An intellectual property obstacle nearly terminated the bivalirudin project. This constraint forced the team to devise a novel "bivalent" molecule, which not only bypassed the patent issue but also resulted in a more potent drug. This illustrates how external limitations can unexpectedly trigger superior innovation.
The blockbuster drug bivalirudin was discovered as an unsanctioned "20% time" project at Biogen. This policy, allowing scientists to explore personal interests, demonstrates how institutionalizing freedom for undirected research can lead to major, company-defining breakthroughs that would otherwise be missed in a rigid R&D structure.
Facing industry-wide skepticism in 2010, Alnylam implemented a highly disciplined R&D strategy. They focused exclusively on targets that met strict criteria: liver expression (where delivery worked), human genetic validation (to de-risk biology), and an early biomarker. This strategic focus was key to their survival and success.
When the industry lost faith in RNAi, Alnylam launched "Alnylam 5x15," a public five-year goal to advance five drugs into the clinic. While it took years to register externally, this bold commitment immediately became a powerful internal rallying cry, injecting hope and focus into the team during a demoralizing period.
Over 20 years, Alnylam raised $7.5 billion. Remarkably, this was evenly split between equity financing from capital markets and non-dilutive funding from pharmaceutical partnerships. This balanced strategy was essential for financing a long, capital-intensive R&D journey while managing shareholder dilution.
During a dismal post-tech-bubble market, Alnylam secured crucial early funding from pharmaceutical giants. These partners saw the long-term potential of RNAi and were willing to invest when public markets were risk-averse, highlighting pharma's role as a source of patient, visionary capital for platform technologies.
In a tough funding environment, John Maraganore cautions against rushing into founding a company. He recommends that aspiring entrepreneurs first spend 5-10 years at a successful biotech. He argues that when capital is scarce, investors prioritize experienced operators, making deep industry experience a critical prerequisite for getting funded.
A pivotal moment for Alnylam came when competitor Surna Therapeutics was acquired by Merck for $1.1B. This external validation of the entire RNAi space significantly strengthened investor excitement about Alnylam, making it easier for them to raise capital and secure large partnerships. A rival's success can lift all boats.
John Maraganore highlights the necessity of a personal support system, like his wife, for a CEO during crises. He argues that you cannot be fully transparent about your deepest fears with your team or board without creating destructive anxiety, making an external confidant essential for resilient leadership.
John Maraganore's transition from science to business wasn't a choice but a reluctant career change forced upon him by Biogen's CEO. This involuntary pivot, which he initially resisted, provided the essential business experience he later needed to become a CEO, demonstrating how career-defining moments can be externally imposed.