Benjamin Zeskind
Analyst · atebemetinib and first-line pancreatic cancer patients
Thank you, Laurence, and good morning, everyone. We are excited to hold this call now that our financing is complete, and we can share feedback from the PanCAN meeting. And I've had a little more time to work on my jokes. Please turn to Slide 3. I Today, we're going to discuss 4 topics: the extraordinary overall survival for first-line pancreatic cancer patients treated with a atebimetinib plus chemo. The favorable tolerability and potential for best-in-class profile, pushing forward the Phase III in first-line pancreatic cancer, new Phase II studies in lung cancer and with our deep cyclic inhibitor pipeline and the financing and strategic investment, which is an unprecedented value creation opportunity for our patients and our shareholders. But first, a little context. 17 years ago, I started Immuneering to help cancer patients live longer. Overall survival has been the goal from the very beginning because nothing matters more to cancer patients than to stay alive and to thrive. So with that context, it is incredibly gratifying to see that we have figured out how to keep so many pancreatic cancer patients alive longer with atebimetinib. There's a common word we hear from people who really get to know atebimetinib, from an investigator giving it to patients to a leading pharma company after extensive diligence to our own team. And that word is transformative. Why? Transformative because it has the potential to treat such a broad range of cancers driven by the MAP kinase pathway, transformative because it has great durability and is not driving resistance in the same way as typical targeted therapies and transformative because of great tolerability. It's been described to us that patients feel almost like their pre-diagnosis cells on atebimetinib. We believe that atebimetinib is a transformative molecule. And last week was a transformative week for Immuneering. Most importantly, we announced the extraordinary overall survival data that you are about to see, showing that we've nearly doubled survival at 9 months in first-line pancreatic cancer patients. In addition, we announced the pricing of a $175 million underwritten offering and a $25 million private placement last week, providing capital from a world-class group of forward-thinking investors and a great strategic partner in Sanofi to not only help fund the Phase III study for atebimetinib in first-line pancreatic cancer patients but also to fund planned near-term combination studies in lung cancer and to advance our preclinical pipeline of deep cyclic inhibitors against additional cancer targets. Stay tuned for more details in the near future on those plans. Based on current operating plans, we expect our current cash and proceeds from the offering to fund the company into 2029. We believe last week was a turning point and Immuneering is a different company this week than it was 1 week ago. And I think that's just starting to sink in. Frankly, it's just starting to sink in with us and even more so externally. And we presented the data at the PanCAN summit yesterday and the most frequent reaction was, wow, congratulations. To have this kind of survival data in first-line pancreatic cancer is just unprecedented. We believe we're in a better position than ever before with a higher probability of success than ever before led by its atebimetinib in pancreatic cancer, but including many other cancer types and other molecules. I've never been more excited or more optimistic about this company's potential to transform cancer by keeping patients alive and helping them thrive. So with that, let's get into the data. Please turn to Slide 4. Here are the latest results from our ongoing Phase IIa study of atebimetinib plus modified gemcitabine/nab-paclitaxel in first-line pancreatic cancer patients using an August 26, 2025 data cutoff. The bottom line is that we believe we've figured out how to keep these patients alive longer. Now with 9 months of median follow-up time, you can see we have a 94% overall survival at 6 months and an 86% overall survival at 9 months. These are extraordinary results. And the key question is, how robust are they? Do they rest on shaky ground or a solid foundation. As I walk you through the data, you'll see that there are many pillars of robustness that we believe support the data, an extremely solid foundation. Starting with the N. This is in 34 patients, which we believe is enough to really say something. In June, with 6 months of median follow-up time, we shared a 6-month overall survival of 94%, and I walked you through all the factors supporting the robustness of that number. And I'm happy to report that with 3 additional months of median follow-up time, we are still at 94% overall survival at 6 months. With all the patients still on study to the right of it, so it's unlikely to change much at this point. At 9 months, we're at 86% overall survival. And while the curve also looks great to the right of that, we're careful not to claim anything beyond our median follow-up time. We were careful in June and we're careful here. And of course, our median overall survival is not yet reached. In fact, the curve is so flat that it's challenging to model right now when it might be reached. These results, in and of themselves are compelling because so many of the patients are staying alive, but they become even more compelling when we compare them to the reported benchmark for standard of care. So with that, please turn to Slide 5. Here, we're plotting the cross-trial comparison between our ongoing study and the pivotal study of standard of care