Changing the Ways We Treat Cancer

Dr. Ben Zeskind, CEO and co-founder of Immuneering, spoke with Pharmaceutical Executive about his company’s approach to treating cancer. Based on the company’s research, he believes that treating tumors at a slower and steadier pace may produce more reliable results that also avoid subjecting patients to some of the worst side effects that often accompany cancer treatment.

Pharmaceutical Executive: Can you discuss the history of Immuneering?
Dr. Ben Zeskind: We started the company 17 years ago with the goal of helping cancer patients live longer and longer until they eventually outlive their disease. We can transform cancer into something that's more of a manageable condition, like HIV, diabetes, or cardiac disease. That's the goal we've been working towards by having a different set of priorities: durability and tolerability.

PE:What is the conventional wisdom when it comes to treating cancer?
Zeskind: Everyone is focused on shrinking the tumors as quickly as possible. If you look at the metrics that are used for overall response rate, there’s a focus on how quickly you can shrink the tumors. Don't get me wrong, shrinking tumors quickly is a good thing, but it's not the only good thing.

When you shrink tumors quickly, you create a sort of Darwinian natural selection where you end up selecting for resistant clones. Ultimately, the tumor comes back, often worse than before. We've seen this movie play out over and over again in targeted therapy where everyone gets excited about a drug, and it works really well for a few months. Then the patients develop resistance and escape and progress. That's arguably the single most important question or issue in cancer today is: how do we keep drugs working longer?

What we saw in our preclinical research, and what we've now clearly demonstrated clinically, is that slow and steady is the way to win the race. We have a deep cyclic inhibition approach: shrink them slowly but surely, and you don't drive the same kind of resistance and escape. It’s much better for patients if you can have a longer, more durable reduction of the tumor. That doesn't drive resistance in the same way.

Ultimately, we want the tumors to go away. It's just how you get there and how durable that effect is. We've shared examples of patients where tumors have been rendered undetectable in multiple organs.

The tumors, in some cases, do go away completely but, at the same time, the way it's happening is slowly but surely. It's a more durable effect. The patients feel better, both because the tumors are being reduced and because we designed a tolerability profile that is very favorable relative to most targeted therapies in oncology. Patients just feel better because they're experiencing fewer side effects.

PE: People will sometimes delay or even forego treatment to avoid serious side-effects, correct?
Zeskind: We think the bar has been set far too low in terms of tolerability for cancer therapies. If you look at most companies and the way they report it, they’re focused on only grade three-or-higher adverse events. Those are really the kind of side effects that could land someone in the hospital. That's how low the bar is set. As long as there's not something that sends the person to hospital, it's considered tolerable. And we just don't agree with that.

We don't think it has to be that way when tolerability is a goal from the start. You can design something that has exceptional tolerability and still has great efficacy. That's what's so unique about the technology that we develop. You get the durability where it keeps working longer. That's important, because when drugs keep working, patients keep living. You want that durability, but at the same time, we're restoring the normal, healthy cadence of signaling on the pathway. We have these pathways for a reason other than for cancer to hijack them.

PE: Are there applications outside of oncology that this approach to treatment approach could be used for?
Zeskind: Our focus is really on oncology, but there's a broad range of cancers. The data that we shared is primarily in pancreatic cancer, but there's possibilities in lung, colorectal, melanoma, and even blood cancers. There's a wide range of potential impact there. Our goal is to ultimately make cancer into a controllable disease that people can live out their normal lives and outlive their disease. That's a big enough goal.