Founder-Mode Medicine: The Antidote to Rare Diseases

Every waking moment, a bolt of genetic lightning strikes an unsuspecting family. It strikes indiscriminately, without regard for background, income, or geography. A long tail of more than 10,000 rare diseases afflicts roughly 400 million people worldwide. Most families, understandably, are overwhelmed and unequipped to respond to a devastating diagnosis in time to matter.

Traditional pharmaceutical companies and life science investors have little appetite for small, fragmented markets when global blockbusters beckon. Most rare diseases are ultra-rare, affecting fewer than 1,000 patients worldwide. Some have patient populations you can count on both hands. But to the industry, the long tail is invisible.

Market failures fester. The rare disease community yearns for a pharma white knight but settles for Sir Ghost-a-Lot. It’s time to introduce the long tail to the invisible hand. Turns out the matchmakers—dare I say kingmakers—have been flying under the radar all along.

Sometimes fate messes with the wrong person.

Sometimes fate messes with the wrong person. A subset of rare disease parents are natural-born entrepreneurs: constitutionally incapable of taking no for an answer and unintimidated by uncertainty. Few have biotech operating experience or scientific training. By conventional wisdom, they’re the last people for the job.

The industry ignores them at its peril. These parents are relentless autodidacts, reading papers past midnight, cold-emailing researchers, organizing patient communities and, of course, fundraising. They somehow do it all with a capital efficiency and speed that would make Chinese biotech blush.

They look nothing like standard-issue biopharma management teams. But they share the rare, much-coveted traits—high-agency chief among them—of the most successful founders in any industry. The résumé is unconventional, but the founder DNA is not.

Investors prize founder-led companies because the founder is the beating heart of the organization and the embodiment of its mission. Paul Graham, co-founder of Y Combinator (YC), the world’s most successful start-up accelerator, calls this hands-on style “founder mode.” Inspired by YC’s model for backing overlooked, undervalued founders, I’d extend Graham’s concept to medicine. After all, who embodies a mission more completely than a parent trying to save their child?

After more than a decade operating in rare disease, I’ve had the honor of working alongside dozens of parents going founder mode on their kid’s disease. Faced with a ticking clock and limited resources, they have spearheaded N-of-1 medicines time and again. In 2018, Julia Vitarello and Tim Yu, MD, PhD, created milasen—the first drug custom-built for a single patient, Julia’s daughter Mila—in less than a year.

That was nearly nine years ago! Many parents have achieved medical firsts since, but the market discounts them as one-offs. A few, most notably John Crowley, have turned a parent’s determination into commercial success. Yet the chasm between the Julia Vitarellos and the John Crowleys still yawns. How do we close it?

All the necessary conditions are in place. The science is no longer limiting. The talent most certainly isn’t. There’s even a market incentive: the Priority Review Voucher (PRV), created by Congress in 2012 to spur rare pediatric disease drug development. 

Companies that win approval for a rare pediatric disease drug earn a voucher that entitles its holder to a priority review—shortening the standard 10-month Food and Drug Administration review clock to six months—for any future drug application. Because four months can be worth hundreds of millions to billions in revenue—think GLP-1s—the vouchers can be sold to bigger drugmakers racing blockbusters to market. 

According to PRV Watch, recent sales have topped $200 million. The very appetite for blockbusters that left rare disease behind can now help bankroll the long tail at essentially zero cost to taxpayers.

The rate-limiting step for too many promising rare disease programs is access to cure capital. We should back parents as founders, not just applaud them as advocates. It should not fall to families to make medicines for their children. But when they step forward, we should meet them with the resources to create treatments and cures at scale.

The founders are locked in. It’s time for the capital to catch up.