“Patients are waiting. These therapies are potentially curative. They’re important for the field.” – Ellen Sigal

On May 17, 2019, Friends of Cancer Research (Friends) and the Parker Institute for Cancer Immunotherapy (PICI) held a public meeting on “Designing the Future of Cell Therapies” to explore forward-looking opportunities in the cell therapy field. The meeting debuted a whitepaper that was created by a multi-stakeholder working group convened by Friends and PICI and can be found here. For a full list of panelists from the meeting, please click here.

Morning Keynote Address

The meeting began with a morning keynote by Richard Klausner, the Founder and Chief Executive Officer of Lyell Immunopharma. In his address, Klausner highlighted recent advancements seen in the field of cellular therapies as being one of the key moments of change in medicine. Klausner framed the issues to be discussed throughout the day by stressing that although the field of cell therapies has garnered much attention and excitement, there is still plenty of work to be done to further understand the impact of these treatments on patients and to continue moving the field forward.

“The goal is to create predictably effective and predictably safe treatments that will revolutionize cancer therapies.” – Richard Klausner

Panel 1: Enhancing Early Phase Development of Cell Therapies

The first panel, “Enhancing Early Phase Development of Cell Therapies,” was moderated by Bruce Levine from the University of Pennsylvania and focused on opportunities to accelerate early discovery through investigational new drug application (IND) and manufacturing flexibility. This multi-stakeholder panel discussion opened with learnings from the successful development of CAR-T therapies. Carl June from the University of Pennsylvania remarked that our understanding of these products and the safety profile associated with CAR-T therapies provides a unique opportunity to reevaluate the regulatory landscape. Michael Kalos, Janssen Pharmaceuticals, then added that preclinical models only give us limited answers, signaling a need to think about these therapies in a different way.

Toni Ribas, University of California Los Angeles, and Crystal Mackall, Stanford University, stated that there is a need for more efficient, cost-effective methods for identifying safety signals and testing new candidates as quickly and safely as possible. Levine then identified three factors contributing to lead time and cost of manufacturing cellular therapies: manufacturing of the vector, characterization of the product, and time of manufacturing. The panel agreed that successful identification of targets on tumor cells is a key challenge in the development of CAR-T therapies for solid tumor cancers. Panelists were also quick to point to the need for identifying biomarkers to help find the appropriate patient populations to receive a cell therapy.

The panel then highlighted several topics and needs that were discussed in the meeting whitepaper, including:

• Additional flexibility to make manufacturing changes and better data sharing to support them
• Potential reductions in GMP requirements that would save time without having negative safety impacts on patients as well as the “Parent-Child” IND alternative, enabling a more iterative process
• Early communication between drug sponsors and the FDA to discuss preclinical studies necessary for the initiation of early phase clinical trials

Ann Keane, Lyell Pharmaceuticals, also emphasized the need to more efficiently move drug candidates into earlier clinical trials so that sponsors are enabled to eliminate unsuccessful drug candidates quickly, while Yuan Xu, Legend Biotech, stressed the need to move toward implementing these concepts.

The panel concluded by discussing the challenges FDA, particularly the Center for Biologics Evaluation and Research (CBER), faces in preparing to handle a potentially larger volume of applications and requests. Kimberly Schultz from the FDA noted that early and frequent interactions between sponsors and the FDA are encouraged and should be mutually beneficial. It was also noted that guidance is being explored to further facilitate the development of these novel therapies.

Panel 2: Processes to Enable Adaptive Manufacturing Processes During Late Stage Development and Post-Approval

The second panel, “Processes to Enable Adaptive Manufacturing Processes During Late Stage Development and Post-Approval,” was moderated by Alex Marson from the University of California San Francisco and panelists discussed opportunities to accelerate the optimization of cell products during late stage development and post licensure.

Zenobia Taraporewala from the FDA discussed the current regulatory framework and processes for incorporating manufacturing changes into a cell therapy development program. She noted FDA’s willingness to work with sponsors throughout the review process and indicated that early interaction can allow FDA to anticipate potential modifications and help guide sponsors through the process. Other panelists highlighted the importance of collaborating with the FDA and sharing process learnings to advance change.

The panel then pivoted to discussing mechanisms in place to monitor manufacturing changes and the impact of these changes on product safety and efficacy. Mayo Pujols, Novartis, and Axel Hoos, GlaxoSmithKline, noted that these therapies are individualized in nature, and therefore require flexible manufacturing processes. They indicated that there needs to be a manufacturing environment that allows variations to be made to products, so they have the greatest impact for the most patients. Tim Moore from Kite, A Gilead Company, noted that as we learn more about these products, there are more opportunities to advance guidance and move at a faster pace.

Lisa Butterfield from the Parker Institute for Cancer Immunotherapy discussed the uncertainty in which product attributes should be monitored and are indicative of potential changes in safety and efficacy. This can result in added cost and time. She noted that data sharing presents an opportunity to better understand what product attributes should be monitored over time and could lead to the development of best practices.  Alison Moore, Allogene Therapeutics, stressed that it can be difficult to articulate the risk associated with certain modifications and data sharing can provide an opportunity to build our product quality understanding.

“We shouldn’t do anything less than try to develop these as fast as we can. Part of the onus is on us, and we’ll do whatever we can to help find ways to reduce cost and facilitate access.” – Peter Marks

Fireside Chat: Future Directions for Cell & Gene Therapies

The meeting concluded with a fireside chat moderated by Laurie McGinley, The Washington Post, and focused on the future directions for cell and gene therapies. The panel began with Peter Marks from the FDA noting that FDA needs to do a better job of communicating the flexibility that currently exists, so that institutions will feel comfortable utilizing this flexibility. He noted that additional guidance may be needed to clarify this flexibility where possible and that further education of the community through talks with individuals and at meetings may be useful.

Steve Rosenberg, National Cancer Institute, echoed this need for guidance and asserted that because institutions are overly risk-averse, they currently are not taking advantage of the flexibility FDA provides. New guidance from the FDA may decrease their aversion to risk by better clarifying what is and what is not allowable. Rosenberg also emphasized that the most limiting factor in the development of cell therapies is the desperate need for new targets unique to cancer cells. Arie Belldegrun, Allogene Therapeutics, indicated that the whitepaper can serves as a departure point for greater collaboration and data sharing between developers of cellular therapies and with the FDA.

“Care needs to be delivered to those that need it, not just the ones that can afford it.” – Steve Rosenberg

Tom Whitehead from the Emily Whitehead Foundation provided an impactful account of his daughter Emily’s treatment experience and shared the challenges of finding a clinical trial to save his daughter’s life. He noted that had the FDA not efficiently approved Emily’s request to be enrolled as the very first patient in a CAR-T Phase I clinical trial, she likely would have been transitioned to hospice care. He emphasized the dramatic recovery Emily has seen since her treatment in 2012 by sharing that Emily had recently completed a 5k with her a family, a feat once deemed unimaginable. He noted that other patients and families reach out to them daily seeking help and indicated the need for improved access to cell therapy products through efforts aimed at increasing affordability and physician education.

Friends of Cancer Research and the Parker Institute for Cancer Immunotherapy will continue to pursue solutions proposed in our whitepaper as well as work toward implementing the concepts discussed at this meeting. Those concepts include exploring opportunities for improved data sharing, getting these treatments to patients safely and efficiently, accelerating the optimization of cell products during late stage development and post licensure, and informing additional FDA guidance on cell therapies to get these treatments to patients safely and efficiently.