The ‘transformative power’ of gene editing, with David Sourdive, Cellectis

‘Gene editing has a very transformative power in adaptive T cell therapy. In gene editing, we can make T cells do much more than they would normally do without being engineered.’ In this far-ranging interview, David Sourdive, Executive Vice President of Corporate Development at Cellectis, outlines the exciting updates from Cellectis’ current CAR-T therapy projects, from manufacturing, to clinical trials. He details his hope for the future and highlights the challenges that working with T cells can bring.

The possibilities of using gene editing to leverage the power of T cells into ‘better killers’ to ‘overcome the defence mechanisms of tumour cells’ are clear for Sourdive. Whilst acknowledging the current successful use of autologous treatments, he believes the industry is moving towards the possibility of ‘real pharmaceutical off the shelf T cell products’. There is an undeniable enthusiasm from Sourdive about gene editing to ‘maximise the power of T cells’, which can develop treatments that will meet the standard of care that chemotherapies and antibody therapies have.

Continue reading “The ‘transformative power’ of gene editing, with David Sourdive, Cellectis”

The importance of creative solutions in cell therapies

Pim Hermans, Director of Ligand Discovery at Thermo Fisher Scientifics, emphasises the importance of the symbiotic relationship Thermo Fisher has with their customers. For Hermans, this was key for their breakthrough product – ‘affinity products…for purification of biotherapeutics’ – which has been ‘really adopted by the industry’. It is widely used in the manufacturing of medicines, ‘especially in the gene and cell therapy field’. His example is the current use of AAV, which is now being used in ‘manufacturing at a large scale’.

By seeing customers as partners, Hermans’ philosophy is that ‘together we can make our products to suit the needs of their molecules’. He is confident in their ability to produce intuitive products and ‘do the best we can to provide the solutions’. He acknowledges ‘it can be challenging, but we are there to face those challenges together to try to solve problems to make good products’. This has been paramount to the evolution of cell and gene therapies.

Speaking of the new projects Thermo Fisher are currently working on, Hermans talks of the ‘next stage’ that will result from gene therapy evolution. He highlights the lentivirus as a new challenge, due to its nature as a more demanding viral vector, but a challenge he is eager to embrace.

Watch the full interview, filmed at Cell Therapy Manufacturing & Gene Therapy Congress, with Pim Hermans above or here.

Developing automated cell processing strategies with Olivier Waridel, GE

As previously the CEO of medical device company Biosafe and now GM of Cell Banking & Point of Care at GE Healthcare, Olivier Waridel understandably feels positive about the recent partnership between the two companies. For him, the collaboration broadens the possibilities for both companies, ultimately working towards a ‘full solution for players in the CAR-T and immunotherapy space’.

‘Automatising’ cell processing is one of the developments Waridel has worked on and is most proud of. Using the example of cord blood banking Waridel outlines the process development ‘all the way from a sample in a bag to the cyro-preservation tank…[we] developed the tools for the whole processing of that in the laboratory’.

Cord blood banking is just one such example, and Waridel goes on to explain his work in ‘the clinical trials going on in the regenerative medicine space where it is required to have a closed system and automation for orthopaedic, cardiovascular and other trials that are going on. Our instruments can automate the process in the operating room; getting the cells ready for the re-infusion into the patient.’

The cell therapy space is a natural progression for Biosafe, allowing them to build on their previous experience of automating the cell processing line. Waridel explains how they use the same technology they already employ, but are also introducing a new instrument, Sefia, which has been specifically developed for the cell therapy space. Sefia will assist them with ‘running through the different cell manipulations and will help with the delivery to the end patient’.

In terms of differentiating their product from similar instruments on the market, Waridel highlights that Biosafe’s is centrifugation based:

‘The beauty is the technology in itself, so it allows us to process volumes and the way the cells are centrifuged allows us to go into detail into which lap of cells we are collecting and offers a lot of flexibility.’

The technology also allows them to include customers within the process development, building increasingly fluid relationships. Waridel aims to increase ‘reliability and stability’, and therefore increase the number of patients they can treat.

Watch the full interview, filmed at Cell Therapy Manufacturing & Gene Therapy Congress, with Olivier Waridel above, or here.

‘The emerging technology revolution that is our cell and gene therapy space’

The gene editing tools and strategies for successfully taking a gene therapy to market.

Michael Mendicino, Owner, Chief Consultant & Advisor at Hybrid Concepts International, is excited to ‘be part of the emerging technology revolution that is our cell and gene therapy space’. We caught up with him at Cell Therapy Manufacturing & Gene Therapy Congress to discuss the current trends in gene therapies.

