think about that and just think back to the hazard ratio, right? When patients lose weight, it has a negative impact on survival. Patients gaining weight, you know, this is really good news for the survival of patients. Again, that's a separate and independent mechanism that you don't see in RAS inhibitors. That's a unique to atezolizumab.
You know, when something so important as a patient's life is at stake, you know, why just use one mechanism when you can have three mechanisms that are all working towards survival, shrinking the tumors, counteracting cachexia, and preserving body mass, and then reducing side effects so patients can maintain their performance status, so you can have, you know, full dose combinations? I think these are really important things. It, you know, it all contributes to overall survival, but it also makes a real difference for patient... You know, this patient, Dr. Pelster, has described, you know, had so much pain and weakness. She needed friends and family to bring her to appointments.
She had a, you know, was part of a walking club in her neighborhood that she had to stop doing when she got sick. What we're really happy and proud about is that after five months on study, as of the data cutoff, this patient regained the ability to drive independently and was able to rejoin the walking group in her neighborhood, as Dr. Pelster has said. Really just great to see these quality of life improvements that mean patients are not only surviving, but they're thriving. I think this is really what can happen when you have not just 1 mechanism to promote overall survival, but three mechanisms.
The, you know, the survival that we're seeing, as I mentioned, really has us excited for the P III study. This is our P III study. It's called MAPKeeper 301. It's a global randomized pivotal trial designed to demonstrate a best-in-class profile in first-line pancreatic cancer. Fairly plain vanilla design, atezolizumab plus the modified gem/nab that we've been talking about, randomized against standard of care gemcitabine/nab-paclitaxel, in the first-line setting. Overall survival is the primary endpoint, but important secondary endpoints that we mentioned, including quality of life. As I said, we expect to dose the first patient mid-year, and a top-line readout about two years later. We're really excited for this trial.
To summarize what I've been saying, then we'll leave some time for questions. You know, our company is focused on improving survival in first-line pancreatic cancer and beyond. Leading the way is atebimetinib, which is the first in a new category of oral drug candidates that we developed called Deep Cyclic Inhibitors, designed to improve overall survival by three mechanisms. It's important to emphasize, we developed this in-house. This isn't something that we licensed in from another company. We developed it in-house. It's novel composition of matter. Our chief scientific officer is one of the inventors on the atebimetinib patent, which, by the way, a composition of matter patent just was granted in the U.S. this summer.
Nice long exclusivity into at least 2042, probably more like 2044 with extensions. This is a new category. We developed Deep Cyclic Inhibitors with these three mechanisms to improve overall survival. It's great to see 64% overall survival at 12 months that we announced in January in our ongoing P II a study in first-line pancreatic cancer patients. Nearly double the benchmark at 12 months, as I mentioned, more than double the benchmark at the median follow-up time. Our P III we, you know, we have full alignment with FDA and EMA. We're funded and, you know, approaching first patient dose in first-line pancreatic cancer.
It's a global randomized trial versus standard of care, with overall survival as the primary endpoint, which is the thing we've been working towards by three distinct mechanisms, each of which is well-established to improve survival, shrinking tumors durably with less resistance, preserving body mass and counteracting cachexia, and minimizing side effects, so you maintain performance status and maximize combinability. Again, just a broad potential, because we're targeting MEK. This is applicable to RAS, RAF, and other MAPK-driven cancers, about half of all tumors. We have a P II o f atezoliamab in combination with Libtayo, an anti-PD-1, in lung cancer. We expect to dose the first patient in the second half of this year, with quite a few other combinations to follow.
We have a preclinical pipeline of Deep Cyclic Inhibitors, you know, that have similar mechanisms that we're quite excited about. With that, I want to thank everyone for listening, and I'll pass it to Jay for any questions.
Thank you, Ben. Really appreciate your bringing us up to speed and all the. Again, really impressive data. Thank you also for the perspective that you've put around that and describing those three drivers of overall survival. That's super helpful. I guess our question is, can you share any additional feedback that you've gotten from KOLs? Especially, which of those three differentiating features do or maybe others, do KOLs consider the most important for atebi?
