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25 Years in Biotech

Opinion

Xconomy Boston — 

That is a sobering headline to write.

Twenty-five years ago at this time of year, I was graduating from college with no job, a pretty choppy economy, a bunch of student loans, a resume that included things like a summer research internship catching salamanders, and an aspiration to “get into biotech.”

I look back and think how naive I was and find it a bit stunning. Recall, this was both pre-internet and pre-email. I believe I wrote to BIO for information on the industry. At the time, I had absolutely no connections, but I figured out that there was a lot going on in Boston. It took me a couple of months to realize that new college graduates weren’t being hired long-distance, so I finally took the plunge and moved to Boston with no job or money (a daunting prospect), at which point I started reading the want ads in the Sunday Boston Globe. That’s how I got started.

In 1990, Epogen (epoetin alfa) had just been approved. Biogen was 12 years old, Regeneron was two, and Vertex was one. The first antibody therapeutic, OKT3, had been approved in 1986, but it was murine (yes, an antibody from a mouse, not from a human). Figuring out how to “humanize” antibodies—which was essential to enabling them to really work as therapeutics—was still a work in progress. It wasn’t yet 1992, the year that the European Community member states were to form a single market. Europe was still fragmented, but everyone was preparing for that to change and trying to guess what it would be like. BIO hadn’t even held its first convention yet; that wouldn’t happen until 1993.

Some things feel very different from 1990

“Pharma” and “biotech” have grown much closer since then. Today there are many people who have worked in both environments—something that was rare 25 years ago. A multitude of collaborations and alliances have built further understanding and relationships across companies, but they have also created a co-dependency in the industry. The maturing of the contract research industry in parallel has created both more flexibility for pharma operating models and additional possibilities for biotechs to access capabilities and capacity without building everything internally. In 1990, pharma and biotech were two very different groups and were considered separate industries. Today, it’s really a deeply interconnected continuum.

Someone always used to compare the entire market cap of the biotech industry to the market cap of Merck, which was the leader of the pharmaceutical industry. I don’t know exactly at what point the line was crossed, but it’s been some time. Today, we generally don’t think in those terms, at least in part because there are now individual biotech companies that have a larger market cap than Merck. I’m not sure exactly what that signifies, but at the very least it points to maturity—not just of those companies, but of the industry. To compare a whole industry to one other company is to trivialize the industry in some way—and that doesn’t happen any longer.

In 1990, one of the diseases that was of intense focus for the industry was HIV and the complications of AIDS, such as opportunistic infections. It is a terrible, heartbreaking disease, and at that time it was still daunting scientifically. It is incredible to see what spectacular progress there has been. What was once a nearly hopeless situation for those patients is now so much more manageable, even though many challenges remain.

Recurring themes or “plus ca change, plus le meme:”

Pipeline gaps in pharma. It’s just really, really hard to have a pipeline produce on a predictable basis. We’re not making widgets.

Financing “windows.” In 1990, the crash of 1987 wasn’t that far in the past, funding was still tight, and the economy was not strong. No one knew the 1991-92 window was just about to bust open. Later, fallout from the internet bubble of 1999-2000 was quickly followed by the genomics bubble of 2000-2001. The meltdown of 2008-2010 was unprecedented, however, as is the tremendous degree of capital availability in the past two to three years.

Partnering ‘trends’ oscillating between early stage and late stage alliances being dominant. Every time I read an article describing the current trend (whatever it may be), it feels like déjà vu all over again.

While far from comprehensive, there are a number of “then & now” contrasts that come to mind when I compare 1990 to 2015.

GENES

Then: Human Genome Project just recently started. Had not yet found the genes for Huntington’s disease or BRCA1. First gene therapy trial just starting.

Now: We’re nearly at the “$1,000 genome” and redefining many diseases based on their genetics rather than symptoms. But our view of genetics has gotten more complex as we’ve come to appreciate the critical roles of epigenetics and the many dimensions of the biology of RNA.

REIMBURSEMENT & HEALTH CARE COSTS

Then: Barely on anyone’s radar. In a survey of factors influencing product pricing, this came in last (Biotech 90: Into the Next Decade; Burrill/Ernst & Young).

Now: Has become a dominant theme for the industry and society in general.

FDA

Then: Fast-track process had just recently been established.

Now: Over the years, we have seen many initiatives that create new ways to engage with the agency, especially for serious diseases.

PHARMA M&A

Then: Lots.

Now: Lots.

MOLECULES

Then: Small molecules still ruled and large pharma focused almost entirely on this modality. Proteins were still very tricky, and because they couldn’t be taken orally, they were viewed as niche. Humanization technologies for antibodies being developed, but still imperfect.

Now: The list is a lot bigger: Small molecules. Proteins (particularly mAbs). Oligonucleotides (antisense & myriad forms of RNA). Gene therapy & genome editing. Nanoparticles. Large pharma companies have become nearly modality-agnostic, and focus on matching molecule to biological goal.

CORPORATE VENTURE CAPITAL DYNAMICS

Then
:
There were only two pharma corporate VCs—JJDC (Johnson & Johnson Development Corporation) and SR One (GlaxoSmithKline)—and limited partners in regular venture funds were traditional private equity investors, not corporations.

NowAlmost all pharma companies have a venture fund and/or they’re a limited partner (LP) in one or more independent venture fund. Many (most?) independent venture funds have one or more pharma LPs.

CAMBRIDGE REAL ESTATE

Then
:
Empty lots up and down Sidney Street. The Necco factory on Lansdowne Street was still making candy—you could smell sugar in the air when you walked by.

Now: Too many construction sites to count, and there’s still not enough space. Many more coffee shops.

LOCAL SUSTENANCE

Then
:
Legal Sea Foods & the food trucks at MIT for Kendall Square. Middle East for Central. No Starbucks (they were still in Seattle).

Now: Grateful to have many more options! And glad the old standards are still there.

Twenty-five years later, I’m still in Boston, and I did “get into biotech.” I’ve definitely learned a few things along the way, one of the most important being that the learning curve is endless and relentlessly steep in this industry.

Just think where we’ll be in 2040.