Focus on Complexity and Variability of Solid Tumors, and How DCVax®-L Addresses Them

BETHESDA, Md., January 25, 2019 – Northwest Biotherapeutics (OTCQB: NWBO) — (“NW Bio”), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, announced that its CEO, Linda Powers, presented at the Phacilitate Leaders World 2019 Conference in Miami, Florida. The slide deck from this presentation can be found on the Company’s website at www.nwbio.com.  

Ms. Powers noted that although immune therapies have made great progress on blood cancers, the key challenge for immune therapies lies in treating solid tumors because solid tumors comprise at least 80% of all cancers and they are much more complex and variable. Ms. Powers noted that there is extensive variation (i) among solid tumor cancers, (ii) between patients with the “same” cancer, (iii) within a single patient over time and (iv) even within a single solid tumor in a single patient at a single moment in time.  (Biopsies taken from different locations within a single tumor can yield different results.)  Ms. Powers described how DCVax®-L is tailored to address these challenges.

Focusing on Glioblastoma brain cancer, Ms. Powers noted that the standard of care was established 14 years ago in 2005, when chemotherapy was approved to be added to surgery and radiation based upon adding 10 weeks of survival. She reviewed the enormous expansion of scientific knowledge in the years since then, with extensive knowledge today about the disease and relevant patient characteristics – but without this expanded scientific knowledge translating into any meaningful improvement in median survival times of patients. Median survival was about 14.6 months in 2005, and today is still only about 15-17 months.

Ms. Powers described the results of an academic review of the clinical trials for Glioblastoma which were conducted between 2005 and 2016:  417 clinical trials were conducted, involving approximately 32,000 patients; only 16 of those trials were Phase 3 trials, and only one of the Phase 3 trials reached a positive result extending patient survival. (That trial involved a medical device.) [1]

It is noteworthy that, contrary to the approach taken by DCVax-L, these failed cancer treatments  typically used a “silver bullet” approach: a single active agent aimed at just one target on the cancers or just a few targets (e.g., bi-specific, tri-specific or a half-dozen or so targets).  It is a real question whether such narrow approaches are realistic against the enormous complexity and variability of solid tumors. 

Ms. Powers described the large publicly funded Cancer Genome Atlas project that analyzed and profiled solid tumors, starting with Glioblastoma. Their initial findings, published in 2008, reported that analysis of 91 tumor tissue samples, looking at just 601 genes, found 453 mutations in 223 unique genes. [2]  Their broader findings, published in 2013, reported that analysis of 291 tumors found 21,540 mutations, including a variety of different types of mutations. [3] 

Building upon the Cancer Genome Atlas findings, the NIH commented that “it is now evident that glioblastoma growth is driven by large signaling networks that have a functional redundancy that permit adaptation of the tumor in response to targeted molecular treatments”. [4]  Ms. Powers pointed out that such redundancy and adaptation provide escape routes that help tumors escape from treatments. 

The Company believes that a “silver bullet” treatment approach is unlikely to be effective against such enormous variation in tumors and such escape mechanisms.  Ms. Powers noted that, in addition to Glioblastoma, other types of solid tumors also involve extensive variations and corresponding treatment challenges.  To date, only limited numbers of patients (e.g., 5-30% for various cancers) have been reported to respond to immune therapies for solid tumors, including checkpoint inhibitors.  In light of the extensive variation among solid tumors, a patient’s version of a cancer may or may not express a particular single target or couple of targets.

Ms. Powers explained that the approach taken by the Company’s DCVax therapies uses Nature’s system and is the opposite of a “silver bullet” approach:  i.e., many active agents against many targets, rather than a single active against just one or a few tumor targets.  DCVax-L is designed to achieve this through 3 key characteristics:

• Uses the master cell of the immune system:  dendritic cells (DCs)

Mobilizes the overall immune system, both T cells and other active agents

DCs have a large multiplier effect, mobilizing both large numbers of T cells and diverse T cells (diverse both as to tumor targets and as to types of T cells – helper T, killer T, etc.) 

• Is fully personalized

Avoids Russian roulette at the outset, as to whether the patient’s tumor expresses the treatment target — fits the patient’s version of the cancer.

• Uses ALL tumor antigens (i.e., targets), not just one or a few targets

Minimizes tumor escape after treatment. (When treatments target just one or a few antigens, tumors stop expressing those.)

The Company has been testing this approach in its Phase 3 trial of DCVax-L for newly diagnosed Glioblastoma, and is now working on various stages of preparations towards completion and unblinding of the trial.  As previously reported, the blinded interim data (i.e., data from the treatment and placebo arm of the trial combined) through October 2018 indicate that:

• Median survival of all 331 patients in the trial, from surgery, was 23.1 months.

• The top 100 patients – 30% of all patients in the trial – have a Kaplan Meier median survival of 58.4 months. 

• Apparent survival extensions are seen across the range of patient demographics and characteristics, both in patients with favorable prognostic factors and patients with unfavorable prognostic factors (age, physical condition, number of immune cells, full or partial surgical removal of tumor, status of MGMT gene, etc.)

• The safety profile has been excellent:  with the DCVax-L product administered over 2,000 times, only 7 of the 331 patients (2%) experienced any “serious adverse event” that was deemed at least “possibly related” to the treatment.  DCVax-L does not involve any hospital inpatient or ICU stays, as some other immune therapies do, and does not require additional drugs to manage side effects.

The presentation concluded with a review of the practicality of DCVax-L for commercialization.  Ms. Powers noted that all doses for a patient are manufactured in a single batch and stored frozen, that this enables repeated dosing of patients over a multi-year period, and that such doses are all “off the shelf” after the initial manufacturing.

[1]  Neuro-Oncology. 20(8) 1034-1043, 2018

[2]  Nature. 2008 Oct 23; 455(7216):1061-8

[3]  Cell. 2013 Oct 10; 155(2): 462–477

[4]  NIH News Release, October 28, 2013, Genomic Understanding of Glioblastoma Expanded  

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 broad platform technologies 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.”  The Company is also pursuing a Phase I/II trial with DCVax®-Direct for all types of inoperable solid tumor cancers.  It has completed the 40-patient Phase I portion of the trial, and is preparing for Phase II portions.  The Company previously conducted a Phase I/II trial with DCVax®-L for metastatic 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 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 statements.  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 complete its clinical trials on a timely basis, uncertainties about the clinical trial results and data, 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.

CONTACT

Les Goldman

240-234-0059    

lgoldman@nwbio.com