R&D departments in large pharmaceutical companies often resist repurposing projects. Their leaders are rewarded for discovering new chemical entities, not for finding new applications for existing drugs, creating an internal funding barrier that business units must overcome.
In the real world, the selection of a therapeutic modality like an antibody or peptide is often driven by a company's existing expertise and technology platform rather than a purely agnostic approach to finding the single best tool for a clinical problem. Organizations default to the tools in their toolbox.
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.
Drug developers often operate under a hyper-conservative perception of FDA requirements, avoiding novel approaches even when regulators might encourage them. This anticipatory compliance, driven by risk aversion, becomes a greater constraint than the regulations themselves, slowing down innovation and increasing costs.
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.
The fear of toxicity pushes many companies to pursue the same few well-validated targets, leading to an average of nine assets per target. This hyper-competition not only crowds the market but, more importantly, leaves vast patient populations without effective options because their diseases lack these "popular" targets.
A significant number of Eli Lilly's compelling inventions came from unsanctioned projects. The company intentionally provides budget flexibility and avoids micromanagement at its R&D sites, allowing scientists to pursue their curiosity.
The Orphan Drug Act successfully incentivized R&D for rare diseases. A similar policy framework is needed for common, age-related diseases. Despite their massive potential markets, these indications suffer from extremely high failure rates and costs. A new incentive structure could de-risk development and align commercial goals with the enormous societal need for longevity.
The fastest, cheapest path to drug approval involves showing a small survival benefit in terminally ill patients. This economic reality disincentivizes the longer, more complex trials required for early-stage treatments that could offer a cure.
With clinical development cycles lasting 7-10 years, junior team members rarely see a project to completion. Their career incentive becomes pushing a drug to the next stage to demonstrate progress, rather than ensuring its ultimate success. This pathology leads to deferred problems and siloed knowledge.
To avoid the pitfalls of scale in R&D, Eli Lilly operates small, focused labs of 300-400 people. These 'internal biotechs' have mission focus and autonomy, while leveraging the parent company's scale for clinical trials and distribution.