gemcitabine/nab-paclitaxel in first-line pancreatic cancer, the MPACT study. What you can see is that patients in our study show a 27-point separation from standard of care at 6 months with 94% OS. That separation grows to 39 points at 9 months with 86% overall survival, nearly double the recorded benchmark for standard of care. It's great to see the separation growing with additional follow-up time as the durability that we designed into atebimetinib, making it harder for the tumor to adapt and develop resistance really shines through. The sheer magnitude of the separation lends another pillar of robustness to the results. But let's say you want to be in atebimetinib skeptic, getting harder and harder to do that, but let's say you do. Even if you want to take the most pessimistic view of the data that's statistically justifiable, you take the bottom end of our 95% confidence interval. And even then, we have a 10-point separation at 6 months, which grows to a 19-point separation at 9 months. So the fact that even the bottom of our 95% confidence interval shows such good separation with standard of care is another pillar of robustness supporting these incredible overall survival results. Now gemcitabine/nab-paclitaxel is the most relevant standard of care benchmark because it's the most common global standard of care, it's the control arm in our planned Phase III design. It's what we're combining with, and it's the treatment most commonly given to older patients with a wider range of fitness levels like the ones in our study. But there are 2 other standard of care treatment for first-line pancreatic cancer. So let's see how our results compare to those. Please turn to Slide 6. Here, we are fighting the cross-trial comparison between our data and the pivotal studies for all 3 standard of care treatment. You can see that we have clear separation not only from gemcitabine/nab-paclitaxel in orange, but also from FOLFIRINOX in green and NALIRIFOX in red. And again, even the bottom of -- end of our 95% confidence interval clears the reported 9-month overall survival for all 3 standard of care treatment. So the fact that we show such a strong separation in overall survival compared not only to the most relevant standard of care, but even to harsher regimens that are typically reserved for younger, higher fitness patients adds another pillar of robustness to our results. Overall survival is the gold standard endpoint in oncology. It's the basis upon which pancreatic cancer drugs have been approved, it's the primary endpoint in our planned Phase III trial design. Everything else is a surrogate endpoint that tries to predict overall survival. But it's still helpful to look at those surrogate endpoints to help assess the robustness of the overall survival result. Now there have been companies that have had interesting OS data but the other metrics don't show separation with standard of care. That's just not the case here. We see a strong separation across many different surrogate endpoints, including progression-free survival, overall response rate, disease control rate, waterfall plots, spider plots and tolerability, all of which lend robustness to the overall survival results. So let's start with progression-free survival. Please turn to Slide 7. Here, you can see our progression-free survival results. We have an excellent 70% progression-free survival at 6 months and 53% progression-free survival at 9 months. Now at this time, we also have a median progression-free survival that we're very happy with at 9.6 months. That's more than a 4-month separation from gemcitabine/nab-paclitaxel in the MPACT study and more than a 2-month separation from NALIRIFOX, which is typically given to the younger, higher fitness patients. But I want to point out that we believe this median PFS has the potential to get even better. You can see there are 5 patients on treatment to the left of this, and we've checked at the time of the data cutoff, and they are generally doing well. So we're optimistic that in the coming weeks and months, some are likely to move past 9.6 months, which would pull off the curve and further extend the median progression-free survival. Now over the last few days since we announced the data, one of the most frequent questions we've been asked is, to what extent can we help patients with liver metastases. Historically, pancreatic cancer patients with liver metastases have had a slightly worse prognosis than those with non metastases when treated with chemotherapy. So we took a look, about half of the patients in our study had liver met. And when we look specifically at that subset of 16 patients, we found that the median progression-free survival is 9.6 months, the same as in our full 34-patient intent-to-treat population. The median overall survival is also not yet reached in that subset, same as in the full 34-patient intend-to-treat population. We believe this is great news for pancreatic cancer patients with liver mets because it suggests that our results are just as applicable to them. And this doesn't surprise us because we see multiple instances of liver met shrinking, including in our longest running patient from Phase I, who has now been on treatment over 18 months with multiple liver mets that have shrank over time. The strength of the progression-free survival data, both in patients with liver mets and in the full population, adds additional pillars of robustness, supporting our extraordinary 86% overall survival at 9 months. Please turn to Slide 8. Here, we plot the cross-trial comparison between our progression-free survival data and the pivotal study of gemcitabine/nab-paclitaxel. You can