PIP Approval Is A Pre-Requisite for Application for Approval of A New Medicine for Adult Patients

Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax^® personalized immune therapies for solid tumor cancers, today announced that it has received approval from the UK Medicines and Healthcare Products Regulatory Agency (MHRA) for the Company's Pediatric Investigation Plan (PIP).  The development, regulatory review and regulatory approval of a PIP is a pre-requisite for application for approval of a new medicine for adult patients, such as DCVax^®-L. 

The Company's approved PIP includes 2 clinical trials: one for newly diagnosed pediatric high grade glioma (HGG), and one for recurrent pediatric HGG. In each of the 2 pediatric trials, 24 patients will be treated with DCVax-L on the same treatment schedule as in the Company's Phase III trial in adult glioblastoma patients. 

The primary endpoint for each of the 2 pediatric trials will be overall survival, determined by comparing the survival of DCVax-L treated patients to matched contemporaneous external controls.  The external controls will be identified using the same methodology as was used to pre-specify the external controls in the Statistical Analysis Plan for the Company's Phase III trial in adult patients. 

Under applicable UK law, when a new medicine is developed for adult patients, that medicine must also be tested for potential application to pediatric patients. The sponsor must develop an overall Plan to select the specific form or stage of the disease to be treated, to adapt the dosing and administration of the medicine for pediatric physiology, and to evaluate the safety and efficacy of the medicine in pediatric patients. Further, the Plan must include not just general focus areas, aims and approaches -- it must include the full design of the specific clinical trials to be carried out, including all aspects required for clinical trial approvals, such as the patient population, eligibility criteria, stage of disease, treatment regimen, trial design and endpoints. 

The Plan developed by the sponsor must go through a series of stages of regulatory review and comment to reach a final approval by regulators.  This process can typically take more than a year.

The final regulatory approval of the PIP must be obtained before a sponsor may submit a Marketing Authorization Application (MAA) for approval to commercialize the new medicine for adult patients.  The approval may include a deferral allowing the pediatric clinical trials to actually be carried out after the MAA has been submitted, but the PIP approval itself must have been received before an MAA can be filed and go through compliance check.

Northwest Biotherapeutics worked with expert consultants for months to develop a PIP tailored for application of DCVax-L to pediatric cases of HGG. The Company submitted its proposed PIP to the MHRA in February 2022, and has been going through the regulatory review process since then.  On August 17, the Company received final approval of the PIP from the MHRA.

The Company's approved PIP includes a deferral under which the pediatric trials are anticipated to be undertaken after an MAA application has been submitted.

About Northwest Biotherapeutics

Northwest Biotherapeutics is a biotechnology company focused on developing personalized immunotherapy products designed to treat cancers more effectively than current treatments, without toxicities of the kind associated with chemotherapies, and on a cost-effective basis, in both North America and Europe.  The Company has a broad platform technology for DCVax^® dendritic cell-based vaccines.  The Company's lead program is a 331-patient Phase III trial of DCVax^®-L for newly diagnosed Glioblastoma multiforme (GBM).  GBM is the most aggressive and lethal form of brain cancer, and is an "orphan disease."  This Phase III trial has been completed and top line data was presented by a key investigator at a recent scientific meeting. The Company also plans to pursue development of DCVax^®-Direct for inoperable solid tumor cancers.  It has completed a 40-patient Phase I trial and plans to prepare for Phase II trials as resources permit. 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 future treatment of patients using DCVax and future clinical trials, 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.  We cannot guarantee that we actually will achieve the plans, intentions or expectations disclosed in our forward-looking statements and you should not place undue reliance on our forward-looking statements.  Actual results may differ materially from those projected in any forward-looking statement.  Specifically, there are a number of important factors that could cause actual results to differ materially from those anticipated, such as risks related to the Company's ability to enroll patients in its clinical trials and complete the trials on a timely basis, uncertainties about the clinical trials process, uncertainties about the timely performance of third parties, risks related to whether the Company's products will demonstrate 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 results 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.