Snakes, Ladders, and Pharma Megabucks

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Kevin Mayer Senor Editor Genetic Engineering & Biotechnology News

Immersive Workshop Dramatizes How Open Innovation Can Mitigate Biopharma Risk

God does not play dice with the universe. This view was expressed by no less an authority than Albert Einstein. But even Einstein might have agreed that the Old One does seem to keep one die aside for biopharma, where new drugs are always a gamble.

To dramatize the role of chance in biopharma decision-making, a Berlin-based consultancy called Catenion has designed a simulation game. It’s called Risky Business. And, yes, the game does require each player, or rather each team of players, to toss a die at intervals to determine whether drug development projects survive or perish.

Besides a die, each team receives project cards, infusions of pharma megabucks (PMBs), and a board that resembles a ledger sheet. At intervals, teams also receive special cards—Lawyer Cards, Scientist Cards, Management Cards—that may brighten or dim a project’s prospects.

Risky Business may sound like Monopoly, but it’s more like a devilishly recursive version of Snakes and Ladders. In Monopoly, nothing succeeds like success, and nothing fails like failure. In Risky Business, however, the ups and downs are more manageable. No isolated success is so great as to justify complacency. No isolated failure is so crushing as to justify despair.

Because it demands relentless fiduciarity, Risky Business instructs better than it entertains. (You’re safe, Milton Bradley!) But Risky Business is probably no more complicated than it needs to be to achieve some degree of realism. Die rolling aside, Risky Business is not just a game of chance. It is designed to give biopharma-emulating teams enough breathing room to explore different development strategies. For the most part, these strategies involve partnering arrangements and the spreading of risk.


Jason Wong and Lili Blumenthal, graduate students at NYU Langone Medical Center, calculate the net value of the assets held by their mock biopharma, the “Red Yellow” company, after seven rounds of the Risky Business game.

Fun for the Whole Enterprise

Although Risky Business would seem most relevant to operational, marketing, and financial executives, the game has value for commercially minded scientists, too. Recently, the game was played at the New York Academy of Sciences, which drew a crowd of graduate students and postdocs in the life sciences.

The presence of so many scientists may have influenced some of the remarks offered by Matthias Krings, Ph.D., a senior partner at Catenion. For example, Dr. Krings recognized that many players object to the game’s reliance on die rolls. Surely, a scientist might think, drug development cannot be reduced to a numbers game.

Of the people who play Risky Business, scientists are the most likely to identify with the first scientist/businessman, Thales of Miletus. The game, however, implicitly questions Thales’ relevance.

According to legend, Thales was challenged to explain why anybody should care about his scientific philosophy, since the supposedly impractical philosopher had failed to profit by it. Thales responded by acting on his prediction of a bumper olive crop. He reserved all the olive presses he could, securing low rates, then he waited for the harvest. Sure enough, the olive crop was unusually large, and Thales made a fortune by subletting his olive presses at a premium.

The story of Thales’ olive presses is appealing because it suggests that if you’re smart enough, you can, if you choose, enrich yourself fairly easily. Yet Thales would have suffered a serious loss if his prediction about the olive crop, which amounted to a prediction about the weather, had proved wrong.

The legend of Thales, on closer examination, simply tells us that it would be convenient if we knew the future—which is, unfortunately, exactly what biopharma doesn’t know. Biopharma cannot predict which drug candidates will succeed. Consequently, it must submit to a grueling winnowing process, one in which drug candidates fail only after promising beginnings (and sometimes promising middles) eventually reach disappointing ends.

When the winnowing process is experienced at second or third hand, through journal articles or PowerPoint presentations, readers or seminar attendees may feel all but untouched. To create deeper impressions, Catenion developed Risky Business. Through this game, Catenion helps players experience vicariously what biopharma executives experience for real.

Each round in Risky Business lasts seven minutes and corresponds to a period of roughly three years, long enough to complete a phase of clinical development. At the end of each round, a die is rolled once for each drug project. Low rolls (1–3) determine a trial’s success; high rolls (4–6), a trial’s failure. Because each trial phase has a 50% chance of success, the chance that three successive trial phases in Risky Business will all succeed is 12.5%—somewhat better than the real rate, which the authors of a 2014 Nature Biotechnology article put at 10.4%.


Matthias Krings, Ph.D., a senior partner at Catenion, appears in the far right of this image, offering guidance to players of Risky Business at the New York Academy of Sciences.

Is Science in the Cards?

Risky Business conveys a high-level view of clinical development, so it necessarily downplays certain details. For example, while project cards display a drug’s indications, these indications don’t matter for purposes of portfolio management. What matters are each drug’s projected costs and anticipated returns. Labels such as “Lifestyle: Aging” or “Cancer: Breast Cancer” might as well have been replaced with nonsense words.

After a few rounds, the game acquired a formalized, abstract feel. It seemed quite indifferent to factors such as diseases, disease mechanisms, or therapeutic modes of action. But such abstraction may be unavoidable—or even desirable, since it could, Dr. Krings hinted, facilitate decision-tree analysis and other strategic exercises.

Still, a reductive approach that takes scientific details out of the equation could rankle scientists—not that any objections arose from the scientists who played Risky Business at the New York Academy of Sciences. The scientists in attendance, however, may represent a self-selected group that is already curious about alternatives to traditional scientific careers.

The Risky Business event was presented by the Academy’s Science Alliance, which organizes seminars, workshops, and courses that “align scientific training with workforce needs.” For example, the Science Alliance recently offered a 36-hour “business of science” certificate program. Those completing the program, which was designed to turn academic scientists into business-ready professionals, received a “SciPhD.”


Hedged Bets

According to the Science Alliance, Risky Business events give participants a chance to re-examine the role of in-house R&D while considering the advantages of open-innovation networks. Risky Business participants at the New York Academy of Sciences, it turned out, were spared a lecture on open innovation. Instead, they got to explore the potential advantages of striking single-asset deals, a relatively simple form of open innovation.

R&D activities, says Deloitte, may be either closed or open, or somewhere in between. Ranging from closed to open, companies may engage in pure outsourcing; licensing, mergers, and acquisitions; and collaboration, co-development, and joint ventures. Truly open innovation, still uncommon in biopharma, encompasses open-source approaches, the sharing of technology and skills. When drug candidates are sourced through open innovation, their success rates, a Deloitte study finds, are about three times higher than those for drug candidates sourced through in-house R&D.

Networking, then, may benefit biopharma firms and biopharma professionals alike. In any event, both are hedging their bets, whether by restructuring their portfolios or revamping their resumes. They know all too well that time and chance happen to us all. And should anyone tell them that God, or the market, does not throw dice, they might recall that Einstein’s remark moved Niels Bohr to quip, “Stop telling God what to do.” That is, they might accept that if risk is unavoidable, it is better managed than denied.







































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