To achieve an affordable price for its advanced cancer test, Delphi prioritizes algorithmic complexity over "wet lab" complexity. This strategy keeps physical sample processing simple and low-cost, putting the innovation into scalable software (AI/ML) to analyze the data, which is key for mass adoption.

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.

Yosemite provides unrestricted grants to academic scientists, de-risking novel research and building relationships. This early support creates a unique deal flow engine, leading to investment opportunities in companies that later spin out from this foundational work.

Two dominant strategies are winning. Companies can either be the absolute best at one specific thing (e.g., musculoskeletal care, women's health) or build a platform that aggregates these best-in-class solutions into a seamless 'digital front door' for insurers and corporations.

Unlike incumbents, new biotech and pharma companies often lack established sales forces. They launch with a 'digital first' go-to-market strategy, turning to platforms like Doximity early in their lifecycle. This creates a new and rapidly growing customer segment for Doximity, independent of the incumbents' slower transition.

A crucial piece of advice for biotech founders is to interact with patients as early as possible. This 'patient first' approach helps uncover unmet needs in their treatment journey, providing a more powerful and differentiated perspective than focusing solely on the scientific or commercial landscape.

Yosemite's investment portfolio shows a bias towards "first in class" or potentially curative "last in class" therapies. This indicates a higher tolerance for innovation risk, betting on novel modalities and groundbreaking science over safer, incremental advances.

Instead of relying solely on traditional LPs, Vi Ventures actively brings in families affected by autoimmune diseases as for-profit investors. This model creates a community of highly motivated stakeholders, fostering accountability and a direct connection to the patient experience, while still maintaining market-rate return objectives.

While focused on oncology, Yosemite's portfolio company Tune Therapeutics is using epigenetic editing to develop a functional cure for Hepatitis B. This is a strategic cancer play, as chronic Hepatitis B is the leading global cause of liver cancer.