On May 6, Friends of Cancer Research (Friends) and the Parker Institute for Cancer Immunotherapy co-hosted a public meeting, “Unlocking Next-Generation Therapies” to explore opportunities to advance next-generation therapies, including innovative approaches in cell therapy development. The oncology landscape has shifted dramatically over the last 30 years, transitioning from chemotherapy-based treatment toward molecularly and immunologically driven approaches, including chimeric antigen receptor T-cell (CAR-T) breakthroughs. While science has matured into a reality that can potentially cure previously incurable diseases, the operational frameworks governing these therapies remain under significant pressure, such as regulatory and manufacturing hurdles that do not always align with the unique complexities of cell and gene therapies. To maintain U.S. lead in innovation, the focus must shift from identifying problems to operationalizing efficiency within the oncology ecosystem.
- Joint Issue Brief: https://friendsofcancerresearch.org/wp-content/uploads/Regulatory-and-Operational-Considerations-for-Cell-Based-Therapies-Issue-Brief.pdf
- Presentation Slides by Mark Stewart, Friends: https://friendsofcancerresearch.org/wp-content/uploads/2026-Unlocking-Next-Gen-Therapies-Meeting-Presentation-Slides.pdf
- Friends Cell & Gene Therapies Project Page: https://friendsofcancerresearch.org/cell-gene-therapies/
Key Takeaways
- Clinical Development is Moving Faster than Manufacturing Readiness: Strong early efficacy signals can accelerate clinical development, but Chemistry, Manufacturing, and Controls (CMC) scale-up, process development, and manufacturing readiness often require more time. This mismatch can create delays between promising clinical results, regulatory submissions, and broader patient access.
- Early-Phase Development Needs More Predictable Starting Points: Early-phase development for cell-based therapies would benefit from clearer starting points for core protocol elements, including dose-limiting toxicity (DLT) definitions and safety monitoring, patient selection, and where relevant, pediatric inclusion. Common foundational frameworks could improve predictability while preserving flexibility based on product type, disease context, mechanism of action, patient population, and unmet need.
- U.S. Competitiveness Depends on Reducing Avoidable Friction: Global competition is increasing pressure on the U.S. development ecosystem, particularly as other countries, such as China, have regulatory paradigms that allow them to move quickly to generate clinical data and iterate across programs. Maintaining U.S. leadership will require improving regulatory predictability, strengthening research and manufacturing infrastructure, and reducing unnecessary operational delays without lowering standards for safety and efficacy.
- Personalized Therapies Need Scalable Delivery Models: Highly personalized cell-based therapies have shown promise in specialized academic settings, but broader patient access will require sustainable delivery models that can move beyond localized expertise and reach patients across more care settings.
- CMC Flexibility Should Extend Across the Product Lifecycle: A lifecycle approach to CMC could help align expectations for specifications, comparability, validation, and manufacturing changes with the stage of development and actual product risk. Leveraging prior knowledge, platform experience, and fit-for-purpose approaches may help reduce unnecessary burden while maintaining product quality and patient safety.
Session 1 – Modernizing Early Phase Clinical Development Approaches
Key Takeaway
Early-phase development for cell-based therapies would benefit from clearer, more predictable starting points for core protocol elements, while preserving flexibility to adapt based on product type, disease context, patient population, and emerging data.
Session 1 explored opportunities to modernize early-phase clinical development, including investigational new drug (IND) readiness, patient selection, protocol design, non-clinical flexibilities, and the relationship between early clinical progress and CMC readiness.
The session began with a presentation by Mark Stewart (Friends) and was moderated by Lola Fashoyin-Aje (Clinical-Regulatory Strategy Consulting), with panelists Steven Fleischer (FDA), Vijay Kumar (FDA), M Travis Quigley (Kelonia Therapeutics), Rosanna Ricafort (Bristol Myers Squibb), Nirali N. Shah (NCI), and Chris White (Friends Advisory Advocate).
The Early-Phase Experience in Practice and Global Trends
The session opened by grounding the discussion in the realities of early-phase cell therapy trials, where decisions often need to be made with limited data, evolving science, and urgent patient need. In that context, pediatric enrollment was discussed as an area where rigid adult-first sequencing may not always be appropriate. Instead, speakers highlighted the need to consider disease context, mechanism of action, ethical considerations, and unmet need when determining whether earlier pediatric inclusion may be justified.
Kumar described FDA’s movement toward “a more disease context-sensitive, mechanism-aware framework for pediatric eligibility”, where pediatric enrollment is considered as a central design question earlier in development planning, rather than as an issue deferred to the post-approval setting.
