From The Editor | April 29, 2022

Lineage Cell Therapeutics' CEO Talks Clinical Trials, In-House Manufacturing


By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1

Regenerative medicine and therapeutic stem cell therapy GettyImages-1334489810

Lineage Cell Therapeutics’ CEO, Brian Culley, and I discussed the clinical-stage biotech’s existing plans for developing novel cell therapies for unmet medical needs. We discuss their cell therapy currently in clinical development for patients with acute spinal cord injuries as well as their cell therapy platform in development for cancer and why manufacturing large-scale amounts of whole cells consistently and within specifications is far more complex than manufacturing a single compound. Read on to get Culley’s take on the company’s near-term future. 

  1. Explain Lineage Cell Therapeutics’ OPC1 and VAC2.

OPC1 is an oligodendrocyte progenitor cell therapy currently in clinical development for patients with acute spinal cord injuries (SCI). OPCs are naturally occurring precursors to the cells which provide electrical insulation for nerve axons in the form of a myelin sheath. OPC1 has been tested in 30 patients to date; 5 patients with thoracic injuries and 25 patients with cervical injuries. Results from the larger Phase 1/2a trial revealed that 96% of patients experienced improved motor function and 32% of patients gained two or more levels of function in a 12-month period on an ISNCSCI score. Robust motor recovery in upper extremities was maintained for multiple years and MRI scans confirmed formation of a durable cell matrix in 96% of patients.

VAC2 is a cell therapy platform in development for cancer. It consists of an allogeneic “off the shelf” production of mature dendritic cells (DCs), which are manufactured and engineered to express a tumor-selective antigen found in cancer cells but not normal cells. Preliminary results from the ongoing Phase 1 study of VAC2 in patients with advanced and resected non-small cell lung cancer (NSCLS) showed that VAC2 is well tolerated and demonstrated potent induction of immune responses, with high levels of peripheral antigen-specific immunogenicity observed at multiple time points. This study was conducted by Cancer Research UK and Lineage plans to submit an IND for further VAC2 studies in 2022.

  1. Explain the Lineage Platform’s three processes – expansion, differentiation, and development, and why they are necessary to OPC1 and VAC2 other indications.

Our innovative cell therapy platform allows us to manufacture specific cell types of the human body starting from pluripotent progenitor cells. Using our in-house manufacturing abilities and differentiation protocols, from a frozen vial of self-renewing stem cells, we can provide the instructions to differentiate these cells into various specialized cell types found in the human body. For example, RPE cells (retina cells) for the treatment of dry age-related macular degeneration, oligodendrocyte progenitor cells (spinal cord cells) in the case for our OPC1 program as a cell therapy to treat spinal cord injury, or dendritic cells (innate immune cells) for our VAC2 program, as a vaccine for cancer. Our pluripotent cell technology has the potential to generate many different cell types and continuously broaden our pipeline. In addition, our platform features a scalable system for production of a large number of cells in a single lot, offering lower manufacturing costs, high product consistency, and an off-the-shelf formulation to provide easier use by physicians.

  1. CellCure Neurosciences Ltd is Lineage’s in-house manufacturing facility. Explain how in-house cGMP enables Lineage to produce clinically compatible post-production processing.

Manufacturing large-scale amounts of whole cells consistently and within specifications is far more complex than manufacturing a single compound. That complexity is more easily managed when you have 24-hour oversight of your process versus outsourcing it to a contract organization with multiple clients and frequent staff changes. Additionally, a complex process offers many opportunities to identify patentable subject matter. An internal team can be empowered to find new intellectual property. That exploratory aspect is often not part of a CRO agreement and when it is, the IP may need to be shared with the CRO. If you own your manufacturing facility, you also can run multiple processes with the same experienced team, offering significant cost-savings across multiple programs.   

  1. Talk to us about Lineage’s plans for the next 12 months.

Lineage is anticipating a busy 2022. The company is benefitting from the valuable license agreement it entered with Roche/Genentech for its lead asset and awareness is growing about how our technology can provide clinical outcomes beyond the reach of traditional approaches. We are working to advance two unpartnered clinical-stage programs into their next phase of clinical testing this year, in both spinal cord injury and oncology, as well as advancing our two preclinical programs toward the IND stage. As we proceed, we believe Lineage will become a leader in regenerative medicine through the transplant of specific cell types to treat significant unmet medical needs.