At Immuneering, we’re engineering a new class of targeted therapies that significantly change the course of cancer treatment. Our Deep Cyclic Inhibitors are designed to minimize cumulative toxicities, allowing patients to stay on therapy without compromising quality of life. Simultaneously, they disrupt cancer’s rapid adaptive behaviors, reducing resistance and enabling longer-lasting therapeutic benefit. Together, these elements underscore our commitment to fundamentally reshaping how cancer is treated.
The Challenge: Cancer’s Ability to Adapt
Conventional cancer therapies are designed for sustained, continuous inhibition of cancer pathways. While this approach often induces rapid initial tumor regression, the predictable selective pressure from continuous inhibition creates an environment where cancer can adapt and build drug resistance, as well as “on-target” toxicity leading to adverse side effects for patients.
Immuneering is challenging these limitations with its novel Deep Cyclic Inhibitors designed to address cancer’s rapid adaptability, resistance, and to address the substantial toxicity that results from continuous pathway suppression with conventional therapies.
Deep Cyclic Inhibitors: Outpacing Cancer Adaptation
Deep Cyclic Inhibition introduces a new therapeutic framework by changing how and when signaling is suppressed. Because tumors activate fast-acting adaptive resistance mechanisms within 24 hours, our Deep Cyclic Inhibitors are engineered to apply potent MEK inhibition, a key control point in the MAPK pathway, for a short window and then release that pressure. By pulsing treatment at intervals shorter than the tumor’s adaptive response time, our Deep Cyclic Inhibitors aim to disrupt both rapid and slower resistance processes in a more sustainable way.
Deep Cyclic Inhibition’s mechanism provides dual benefits not achievable through continuous inhibition. By cycling treatment faster than tumor adaptation, our Deep Cyclic Inhibitors drive more durable tumor suppression. Simultaneously, the off-period allows healthy cells to restore their normal signaling rhythm. This improves patient tolerability and reduces the side effects typically associated with cancer treatments so that patients don’t have to choose between treatment and quality of life.
Clinical Advantages of Deep Cyclic Inhibition:
Durability of Anti-Tumor ActivityRather than applying static pressure, our Deep Cyclic Inhibitors are engineered to pulse a potent, intermittent force that prevents the tumor from establishing a defensive rhythm and to outmaneuver tumor adaptation and resistance.
Improved Quality of Life for Patients During TreatmentHealthy cells have time to recover during the “off” period, helping to improve tolerability and reduce cumulative toxicities. This approach enables patients to continue treatment while maintaining quality of life – including patients who are sensitive to current standard-of-care regimens.
Versatility as Monotherapy or Combination TherapyDeep Cyclic Inhibition’s intermittent signaling profile and robust tolerability make it suitable both as a standalone therapy and as a foundation for combination regimens. Its compatibility with chemotherapy, immunotherapy, KRAS inhibitors, and other targeted agents supports multidrug strategies for complex and evolving cancers.
Cancer isn’t smart, but it has a powerful trick: the ability to adapt. When treatment involves steady, predictable, selective pressure, as most conventional therapies do, it actually makes adaptive resistance easier for tumors. With our Deep Cyclic Inhibitors, we deliver a daily rhythmic drug pulse that removes therapeutic predictability. The tumor loses a key advantage, creating the potential for more durable control, better tolerability, and stronger long-term outcomes for patients. We shrink tumors differently.
– Brett Hall, PhD, Chief Scientific Officer, Immuneering
MEK: A Strategic Target in MAPK-Driven Cancers
MEK is a key intervention point within the MAPK pathway, serving as a convergence node for diverse upstream drivers such as RAS mutations, RAF alterations, and other MAPK dysregulations. Its central position means it can be targeted to influence multiple upstream drivers without individually targeting each mutation. This is especially relevant in cancers like pancreatic cancer, where MAPK pathway activation is nearly universal. MEK’s biological role therefore makes it a highly effective target for Immuneering’s Deep Cyclic Inhibitors aimed at reducing tumor growth and minimizing toxicity.
How Deep Cyclic Inhibition Addresses Limitations of Current Cancer Therapy
| Limitation of Continuous Inhibition Approaches | Deep Cyclic Inhibition Solution |
|---|---|
 Rapid adaptive resistance |  Pulsed inhibition to minimize adaptive resistance |
 Acquired resistance from continuous selective pressure |  Deep intermittent pressure reduces the emergence of resistant clones |
 Toxicity from continuous pathway blockade |  Restoration of transient signaling in healthy cells improves tolerability |
 Initial shrinkage followed by rebound |  Durable, steady tumor control that limits escape routes |
 Poor tolerability in patients |  Improved tolerability supports broader patient eligibility and sustained dosing |
Atebimetinib: The First Deep Cyclic Inhibitor of MEK
Atebimetinib is an oral, once-daily Deep Cyclic Inhibitor of MEK in late-stage clinical trials for first-line pancreatic cancer. In parallel, atebimetinib is being evaluated in Phase 2 clinical studies in lung cancer, both as monotherapy and in combination regimens. Together, these programs reflect the potential of our Deep Cyclic Inhibitors to address a range of cancers while prioritizing durability, tolerability, and the ability for patients to remain on treatment.