Unlike tech investing, where a single power-law outlier can return the entire fund, biotech wins are smaller in magnitude. This dynamic forces biotech VCs to prioritize a higher success rate across their portfolio rather than solely hunting for one massive unicorn.

BridgeBio's unique structure creates dedicated subsidiaries for each program. This empowers small, focused teams closest to the science to make key decisions—"play calling on the field"—without layers of bureaucracy. This model dramatically accelerates development, leading to unprecedented output of new drugs.

To maintain a competitive edge, BridgeBio only pursues programs that are either "first in class" (a novel treatment where none exists) or "best in class" (a demonstrably superior option, like an oral pill versus a daily injection). This strict strategic filter is the core of their entire R&D pipeline selection process.

The old assumption that small biotechs struggle with commercialization ("short the launch") is fading. Acquirers now target companies like Verona and Intracellular that have already built successful sales operations. This de-risks the acquisition by proving the drug's market viability before the deal, signaling a maturation of the biotech sector.

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.

Apogee built its strategy around known biological mechanisms, focusing innovation solely on antibody engineering. This allowed them to de-risk assets early and efficiently (e.g., proving half-life in healthy volunteers). This clear, stepwise reduction of risk proved highly attractive to capital markets, enabling them to raise significant funds for late-stage development.

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.

Renowned gene therapy pioneer Jim Wilson was forced to spin out ultra-rare disease programs into a new company after his initial venture failed to attract VC funding. This demonstrates that even elite scientific leadership cannot overcome investor disinterest in this segment without powerful, predictable government incentives like transferable priority review vouchers.

DFJ Growth Partner Barry Shuler details their strategy of avoiding herd investments by focusing on 'life tech'—the intersection of life sciences and technology. This contrarian approach allows them to back brilliant but lesser-known visionaries in emerging fields like population genomics, where they see immense potential.