When a promising ALS drug failed Phase 2 trials, the company shut down. The drug's original founder, Dr. Ari Azhir, still believed in the science, repurchased the asset and all its data, and ultimately uncovered its true potential, leading to a new FDA application.

Despite facing a patent cliff of up to $300 billion by 2030 and knowing that most innovation is externally sourced, big pharma's M&A activity remains surprisingly tepid. This paradox suggests a major disconnect between strategic necessity and the industry's current risk appetite or deal-making capacity.

The industry's costly drug development failures are often attributed to clinical issues. However, the root cause is frequently organizational: siloed teams, misaligned incentives, and hierarchical leadership that stifle the knowledge sharing necessary for success.

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.

A major source of unproductivity in drug development isn't the time spent reaching a clinical milestone. Instead, it's the 'white space' after data is received—the delay in analyzing results and making a firm go/no-go decision, which stalls the entire program.

Despite shedding over 22,000 jobs, large pharmaceutical companies are aggressively investing in external assets. This counterintuitive trend is driven by the urgent need to fill revenue gaps from a looming $300 billion patent cliff, signaling a major strategic shift from internal R&D to external innovation acquisition.

The "takeout candidate" thesis often fails because corporate development teams at large firms won't risk their careers on optically cheap but unprofitable assets. They prefer to overpay for proven, de-risked companies later, making cheapness a poor indicator of an impending acquisition.

M&A is often framed as a win, but it can be detrimental to patients. The acquisition of an aggressive, fast-moving biotech by a large pharma company can lead to slowed development timelines and more conservative regulatory strategies, ultimately delaying access to life-saving treatments.

GSK's CSO reveals their "bolt-on" deal-making focuses on late-stage clinical assets that may have failed trials or have suboptimal profiles. They acquire these assets when they believe a better trial design or repositioning can unlock the molecule's true potential, as exemplified by their acquisition of Momalotinib.