The panel also discussed the growing use of early clinical data generated outside the U.S. These studies may offer advantages related to cost, speed, and access to patient populations with different prior treatment histories. However, they also raise questions about manufacturing standards, adequacy of non-clinical safety packages, data integrity, and applicability to U.S. patients and SOC. These issues underscored the importance of early FDA alignment on how evidence will be evaluated and what additional data may be needed to support U.S. development. The patient perspective also reinforced the need for better trial awareness and education, so patients can make informed decisions about potential participation earlier in their treatment course.
IND Readiness, Protocol Design, and Non-Clinical Flexibilities
Panelists discussed ways to reduce barriers during IND preparation, including optimizing the non-clinical package through early FDA interactions, leveraging existing knowledge from similar products, and using new approach methodologies (NAMs) to safely reduce unnecessary animal testing where scientifically appropriate. The discussion also emphasized the need for flexible early-phase clinical protocols that empower safety review committees to respond to emerging data—such as dynamically adjusting dose ranges or implementing prophylactic therapies—without triggering cumbersome and unnecessary amendment processes.
Establishing a Common Foundational Framework & Aligning CMC
A recurring theme was the need for more predictable starting points for core protocol elements, including DLT definitions, safety monitoring, and sentinel dosing. Panelists noted that variability across sponsors can create avoidable friction during IND review and supported a common foundation framework that could be tailored to the specific disease context, product type, and patient population.
The discussion also highlighted the disconnect that can occur when clinical development accelerates faster than manufacturing readiness. Strong early efficacy signals may support rapid clinical advancement, but CMC scale-up, process development, and manufacturing readiness often require more time. Early and transparent FDA engagement was viewed as important to ensure CMC timelines and process updates remain aligned with clinical development.
How Early Decisions Shape the Downstream Development Pathway
Panelists emphasized that early investments in predictive sciences, AI, and machine learning may help support high-quality decisions at key inflection points. The discussion also addressed how early evidence can shape later-stage development expectations, including when single-arm studies may be appropriate and when randomized trials may be expected to demonstrate clinical benefit.
Session 2 – Operationalizing Risk-Based CMC Flexibility Across the Product Lifecycle
Key Takeaway
CMC flexibility should be applied across the product lifecycle from early clinical development into post-approval changes. A risk-based approach to specifications, comparability, validation, and manufacturing changes can help reduce unnecessary burden while maintaining product quality and patient safety.
Session 2 explored opportunities to operationalize risk-based CMC flexibility across the product lifecycle, including approaches to validation, comparability, release specifications, and manufacturing changes. The session was moderated by John Connolly (Parker Institute for Cancer Immunotherapy), with panelists Ben Beneski (Allogene Therapeutics), Marc Better (Pharmefex), Magdi Elsallab (Harvard Medical School), Arvind Natarajan (Iovance Biotherapeutics), Alexandra Beumer Sassi (AstraZeneca), and Kimberly Schultz (FDA).
CMC in Practice and Friction Points
The discussion highlighted that CMC challenges vary across product types and development settings. Panelists noted the tension between the time needed to develop deep product and process understanding and the pressure to move promising therapies quickly through development. For autologous tumor-infiltrating lymphocyte (TIL) therapies, variability in patient starting material across multiple indications can complicate manufacturing consistency. For allogeneic CAR-T therapies, large-scale manufacturing may result in a relatively small number of clinical batches, limiting the data available to set specifications and manage gene editing components. Academic developers may face additional challenges when transitioning multiplex gene-edited products from animal models to GMP IND-enabling studies, particularly when working with novel or heterogeneous starting materials.
Specification Development Across the Lifecycle
Panelists emphasized that specifications are often set early with limited data but can influence product quality expectations throughout development and after approval. A true lifecycle approach was emphasized where sponsors set wide acceptance criteria during early development (acting as check-ins rather than restrictive limits) and differentiate between critical quality attributes tied to safety (e.g., vector copy number) and other attributes used to monitor product quality and process consistency. One proposed approach included tiering specifications based on their relationship to safety (tier 1), process consistency (tier 2), and ongoing monitoring (tier 3).
Panelists also discussed the value of defining prospective milestones (e.g., pre-pivotal, pre-PPQ, pre-commercial) to reevaluate specifications as additional product and process knowledge accumulates. This approach could help avoid overly narrow early numerical specifications that fail to reflect normal process variability and may trigger unnecessary concerns.
