Tiny player picks up $30M to go after CAR-T's biggest challenges
Of all the challenges associated with reengineering CAR-T therapies — which have been wildly successful in treating certain blood cancers — to attack solid tumors, toxicity often ranks near the top.
“If there is no therapeutic window, the trial will be terminated,” Simone Song, founder and managing partner at ORI Capital, told Endpoints News.
It was the reason why ORI, a Hong Kong-based healthcare VC firm focused on cancer, metabolic disorders and neurodegenerative diseases, decided to incubate a startup by the name of AffyImmune back in 2017. And it’s why Song’s team is handing over another $30 million to fund a first-in-human trial that kicked off late last year and send a second CAR-T therapy into the clinic.
The issue underlying CAR-T’s toxicity problem has been well-documented. While hematological malignancies can be easily hunted down by markers like CD19 and BCMA (and clinicians can prevent side effects simply by wiping out B cells, the only other cell type expressing those antigens), it’s much harder to distinguish between solid tumor cells and organs. Programming the CAR-T cells to attack any cell bearing those tumor-associated antigens inevitably hurts normal cells, too. Tumor-specific antigens have been elusive.
Co-founded by two scientists who worked together as postdocs at Tim Springer’s Harvard lab, AffyImmune’s proposed solution zeroes in on the binders on CAR-T.
When studying the interaction between an antigen called ICAM1 and its natural ligand, Moonsoo Jin and Gang Song tested multiple “affinity variants” — single chain monoclonal antibodies sporting different structures — against ICAM1. What they found was that the tightest binders, which have traditionally been favored, are not necessarily the best. Rather, some of the weaker binders (which they describe as being in the nanomolar range) appeared to be better at eliminating tumors.
Besides, these weaker binders would spare healthy cells with low expression of the target in favor of tumor cells, which tend to have much higher expression, said Eric von Hofe, president and COO. By tailoring an affinity level to each target based on its expression on normal cells, AffyImmune believes its tuning method draws that thin line for CAR-T cells to separate friend from foe.
“For each target we look at, essentially we’re cleaning them up,” he said.
They also just look more like the natural receptors immune cells use to bind to tumors, said von Hofe, mimicking the physiological interaction. That comes with other indirect benefits: The T cells don’t get overstimulated or exhausted too quickly, and theoretically can function for longer, killing more cancer cells.
“It’s an easy concept, but to [get to] the exact level it takes a lot of work,” Song said. “It has taken them a lot of work to find the exact right level.”
The Series A+ is admittedly modest by CAR-T standards these days, especially for a clinical-stage outfit. Over the last four and a half years, von Hofe — the first employee to join Jin, now the CEO — has grown the crew to nine, maintaining a lean operation focused on securing the first clinical proof-of-concept.
AffyImmune is first testing its lead drug in thyroid cancer, but said ICAM1 is found in a range of other cancer types ranging from gastric cancer to triple negative breast cancer. At the same time, there’s a second part to its “tune and track” platform — a somatostatin receptor that allows infused CAR-T cells to be “seen” in real time through an FDA-sanctioned radio label tracer and PCP or CT scans.
“Down the road, I mean possibly we could see about combining with other technologies if there’s a true enhancement, but we’ve been pretty — I wouldn’t say conservative, but we’ve just stuck with things that are known to work,” von Hofe said. “Some other companies are trying to do all kinds of very high tech things, and it’s very exciting, and they bring in a lot of money doing it. As I mentioned, AffyImmune’s focus has been getting functional CAR-T cells that are more functional than other CAR-T cells out there, with this affinity tune, tracked, get those into the clinic, show there’s a benefit to the patient, and then expand on that.”