Instead of relying on finding novel targets, a key strategy in neuropsychiatry is to revisit failed compounds that showed efficacy signals. Companies use modern chemistry and delivery to engineer solutions that separate efficacy from the historical liabilities that halted development, turning past failures into new opportunities.

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.

Transgene pivoted from "off-the-shelf" to individualized cancer vaccines not by starting over, but by leveraging its deep, four-decade-long expertise in viral vectors and payload integration. This highlights how legacy know-how can be a critical asset in strategic company shifts.

After joining Amarin, Doogan immediately faced a failed Phase 3 program. Instead of closing down, the team re-evaluated their existing science and successfully repurposed a product originally for Huntington's disease to treat hypertriglyceridemia, ultimately leading to FDA approval and commercial success.

Successful biotech leadership requires a clear decision-making hierarchy. Dr. Bahija Jallal advocates for a framework where patient welfare is paramount, followed by scientific rigor. Financial success is treated as a byproduct of excelling in the first two areas, not the primary goal.

Despite FDA readiness for a final Phase 3 trial, Connect Biopharma chose to run more Phase 2 studies. They discovered their long-term asthma drug worked in hours, not weeks, and are now pivoting to prove its value in acute, emergency situations, which informs a stronger, more targeted Phase 3 design.

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.

The fundamental purpose of any biotech company is to leverage a novel technology or insight that increases the probability of clinical trial success. This reframes the mission away from just "cool science" to having a core thesis for beating the industry's dismal odds of getting a drug to market.

An analysis revealed that buying a portfolio of biotech firms with poor data in 2022 would have yielded better returns than buying those with great data. This counterintuitive finding highlights the market's tendency to over-punish initial failures and undervalue the potential of strategic pivots.