Unlike most trials that avoid patients who failed other therapies, Corvus intentionally included them, considering it a 'stacking deck against yourself'. This high-risk bet, based on their drug's unique mechanism, paid off by showing efficacy in a tough-to-treat population and demonstrating a lack of cross-resistance.

Before a major initiative, run a simple thought experiment: what are the best and worst possible news headlines? If the worst-case headline is indefensible from a process, intent, or PR perspective, the risk may be too high. This forces teams to confront potential negative outcomes early.

A pre-mortem asks a team to imagine their project has already failed spectacularly. By explaining the hypothetical failure, they uncover potential risks and can build mitigation strategies, effectively using the power of hindsight bias in advance.

Progress in drug development often hides inside failures. A therapy that fails in one clinical trial can provide critical scientific learnings. One company leveraged insights from a failed study to redesign a subsequent trial, which was successful and led to the drug's approval.

For an upcoming trial in a new indication, the company is optimistic because its trial design specifically addresses perceived flaws from a competitor's (BMS) similar but unsuccessful study. This demonstrates a sharp R&D strategy that learns from public market failures to de-risk its own pipeline.

Before embarking on a high-stakes journey, you must be curious about everything that could go wrong. Conduct a 'premortem' by imagining specific failure scenarios in advance ('what if this breaks?'). This allows you to methodically identify potential problems and develop contingency plans before taking the leap.

To save money, Rhythm's leadership considered canceling a clinical study because the prevailing scientific logic suggested their drug wouldn't work. The study's unexpected, resounding success became the company's pivotal turning point, highlighting the value of pursuing scientifically contrarian ideas.

Before committing capital, professional investors rigorously challenge their own assumptions. They actively ask, "If I'm wrong, why?" This process of stress-testing an idea helps avoid costly mistakes and strengthens the final thesis.

The company intentionally makes its early research "harder in the short term" by using complex, long-term animal models. This counterintuitive strategy is designed to generate highly predictive data early, thereby reducing the massive financial risk and high failure rate of the later-stage clinical trials.