Fireside Chat, Interview
Big Ideas in 2024: Programming Medicine’s Final Frontier with Jorge Conde
- Core Thesis: Jorge Conde (General Partner, a16z Bio + Health) proposes "programming medicine" as the 2024 big idea, drawing an analogy between reusable rockets (SpaceX) and programmable medicines to revolutionize biotech.
- Problem Statement: Traditional drug development is characterized as a bespoke, "one-time use" process where one molecule has no bearing on the next, resulting in a cycle that is painstakingly time-consuming, risky, and expensive.
- Development Timeline:
- The average time to develop a drug and reach patients is 10 to 15 years.
- Drug discovery phase: Variable duration, often taking many years to identify targets.
- Pre-clinical development: Conducted in dishes, cells, or animal models; takes multiple years to assess toxicity, metabolism, and absorption.
- Clinical development: Phases 1, 2, and 3 take 5 to 7 years.
- Regulatory approval: FDA review and filing can take 1 to 2 years post-trial.
- Proposed Paradigm Shift: Programmable medicines (e.g., gene therapy, gene editing) allow for the reuse of delivery "vehicles" (rockets) while swapping out genetic "cargo" (payloads), enabling a new molecule to be developed for a different disease without reinventing the delivery system.
- Regulatory Evolution (FDA):
- The FDA is adopting a "rigorous yet adaptive" approach, similar to the FAA's aviation safety model.
- Office of Therapeutic Products: A newly launched office dedicated to finding paths for evaluating and approving reusable therapeutic components.
- Operation Warp Speed for Rare Disease: A pilot program mirroring the COVID vaccine speed to experiment with flexible regulatory processes for intractable rare diseases.
- Key Milestone:
- The first CRISPR therapy (developed by Vertex Pharmaceuticals and CRISPR Therapeutics) has been approved for sickle cell anemia and beta thalassemia.
- This approval represents a "functional cure" by editing cells outside the body and re-infusing them.
- Speed Metric: Approval was achieved in just over 10 years from the initial scientific discovery of CRISPR, a speed unprecedented compared to the standard 10–15 year drug development cycle.
- Challenges and Blockers:
- Permanence and Safety: Unlike reversible pills, genetic edits are permanent; errors or toxicity could have irreversible consequences, requiring high regulatory rigor.
- Logistical Accessibility: Treatment involves complex, multi-month hospital stays (e.g., cell removal, editing, and re-infusion), limiting patient access.
- Cost: Therapies currently cost on the order of millions of dollars (e.g., Novartis therapy at $2.1 million) due to high R&D and manufacturing complexity.
- Call to Action for Builders:
- Developers must focus on engineering biology to scale manufacturing, reduce costs, and improve precision to address toxicity and permanence issues.
- The ultimate goal is to apply exponential scaling (similar to software) to lower costs from millions to thousands of dollars.
- Forward-Looking Statement: While an exponential cost curve for biology has not yet been fully realized, the potential for biology to scale remains the central hope for making programmable medicines widely accessible.