Advanced-Modalities-And-The-Decisions-That-Define-Them

This panel discussion from the Danaher Summit 2026 brings together four industry leaders — Campbell Bunce (Abzena), Hendrik Dietz (CBTX), Mike Henney (Bicycle Therapeutics), and Dan McGrath (Sarepta) — to examine the manufacturing, regulatory, and supply chain challenges of advanced modalities including in vivo CAR-T therapy, radiopharmaceuticals, and novel nucleic acid delivery systems. A recurring theme is that no manufacturing or regulatory playbook exists for these modalities, forcing developers to educate regulators, build orthogonal data packages, and design for manufacturability from day one. The panel concludes that the primary bottleneck is not scientific innovation but the last-mile challenges of manufacturing, regulatory clarity, CDMO selection, and supply chain resilience.

Key Takeaways

Advanced modalities lack established regulatory or manufacturing playbooks; developers must proactively educate regulators through risk-based, orthogonal data packages showing integrated structure-function-PKPD-safety relationships rather than presenting standard data sets with gaps.
CBTX's in vivo CAR-T platform uses immune-quiet single-stranded DNA (7,000 bases, produced by microbial fermentation invented 12+ years ago) delivered via targeted LNPs decorated with two surface ligands — none of which have been tested in human patients.
Bicycle Therapeutics' radiopharmaceuticals have a 10-hour half-life, compressing the entire manufacture-to-dose window to under 10 hours and demanding a completely different supply chain paradigm from conventional pharmaceuticals targeting 3-5 year shelf life.
Lead-212 for targeted alpha therapy currently depends almost entirely on a single aging DOE High Flux Reactor at Oak Ridge; Bicycle Therapeutics addressed this vulnerability by leasing 400 tons of reprocessed uranium in partnership with the UK National Nuclear Decommissioning Agency.
Novartis, the only company with a radiopharmaceutical supply chain playbook via Pluvicto, invested tens of billions of dollars in infrastructure and still struggled in its early years — a bar smaller biotechs must address through CDMO networks and creative upstream supply agreements.
CDMO selection for advanced modalities fails when CDMOs are motivated to fill manufacturing suites rather than develop genuine modality-specific expertise; panelists advocate patient-centered, risk-sharing, multifaceted partnerships that include specialist scientific vendors.
Early outsourcing of development technologies to CDMOs erodes platform IP value when a biotech later seeks strategic partnerships or acquisition, pushing resource-constrained companies to build in-house expertise in parallel with external partners.
Developability — treating manufacturability and scale-up as priority design criteria from the earliest stage through iterative design-make-test-redesign cycles — is essential for novel modalities because bench-scale success does not guarantee clinical-scale feasibility.