WCM realized their portfolio became too correlated because their research pipeline itself was the root cause, with analysts naturally chasing what was working. To fix this, they built custom company categorization tools to force diversification at the idea generation stage, ensuring a broader set of opportunities is always available.

Many LPs focus solely on backing the 'best people.' However, a manager's chosen strategy and market (the 'neighborhood') is a more critical determinant of success. A brilliant manager playing a difficult game may underperform a good manager in a structurally advantaged area.

Standard quant factors like expanding margins and avoiding capital raises are negative signals for development-stage biotech firms. These companies must burn cash to advance products, rendering traditional models useless. The only semi-reliable quant metric is Enterprise Value to Cash.

The biotech sector lacks mid-cap companies because successful small firms are typically acquired by large pharma before reaching that stage. This creates a barbell structure of many small R&D shops and a few commercial giants. The assets, not the companies, transition from small to large.

Private VCs with board seats operate deterministically, using their influence to 'make sure' a drug succeeds. Public fund managers operate probabilistically, accepting imperfect information in exchange for liquidity. They must calculate the odds of success rather than trying to directly shape the outcome.

The underperformance of active managers in the last decade wasn't just due to the rise of indexing. The historic run of a few mega-cap tech stocks created a market-cap-weighted index that was statistically almost impossible to beat without owning those specific names, leading to lower active share and alpha dispersion.

The sign of a working diversification strategy is having something in your portfolio that you're unhappy with. Chasing winners by selling the laggard is a common mistake that leads to buying high and selling low. The discomfort of holding an underperformer is proof the strategy is functioning as intended, not that it's failing.

Investors rarely sell a fund for outperforming its benchmark too aggressively, but they should consider it. Research by Vanguard's John Bogle tracked the top 20 funds of each decade and found they almost always became significant underperformers in the following decade, demonstrating the danger of chasing past winners.

While biotech seems exceptionally volatile, data shows its average 60% annual peak-to-trough drawdown isn't dramatically worse than the ~50% for typical non-biopharma small caps. The perceived risk is disproportionate to the actual incremental volatility required for potentially asymmetric returns.