By Melane Sampson
Immuneering (NASDAQ: IMRX) is challenging conventional approaches of sustained inhibition in oncology by pioneering a novel class of therapies designed to outsmart cancer’s ability to adapt. With a proprietary platform focused on deep cyclic inhibition (DCI), the company is advancing a pipeline of oral small molecule drugs aimed at improving both overall survival (OS) and tolerability for cancer patients.
“OS is the gold standard in oncology, and it has been our goal since we established Immuneering 17 years ago, because in cancer, nothing matters more than keeping patients alive and helping them thrive,” Ben Zeskind, PhD, co-founder, president and CEO of Immuneering, says in an interview with BioTuesdays.
Dr. Zeskind explains that most conventional cancer therapies—such as chemotherapy—are designed for sustained, or continuous, inhibition of cancer pathways. While this leads to rapid tumor shrinkage initially, it also drives cancer to adapt and develop resistance. As a result, tumors shrink quickly but temporarily. Sustained inhibition also suppresses transient signalling in healthy cells, leading to many adverse events, including significant toxicity.
In contrast, Immuneering’s proprietary DCIs are an entirely new category of cancer medicines designed to pulse faster than tumors can adapt, so tumors shrink slowly but durably. DCIs aim to outwit cancer’s adaptability and restore full transient signalling to healthy cells, with the goal of leading to fewer adverse events, longer OS, and higher quality of life.
“What researchers have found is that tumors have two layers of resistance,” Dr. Zeskind says. “The first is acquired resistance, where cells in the tumor mutate and get around the treatment—and Dr. Robert Gatenby at the Moffitt Cancer Center showed that you can counteract acquired resistance with intermittent treatment on a 4-6 week cycle. But there’s also a faster mechanism called adaptive resistance, and that actually starts within 24 hours. That’s when the tumor rewires itself and uses different pathways if one of them is blocked.”
“So, what we found is that if we want to get ahead of both acquired and adaptive resistance, we needed to cycle not on a 4-6 week timeframe—we needed a cycle time faster than 24 hours to scramble both of the tumor’s resistance mechanisms. And that’s where the DCI approach shines,” he adds.
By designing treatments that pulse at intervals shorter than cancer’s adaptive response time of less than 24 hours, DCIs aim to prevent both acquired and adaptive resistance. This approach not only slows tumor growth more sustainably but may also reduce the side effects typically associated with cancer treatments.
Unlike traditional therapies that keep constant pressure on tumors, Immuneering’s DCI drugs hit hard for a short window, then release—allowing healthy cells to recover their natural signaling rhythm. According to Dr. Zeskind, cancer cells often revert to using the same signaling pathways once inhibition stops—essentially being deceived repeatedly.
“Cancer isn’t really very smart—it just has one really good trick, which is its ability to adapt,” he contends. “The problem is that when you give a tumor a steady, predictable selective pressure, as most conventional cancer therapies do, you’re just making it really easy for the tumor to adapt.”
Dr. Zeskind emphasizes that Immuneering’s strategy allows for more durable tumor control, improved tolerability, and potentially better long-term outcomes because tumors adapt to predictability. “When we pulse treatment in this way, the tumor loses its advantage,” he adds.
The company’s lead product candidate, atebimetinib, is an oral, once-daily DCI of mitogen-activated extracellular signal-regulated kinase (MEK) and is designed to improve tolerability and expand indications. MEK is a key control point in the mitogen-activated protein kinase (MAPK) pathway, which is pathologically activated in a majority of cancers, including approximately 97% of pancreatic cancers. Targeting MEK blocks a broader range of MAPK pathway alterations because it is further downstream, creating the potential for more durable benefit.
In a Phase 2a trial, patients with advanced pancreatic cancer treated with atebimetinib plus modified gemcitabine/nab-paclitaxel (mGnP)—a standard chemotherapy—demonstrated a remarkable 86% OS at nine months, compared to ~47% with standard of care. Progression-free survival (PFS) was also significantly higher at 53% versus ~29%.
“Our 94% OS at six months was extraordinary, and with continued follow-up, the 86% OS at nine months shows even more separation from standard of care,” Dr. Zeskind points out. “And we’re achieving this with a therapy that is also well-tolerated.”
Supporting metrics like overall response rate (ORR) and disease control rate (DCR) further validate the durability of the response. Atebimetinib achieved a 39% ORR—nearly double the 23% benchmark from the MPACT study—and an 81% DCR versus 48% in standard of care. Notably, all responses were confirmed and expected to increase as patients continue treatment.
Traditional metrics, Dr. Zeskind notes, don’t always capture the value of slow, steady, and sustained tumor regression. “This isn’t about rapid shrinkage followed by resistance. It’s about long-term control—that’s where survival gains come from. Slow and steady wins the race.”
Immuneering’s treatment strategy also prioritizes tolerability, a factor often underappreciated in oncology drug development. Adverse events in the study were limited—primarily neutropenia and anemia—both associated with chemotherapy, not atebimetinib monotherapy.
“There’s a ‘no pain, no gain’ mentality in oncology, but we believe you can extend life without making patients suffer,” Dr. Zeskind says. “Of course we believe that the main reason our patients are living longer is because we are shrinking their tumors slowly and steadily—but it certainly helps that our drug has a robust tolerability profile. And the FDA’s draft guidance now recognizes that tolerability is linked to OS, not just quality of life.”
In August 2025, the FDA’s draft guidance emphasized the importance of OS in oncology trials, stating that OS should be the primary endpoint when feasible.
Despite a median patient age of 69—older than in typical pivotal studies—the OS benefit was even more striking, underscoring the robustness of the data. “There is no such thing as easy pancreatic cancer,” Dr. Zeskind asserts. “The fact is our patient population was more challenging—the pivotal studies patients were in their low to mid-60s. Age is a negative prognostic factor in pancreatic cancer, and the fact that we were able to show such a large separation from standard of care—that’s just all the more robust, in that we achieved this in a meaningfully older group of patients.”
Based on these results, Immuneering plans to initiate a global Phase 3 trial of atebimetinib plus chemotherapy in first-line pancreatic cancer, with OS as the primary endpoint. The company expects regulatory feedback by Q4 2025 and aims to begin dosing patients by mid-2026, with topline results anticipated in mid-2028.
Meanwhile, planning for two lung cancer studies are underway, supported by agreements with Regeneron Pharmaceuticals (NASDAQ: REGN) and Eli Lilly (NYSE: LLY) to evaluate atebimetinib in combination with their respective cancer therapies. Immuneering will also continue to advance its preclinical pipeline, backed by recent proceeds from a public offering and a private placement from Sanofi (EPA: SAN).
The MAPK pathway, which atebimetinib targets, is used by a wide array of cancers, including colorectal, melanoma, AML, and breast cancer. “Pancreatic cancer is just the beginning,” Dr. Zeskind concludes. “We’re really excited about building a platform to transform how cancer is treated across many indications.”
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