Vectalys, a biotech company specialized in manufacturing lentiviral solutions for gene delivery, and FlashCell, a company developing non-integrating lentiviral delivered RNA therapeutics, have merged to create Flash Therapeutics, a new privately held gene and cell therapy company.

Flash Therapeutics will work to advance the complementary businesses in the areas of development of novel RNA therapeutics based on LentiFlash, a non-integrative lentiviral delivery technology, as well as contract development and manufacturing to support discovery through GMP production for lentivirally-delivered RNA and DNA therapies. 

The company’s lentiviral development and production business, which will continue to operate under the Vectalys manufacturing platform name, will expand as part of Flash Therapeutics to include scalable GMP manufacturing capabilities. The GMP facility is expected to become fully operational in 2019.

Pascale Bouillé Ph.D., chief executive officer of Flash Therapeutics, discusses the challenges and advances in the cell therapy industry and the manufacturing technologies that will take these advanced therapeutics to the next level. –KB
 
Contract Pharma: What are the biggest challenges the cell therapy industry faces?
 
Pascale Bouillé: Now that the concept of cell therapy has been validated in clinical trials and in approval of the first products, the key challenges are optimizing gene transfer technologies and developing scalable manufacturing technologies. In some ways we are at a similar point in the evolution of cell therapy to the early days of genetic engineering in the late 1970s-early 1980s.
 
CP: In what areas are you seeing advances?
 
PB: Recent clinical trials have provided real advances in terms of cell manufacturing procedure and its relationship with efficacy and safety in patients. Once the CAR T cells proof-of-concept was obtained, significant differences in terms of therapeutic value have been observed in trials depending on vector design and specifications, cell transduction or cell engraftment.
 
CP: How do technology solutions play into various stages of cell therapy development, manufacture and delivery processes?
 
PB: Technologies must be translated from small- to large-scale manufacturing processes, despite the fact that the engineered cells’ specifications were not clearly defined from the onset. Cell viability and phenotype are key specifications that must be assessed and taken into account for the product manufacturing validation and qualification. Delivery technologies need to be evaluated not only on the basis of their transfection or transduction efficiency, but also of their impact on cell state, proliferation and metabolism.
 
CP: Please briefly describe the lentiviral delivery technology being offered by Flash Therapeutics.
 
PB: Our technology enables highly efficient RNA delivery and transient RNA expression while preserving original cell phenotype and cell viability. Lentiviral delivery technologies harness expertise from HIV research to introduce genetic material into cells without damaging cell viability and function. Lentiviral vectors that have initially been developed from HIV lead to stable expression thanks to DNA integration into host genome. LentiFlash is a next generation technology that combines the delivery efficiency of viral vectors with the safety of RNA delivery.

LentiFlash significantly expands the range of initial potential applications of lentiviral vector technology to advanced technologic approaches suitable to transient expression – e.g. gene editing, next generation immunotherapy, and regenerative medicine.
 
CP: What expertise is essential for manufacturing gene and cell therapeutics?
 
PB: “Gene and cell therapeutics” imply that product manufacturing designs are implemented according to the clinical protocol. Cell culture and amplification, vector design and manufacturing, cell transduction are protocols that need to be optimized together to give the best engineered cells in terms of efficacy and safety.

Flash Therapeutics will be offering these core strengths in our scalable GMP production facility, which is being established in partnership with Hospital Saint-Louis, Lariboisière, Fernand Vidal (Assistance Public Hospitals of Paris AP-HP). The facility will be both developing and producing gene and cell therapy drugs and is expected to be operational in 2019.
 
CP: How are the challenges associated with the manufacture of cell therapies being overcome?
 
PB: Advanced gene and cell technologies must be associated while preserving the final engineered therapeutic—the “end product.” Delivery technology is a key aspect that must be designed depending on the expected duration expression and cell preservation. Whenever possible, RNA vs. DNA delivery technologies must be preferred for safety purposes.
LentiFlash technology, which has demonstrated its capacity to allow efficient RNA delivery as well as transient/short term RNA expression, will help the industry overcome the critical challenges of combining a delivery efficiency and a transient expression with a safe and efficient RNA delivery. This challenge will be particularly acute with the emergence of new technologies such as gene editing, as well as next-generation cancer immunotherapies (involving cell types beyond T cells).
 
CP: What is the demand for contract services for cell therapeutics in European markets?
 
PB: Rapid growth in clinical study of gene and cell therapy is expanding the worldwide need for lentiviral technology manufacturing and expertise. Biotech and pharma companies, as well as academic labs, need CDMO experts to provide a continuum of manufacturing support from discovery to clinic. This is particularly important because the cell being manufactured is the product.

Flash Therapeutics, through its Vectalys lentiviral-based research and bioproduction capabilities, is providing that continuum. Vectalys has long provided development and manufacturing expertise for discovery and preclinical; we are in the process of adding a GMP manufacturing platform dedicated to clinical use. The GMP capability will become operational in 2019.
Both the integrative lentiviral and non-integrative LentiFlash vectors have been designed and manufactured using Vectalys’ proprietary manufacturing platform that’s been validated through preclinical testing on stem and primary cells. Manufacturing and delivery technologies design provide a comprehensive offer from discovery to clinical applications (from expression cassette design to cell and gene engineering), as well as expertise and support.
 
CP: On what scale can these therapies be manufactured?
 
PB: All these therapies need to be scaled-up and scaled-down to complement the requirements at each stage of the clinical development. The objective is to maintain the same vector and cell specifications at all clinical stages to make these therapies as reproducible as possible between patients and clinical stage development. Since the manufacturing process has a strong impact on the cell product, it must be defined and industrialized very early, at the lower end of GMP manufacture.

At Flash Therapeutics, we can provide from 1 ml to 60 ml at 109 TU/ml per batch. Depending on regulatory requirements, it may be suitable to provide several batches to demonstrate the product specification’s reproducibility.