Northwest Biotherapeutics Moves From Optimization of Flaskworks Prototype to Fabrication of GMP-Compliant Units For Installation, Validation and Final Testing Prior to Regulatory Certification

Accompanied by Broad Patent Coverage

BETHESDA, Md., Feb. 6, 2024 /PRNewswire/ -- Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax^® personalized immune therapies for solid tumor cancers, announced today that the key development work for the Flaskworks manufacturing system has been completed and an external vendor has been engaged to produce GMP-grade units of the system. In addition, the patent coverage of the Flaskworks system has been expanded: the foundational patent has been issued in the U.S. (and elsewhere) and an additional new patent application has been filed. The Company believes that this broad patent coverage will help it build a strong franchise.

The Company believes that the Flaskworks system will play a central role in enabling the efficient and timely scale-up of manufacturing to make DCVax-L products for large numbers of patients, and in reducing the manufacturing facility costs. The Company further believes that these efficiencies will be pivotal for enabling the DCVax-L platform to be affordable and potentially suitable for widespread use as a frontline therapy.

As the Company has previously reported, including at its Annual Meeting in December 2022, the Flaskworks system has been under intensive development for a number of years. Several fundamentally differing approaches and system designs were developed, tested, modified and re-tested until the best one was determined.

These efforts have required a combination of engineering, physics and biology expertise. This included both big-picture conceptual design work, and highly detailed work on factors such as the specific flow rates of liquids and materials through the system, shear forces and pressure on the cells in each part of each of multiple cell culture vessels on the machine at each time point, cell expression profiles, surface markers and functional characteristics, and countless other metrics.

Development Work That Has Been Completed

This work has now been completed and has included:

• Determining the fundamental type of mechanized approach to most closely mirror the existing manual process of manufacturing DCVax-L;
• Designing and creating a new machine to implement this approach;
• Making numerous prototype units and progressively optimizing the system;
• "Closing" the manufacturing process so that it does not involve any "open" steps (i.e., open to the air in the manufacturing lab) and therefore does not need to be conducted in the most sterile and most burdensome and expensive type of manufacturing lab;
• Automating key steps in the manufacturing process involving isolation of the desired immune cells, feeding and culturing those cells, and extracting them from the culture vessel (which involved special difficulty, as described below);
• Producing finished DCVax-L products with substantially the same composition and percentage purity of dendritic cells, the same biologic profile and functional characteristics of the cells, and the same yield in number of doses as with the existing manual process.

The special difficulty involved in developing the Flaskworks machine was that, unlike other cell types, the dendritic cells tightly adhere to the surface of the culture vessel (similar to barnacles). Extracting them from inside the culture vessel without damaging the cells or reducing the yield of doses was extremely challenging. Other cells (including T cells) are generally cultured suspended in liquid in a bag, which makes it much easier to move them through processes. Many companies have developed or are developing machines to handle such other cell types - but not adherent cells.

The tight adherence of dendritic cells is essential for 3 main reasons: (a) to isolate the specific desired cell population and remove others, (b) to assess the health of the patient's immune cells (if the cells do not adhere tightly, they are likely not healthy) and (c) to start the activation of the dendritic cells (the adherence triggers the start of activation).

Anticipated Benefits of the Flaskworks System

The Company believes that implementing the Flaskworks system will deliver multiple benefits:

• Manufacturing using the "closed" Flaskworks system can be done in lower grade clean rooms (grade C labs) that are substantially less expensive to build out and to operate than the higher grade clean rooms (grade B labs) required for the existing "open" process. As the Company has previously reported, it has purposefully built out its Sawston facility in stages, both to manage capital expenditure and in anticipation of being able to transition away from the more expensive labs as manufacturing technology advanced.
• Manufacturing using the "closed" Flaskworks system will also enable products for multiple patients (potentially up to a dozen or so) to be produced in a single (larger) manufacturing lab at the same time. Under the present "open" process (as with most cell therapy production processes to date), only 1 patient's product can be made at a time in each manufacturing lab, and the lab must go through special cleaning in between each product.
• With the Flaskworks machine performing the manufacturing process steps, the manufacturing personnel will only need to operate and oversee the machine and transfer culture vessels onto and off of the machine for these manufacturing steps rather than performing the steps by hand. This will be crucial for scale up to producing DCVax-L for very large numbers of patients, because the personnel can be drawn from a much wider pool and not just the very limited number of technicians able to perform the process steps by hand in an essentially artisan process.