Comparability, Prior Knowledge, and Platform Approaches
The panel also discussed practical challenges with traditional comparability expectations, particularly when split-run or statistically powered equivalence testing is not feasible. For allogeneic therapies, split-donor comparability studies may require more doses than are clinically needed and may be difficult to conduct with fresh donor material across dispersed sites. For autologous products, patient starting material variability can make it difficult to distinguish true process or analytical variability from underlying patient-to-patient differences. While split-run studies are the preferred approach by the FDA, the agency acknowledges logistical limitations and adjusts expectations based on the phase of development and depth of process characterization. Several strategies were noted to support comparability in these settings, including qualified scale-down models, expectation-based approaches, and the use of prior knowledge.
Platform data may help inform operating range parameters, analytical method performance, control strategies, formulation processes, stability testing, and shared product quality attributes. However, academic developers may lack the massive datasets of large industry sponsors, underscoring the need for more tailored regulatory advice and collaborative approaches to building shared knowledge.
Aligning CMC Expectations to Product Risk
A recurring theme was the need to calibrate CMC expectations to actual product risk and development stage. Panelists discussed Process Performance Qualification (PPQ) as one area where traditional at-scale expectations may be challenging, particularly for cost-prohibitive for expensive ancillary materials, such as guide RNAs or Cas9 enzymes. More creative approaches, such as combining limited large-scale runs with qualified small-scale lots, could help generate meaningful process characterization data while reducing unnecessary cost and burden.
The discussion underscores the importance of phase-appropriate expectations, especially when working with novel complex edits. Exploring non-conventional mechanisms, such as the Bespoke Gene Therapy Consortium, was encouraged to help distribute costs, support pre-competitive work, and generate knowledge that can inform future development programs.
Fireside Chat – Predictability in Drug Development in an Evolving Policy Environment
Key Takeaway
Maintaining U.S. leadership in drug development will require renewed investment in basic research infrastructure that fuels biomedical innovation and a concerted effort to address costly structural inefficiencies across the clinical trial ecosystem. To navigate global competition and funding uncertainty, stakeholders should prioritize streamlining IND processes and ensure FDA has the clear congressional direction, resources, and flexibility needed to foster a predictable regulatory environment.
The Fireside Chat provided a broader policy lens on the future of drug development in an evolving policy environment, including the impact of National Institutes of Health (NIH) funding pressures, drug pricing dynamics, FDA leadership changes, global competition, and congressional action may shape the U.S innovation ecosystem. The panel discussion highlighted a recurring theme from the meeting: scientific advances will only translate to patients if development, regulatory, and operational systems can keep pace. The session was moderated by Jeff Allen (Friends), with panelists Christopher R. Heery (Arcellx, Inc), David Kaufman (Third Rock Ventures), and Julie Tierney (Leavitt Partners).
Macro Environment and Investment Strategy
The discussion opened by highlighting the current tension between rapid scientific innovation and increasing uncertainty across the broader policy environment. It was noted that while the investment market is currently seeing healthy mergers and acquisitions activity driven in part by patent cliffs, sustaining this requires a robust academic innovation ecosystem to efficiently source new ideas. Clinical-stage biotech companies must present a clear commercial use case to attract capital. In cell therapy, this has contributed to growing interest in off-the-shelf approaches, as the cost, complexity, and capital requirements associated with scaling autologous therapies can deter investors.
Global Competition and the Pressure to Move Faster
The panel discussed growing global competition, particularly from China, where lower costs and faster clinical iteration are creating new pressures for U.S. drug development. This trend can be framed as both a challenge and an opportunity, China’s lower cost structure allows companies to establish a clinical wall of data through rapid clinical iteration across multiple indications, ultimately benefiting patients, but it also raises questions about how the U.S. can remain a preferred environment for early clinical development. Rather than focusing solely on blocking data generated in China or other countries, the U.S. should prioritize creating a more receptive and predictable regulatory environment, including streamlining the IND process.
Structural Inefficiencies and the Future of US Innovation
To maintain U.S. competitiveness, panelists noted that the U.S. must quickly reverse the degradation of its basic research infrastructure, as the ecosystem relies heavily on relationship-based networks and risk-taking. They also addressed the burden created by procedural complexity and trial execution inefficiencies. Development resources are often diverted to box checking exercises, a systemic inefficiency fueled by the clinical trials industrial complex, but may not meaningfully improve evidence generation, patient safety, or patient access.
