Northwest Biotherapeutics Announces That A Marketing Authorization Application Has Been Submitted To The UK MHRA For DCVax®-L For Glioblastoma

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Northwest Biotherapeutics (NWBO) announces the submission of a Marketing Authorization Application for DCVax-L for glioblastoma brain cancer, seeking approval for both newly diagnosed and recurrent patients. The application also requests to be considered under the MHRA's rapid 150-day review pathway. The company's international Phase III trial demonstrated a statistically significant and clinically meaningful extension of median survival in both newly diagnosed and recurrent GBM patients treated with DCVax-L. The treatment aims to address the extensive heterogeneity of GBM and overcome the immunosuppressive microenvironment around the tumor, with potential applicability for most types of solid tumors. The Company also had positive results in its Phase 1 trial of DCVax-Direct for inoperable solid tumors.

Culmination Of Over 20 Years Of Research And Clinical Development

BETHESDA, Md., Dec. 21, 2023 /PRNewswire/ -- Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax^® personalized immune therapies for solid tumor cancers, announced today that a Marketing Authorization Application (MAA) was submitted yesterday to the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK for DCVax®-L for glioblastoma brain cancer.

The MAA seeks approval for commercialization of DCVax-L for both newly diagnosed and recurrent glioblastoma (GBM).  The application also requests to be considered under the MHRA's rapid 150-day review pathway, which the agency has established for new medicines for serious unmet medical needs. 

"We are very excited to reach this important milestone as the culmination of more than 20 years of research and clinical development," commented Linda Powers, Company CEO.  "We are extremely grateful to all of the parties who have made this possible, including the patients, the investigators and the shareholders whose patience and support have been invaluable. We believe DCVax-L can offer a much needed new treatment option for GBM patients, both alone and in combination with other treatment agents. We look forward to bringing the treatment to as many patients as possible, including in community settings where most patients are treated."

GBM is the most lethal and most common form of primary brain cancer.  Despite well over 400 clinical trials of a wide range of treatment agents, patient survival in newly diagnosed GBM is only 15-17 months and has not meaningfully improved in 20 years; survival in recurrent GBM is only 6-8 months and has not improved in 30 years.    

The Company's international Phase III trial demonstrated a statistically significant and clinically meaningful extension of median survival in both newly diagnosed and recurrent GBM in patients treated with DCVax-L compared with independently selected, matched, contemporaneous, pre-specified external controls.  The trial also demonstrated more than doubling of the percentage of patients alive at 5 years in newly diagnosed GBM, and more than doubling of patients alive at 3 years after tumor recurrence in recurrent GBM patients, although the numbers of patients available for comparison at late time points was small, especially in the external control populations.

One of the key factors making GBM so difficult to treat is that it is an extremely heterogeneous tumor.  "Accumulating evidence suggests that intratumor heterogeneity likely is the key to understanding treatment failure" in GBM (Sottoriva, PNAS, 2013).  Another key challenge is that as GBM develops, it induces an immunosuppressive microenvironment which compounds the difficulty of mounting an effective immune response against the tumor - especially within the central nervous system, which is an immune privileged space behind the blood brain barrier. DCVax-L is designed to address both of these key challenges. 

As the Company previously reported, proteomic studies have demonstrated that a single tumor lysate sample contained tens of thousands of different peptides and, out of this pool, the dendritic cells selected, processed and presented over 600 different peptides (tumor targets) to T cells.  T cell studies (TCR sequencing and T cell clonal expansion assays) analyzing the breadth and strength of T cell response following DCVax-L treatment have found extensive responses, including clonal expansion of up to 800 T cell clones at month 4 and up to 1200 T cell clones at month 8 in the samples studied.  Each T cell clone focuses on a particular and distinct target.  In individuals not being treated with the vaccine, only 2 – 20 new T cells clones are seen between month 4 and month 8.  

The results of these proteomic, T cell and other studies provide support for what the Company believes to be the mechanism of action of DCVax-L:  i.e., mobilizing a broad spectrum and strong de novo T cell response that addresses the extensive heterogeneity of GBM and overcomes the immunosuppressive microenvironment around the tumor.

The Company believes that this mechanism of action will be applicable for most types of solid tumors.  Solid tumors comprise approximately 90% of all cancers, and a key difficulty that other treatment approaches have encountered with solid tumors is their heterogeneity. 

The Company has already had positive results with DCVax-L in some compassionate use cases with other diverse solid tumors. The Company looks forward to building on its experience with DCVax-L in GBM and the compassionate use cases to address a wide range of other operable solid tumors. 

The Company also had positive results in its Phase 1 trial of DCVax-Direct, in which more than a dozen diverse types of inoperable solid tumors were treated.  DCVax-Direct involves essentially the same mechanism of action as DCVax-L, except that the tumor target proteins are taken up by the dendritic cells in situ in the tumor following intra-tumoral injection, rather than from tumor lysate from a surgically resected tumor tissue sample. The Company looks forward to resuming its clinical development of DCVax-Direct for a wide range of inoperable solid tumors.  

For the GBM MAA, the Company anticipates that the review process will be a period of intensive and extensive further work involving responding to questions and requests for further information by the regulatory authority as well as preparing for and undergoing detailed inspections of the contract research organizations (CROs) that managed the trial, the Sponsor, the Trial Master File, a number of individual trial sites selected by the regulator from among the 94 sites that participated in the trial, the GMP facility and manufacturing information. 

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. 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                                                                      
804-513-4758                                                                   
dinnes@nwbio.com                                                                                           

Les Goldman
240-234-0059
lgoldman@nwbio.com

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SOURCE Northwest Biotherapeutics

FAQ

What did Northwest Biotherapeutics announce?

Northwest Biotherapeutics (NWBO) announced the submission of a Marketing Authorization Application for DCVax-L for glioblastoma brain cancer.

What is the purpose of the application submitted to the MHRA in the UK?

The application seeks approval for commercialization of DCVax-L for both newly diagnosed and recurrent glioblastoma (GBM) and requests to be considered under the MHRA's rapid 150-day review pathway.

What did the international Phase III trial demonstrate?

The trial demonstrated a statistically significant and clinically meaningful extension of median survival in both newly diagnosed and recurrent GBM in patients treated with DCVax-L compared with independently selected, matched, contemporaneous, pre-specified external controls.

What is the key challenge in treating GBM?

One of the key challenges in treating GBM is its extreme heterogeneity and the presence of an immunosuppressive microenvironment around the tumor.

What is the mechanism of action of DCVax-L?

DCVax-L is designed to mobilize a broad spectrum and strong de novo T cell response that addresses the extensive heterogeneity of GBM and overcomes the immunosuppressive microenvironment around the tumor.

What are the potential applicability of the mechanism of action of DCVax-L?

The company believes that this mechanism of action will be applicable for most types of solid tumors, with positive results in compassionate use cases with other diverse solid tumors and in its Phase 1 trial of DCVax-Direct for inoperable solid tumors.

What is the next step for the GBM MAA?

The next step involves a period of intensive and extensive further work involving responding to questions and requests for further information by the regulatory authority, as well as preparing for and undergoing detailed inspections of various trial-related entities.

What did the Company look forward to building on?

The company looks forward to building on its experience with DCVax-L in GBM and compassionate use cases to address a wide range of other operable solid tumors, as well as resuming its clinical development of DCVax-Direct for a wide range of inoperable solid tumors.