Baby biotech grows up: Review of "The Antidote" by Barry Werth

How do you build a drug company? That's the question Barry Werth asked in Billion-Dollar Molecule, his engaging and accessible tale of Vertex Pharmaceuticals' early history. In it, Werth recounted the science and business behind Vertex's first five years as it sought to exploit the emerging discipline of "rational drug design". But five years is barely long enough for a biotech to reach adolescence. As Werth's story came to a close in 1994, Vertex's irrepressibly confident founder and CEO, Joshua Boger, was convinced the company could and would someday be a leading force in drug development, even though clinical trials on Vertex's first in-house drug candidate were still a year away. Boger remained optimistic, but his company's transition to pharma adulthood had barely begun.

Fast-forward two decades: Vertex now has over $1B in revenues from two marketed drugs and is on the cusp of completely redefining the treatment of cystic fibrosis, until now a uniformly progressive and fatal disease. Meanwhile, during the same period scores of other biotechs failed in their efforts to develop safe and effective drugs, and of the few that succeeded, many have been acquired by pharma giants.

Which begs the question: how does an aspiring biotech become a major independent global pharma? In Werth's latest book, The Antidote (Simon & Schuster), he returns to Vertex to seek the answer, once again embedding himself in the organization, its operations and its strategic decisions.

Whereas the narrative drive in Billion-Dollar Molecule stemmed from the scientific advances, The Antidote tells a more complicated story. That's not entirely unexpected: evolving from a preclinical biotech to a commercial-stage drug company means surviving a wide range of scientific, clinical, regulatory, commercial, financial and organizational challenges. As in his prior book, Werth doesn't shy away from technical details, and The Antidote has plenty of "inside baseball" for pharma industry cognosenti who want to dive into tablet formulation, ion channel and enzyme biochemistry, clinical trial biostatistics, follow-on stock offerings and pharma sales strategies - sometimes in back-to-back paragraphs.

But although these nitty-gritty details are important and interesting, Werth uses them as the backdrop to ask a more broadly relevant and philosophical question: not just how to build a large drug company, but what to grow up to become? Boger's obsession with his former employer, Merck, was not just to beat them at making better drugs. It was also to surpass their influence and power without destroying the essence of Vertex's entrepreneurial, science- and patient-focused culture:

Boger's "social experiment" was designed to encourage self-selected leaders who not only would do excellent science but also grasped viscerally that the decline of Big Pharma was due less to cluelessness at the bench or fecklessness on the executive floors and in the boardroom than to the immobilizing sludge of middle management in between, which even at Merck had led to project heads prioritizing how many compounds a group made over whether or not they did anything useful. Boger wanted champions, people who would passionately disagree with each other and with him, who in the end would push groups and projects ahead because they had smarter ideas, worked harder, generated more compelling data, and persisted when others would quit.

Boger's quest to build a "New Pharma", as opposed to a "Big Pharma", has been a holy grail in the industry for many years, fed by several interwoven narratives about the latter: Internal R&D paralyzed by bureaucracy and risk-aversion, with cannibalization of biotech products and companies their only means of survival. Senior leaders more concerned with placating Wall Street than bringing innovative therapies to market. A continued reliance on high-priced, me-too drugs to drive and sustain growth. A willful disregard of basic ethical standards in development and commercialization. Each of these narratives has at least some element of truth to it, and together they have long fueled the desire of folks like Boger to succeed on different terms.

What's unique about Vertex is the religious zeal with which Boger personally regarded the issue of corporate culture. His influence was unmistakeable on Vertex's values (Fearless pursuit of excellence - innovation is our lifeblood - "we" wins), its encouragement of professional risk-taking, and its wholehearted embrace of the positive role it could play in national and global health policy. Peter Mueller, Vertex's Chief Scientific Officer, summed it up: "The one thing that made the company is that we were able to move Josh's original vision that he had, which, in a nutshell, is: you have to be on the forefront and the frontiers, constantly. ... It wouldn't have been good enough to be great in clinical. You have to be great in everything. ... [T]hat's what made Vertex Vertex, at the end of the day."

Werth's key question is whether that unique culture was truly embedded in Vertex's DNA, or if it was wholly dependent on Boger's continued presence and influence. One answer lies in the company's continued positive trajectory after Boger's departure as CEO in 2009. New leaders took charge, the organization grew, clinical trials progressed, exciting discoveries were made - and drugs were launched, bringing Vertex closer into the orbit of the global pharma giants. Outwardly, Vertex enjoyed - and continues to enjoy - in the post-Boger era a level of success that sets it apart from most other biotechs on the planet.

But back to Werth's question: has Vertex successfully become a "New Pharma" or (merely) a big and successful one? Now in its "young adulthood", seasoned industry veterans lead key functions at Vertex with a level of staid maturity, and few old-time employees or attitudes remain. Vertex today is no longer a cocky young upstart, known by the press and stock analysts for hyped-up R&D claims and a "trust us" message to investors. This more mature Vertex drives science forward and delivers new therapies, but it also simultaneously manages the Street's financial expectations quarter to quarter - reflected in what Werth at one point calls an "uncommon equilibrium" between Vertex (the company) and VRTX (the stock market). Vertex has exhibited a sort of convergent evolution with its Big Pharma predecessors, suggesting there is little room to "be different" when it comes to getting drugs past FDA or successfully launching them into the market under sharp scrutiny from investors, regulators and the public.

So yes, Vertex has succeeded - but perhaps without the brash iconoclasm that Werth captured in Billion-Dollar Molecule. Werth asks if there are signs of the "creative DNA from its early days" that sprang from every page of his prior tale, but in The Antidote's later chapters, few are to be found. Indeed, if one had to pinpoint the moment at which the "old" Vertex seems to have metamorphosed into the "new" one, it might be Vertex's glitzy company-wide gala celebration in 2011, a few months after the launch of Incivek for hepatitis C. It's hard not to feel wistful and disappointed when the wife of an exec from the old guard dismisses the rah-rah excess in one disparaging word: "Corporate".

Some may find it academic to ask whether Vertex has maintained its unique biotech culture. After all, the company has beaten the odds in biopharma financially and clinically, and if its culture has evolved in the process, so what? But as Werth tells the story of Vertex's teenage and early adult years, it's hard not to dream of what the full realization of Boger's "social experiment" could look like: an innovative, productive, science- and patient-focused, respected global pharma company that retains the culture and drive of a freshly-minted biotech. Sometime, somewhere, a future biopharma CEO will hopefully read The Antidote and be inspired to continue the quest.