Immuneering Corporation: The Prospects Of Universal RAS Inhibition

Topline Summary

Immuneering Corporation (NASDAQ:IMRX) is a biotech developing novel small molecules directed at MEK, with the unique angle of pursuing cyclical inhibition, rather than continuous shutdown of their targets. While this is an interesting concept, they're still quite early in development, and cash is going to present a challenge, likely before promising results are on deck.

Pipeline Overview

IMM-1-104

The first developmental project to be taken to clinical studies by IMRX is IMM-1-104, an allosteric dual-MEK inhibitor that the company hopes can target multiple nodes of signaling, particularly from RAS mutations. Current MEK inhibitors compete for the active site of MEK1 and MEK2, whereas allosteric inhibition binds the complex of MEK1/2 and its substrate, essentially locking down the enzymes only once they've been activated.

In this way, IMRX has shown an ability to achieve deep inhibition of downstream signaling associated with activating KRAS mutations in a range of tumor models.

The company presented first-in-human data at the AACR 2023 annual meeting this past spring. The data showed favorable pharmacokinetics and target inhibition (downstream phosphorylation of the ERK protein, a common readout of RAS activity). No dose-limiting or serious toxicities were observed to date.

This poster also presented the results of 3D tumor modeling, suggesting that IMM-1-104 is active in a wide variety of KRAS-driven tumor models.

In June, IMRX announced that the dose escalation phase of their study had been completed, and they have commenced a dose expansion study to try and arrive at a recommended phase 2 dose, which they expect to present in early 2024.

IMM-6-415

IMM-6-415 is also a dual-MEK inhibitor functioning on the same premise as IMM-1-104, but with adjustments to its chemistry intended to make its half-life shorter. This should allow for deeper cyclical inhibition of MAP kinase signaling. Preclinical findings suggest that this type of inhibition can synergize with immune checkpoint blockade in RAS-mutant tumors.

IMRX plans to file an IND to initiate first-in-human studies in Q4, 2023.

Financial Overview

At the end of Q2, 2023, IMRX held $104 million in cash and equivalents, with another $5 million in marketable securities. Total current assets were $111.5 million.

Their loss from operations was $13.5 million, but after offsetting interest and other income, their net loss for the quarter was $12.2 million. For the first 6 months of 2023, IMRX had net positive cash flow due to maturation of marketable securities and a public offering of common stock yielding $28.2 million.

Given this current net loss figure, IMRX has upwards of 9 quarters of cash left to fund operations. This assumes that they're able to control the growth of their expenses, which rose from $11.7 million in Q2 2022 to $13.5 million in Q2 2023.

Strengths and Risks

IMRX touts multiple programs in their pipeline, mostly in the discovery phase, that have not yet been disclosed publicly. Their main thesis rests on this idea of cyclical MAP kinase inhibition, since both of their drugs seek to accomplish that.

What they've demonstrated convincingly so far is that this inhibition can be achieved in humans. However, this has not yet translated into whether that will slow, stop, or reverse cancer growth. The concept of cyclical target inhibition sails against prevailing winds in oncology, which hews to the understanding that you need to constantly pressure the target of interest in order to achieve a therapeutic effect.

This concept of constant inhibition has support, since we have a huge number of targeted agents that work on this principle. Cyclical inhibition has not been shown to have such an effect. That said, few, if any, targeted therapies work for pancreatic cancer, and overall the KRAS-mutated cancers have long been a stumbling block for oncology, so new ideas are desperately needed to move the field forward.

So IMRX has a very interesting idea here. But it's still very early days. We are not going to see bona fide efficacy data for quite some time. If I had to guess, it's possible we could get some interim read of a phase 2 trial by maybe 2025. By then, cash will be running quite low, assuming nothing else happens financially in the meantime.

That's the risk you'd take in being an early adopter to this, substantial dilution with the hope of recouping the damage on an unproven idea. There's reason to be cautiously optimistic about the science, but at this point, I don't know if that ascends all the way to confidence in the long-term outlook for an equity.

Bottom-Line Summary

IMRX has something unique going on with this cyclical RAS inhibition. Like a lot of things in oncology that look promising, I'm very curious to find out whether it works or not. That does not translate into a good investment. This is a wait and see for me until more data can demystify whether it's going to show signs of life that are not preclinical. So far, not much! But I'm going to keep IMRX on the radar for further development.