There's a strong reluctance in venture capital to fund companies that are number two or three in a category dominated by a "kingmaker"—a startup already backed by a top-tier firm. This creates a powerful, self-fulfilling fundraising moat for the perceived leader, making it unpopular to back competitors.

Startups often fail to displace incumbents because they become successful 'point solutions' and get acquired. The harder path to a much larger outcome is to build the entire integrated stack from the start, but initially serve a simpler, down-market customer segment before moving up.

Incumbents are disincentivized from creating cheaper, superior products that would cannibalize existing high-margin revenue streams. Organizational silos also hinder the creation of blended solutions that cross traditional product lines, creating opportunities for startups to innovate in the gaps.

When introducing a disruptive model, potential partners are hesitant to be the first adopter due to perceived risk. The strategy is to start with small, persistent efforts, normalizing the behavior until the advantages become undeniable. Innovation requires a patient strategy to overcome initial industry inertia.

Large incumbents struggle to serve newly-formed startups because these customers offer low initial revenue but require significant sales and support. This P&L constraint creates a protected 'greenfield' market for new vendors to capture customers early and grow with them.

Instead of dismissing harsh criticism, extract the underlying truth. A brutal investor rejection focused Gamma on intertwining product and growth from the very beginning, acknowledging the difficulty of competing against incumbents. This became a foundational part of their strategy.

A major market opportunity exists when one side of an industry (e.g., insurance companies) adopts new technology like AI faster than its counterpart (e.g., hospitals). Startups can succeed by building tools that close this technology gap, effectively 'arming the rebels' and leveling the playing field.

Responding to Wall Street pressure to de-risk, large pharmaceutical firms cut internal early-stage research. This led to an exodus of talent and the rise of contract research organizations (CROs), creating an infrastructure that, like cloud computing for tech, lowered the barrier for new biotech startups.

Unlike typical tech disruption, healthcare often requires collaboration. Startups effectively "rent" distribution and patient access from incumbents. In return, incumbents "rent" cutting-edge innovation from startups, creating a necessary symbiotic relationship.