Policy Solutions and Congressional Action
Looking ahead, panelists discussed the potential role of Congress in shaping a more predictable development environment. The upcoming user fee reauthorization was identified as an important opportunity to provide FDA with clear direction, adequate resources, and policy guardrails that support efficient, science-based reviews. Rather than calling for wholesale reform of the regulatory system, the discussion focused on targeted opportunities to improve predictability and procedural efficiency. This included revisiting aspects of the adequate and well-controlled trial framework, supporting FDA’s ability to modernize internal processes, and ensuring the agency has the resources and flexibility needed to keep pace with scientific innovation.
Session 3 – Strengthening the Future of Cell-Based Gene Therapy Development
Key Takeaway
Advancing cell-based gene therapies will require evaluating whether current pre-IND and IND processes can better support timely first-in-human and early-phase investigation of innovative approaches, while maintaining appropriate safeguards for patient safety. More predictable and practical reforms, including clearer expectations for early development, long-term follow-up, platform iterations, and therapy delivery across care settings, could help reduce unnecessary barriers and expand patient access.
Progress and Gaps in Cell-Based Gene Therapy Development
The final session examined recent progress in cell-based gene therapy development and remaining barriers to broader patient access, including regulatory predictability, early-phase development pathways, platform iterations, long-term follow-up, and delivery beyond specialized centers. The session was moderated by Lizzy Lawrence (STAT) with panelists George Eastwood (Emily Whitehead Foundation), Grace Graham (FDA), Priti Hegde (Kite, A Gilead Company), Timothy Hunt (Alliance for Regenerative Medicine), and Carl June, (University of Pennsylvania).
The patient perspective emphasized the need to scale these therapies beyond the first few patients to reach the 80% who still lack access. The panelists highlighted efforts to generate evidence supporting a reduction in long-term follow-up requirements for commercially available CAR-T therapies from 15 years to 5 years, as one example of a practical reform that could reduce burden while maintaining patient safety.
The science has advanced rapidly—with innovations, such as in vivo delivery and treatments for autoimmune diseases—but regulatory strategies do not adequately differentiate between treating end-stage lethal cancers and conditions that are serious but not immediately life-threatening. The panelists raised the possibility of more differentiated pathways for early academic discovery and later-stage commercial development, including more flexible investigator-initiated trial models for early exploration. The FDA’s plausible mechanism guidance was a significant step in signaling a path out of the IND stage for N of 1 or small population diseases, and the agency is actively working on differentiating requirements for first-in-human versus later-stage trials.
FDA Personnel Changes, Consistency, and Leadership
Addressing recent turnover and acting leadership at the FDA’s Center for Biologics Evaluation and Research (CBER) and Center for Drugs Evaluation and Research (CDER), panelists also addressed recent personnel changes and acting leadership at FDA, noting the importance of retaining expertise, hiring new talent, and blending institutional knowledge with new perspectives.
The discussion reflected concerns from the rare disease community about increasing regulatory uncertainty, including Complete Response Letters and requirements for randomized controlled trials in rare disorders. Panelists emphasized that regulatory flexibility cannot emerge bottom-up from risk-averse junior reviewers, but must be driven top-down by management that prioritizes resolving problems early rather than just identifying them.
Bureaucracy, Platform Iterations, and IND Reforms
The discussion also highlighted how institutional and regulatory processes can slow early discovery, including delays related to contracting, material transfer agreements, and IND preparation. To speed discovery and reduce the FDA’s workload, it was raised whether certain early-stage, autologous ex vivo engineered cell approaches could be evaluated through more localized oversight models rather than going through a full FDA IND process, akin to bone marrow transplants. It was noted that the FDA welcome creative dialogue but noted that statutory changes requiring congressional action would be needed to alter interstate commerce rules for INDs.
The panel also discussed the lack of efficient pathways for platform iterations—such as changing the targeting binder or viral vector on an established in vivo cell therapy—which takes years in the U.S. compared to months in countries, such as China, eroding global competitiveness.
PDUFA, Technology, and Resources
Looking ahead to the upcoming PDUFA reauthorization, the panel discussed opportunities through the upcoming PDUFA reauthorization to improve FDA processes, including meeting management and inspection scheduling. Panelists also highlighted the potential for AI tools to support regulatory review and development workflows, such as summarizing large submissions, supporting trial matching, or helping manage agency workload. The discussion noted the utility of AI but urged a practical approach—such as using it to review thousand-page documents or for trial matching—rather than dismissing its utility, to secure patient trust and streamline the minutia.