Everyone loves an in vivo CAR-T story right now.

Eli Lilly paid $2.4 billion for Orna. Another $400M-ish for Kelonia. Bristol Myers grabbed Orbital. AstraZeneca dropped a Nature Medicine paper showing 80% response rates with in vivo BCMA CAR-T in multiple myeloma.

All of those stories have one thing in common. They program T cells. 

CREATE Medicines just dosed the first patient with something different. MT-304 programs T cells and NK cells and myeloid cells in vivo to get a multi-pronged immune response.

So you get CAR-T, CAR-NK, AND CAR-M in one shot. Nobody else is doing this.

The only thing that comes close was Interius (now Kite), targeting CD7 to get CAR-T and CAR-NK. But this? All 3? Nope, it’s first-in-class.

I’m not super sure how they’re doing this – they seem to be keeping this pretty close to the vest. It’s clear that the surface target is something that is expressed across each immune cell lineage – allowing them to target all at once.

But think about this for a second.

Every CAR program you’ve read about for the last decade has been a CAR-T, or CAR-NK, or CAR-M cell. CREATE’s multi-immune platform is, essentially, an in-vivo CAR-immune effector platform.

It uses an NKp44-based CAR construct that signals through DAP12.

This wiring will turn the patient’s own T and NK cells into tumor killers while pulling in myeloid cells to repolarize the tumor microenvironment from the inside.

The target? HER2-positive solid tumors — starting with breast cancer.

You might recognize this company under another name.

Until October 2025, CREATE was called Myeloid Therapeutics. The rebrand signaled a platform expansion beyond myeloid cells to multi-lineage immune programming. MT-304 is the first clinical asset that proves the point.

And here’s the thing nobody’s talking about.

CREATE has already dosed more than 40 patients across its earlier programs (MT-302 in epithelial tumors, MT-303 in hepatocellular carcinoma). Over 200 doses delivered in total with no cumulative toxicities and at least one confirmed partial response at 16 months.

So I guess we shouldn’t really think of them as “cool new tech that probably won’t work”, and start thinking, “ummm, this might actually be something real.”

The HER2 target matters because HER2 is…insanely crowded.

Daiichi – with their T-DXd – owns the ADC space. There are dual-payload ADCs chasing resistant HER2 tumors. There are bispecifics, engagers, and combination regimens.

CREATE isn’t trying to be another ADC or bispecific.

They’re a bona fide IN VIVO immune cell reprogramming platform. You show up, you get an infusion, your own immune cells – T, NK and myeloid cells – get reprogrammed for a few days.

…oh…and the platform is redosable.

We’ll see if the clinical data backs it up.

But the fact that CREATE is the only in vivo CAR company hitting HER2 solid tumors with a multi-immune approach puts them in a category of exactly one right now. And with backing from ARCH, 8VC, Hatteras, Alexandria, and Newpath, they have the runway to find out.