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.

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.

After years of focusing on de-risked late-stage products, the M&A market is showing a renewed appetite for risk. Recent large deals for early-stage and platform companies signal a return to an era where buyers gamble on foundational science.

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.

Synthakyne operates as a specialized 'cytokine engineering shop.' It develops its own assets in high-value areas like oncology (IL-2, IL-12) while simultaneously licensing its platform for other indications, such as inflammation, through major partnerships with Merck and Sanofi. This strategy generates capital and validates the core technology.

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.

Astute biotech leaders leverage the tension between public financing and strategic pharma partnerships. When public markets are down, pursue pharma deals as a better source of capital. Conversely, use the threat of a public offering to negotiate more favorable terms in pharma deals, treating them as interchangeable capital sources.

Winning a 'Golden Ticket' from a major pharma company like Servier provides more than just lab space. It acts as a powerful external validation of the science, which in turn helps the startup gain credibility to win additional awards and attract investment from other major players like Eli Lilly and Ono Pharma.

With patent cliffs looming and mature assets acquired, large pharmaceutical companies are increasingly paying billion-dollar prices for early-stage and even preclinical companies. This marks a significant strategic shift in M&A towards accepting higher risk for earlier innovation.