For Mendicino, the improvement in gene editing technologies is one of the most important recent developments in the industry. Although not necessarily a new or unfamiliar concept, he emphasises that the new technologies that are continuously emerging, such as Zinc Finger, TALENs and CRISPR, are vital to the future of gene therapies.

Mendicino sees a number of potential breakthroughs that are currently in the process of development that will allow for these new technologies to become viable treatment options:

‘For 2017 everyone is looking to see a licenser for marketing authorisation for the CAR-T product either coming from Novartis or from Kite Pharma. I think that will be tremendous for the field and will legitimise the field, not only for the companies that apply for the BLA (Biologics License Application) and get approval , but also for other companies that are not that far behind them, specifically in the CAR-T space, but also in cell and gene related product spaces.’

When building a BLA strategy that meets all the requirements, Mendicino breaks it down into three disciplines that need to be considered separately, as well as in conjunction with each other. Firstly, there is the ‘chemistry, manufacturing or controls’, or the ‘quality’ of the product. The second is ‘pharmacology and toxicology’, also known as the ‘pre-clinical or the non-clinical’, and the third is the clinical. Often these three considerations are handled in parallel, but this may need revising throughout the process. This is due to factors such as the product itself, as well as ‘the clinical indications sought, the patient population, the recruitment rates and whether or not the company has gone through some major CMC change that required scale up for commercial inventory.’

Watch the full interview as Michael Mendicino explores the methods of helping gene therapies progress to market above or here.

Comparability for advanced therapy medicinal products with Christopher Bravery

For a recent KNect365 webinar, Christopher Bravery from Advanced Biologicals discussed the challenges of comparability for the ‘more complex’ biological molecules. He went into a detailed examination of purification, characterisation and activation, and their position within the space of biological comparability. Here we summarise the in-depth discussion that offers guidance and advice for those looking to meet the requirements of comparability for their molecules. 

LISTEN TO THE WEBINAR HERE

First, Bravery outlines the differences between small molecules and biologicals which makes the characterisation of them a greater challenge for pharmaceutical companies. For small molecules, it is possible to know the exact molecular structure. When a cell substrate is introduced, the ‘manufacturing process is less clear’ as the ‘windows of characterisation are fogged with variability.’ This makes comparability much more challenging for cell based products as you are unable to define the molecular structure as easily. The proteins and the cell itself all vary in their phenotype, and are often more heterogenous, which adds to the uncertainty in the measurements taken.

Bravery defines comparability for biologics as the ‘need for a change in the process’ when the development is incomplete, either at post-approval or late stage. At this point, you should have characterised the raw materials to ‘understand critical quality attributes to establish process parameters’. He uses a hypothetical case study for a CAR-T product to demonstrate where comparability can need to be used within a development system, highlighting the area of ‘activation.’ (see diagram top)

Continue reading “Comparability for advanced therapy medicinal products with Christopher Bravery”

Proving the efficacy of cell therapy treatments to convince investors

‘What convinced investors, and what convinced our alliance partners were the clinical result we had in chronic lymphatic leukaemia, I think that’s important. I think with animal models, they are very helpful in a sense, in just the bare bones test system, but to prove efficacy, in the end is to run clinical trials.’ Jan Joseph Melenhorst, Director of Product Development & Correlative Sciences Laboratory from the University of Pennsylvania, discusses the necessary steps that must be taken for their cell therapy to become a viable treatment option.

Within his department at the university, Melenhorst examines the post infusion specimens of cells to better understand the potency and toxicity of the cells they infuse into patients. To enhance the potency of cells, additional gene editing tools can be included to modify the genome of the T-Cells and further enhance the expression of the targeting gene. Melenhorst speaks of his own experience with the CRISPR-Cas9 gene editing tool, but also draws upon the use of TALENs, stressing its importance to ‘the future of autologous and allogeneic cell therapies’. It is the autologous therapies Melenhorst believes are the current future of CAR-T therapy. Continue reading “Proving the efficacy of cell therapy treatments to convince investors”

Sourcing raw materials for cell therapy manufacture – Dieter Hauwaerts, Celyad

‘Start working on raw materials early on’ – for Dieter Hauwaerts, Vice President of Operations at Celyad, the way to combat one of the biggest challenges in cell therapy manufacture is clear.

Limited availability of raw materials is a major issue for large scale manufacture of new therapies, but planning well in advance can help mitigate it: ‘In process development, take into account the quantity and quality of raw materials you will need in a clinical stage or commercial manufacturing process and build good relationships with suppliers.’

However, even with the necessary raw materials, Hauwaerts still sees issues with ‘the way we can manufacture products in a reliable and consistent way’, though he hopes that in 2017 automation will begin to negate this.

Watch the full exclusive interview with Hauwaerts – filmed at Cell Therapy Manufacturing & Gene Therapy Congress 2016 – above or here.