For years, researchers called most of the human genome “junk DNA.” Non-coding regions. Sequences that didn’t make proteins anyone cared about. Evolutionary leftovers.

Turns out cancer cells don’t follow the same rules – shocker.

Tumors aberrantly transcribe and translate large chunks of this supposedly silent DNA, producing proteins that healthy cells don’t make. Those proteins get chopped into peptides, displayed on MHC molecules, and the immune system should, in theory, recognize them as foreign.

Researchers call them cryptic antigens, or aberrantly expressed tumor-specific antigens.

Epitopea, a transatlantic biotech with labs in Montreal and Cambridge UK, built a whole company around this idea. On April 23, they got MHRA clearance to start OVACT, their first-in-human Phase 1/1b trial of CryptiVax-1001, an off-the-shelf RNA-based cancer vaccine, in advanced high-grade serous ovarian cancer.

The trial will enroll patients who are homologous recombination proficient (HRP+) and BRCA-wildtype. Meaning the ones for whom PARP inhibitors don’t work. Meaning the ovarian cancer population with the worst options. Principal investigator is Professor Susana Banerjee at The Royal Marsden in London.

Here’s what makes the Epitopea approach meaningfully different.

Their proprietary CryptoMap platform uses immunopeptidomics and mass spec to identify which cryptic antigens actually make it to the tumor cell surface. In a Nature Cancer publication, they showed that of 589 non-redundant tumor antigens they found across melanoma and NSCLC, only 1% came from mutated sequences. Roughly 37% were cryptic.

And those cryptic antigens were immunogenic, shared across patients, and connected to checkpoint inhibitor responses.

That last part is SUPER important.

If your antigen is shared across patients and shared across tumor types, you can make an off-the-shelf vaccine instead of a personalized one.

Pharma likes this one.

In February 2025, Merck signed a deal with Epitopea worth up to $300 million per product. Merck gets exclusive rights to develop and commercialize therapeutics against Cryptigens that Epitopea identifies for prespecified tumor types. Epitopea also has a non-exclusive license with Genevant for mRNA-LNP delivery of their aeTSAs.

Ovarian cancer is a smart first indication. It’s immunologically active.

There’s a clearly defined patient population (HRP+, BRCA-wildtype) that desperately needs options. And the readouts are biomarker-rich because you can measure immune responses to specific antigens.

We already covered how Debiopharm got Fast Track for a PKMYT1/WEE1 combo in platinum-resistant ovarian, and Acerand’s PARP1-selective inhibitor showed 67% response rate in ovarian.

The treatment-resistant ovarian space seems to be heating up.

But cancer vaccines have a…troubled history.

IO Biotech went from Breakthrough Therapy Designation and a Phase 3 with Merck to bankruptcy in a matter of months when the FDA said no. Therapeutic cancer vaccines have burned a lot of investors. Epitopea is well aware.

What’s different this time is the antigen discovery.

IO Biotech targeted IDO and PD-L1-derived peptides. Most other failed vaccines targeted one or two well-known tumor-associated antigens that turn out to be present on normal tissue too.

Epitopea is targeting peptides that only appear on cancer cells, derived from parts of the genome healthy cells don’t transcribe. If the biology holds, the off-target problem that killed previous vaccines just isn’t there.

First patient expected later in 2026. Early immunogenicity data will be the first proof point. Clinical responses come later.

The Merck deal should give some confidence that the platform is – at least somewhat – legit. The MHRA clearance validates the regulatory path. Now we find out if the cryptic antigen thesis survives contact with human patients.