That's a great question, Jay. I think they're all important, you know, and I think that's what has KOLs so excited, right? I mean, this atezoliamab is a triple threat. It's a triple threat. It's got three, you know, a triad of three distinct mechanisms that all, you know, drive survival, right? I think that's something that really emerged through our conversations with KOLs and investigators, right? I mean, you know, these are also great things for patients. They enhance their quality of life when they have fewer side effects, when you know, when you can preserve body mass and counter cachexia. That's great, but it's a little bit qualitative, right?
It's, it's a little, it's a little hard to quantify. You know, I think what's really exciting and what we've heard in a lot of these conversations is that these are mechanisms that have been clearly established to have an impact on overall survival. I think that's why it's important to put out these kind of hazard ratios, right? You know, when a patient's performance status declines, you know, it dramatically increases their risk of death. When a patient has weight loss in pancreatic cancer, dramatically increases their risk of death.
When you know, when you have drugs out there, other alternatives being explored, where the, you know, the patients have vomiting, they have nausea, they have mouth sores, you know, it's a lot harder to, we believe, to kind of be stable or gain weight. Those are things that matter for survival, as well as for quality of life. You know, when patients have harsh side effects, it can, it can really affect their, you know, their performance status. You know, I think appreciating that each of these mechanisms together, is what makes atezoliamab so unique, really whether it's relative to RAS inhibitors or prior MEK inhibitors.
You know, I think this is what KOLs have been really excited about in our conversations. Look, you know, our P II was at 18 centers, there's not you know, the word is still spreading about atebimetinib, right? There's a lot of folks out there that haven't heard of it yet or sort of don't really know about its characteristics, we've been working hard to change that, to really spread the word and get the word out. I think the more people see the data, understand the mechanisms and, you know, really understand all of what's driving this kind of exciting survival, right?
Shrinking tumors, preserving body mass, minimizing side effects, all helping patients, we believe, live a lot longer than they otherwise would, and that's been our goal from the start. That's been really exciting.
Awesome. Well, thank you. That's super helpful. Yeah, the framework is very clear. Thank you for providing that explanation. I guess just going to the data that you mentioned plans to report some additional data from your expanded cohort in the first half of this year, you kind of qualitatively commented on the OS trend that you're seeing out to 13 months or so. How would you like to set investor expectations for the combined data set? You mentioned that fortunately, you have over 50 patients now. What sort of expectations do you want to set for patients in terms of the follow-up duration that you plan to share? How to think about OS rates and any other data points that you might disclose?
Yeah, yeah. Thanks, Jay. Again, you know, happy to, happy to share again here the data that we shared in January, right? With the 13.4 months median follow-up and the December 15th cutoff. You know, really just kind of reiterating or re-emphasizing what, you know, what we said in January, which is that this, you know, this broader cohort of over 50 patients, while it does have a shorter median follow-up time than the 34, you know, it is a larger cohort, right? It's, you know, it's 20 some odd additional patients.
The, you know, the fact that we, you know, we said in January that the overall survival is trending consistently, you know, I think is really an important piece of news that we shared in January. You know, I think, as with anything in oncology, sort of the more patients, in which you see a consistent trend, you know, the more it kind of lends robustness to that kind of a result. I, you know, I think, in the first half of the year, as, you know, as it approaches sufficient median follow-up time, we're excited to share more on that expanded cohort.
Okay. All right. Well, we're looking forward to that, as I know a lot of investors are as well. I guess moving on to your P III MAPKeeper 301 study, thank you for sharing that study design with us. I guess, can you just talk a little more about the preparation work that's currently underway, and how is the level of enthusiasm that you're seeing from investigators?
