The Dec 21 MAA submittal PR revisited. It's so solid in detail and information that I (really) enjoy reading it every once and a while. I'm reposting the PR and acknowledging much of the great info provided by red pencil and bolding that we know can be their own storylines (and were). And following that up w the 4 non topline PRs up to data lock which to me shows the MHRA won't run into any data issues during their review. The MIA PRs belong here too but I didn't post them.
Northwest Biotherapeutics Announces That A Marketing Authorization Application Has Been Submitted To The UK MHRA For DCVax®-L For Glioblastoma________________________________________ 21 Dec, 2023, 09:30 ET 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. They said a mouthful here. See below for segments of 4 PRs that went into this endeaver 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.
NW Bio Provides Update On Projected Timing For Data Lock For Phase 3 Trial of DCVax®-L for Glioblastoma Brain Cancer PR Newswire•June 2, 2020 Data Completion Process Nearing Finish Line BETHESDA, Md., June 2, 2020 /PRNewswire/ -- Northwest Biotherapeutics (OTCQB: NWBO)("NW Bio"), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, today reported progress toward data lock for the Phase 3 trial of DCVax®-L for Glioblastoma brain cancer. The Company reported that the final data collection process has been progressing steadily despite ongoing difficulties due to coronavirus-related limitations on operations and restrictions at trial sites. The coronavirus-related difficulties have impacted most aspects of the process, including review processes at sites and even logistical matters such as the shipping of tissue slides. The completion process includes final data collection, identification and resolution of queries, data checking and confirmation, and site sign-offs. All of these functions are performed by independent service firms (not by the Company), with oversight by the Company. The service firms have completed the final monitoring visits to the trial sites (including a number of them virtually). The service firms are in the process of resolving the queries from those final monitoring visits (each monitoring visit can generate new queries), and the firms have completed most of the data confirmations. After the query resolution and data confirmation are finished for a trial site, the site's investigator needs to sign off on the data before it can be locked.... https://nwbio.com/nw-bio-announces-lifting-clinical-hold-dcvax-l-phase-iii-trial-fda-progression-free-survival-events-reached-overall-survival-events-not-yet-reached/
07/24/2020 Northwest Biotherapeutics Announces Completion of Phase 3 Trial Sites' Databases PR Newswire BETHESDA, Md., July 24, 2020 /PRNewswire/ -- Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, today announced that the data collection from all of the clinical trial sites for the Company's Phase 3 trial of DCVax®-L for Glioblastoma brain cancer (the "Trial") has been completed and all of the sites have signed off on the locking of their data.
As noted in the Company's prior reports, in order to reach overall data lock for the Trial, each site's data must go through final collection, review, checking for queries, resolution of queries preparatory steps for locking the site and finally personal sign-off by the lead investigator at each site for that site's data. For that purpose, the lead investigator must undergo training on the system, review the site data, personally complete the confirmation and deliver it to the independent contract research organization (CRO) managing the Trial. Reaching these personal sign-offs by each lead investigator at each of the Trial sites has been a key focus of activity towards data lock for the last couple of months, especially during June and July. At the time of the Company's last report near the end of June, about 30 Trial sites were in varying stages of progress towards sign-off, and about half a dozen Trial sites had not yet completed the preparatory steps necessary to begin the process towards such sign-off. All of the Trial sites are now finished. The independent CRO has obtained all of the investigator sign-offs for their site's data lock. The sites' data includes all of the clinical data gathered in the Case Report Forms throughout the Trial, and now sit in a signed off, locked position with the CRO.... https://www.otcmarkets.com/stock/NWBO/news?id=268605
NORTHWEST BIOTHERAPEUTICS INC (NWBO) just filed a NW Bio Announces Completion of Further Data Gathering For Phase III Trial.
BETHESDA, Md., Aug. 19, 2020 /PRNewswire/ -- Northwest Biotherapeutics (OTCQB: NWBO)("NW Bio"), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, today announced that the remaining outstanding clinical trial data for the Company's Phase 3 trial of DCVax®-L for Glioblastoma brain cancer as described in the Company's last report on July 24, 2020 has now been completed by the specialty analytics firms. With this data now in hand, final quality control checking and confirmation are under way to enable Data Lock.
This further data involves specialty analytics such as genomic profiling for IDH mutations and certain imaging. The independent CRO managing the trial is now integrating this data into the overall trial database containing the clinical data from the trial sites that was already complete and locked as reported on July 24, 2020, in order to complete the overall trial dataset. When Data Lock is reached, the independent statisticians will be given access to the unblinded dataset. The Company will remain blinded while the statisticians make the computations, converting the mass of raw data from the trial into formal tables and listings, and survival and progression measures, to report the trial results.
As previously reported, the statisticians' work is estimated to take a couple of weeks. When their computations are completed, the Company will receive the results of those computations and thereby become unblinded. It is anticipated that the Company's Scientific Advisory Board, the Steering Committee of the Trial and other key medical expert advisors will likewise receive the results, and thereby become unblinded as well.
Northwest Biotherapeutics Announces Data Lock of Phase III Trial PR Newswire•October 5, 2020 BETHESDA, Md., Oct. 5, 2020 /PRNewswire/ -- Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, today announced that the database for the Phase III trial of DCVax®-L for Gliobastoma has been locked. With the database now locked, the independent service firms managing the Clinical Trial are arranging for the independent statisticians to have access to the unblinded raw data from the Trial. Neither the Company nor any party other than the independent statisticians will have access to any unblinded data at this stage. The statisticians will proceed as quickly as possible with analyses of the raw data and prepare summaries of the Trial results for review by the Company, the Principal Investigator, the Steering Committee of the Trial, the Scientific Advisory Board, and a panel of independent brain cancer experts, who will analyze the data with the statisticians in preparation for public announcement and scientific publication. "We are excited to be so close to the finish line now, after such a long road" commented Linda Powers, the Company's CEO. "We are hopeful that DCVax®-L can become an important new treatment option for patients who urgently need more and better treatments for Glioblastoma brain cancer." "We are grateful to the independent service firms and the clinical trial sites who have worked so hard to complete the data collection and confirmation during many months of COVID restrictions and challenges," Ms. Powers continued. "We are also very grateful to our shareholders for their patience and support, which has made all this possible." https://finance.yahoo.com/news/northwest-biotherapeutics-announces-data-lock-133400832.html
