Primer: How To Speak Basic Biotech, From 'Transformative' To 'Valley Of Death'

What "language" are they speaking? People outside of the Whitehead Institute for Biomedical Research in Kendall Square enjoy conversation during lunch. (Jesse Costa/WBUR)
What "language" are they speaking? People outside of the Whitehead Institute for Biomedical Research in Kendall Square enjoy conversation during lunch. (Jesse Costa/WBUR)

The Boston area's booming biotech cluster is a little like a country with its own culture: tribes, hierarchies, social currency, customs. And cultures tend to have languages. So how does one begin to speak biotech?

Damian Garde, who covers national biotech for STAT, recently put together a witty Devil's Dictionary of biotech, but it's largely geared toward shared insider eye-rolling. What follows below is more for Muggles; it's like the pocket phrasebooks carried by visitors who know just a few words in the lingo of the country they visit.

Our chief translator is Jeff Krasner, who long covered biotech for the Boston Globe and now has his own biotech communications company, Emerging BioCommunications.

He begins his partially tongue-in-cheek lesson with buzzwords heard so frequently in biotech circles that they become almost meaningless:

  • Transformative or Transformational — This will change things.
  • Disruptive — This will really change things.
  • Innovative — New.

And a few other all-too-often-heard phrases:

  • Orthogonal thinking — Let's take a look at this from a different angle, and pretend it gives us some wildly keen insight on the problem.
  • Intractable — This is a problem you can't solve. (So we're not going to invest in it.)
  • Patient-centric — This will help people and has value (is demonstrably worth the price).

Now, let's say you want to start a biotech company. Whatever your concept, you're going to need...

Seed financing or Angel financing — a first stage of investment in a startup, sometimes described as "friends and family."

When you begin, you'll be a discovery stage company, and you'll reach the point that you have to...

POC (pronounced "pock") your idea. POC stands for "Proof of Concept," meaning you can show that your molecule or whatever you have works well enough to get funded.

But to get there, you must pass through...

The Valley of Death — Many companies get trapped in this frustrating space, where their technology is promising, but is still too new to validate as a commercial proposition. So investors stay away in droves.

If you make your way out of the Valley of Death, you may also be ready to come out of stealth mode, a sort of double-secret probation arrangement in which a biotech company is formed, hires employees, and conducts research — but doesn’t tell anyone about its existence. The goal is to establish a scientific lead before competitors even know what you’re doing.

And you'll be seeking injections of venture capital known as....

Series A, Series B, etc. — Successive rounds of funding intended to bring a company from discovery stage to clinical trials to an actual product on the market.

If you find investors, you'll need term sheets that spell out who puts in how much money and what they get for it. (Things can get ugly around this later, but let's not go there.) 

Dilution — As a new round of capital is invested in your company, the shares you hold become worth less. (Investors can be "dilution-sensitive" or "insensitive.")

And if your concept seems to be working, it will need....

Pre-clinical testing, which generally means "in animals," (and which you might not want to talk a lot about, because it could lead to uncomfortable questions from animal-rights activists — even though work in animals has long been central to medical research advances.)

If it gets as far as testing in humans, you'll have a clinical stage company and your product will go through...

Phase 1, Phase 2 and Phase 3 — clinical trials in humans testing how well drugs work and whether they cause side effects. (The phases can be subdivided, too, and toward the end you'll hope to pass your pivotal trial, and get approval from the Food and Drug Administration, or FDA, for commercial sales.)

If all goes wonderfully well, you may be offered a very lucrative exit — a deal to sell out to a Big Pharma (drugmaker) company, or go public, or otherwise pay back your investors while keeping a pile of cash for yourself.

And if your exit is successful more than once, you'll become that superior being, a serial entrepreneur. That puts you one step higher than all the regular old entrepreneurs who have run just one company.

And speaking of status, you may run into degree inflation: Even MD-Ph.Ds are common in Kendall Square. And MD-MBAs are on the rise as well. A related phenomenon: title proliferation. Being affiliated with Harvard Medical School is not particularly impressive here either; literally thousands of physicians who work at the various Harvard teaching hospitals can make that claim.

Still, there are royalty types you may want to kowtow before:

  • Partners in the venture capital world.
  • Principal investigators, or PIs, in the academic lab world.
  • And of course, founders and CEOs in the companies.

Not so royal, but key players are the post-docs, post-doctoral researchers who keep pipetting away in the lab even after they get their Ph.D.s. They work for next to nothing and make few demands other than a foosball table and cold-brew coffee on tap. But choose wisely and one of them might just have the key insight or hyper-specialized knowledge about obscure proteins to get your company one step closer to the market.

Among the array of biotech companies, venture capitalists call the well-established pharma companies incumbents, because they're not trying to break in to the business, they're already there.

Chances are, you'll be hearing a lot about some of the buzziest biotech areas, to wit:

I/O — Immuno-oncology, using the patient's own immune system to fight cancer; it seems to be the hottest field in biotech these days. Put it in your "elevator speech" — your brief pitch on why to back your company — and you're halfway there.

Or CRISPR  a nifty new tool for precisely editing genes, which could yield breakthrough cures to genetic diseases. Downsides: There's a major CRISPR patent battle under way, and more hope than proof it can be used to treat human diseases at this point.

Messenger RNA (mRNA)  — A molecule that ferries DNA instructions and is believed to hold promise as a possible vehicle for drugs or vaccines — so much promise that it has generated a bona fide biotech unicorn, Moderna Therapeutics. It remains to be seen if this approach will work, but billions of dollars are betting it will.

Convergence -- The merging of biology with information technology — artificial intelligence, big data — is looking hot to the point of hype, too.

New modalities -- New therapeutic modalities are different ways of tackling diseases. Genetically engineering a Chinese Hamster Ovary cell to produce a useful protein is classical biotech, and pretty much old hat. To get investors really excited, you need to come up with a new way to create and deliver your protein. Like engineering red blood cells to express proteins on their surface, or creating designer platelets that carry hidden packets of cancer-killing medications directly to tumors.

And finally, to keep from sounding ignorant, you may need to bandy about a few of these phrases:

Small molecules — The longtime mainstay of drugmakers (also known as pharma), these are molecules made through chemistry into traditional pills. These days, with biotech, you're typically training cells to produce proteins that can be used as medications. These are not small molecules and often have to be administered differently — often expensively.

IP — intellectual property, not unique to biotech, but you may encounter the sub-tribe of IP attorneys who can help you get the patents for your discoveries — and maybe even help you build a blocking patent portfolio to clinch your claim on your science. Think of it as a patent moat around your company.

Biologics -- a fancy way to say a classic biotechnology drug, such as a protein expressed by an engineered cell, or an antibody produced using recombinant DNA. If it’s working, you might file for a BLA — a Biological License Application — rather than an NDA, the new drug application you’d use for a small-molecule typical drug.

Got all that? So now let's try a few practice sentences:

1. Nobody wants to be a discovery stage company because you're not going to be able to raise your Series B, since you haven't POC-ed your concept yet.

2. I/O is so hot all you have to do is slap that phrase on your pitch deck and investors are lining up to get a piece of your startup.

3. They started out as two guys with a molecule, and there was a lot of interest, but ultimately they couldn’t POC their experimental therapeutic and they got trapped in the Valley of Death.

If you understood all three of those, you can now try generating your own — and congratulations, you're now better equipped to mingle in the Kendall Square bio-milieu...

Readers? Suggestions? Biotech folk, phrases that most drive you crazy? Please leave your suggestions in the comments section below.


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Carey Goldberg Editor, CommonHealth
Carey Goldberg is the editor of WBUR's CommonHealth section.



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