NorthWest Biotherapeutics Inc (NWBO)

[hyperopia]

I noticed that language as well senti. As almost everyone knows, automating the culturing process is absolutely critical to produce at meaningful commercial volumes, so of course Flaskworks would be considered the “centerpiece toward scale-up for potential commercial operations.” To me, that particular language does not give any indication when they anticipate approval of the automated process.

My personal belief is that it has been the intention to have a fully automated production process (which includes the Flaskworks system) when commercial production begins, to have the lowest cost possible for insurance reimbursement, to be commercially viable, and to be able to meet a large patient demand. However, as others have said, there must be contingency plans if this is not possible.

They have been “optimizing” the system for a couple of years now, however, the language “including optimizing yields” is new, and it basically means how many viable dendritic cells per dose, which relates to potency for release specifications. As I’ve repeatedly said, the release specifications for a commercial product are far more strict than for an investigational product, which is made for clinical trials.

According to the following, the clinical trial product that Cognate/Fraunhofer produced manually, minimally contained 60% viable dendritic cells:

murcidencelum
murcidencel

autologous dendritic cells (DCs) derived from peripheral blood mononuclear cells (PBMCs) obtained from glioblastoma patients. A sample of the same patients' glioblastoma is also collected, and a tumour lysate prepared. The purified adherent monocytes isolated from PBMCs are initially grown in media containing granulocyte-macrophage colony-stimulating factor (GM- CSF) and interleukin 4 (IL-4) to induce differentiation into dendritic cells, followed by loading of the dendritic cells with the tumour lysate in culture media supplemented with GM-CSF and IL-4. The final cell suspension contains ≥60% dendritic cells (MHC Class II+, CD86+; CD14-), with ≤40% of the cells in the suspension being other autologous cells, such as T lymphocytes, B lymphocytes, and natural killer cells. The dendritic cells induce T cell proliferation in a co-stimulation assay cell therapy (antineoplastic)

https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl128.pdf?sfvrsn=889fe54b_3&download=true

For their CAR-T clinical trials, Novartis produced ~70% viable cells, but the FDA required 80% viable cells for the commercial product, which they were unable to meet in about 25% of their batches for the first couple of years.

Northwest Bio will certainly have similar discussions with the regulators on commercial specifications for potency, but since Advent did obtain their commercial license using a semi-automated process for DCVax, (which apparently met commercial specifications) this process should be sufficient to garner marketing approval for DCVax.

The Flaskworks’ process will need to produce a highly similar, or better product in sufficient quantity. For the clinical trial, this meant ten doses of 2.5M cells per dose, so I think 25M per batch, may be the target that they were working to hit.