Panel, Conference Presentation
The Global Landscape and Opportunities for Medical Breakthroughs | Global Conference 2025
Milken InstituteUsha Lee McFarling, Jay Bradner, Doug Drysdale, Neil Kumar, Alice Pomponio, Grant Verstandig
- Industry Context: The panel characterizes the current era as a "golden age" of biomedicine driven by precision diagnostics, CRISPR, AI, and targeted therapeutics, though significant capital and time investments are required to cross the "valley of death" between discovery and commercialization.
- BridgeBio's Strategy: BridgeBio focuses on precision medicine by measuring genetic information and manipulating it to target disease sources, citing a recent heart drug debut that mimics a "rescue mutation" found in a specific family in Portugal.
- The company's challenge involves commercializing drugs against established giants like Pfizer despite having superior scientific insights.
- They aim to limit R&D costs to under $10 million and achieve 18 INDs (Investigational New Drug applications) in under three years by removing bureaucratic rate-limiting steps.
- Amgen's "Experiments of Nature": Amgen utilizes population-scale human genetics, particularly from the "Amgen Decode" site in Reykjavik, to identify genetic variants that cause or protect against disease.
- LP(a) Strategy: Identified that elevated levels of LP(a) protein cause heart disease but are unaffected by diet or standard statins; a liver-targeting therapeutic is in development to silence this gene.
- Obesity Target: Discovered mutations in the GIPR protein that reduce activity and protect against obesity; a therapeutic emulating this effect is in Phase 3 clinical trials.
- KRAS Breakthrough: Successfully developed the first drug to inhibit KRAS (a protein previously deemed "undruggable" for decades) by targeting a specific cysteine amino acid, a major paradigm shift in oncology.
- Cancer Prevention Research: Published findings that reduced activity of the GAD34 gene correlates with a 53% lower risk of developing breast cancer, signaling a shift toward preventative therapeutics.
- Zephyr AI's Infrastructure: Zephyr positions itself as an AI layer atop existing health infrastructure to process population health data for up to 86 million patients, focusing on oncology and cardiometabolic diseases.
- Data Utilization: Highlights that while a single US hospital generates ~1 petabyte of data annually, less than 5% is currently used for patient care; Zephyr aims to automate non-clinical tasks to free this data for drug discovery.
- Cross-Disease Insights: Uses AI to identify common biological molecules across different cancer types (e.g., prostate and non-small cell lung cancer), enabling label expansions for existing drugs.
- Democratization: Predicts AI will allow small teams to replicate the therapeutic power of large biotech hubs like "Biotech Beach" by collapsing complex protein sculpting capabilities into agentic systems.
- AI in Drug Development Lifecycle: AI is described as a force multiplier across the entire value chain, from target identification to commercialization.
- Protein Folding: AI systems can now predict protein structures (a problem solved by Google's AlphaFold) in seconds rather than years, allowing for rapid "molecular sculpting" before physical synthesis.
- Clinical Trial Optimization: Amgen's "Atomic" system uses AI to predict the next optimal clinical trial site, aiming to remove 2–3 years from development timelines by expediting patient enrollment.
- Virtual Trials: Proposes running 100 billion "agentic" simulations of patients to identify the most biologically relevant candidates before enrolling real humans in Phase 3 trials.
- Saiban & Mental Health Paradigm: Saiban is developing a modified psychedelic compound for depression, reporting a 75% remission rate in Phase 2 with just two doses administered over a clinical supervision period of 4–6 hours.
- Regulatory & Access Challenges: Acknowledges that societal stigma from the "War on Drugs" era remains a barrier to adoption, despite efficacy effect sizes greater than 2.0.
- Infrastructure Needs: The drug's clinical setting requirements (real estate, specialized staff) necessitate partnerships with real estate investors and the optimization of underutilized infusion centers.
- Global Strategy: Planning public-private partnerships in single-payer markets (like China) to overcome regulatory mindset barriers and scale infrastructure.
- American Cancer Society (ACS) & BrightEdge: The ACS is launching "BrightEdge," an investment arm that blends venture capital with donor dollars to fund innovation across the cancer continuum (therapeutics, diagnostics, and health tech).
- Investment Portfolio: Currently allocated 50% to therapeutics, 25% to diagnostic devices, and 25% to technology.
- Success Story: Acquired a brain cancer company (ModifyBio) started by ACS grantees, which was sold to Merck for $1.3 billion.
- Social Determinants: Investing in solutions for financial navigation (e.g., TaylorMed) to help 80% of cancer patients who dip into lifetime savings to access over 17,000 assistance programs.
- Accelerator: Recently launched a third accelerator focused on digital health and social determinants of health (financial security, food stability, social isolation).
- Funding & Public-Private Gaps: Speakers express concern over federal funding cuts to the NIH ($48 billion/year), warning that while private R&D has grown ($163B to $190B), public funding acts as a "force multiplier" for basic knowledge.
- ROI of NIH: Cites a return on investment of roughly $2.56 for every dollar spent on NIH cancer research.
- Future Risk: Warns that without public investment in fundamental biology, the US could lose its competitive edge to China, which is shifting from contract research to innovative discovery.
- Proposed Solution: Advocates for "Broad 2.0" style public-private partnerships to replace eroding federal support, ensuring diverse hypothesis testing rather than capital concentration in a few institutions.
- Global Genomics & Data Sovereignty: Expanding genetic databases beyond Western populations is critical for capturing variant signals.
- Key Databases: References the 100,000 Genomes Project (UK/Saudi Arabia/Pakistan), the Icelandic cohort, the Finnish FinGen database, and the "All of Us" study.
- Data Sovereignty: Emphasizes the need for cultural sensitivity and consent processes, citing examples in Pakistan and Iceland where researchers collaborate with populations to return findings and ensure drug accessibility.
- Afro-Caribbean Focus: BridgeBio is providing free drug provision in the Caribbean based on specific mutation studies in the Afro-Caribbean setting.
- Beyond Genomics (Multi-omics & Epigenetics): The industry is moving toward integrating multi-omic data (transcriptome, epigenome) and behavioral data to create composite biomarkers.
- Behavioral Pre-omics: 60% of cancer deaths are attributed to behavioral factors (smoking, diet); capturing this data is seen as a major field for prevention and treatment efficacy.
- Epigenetics: Viewed as the "blueprint" for precision medicine, combining behavior, environment, and low-cost testing to turn theoretical promises into clinical practice.
- Biosimilars & AI: AI's role in biosimilars is currently limited to quality measures and optimizing speed-to-market for complex protein therapeutics, whereas its primary impact remains in innovative small molecule and large molecule discovery.
- Complexity: Manufacturing protein therapeutics remains technically difficult even after patent exclusivity, distinguishing it from the rapid commoditization of small molecule generics.