In the oncology R&D world, IL-12 has a rep something akin to nitroglycerine in old Hollywood movies. It’s incredibly powerful, but any false move and … kaboom.

You’re dead.

That makes it the perfect kind of target for drug hunters who like a big challenge, particularly when you’re using it to orchestrate an immune response in a tumor — the classic Holy Grail in these post-PD-(L)1 approval days as investigators try to stack immuno-oncology strategies. And nobody knows that better than Bristol Myers Squibb, which has two of the original checkpoint stars in the portfolio.

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Right around the beginning of the year, we got a close-up look at what happens after a boom ripples through biotech. The crash of life sciences stocks in Q1 was heard around the world.

In the months since, we’ve seen the natural Darwinian down cycle take effect. Reverse mergers made a comeback, with more burned out shells to go public at a time IPOs and road shows are out of favor. And no doubt some of the more recent arrivals on the investing side of the business are finding greener pastures.

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The first lab-made antibody medicine was approved in 1986 — it bound to an antigen known as CD3 on T cells and was meant to prevent kidney transplant rejection. While antibody technology improved, most antibodies were made as blocking agents, neutering clamps that attacked cells and proteins.

But then scientists got creative with their engineering. They made antibody-drug conjugates, or ADCs for short, which attached toxins or drugs to the antibodies, enabling them to kill cells. Then they made CAR-T therapies, which attached a patient’s T cell to the targeting fragment of an antibody, to destroy cancer cells.

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