Next Steps

The next step is to have GMP-compliant (i.e., clinical grade) versions of the prototype Flaskworks machine made with GMP grade materials. A specialized contractor has been engaged to do so. This process is expected to take several months, in part due to ongoing supply chain issues. As soon as the GMP-grade units are delivered, Advent BioServices will undertake final qualification and validation of the GMP units and use engineering runs with the system to collect data in order to submit an application to regulators to approve the use of the system for production of DCVax-L for patients. 

The Company is optimistic about this approach because the Flaskworks system now closely mirrors the existing manufacturing process, and the DCVax-L products manufactured through the Flaskworks system are substantially comparable to the DCVax-L products made through the existing manual process.

Patent Coverage

The Company and Flaskworks have worked to develop strong patent coverage on the Flaskworks system. The foundational patent, with broad claims covering this closed manufacturing system, has issued in the US and elsewhere. In addition, a new patent application has been filed in regard to the new and optimized system and features.

Linda Powers, the CEO of Northwest Biotherapeutics, parent company of Flaskworks, commented: "We are extremely proud of the Flaskworks team's successful development efforts. They combined a lot of creativity with meticulous and rigorous measurements, analyses and testing. We are also proud of the efforts and expertise contributed by the NW Bio team and the Advent BioServices team. The many skill sets brought to bear together were key to the successful development."

Ms. Powers continued: "We are also very pleased to have expanded the scope of our patent coverage on the Flaskworks system. We believe this is a valuable asset that will help Northwest Bio build a strong franchise."

About Northwest Biotherapeutics

Northwest Biotherapeutics is a biotechnology company focused on developing personalized immunotherapy products that are designed to treat cancers more effectively than current treatments, without toxicities of the kind associated with chemotherapies, and on a cost-effective basis. The Company has a broad platform technology for DCVax^® dendritic cell-based vaccines. The Company's lead program involves DCVax^®-L treatment for glioblastoma (GBM). GBM is the most aggressive and lethal form of primary brain cancer, and is an "orphan disease." The Company has completed a 331-patient Phase III trial of DCVax-L for GBM, presented the results in scientific meetings, published the results in JAMA Oncology and submitted a MAA for commercial approval in the UK. The Company has also developed DCVax^®-Direct for inoperable solid tumor cancers. It has completed a 40-patient Phase I trial and, as resources permit, plans to pursue Phase II trials. The Company previously conducted a Phase I/II trial with DCVax-L for advanced ovarian cancer together with the University of Pennsylvania.

Disclaimer

Statements made in this news release that are not historical facts, including statements concerning plans for DCVax are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "expect," "believe," "intend," "design," "plan," "continue," "may," "will," "anticipate," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those projected in any forward-looking statement. Readers should not rely upon forward-looking statements. There are a number of important factors that could cause actual results to differ materially from those anticipated, including, without limitation, risks related to delays or uncertainties in regulatory processes and decisions, risks related to the Company's ability to achieve timely performance of third parties, risks related to whether the Company's products will be viewed as demonstrating safety and efficacy, risks related to the Company's ongoing ability to raise additional capital, and other risks included in the Company's Securities and Exchange Commission ("SEC") filings. Additional information on the foregoing risk factors and other factors, including Risk Factors, which could affect the Company's results, is included in its SEC filings. Finally, there may be other factors not mentioned above or included in the Company's SEC filings that may cause actual plans, results or timelines to differ materially from those projected in any forward-looking statement. The Company assumes no obligation to update any forward-looking statements as a result of new information, future events or developments, except as required by securities laws.

CONTACTS

Northwest Biotherapeutics

Dave Innes
804-513-6758
[email protected]

Les Goldman
240-234-0059
[email protected]

SOURCE Northwest Biotherapeutics