Replies to post #39434 on NorthWest Biotherapeutics Inc (NWBO)

[sentiment_stocks]

The mention of children under "DCVax Product Markets" was also in the 10K from 2014.

[Rkmatters]

big veto.

children are not just small adults. FDA would never approve that and NWBO would never slow down a trial in a RARE disease in adults for an even RARER subpopulation. - Reefrad

I appreciate your candor. Perhaps I can change your "big veto" to a small "maybe, it's possible". I'll try to make a case for it.

Please view the section I referenced from the most recent 10K, released in April 2015. When I read that particular section, my impression is that the Company alludes to a sincere interest in obtaining the entire GBM market. Upon that, they'll go after less grade cancers; though, not before, after. It makes sense to me to consider doing so now, and get that young age cohort in their GBM Orphan designation (7 and 10 year marketing exclusivity). They did temporarily suspend screening for something, and it may very well be that their temporary halt is somehow related to screening. Can't see why recruiting a young age would be so far fetched. I personally can't rule screening is permanently halted until the Company confirms it so. Can you?

Target Markets for DCVax Products

Since our DCVax-L product is potentially applicable to all types of operable solid tumors, and our DCVax-Direct product is potentially applicable to all types of inoperable solid tumors, the potential markets for DCVax products are particularly large. According to the American Cancer Society, 1 in 2 men, and 1 in 3 women in the U.S. will develop some form of cancer in their lifetime. There are nearly 1.5 million new cases of cancer per year in the U.S., and nearly 600,000 deaths from cancer. The statistics are similar in Europe and in much of the rest of the world.

Brain cancer

Brain cancers fall into two broad categories: primary (meaning the cancer first originates in the brain) and metastatic (meaning the cancer first appears elsewhere in the body, but subsequently metastasizes to the brain). In the U.S. alone, on an annual basis, there are some 40,000 new cases of primary brain cancer, and 160,000 new cases of metastatic brain cancer. The numbers are similar in Europe and the rest of the world.

Within the category of primary brain cancer, Grade 4 GBM is the most aggressive and lethal type. Among the approximately 40,000 new cases of primary brain cancer per year in the U.S., at least 12,000 cases are GBM (with some estimates as high as 17,000) and the incidence is increasing.

In addition, brain cancer is a serious medical problem in children 18 years and under. It is the second most frequent type of childhood cancers (after leukemias) and, following progress in reducing death rates from leukemias, it is now a leading cause of childhood cancer deaths.

Very little has changed in the last 30 years in the treatment and clinical outcomes for GBM. With all standard of care treatment today - surgery, radiation and chemotherapy - patients still die within a median of about 14.6 months from diagnosis.

Although many experimental treatments are in various stages of clinical development, the one drug which has been the standard of care chemotherapy treatment for GBM to date, Temodar, achieved market saturation extremely rapidly, within two years of product launch. Temodar added 10 weeks of survival (extending survival from its historical 12 months to the 14.6 months typical today), and did so in a limited percentage of patients. Other drugs approved by FDA for GBM, such as Avastin, did not extend survival at all.

Against this backdrop, we believe DCVax is well positioned for this target market. Further, after seeking regulatory approval for DCVax for the GBM subset of primary brain cancers, in the future we plan to conduct clinical trials and seek approval for other (lower grade) primary brain cancers and for metastatic brain cancers, as well as, ultimately, other types of solid tumor cancers.

As for treating children with GBM with immunotherapy, Annias is already doing it. As such I do not expect to see any road-block from regulators with regards to treating children with DCVax-L. Earlier this month, the National Cancer Institute awarded Annias Immunotherapeutics, Inc with a $1,227,385 grant to fund its peptide vaccine research (pasted below, with relevant/interesting sections highlighted). In my view, NW Bio should be thinking about this children market quite seriously, and soon.

Therapeutic Vaccine Targeting CMV Antigen in Glioblastoma.

DESCRIPTION (provided by applicant): Malignant primary brain tumors represent the most frequent cause of cancer death in children and young adults and account for more deaths than cancer of the kidney or melanoma. Glioblastoma (GBM) is uniformly lethal, and current therapy is non-specific and produces a median overall survival of <15 months. In contrast, immunotherapeutic approaches are exquisitely precise and can eradicate large, well-established tumors in mice and humans even when tumors reside within the "immunologically privileged" brain. However, immunotherapy is limited by the lack of frequent and homogeneously-expressed tumor-specific antigens. We have previously demonstrated that a peptide vaccine targeting the tumor-specific EGFRvIII mutation (PEPvIII) induces immune responses sufficient to eliminate all EGFRvIII-expressing tumor cells in mice and humans without toxicity. Unfortunately, EGFRvIII is heterogeneously expressed and tumors recur as a result of outgrowth of the EGFRvIII negative tumor cells. However, the nearly universal presence and homogeneous expression of cytomegalovirus (CMV) antigens in GBM, but not normal brain, has now been well-established and provides an unparalleled opportunity to subvert these immunogenic viral proteins as tumor-specific targets. In two consecutive clinical trials from our laboratory using dendritic cells (DCs) targeting CMV pp65 in patients with GBM, specific immunologic responses were induced along with remarkably enhanced progression free survival and overall survival. However, DC vaccination is expensive, time-consuming, and commercialization is challenging. In contrast, peptide vaccines are cost-effective, easier to produce, and easier to commercialize. Leveraging our experience with PEPvIII, we have developed a CMV-specific multi-epitope peptide cocktail (PEP-CMV). PEP-CMV vaccination is immunogenic in HLA-A2 transgenic mice and peripheral blood mononuclear cells from CMV seropositive patients with GBM respond to stimulation with PEP-CMV, indicating PEP-CMV is broadly immunogenic in our patient population. We have already shown with PEPvIII that lymphopenia induced by both standard of care temozolomide (TMZ) and dose intensified TMZ can be leveraged to augment immunogenicity and the impact these regimens have on PEP-CMV immunogenicity will be compared in our proposed trial. Additionally, we will examine a novel immunostimulant, tetanus (Td), as an adjuvant to PEP-CMV. In a recent pilot trial from our laboratory, patients randomized to receive Td as vaccine- site pre-conditioning prior to CMV pp65-loaded DC immunization, experienced significantly enhanced PFS and OS in comparison to the control arm. A Td booster was included for site pre-conditioning during PEP-CMV immunogenicity analysis and was demonstrated to significantly enhance IFN¿ secretion of CMV targeted T cells in HLA-A2 transgenics. Therefore, in this proposal, we will test the HYPOTHESIS that vaccination with PEP-CMV after Td skin conditioning will be a feasible, safe, and immunogenic tumor-specific therapy in patients with newly-diagnosed GBM during TMZ chemotherapy, without antigen escape or toxicity.