Where Is the Next Cure? | Global Conference 2024

Panel Overview & Context

• Core Thesis: The biomedicine sector is transitioning from a 50-year era of small-molecule drugs to a "new era" of precise, systems-based therapies (cell-based, gene, and information-based) that offer sustainable cures rather than chronic management.
• Technological Catalysts: Recent breakthroughs include mRNA vaccines, the first FDA-approved CRISPR therapy, and the integration of AI across drug discovery and development.
• Speed of Translation: CRISPR moved from basic science elucidation (10 years ago) to FDA approval for sickle cell disease in just a decade, a pace described as "lightning fast" compared to the traditional 20–25 year timeline.
• Economic Scale:
  • Royalty Pharma deployed $4 billion in 2023 and $25 billion over the last decade to fund biotech and pharma.
  • Moderna invested $2.5 billion over 10 years building its mRNA platform before COVID-19, when the technology was commercially unproven.
  • GLP-1 drugs (biotechnology output) are projected to generate a $100 billion market by 2030, potentially benefiting 9% of the U.S. population.

Innovation Modalities & Strategies

• Reverse Translation Model: Flagship Pioneering (Nubar Afeyan) utilizes a "reverse translation" strategy, starting with a desired biological outcome (e.g., making any protein) and working backward to engineer the necessary platform (mRNA), rather than starting with a specific disease.
• Peptoids Platform: Major Inc. (Aloe Black) is developing peptoids to overcome the "one bug, one drug" bottleneck, offering serum stability, non-immunogenicity, and high target specificity to reduce late-stage failure risks.
• AI as a Mathematical Foundation: Daphne Kohler compares AI in biology to calculus in physics, providing a foundation for principled, engineered predictions that could address the industry's 90–95% clinical trial failure rate.
• Data Dependency: AI's exponential impact is contingent on "web-scale" biological data; currently, AlphaFold succeeded due to massive sequence-to-structure datasets, whereas early-biology and clinical-phase data remain insufficiently collected.
• Preventive Medicine: The panel advocates for shifting focus upstream to "preemptive medicine," using molecular interventions to delay or prevent disease onset before clinical manifestation.

Regulatory Landscape & Acceleration

• FDA Adaptability: Regulatory bodies have demonstrated capacity for rapid approval (e.g., mRNA vaccines) without cutting corners, suggesting that traditional timelines are behavioral expectations rather than scientific necessities.
• Accelerated Pathways vs. Common Diseases: While rare diseases (e.g., sickle cell) benefit from accelerated pathways and leniency, common indications (e.g., heart disease, cancer) still require robust proof of outcome, creating a bottleneck for broad-impact therapies.
• Organ Editing Regulation: The FDA may be more receptive to ex vivo organ editing (treating the organ via perfusion pump) rather than in vivo whole-body CRISPR editing, potentially reducing immunosuppression requirements and regulatory risk.
• UK as a Model: The UK is cited as a leader in data-centric regulation and proactive health planning, contrasting with reactive U.S. models that often prioritize incumbency and slow progression.

Cost, Scalability, & Access

• Pricing Dynamics:
  • CRISPR therapy for sickle cell currently costs ~$2 million per patient in the U.S.
  • In vivo editing and allogeneic manufacturing (e.g., CAR-T) are projected to reduce costs to $10,000–$20,000 or lower, respectively.
  • Historical precedent shows biotech prices often drop by orders of magnitude as technology matures and competition increases.
• Pharmacoeconomics: Payers recognize the ROI for curative therapies; for sickle cell, the lifetime cost of hospitalization and care (~$300,000/patient/year) justifies a high upfront cure cost, especially given the social value of removing patients from Medicaid and re-entering the workforce.
• Global Disparities: The majority of sickle cell patients reside in Africa, while most R&D and high-cost manufacturing capacity remain in the U.S., highlighting a critical access gap.

Emerging Frontiers & Specific Initiatives

• Xenotransplantation:
  • Pig Model: A collaboration involving Royalty Pharma and NYU Langone is testing genetically edited "pygmy pig" kidneys in human decedents to validate organ acceptance before human trials.
  • Perfusion Technology: A normothermic perfusion pump is being used to edit organs (CRISPR cloaking) and rejuvenate them using Yamanaka factors directly in a working human body (decendent model).
  • Timeline: Initial human trials for pig kidneys are targeted for 18–24 months.
• Cancer Vaccines: mRNA platforms are being applied to cancer vaccines (e.g., melanoma), showing 40–50% improvement over Keytruda in early data, with Phase 3 results expected late 2024/early 2025.
• Diversity in Data: Daphne Kohler emphasizes that diverse genetic populations (e.g., African lineages with higher genetic diversity) are crucial for drug discovery and ensuring therapeutic efficacy across different ethnic groups, as current datasets are predominantly European.

Systemic Challenges & Disagreements

• Funding Allocation: Alo Black and Nubar Afeyan disagree with the government's tendency to concentrate massive funding on single indications (e.g., Cancer Moonshot) rather than diversifying bets across multiple high-potential technologies.
• Regulatory Dogma: Sam Kulkarni and Daphne Kohler express frustration that regulatory systems are built for "chronic care" (pay-as-you-go) rather than "curative models," hindering the adoption of one-time, high-impact therapies.
• The "Elephant in the Room": The industry collectively acknowledges the 90–95% failure rate in clinical trials as a major inefficiency driven by poor target selection, which AI aims to solve by identifying the correct therapeutic hypotheses before clinical entry.