Immuneering takes aim at cancer’s ‘superhighway’

In focus with: Ben Zeskind, CEO, co-founder, Immuneering Corp.

Immuneering’s vision: Earlier this year, Immuneering halted development of its preclinical neuroscience program and thrust all of its weight into oncology — focusing on a universal-RAS candidate that delivered promising initial phase 1 results in April.

“We believe that ultimately, every cancer patient deserves a durable complete response,” Zeskind said. “That’s a long-term mission and a long-term goal.”

Why it matters: When Zeskind founded Immuneering in 2008, cancer immunotherapies were coming to the forefront.

“They were having these incredible, durable, complete responses where the tumors and metastases would go away and they wouldn’t come back,” Zeskind said. “But it was only happening in 10% or 20% of the patients.”

The company embarked on a mission to decrease the rates of recurrence.

“We spent the first decade really trying to understand why drugs are working better in some patients than others, mostly using informatics,” he said.

About five years ago, Immuneering started work on a proprietary pipeline of drugs that are now the company’s sole focus. Its lead drug candidate, IMM-1-104, targets RAS-mutated (KRAS, NRAS or HRAS) cancers, a wily type of tumor once deemed undruggable. It has no off switch, like a car with the accelerator jammed to the floor.

RAS mutations are common in melanoma, pancreatic, colorectal, and lung cancers and Immuneering is now testing a novel approach to target them using the mitogen-activated protein kinase (MAPK) pathway.

“There are different roads that cancer can take, but MAPK is the biggest superhighway,” Zeskind said. “So many cancers use this pathway because it’s one of the most effective, in a bad way, in terms of driving inappropriate growth and division.”

More than 50% of cancers use MAPK, making it a prime target in oncology. Other companies, including Erasca and Genentech, are also testing MAPK-inhibiting drugs.

Exploiting cancer’s weakness: Unlike other oncology approaches, Immuneering’s candidate attempts to only kill cancer cells, and avoid healthy ones by targeting one of cancer’s vulnerabilities, Zeskind said.

Both cancer and healthy cells rely on the MAPK pathway but use it differently. Cancer cells need it like a person breathes air — in a constant flow — while healthy cells use the MAPK pathway like water, and only require an occasional glass. The idea behind IMM-1-104 is to deliver a high once-daily dose that wanes quickly, taxing cancer cells and then opening the pathway to give healthy cells their proverbial drink.

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“Because this is targeting the tumor cells in a way that’s not dependent on any specific mutation, it actually has a much broader potential impact.”

Ben Zeskind

CEO, co-founder, Immuneering Corp.

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Zeskind said they’re now in trials to see if by targeting a broader mechanism, instead of a specific mutation, the drug will sidestep the toxicity, drug resistance and narrow efficacy that has hindered other MAPK inhibitors.

“Because this is targeting the tumor cells in a way that’s not dependent on any specific mutation, it actually has a much broader potential impact,” Zeskind said, a prospect that has attracted recent enthusiasm from investors, including Exodus Point Capital Management.

Addressing the skepticism: The company has encountered its share of naysayers, who questioned the safety of its high-dose drug and whether animal results will translate into humans. Can people break down the drug fast enough to induce the intermittent drug holiday that keeps healthy cells alive?

Early-stage trials in people with advanced RAS-mutated solid tumors have allayed some of those fears. So far, no serious adverse events have occurred, Zeskind said.

“We haven’t disclosed all the details of what we’ve seen on the safety front, but overall, it’s encouraging and certainly there were no surprises,” Zeskind said.