BridgeBio's founder saw biotech VCs exclusively funding high-risk "home run" platforms. He built a company to acquire therapies for smaller rare genetic diseases—"singles and doubles"—that were ignored. Aggregating these de-risks the portfolio and creates a major market opportunity.

During market downturns, biotech companies lose the ability to raise capital simply when it's convenient. Financing becomes tied to specific events. The key is timing a fundraise immediately before or after the release of significant clinical data that de-risks the company and attracts new investors.

The fund-of-funds model, often seen as outdated, finds a modern edge by focusing on small, emerging VC managers. These funds offer the highest potential returns but are difficult for most LPs to source, evaluate, and access. This creates a specialized niche for fund-of-funds that can navigate this opaque market segment effectively.

A smaller fund size enables investments in seemingly niche but potentially lucrative sectors, such as software for dental labs. A larger fund would have to pass on such a deal, not because the founder is weak, but because the potential exit isn't large enough to satisfy their fund return model.

Resist the common trend of chasing popular deals. Instead, invest years in deeply understanding a specific, narrow sector. This specialized expertise allows you to make smarter investment decisions, add unique value to companies, and potentially secure better deal pricing when opportunities eventually arise.

In the rare disease space, success hinges on deep patient community engagement. Smaller, nimbler biotechs often excel at creating these essential personal ties, giving them a significant advantage over larger pharmaceutical companies.

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.

When evaluating follow-on opportunities, the conventional wisdom is to look for a Tier 1 VC leading the round. However, a specialized fund with deep industry expertise leading a Series A can be an equally powerful, or even stronger, positive signal for a company's potential and market fit.

Small, dedicated venture funds compete against large, price-insensitive firms by sourcing founders *before* they become mainstream. They find an edge in niche, high-signal communities like the Thiel Fellowship interviewing committee or curated groups of technical talent. This allows them to identify and invest in elite founders at inception, avoiding bidding wars and market noise.