see we have a 26-point separation at 6 months and a 24-point separation at 9 months with a 53% progression-free survival, that's nearly double the benchmark of 29%, lending further robustness to our overall survival results. Please turn to Slide 9. Again, you can see that our progression-free survival is well separated, not only from gemcitabine/nab-paclitaxel but from all 3 standard care treatments. Please turn to Slide 10. Here's our waterfall plot. And it's great to see that the vast majority of patients have lesions that are shrinking. Now there's quite a bit of literature showing that overall response rate is not a great predictor of overall survival in pancreatic cancer. So we acknowledge that this is a surrogate endpoint of limited and questionable value. That said, our overall response rate is excellent. We have a confirmed overall response rate of 39% and which compares favorably with a benchmark of 23% from MPACT. Our June update included 4 unconfirmed PRs that have since confirmed. So again, I'll emphasize that this 39% ORR is based entirely on confirmed responses and not all reported overall response rates are. So it's important to compare apples-to-apples. It's also worth noting that we have several patients who are currently stable disease and are continuing on treatment as indicated by the arrows. And atebimetinib generally shrinks tumors slowly but surely, so we're optimistic that this number could continue to grow over time. In our Phase I, we had a patient who crossed from stable disease to a partial response after 14 months. So low and steady wins the race. Our disease control rate at 81% compares very favorably to the 48% in the MPACT study. So the waterfall plot, the overall response rate and the disease control rate all lend additional pillars of robustness, supporting the really nice 86% overall survival that we're seeing at 9 months. Please turn to Slide 11. Here are our spider plots, showing how the tumors change in size over time. And what you can see is that the vast majority of patients have lesions that are shrinking slowly but surely. We're not the typical targeted therapy that bombards the tumor continuously to shrink at 50% to 60% for a month or 2, and then the tumor adapts and develop resistance and comes rolling back worse than before. Instead, we typically shrink tumors more slowly, but more durably without driving resistance. It's like the old fable of the Tortoise and the Hare. We believe a atebimetinib is the turtle that slowly maturely wins the race. These spider plots, which, by the way, most companies don't show, lend another pillar of robustness to the 86% overall survival we observed at 9 months. Now let's take a look at tolerability. Here, you can see the favorable tolerability profile of atebimetinib plus modified gemcitabine/nab-paclitaxel On Slide 12. We only saw 2 categories of adverse events that occurred at the Grade 3 level in more than 10% of the patients, anemia and neutropenia. Both are associated with the chemotherapy we're combining with and neither were seen in our monotherapy studies. So it's not clear if atebimetinib is adding much, if anything, in the way of grade 3 adverse events over the chemo alone. Now, some people see this slide and the fact that many of the adverse event levels are lower than the MPACT study, and they say is atebimetinib somehow erasing the side effects of chemo? To which we say, it's good, but it's not quite [indiscernible]. We're combining with modified gemcitabine/nab-paclitaxel, which is every other week versus 3 weeks on, 1 week off. It's common for investigators to start with 3 weeks on, 1 week off and then back off to every other week if needed. So a few years ago, Dr. Daniel Hahn and [ Tanios ] Bekaii-Saab the Mayo Clinic studied this, and they found that the modified regimen is better tolerated and demonstrates comparable survival. And they published this in a great paper on at all 2017. And again, if you look at the paper, the tolerability profile is similar to what we're seeing here except we see slightly higher rates of anemia, which we believe are due to older age and perhaps the patients staying on chemo longer. Now in FDA's draft guidance last month, they emphasize that overall survival is both an efficacy and a safety endpoint, meaning that when patients have poor tolerability, it impacts their performance status and they don't live as long. And the converse is also true. When patients have better tolerability, they maintain their performance status and live longer. And we think this helps contribute to the great 86% overall survival we're seeing at 9 months. Now don't get me wrong. The main reason our patients are living longer is that we're shrinking their tumors slowly but surely without driving resistance as you saw on Slide 10 or Slide 11. But we think the totality contributes as well and we have other analysis underway to more fully understand the quality of life benefits we see from atebimetinib. Please turn to Slide 13. Now usually, people get to this point in the data and they say, aha, show us the baseline demographics. Did you somehow have different patients from the pivotal studies of prior standard of care? And the answer is, yes. our population was different. It was actually older. Our median age was 69, while patients in the pivotal studies where they're low to mid-60s. 2/3 of our patients were over the age of 65 versus half or less in the pivotal studies. Otherwise, we're pretty well matched across the other baseline characteristics, including location of metastases. We do see a slight imbalance when we look at the astrological signs in favor of more patients that are Pisces, and