MANUFACTURING


Q. You’ve highlighted an intriguing “bench-to- bedside” collaboration between Scripps and Calibr. What makes that partnership so innovative and productive? A. Previously known as the California Institute for Biomedical Research, Calibr was founded as an independent non-profit research institution by Dr Pete Schultz. The mission of the institute was to create new medicines and accelerate their development by pairing world-class biomedical research with state-of-the-art drug discovery and development capabilities. In 2014, Dr Schultz was named CEO of the Scripps Research Institute, and he merged the two institutes to expand the Calibr model to the unique scientific framework of Scripps Research. This created a great opportunity to work directly with leading professors and principal investigators from Scripps Research to speed up the development of innovative drugs. As Calibr became a part of Scripps Research, we developed a portfolio of drug candidates by taking advanced molecules through IND-enabling studies and early clinical development. This portfolio is based on the innovative small molecules, conjugated peptides and engineered antibodies, as well as gene- and cell- therapy products, to treat cancer, degenerative diseases, and chronic diseases. From a business standpoint, Calibr at Scripps Research has formed collaborations and strategic alliances with industry and non-profit partners. This approach is shaping a new paradigm for advancing non-profit biomedical research to impact patients while re-investing in further innovative research.


Q. You noted, too, that Calibr developed a novel CAR T-cell therapy. What can you tell us about that therapy and its production requirements? A. The switchable CAR-T cell technology, led by Dr Travis Young, VP of Biologics, incorporates an antibody that acts as a switch, activating the engineered cell and directing it to engage the cancer target. This is a first-in-class platform designed to confer the efficacy associated with engineered T-cell therapies, with greater safety and versatility through the incorporation of a control switch. This technology is currently being evaluated for the treatment of certain cancers, including relapsed/refractory B-cell malignancies such as non-Hodgkin lymphoma and chronic lymphocytic leukaemia.


As you may imagine, the manufacturing of a switchable CAR-T cell product can be challenging due to the complexity of its components. The modification of autologous T-cells requires a separate manufacturing campaign for each patient. Each campaign is supported by the development of a complex analytical system for product characterization, in-process control, release and stability. Besides the supply chain of apheresis material and modified cells is implementation, which takes place under strict thermal conditions and requires extended control. The biologics switch is a separate programme, which requires the manufacturing of the bulk drug substance and the finished drug product. Both are supported by formulation, stability, compatibility and comparability studies. Several contract development and manufacturing organizations (CMOs) were involved in the development and manufacturing of a switchable CAR-T cell product in the US and Europe. The management of each CMO requires a high level of expertise in technical details, quality, and project coordination.


Q. Your presentation focused on lessons learned from working with CMOs on that therapy, and you emphasised that CMO selection should begin with “due diligence”. What does that entail? A. Since Calibr has a wide variety of projects, we outsource the process development and manufacturing to CMOs. Any interaction with CMOs should include several basic documents to assure confidentiality; description of required services; assurance of product quality; and legal terms. This involves the following steps: • Execution of non-disclosure agreement


“The majority of CMOs will offer whatever the client wants, and in some cases, their CEOs will agree to a lower cost and a shorter timeline because their technical team does not understand the project complexity.”


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