Yeah, it's extremely high. You know, virtually everyone we've talked with is excited about the study, you know, really unique. Again, a lot of them just hadn't heard of the drug before we approached them. You know, working to raise the profile of atebimetinib. You know, when they see what it can do in shrinking tumors, preserving body mass, minimizing side effects, they're just really excited about what that means for their patients, the ability to survive and thrive. We've had a lot of excitement and enthusiasm among investigators for this study. You know, our preparations are busy and on track, and we expect to dose the first patient mid-year.
Okay. Sounds good. We're looking forward to that. Yeah, maybe you had commented on some of the design features. One of the things that comes up a lot with investors is, does the study allow treatment to continue beyond progression? Is that feature something that is considered unique, and how does it impact trial outcomes?
Yeah. It's a great question, Jay. Treatment beyond progression is something that we've not done a lot of in the study to date, in the 34 patients. Less than 10% of them receive treatment beyond progression. It's gonna be at the investigator's discretion in P III . I think that's important because we've seen, you know, in the few cases where we did allow it, you know, it can make a difference, right? This is an example of a patient who initially had tumor growth, but the investigator requested treatment beyond progression, and you can see clearly that was the right call, given what's happened subsequently.
You know, I think this is just one example, but it's, you know, when you compare studies, particularly across companies, it's really important to know how much that was done. You know, I think there's another company out there that says they're encouraging treatment beyond progression in their first-line study. We've not done it very much. Again, only 9% of patients. That's, you know, that's just something important as a factor to make sure you're comparing apples to apples. You know, again, I think it's important to see the survival data in first line from everyone in this space, right? It's important for patients.
You know, there's multiple P III s that are gonna be dosing patients this year in first-line pancreatic cancer, but we're the only ones that have shared overall survival data to date. I really call upon all the players who are running first-line pancreatic cancer trials and, you know, P III trials, to release their overall survival data. Let's see it. You know, I hope we're all in this for patients. You know, hope it's, hope it's great, but when you don't see it and it's not released, you wonder why. We've, you know, we've been very transparent. We've released our overall survival data. We've released our baseline demographics, and I think it's all pretty great.
Excellent. That's super helpful, and thanks for highlighting that case study for us as well. It's really, really encouraging to see that. I know you commented about this briefly at the beginning, but can you just talk about your vision for where atebi is gonna eventually fit into the evolving first-line pancreatic cancer treatment landscape? Then also additional opportunities for, you mentioned your combination studies? What about other indications and I guess just top priorities for Immuneering in 2026?
Yeah. I mean, look, if the P III confirms this kind of a survival advantage over standard of care, you know, we believe atebimetinib will become, you know, the standard of care in first-line pancreatic cancer. Look, even if another drug, even maybe one that gets a lot of attention, right? Even if it could show this kind of survival, but with a, you know, a less attractive tolerability profile, right? Without that ability to minimize side effects that's so important for performance status, without the ability to preserve body mass. You know, I think again, when you're dealing with someone's life, why just put all your eggs in one basket?
Why rely on one single mechanism when you can have three mechanisms that are all working together to promote survival? You know, I think there was sort of an old generation, where it was just focused on shrinking the tumor at all costs. It doesn't matter if the patient's covered with rashes and, you know, plagued with, you know, food poisoning, like, symptoms of nausea, vomiting, and diarrhea, as long as you shrink the tumor. I think, I think we're kind of the first of this new generation, this new category, where you can, you know, you can shrink the tumors very effectively, durably, slowly, surely.
You can preserve body mass with 84% of our patients stable or gaining weight, and you can really minimize side effects. I think that ultimately is gonna help patients live longer 'cause you got three mechanisms working towards that, it's gonna really improve their quality of life, and we want our patients to not just to survive, but to thrive.
Excellent. All right. I think we'll wrap things up there. We're a little bit over time, but appreciate the extra time you shared with us here today. Thanks, Ben, again, for bringing us up to speed and all the great work you guys are doing, and we'll look forward to future updates.
Sounds great. Thanks for having us, Jay. Thanks everyone for listening.
Our pleasure. Thanks, everybody.