we're looking into the significance of that. As I mentioned earlier, patients with lung mets historically have a better prognosis. And as you can see in the footnote, we have 35%, which is the same percentage of those in impact, and many overlap with other metastases. Now historically, patients with liver or peritoneal metastases have worse prognosis. And as you can see, most of our patients fall in those categories, similar to MPACT. And as noted earlier, the progression-free survival for those with liver mets is identical to the overall intent-to-treat population progression-free survival in our study. Meaning that patients with liver mets do just as well on our study, which is great news for those patients. The fact that we're able to show an 86% overall survival at 9 months in a meaningfully older population runs another pillar of robustness to our results. Please turn to Slide 14. Our next step is to run a global randomized pivotal Phase III study evaluating atebimetinib plus modified gemcitabine/nab-paclitaxel in first-line pancreatic cancer patients. This is a straightforward plain vanilla design with overall survival as the primary endpoint in line with last month's FDA guidance that said overall survival was the most appropriate endpoint in diseases like pancreatic cancer. This trial has one question and one answer. This design, of course, is subject to change based on regulatory feedback. Speaking of which, please turn to Slide 15. We're guiding to sharing regulatory feedback and initiating the study by the end of the year, then dosing the first patient by mid-next year and a top line readout approximately 2 years later. But it's not as if we'll go dark for 2 years. We have combination studies planned in lung cancer. We've guided to an update from this cohort at a meeting next year and our preclinical pipeline of deep cyclic inhibitors designed to bring the same tolerability and durability to other targets is progressing steadily as well. Importantly, with last week's funding announcement, we believe we are now funded through the Phase III readout and all the other catalysts I mentioned with runway expected into 2029. Slide 16 to 21 have additional information on how we designed atebimetinib to achieve the kind of durability and tolerability we're seeing. These slides are on our website for reference. And I'll just emphasize that we designed atebimetinib in-house. It's novel composition of matter, and we just had our U.S. composition of matter patent granted with exclusivity expected into at least late 2042, with additional patent applications pending that extend exclusivity into late 2044. Now please turn to Slide 22. As I mentioned earlier, we're planning 2 combination studies in lung cancer, the first through an agreement with Regeneron to combine with their anti-PD-1, Libtayo. And the second one through an agreement with Eli Lilly to combine with their second-generation KRAS G12C inhibitor, olomorasib. We're happy to be working with both of these companies. And of course, we're thrilled to have the strategic investment from Sanofi that we announced a few days ago. Given that the MAP kinase pathway drives the majority of all cancers, we're just getting started with pancreatic cancer and lung cancer and then likely colorectal cancer, melanoma, AML, breast cancer and many others. This broad applicability, combined with the unique observed durability and tolerability make atebimetinib an ideal backbone for a wide variety of combinations. It truly has the potential to be a pipeline in a product, and we are just getting started. Please turn to Slide 23. In conclusion, we've demonstrated an extraordinary ability to keep pancreatic cancer patients alive longer, with overall survival of 94% at 6 months and 86% at 9 months. Both dramatically separated from any current standard of care in first-line pancreatic cancer. And we believe these results are incredibly robust. We believe they're supported by the 95% confidence interval, the progression-free survival we're seeing, the waterfall plots with overall response rate and disease control rate, the spider plot, our tolerability data and the fact that we observed all of this in a meaningfully older population and that it works just as well in liver met patients. And we have an exciting set of catalysts coming up in the coming weeks, months and years. Please turn to Slide 24. Today, we discussed extraordinary overall survival for first-line pancreatic cancer patients treated with atebimetinib plus chemo. We discussed favorable tolerability and the potential for best-in-class profile. We're pushing forward to Phase III in first-line pancreatic cancer, the new Phase II studies in lung cancer and with our Deep Cyclic Inhibitor pipeline, and we talked about the financing and strategic investment, which enables unprecedented value opportunity for patients and shareholders. Speaking of which, I want to thank all the patients and their caregivers the investigators, team members, along with our partners and our investors. We're frequently told that atebimetinib is a transformative molecule. And last week was a transformative week between sharing these incredible overall survival results and raising enough money to fund not only our Phase III study, but also our 2 lung combination studies and our preclinical pipeline with runway into 2029. The impact of last week is still syncing in for all of us, but we believe Immuneering has entered a new era as a well-funded company with a great strategic investor and highly compelling data. I've never been prouder of our team or more excited for the value we can create for our patients and our shareholders. Operator?