Replies to post #315138 on NorthWest Biotherapeutics Inc (NWBO)

[SweatpantKing]

How funny. Thanks

[alphapuppy]

India, you have important things to say about NWBO. However it’s impossible to read your posts.

There are things in the written word, called a paragraphs in which separate ideas in a long written section of words are separated by a space or an extra line.

These paragraphs allow people to read very large post such as yours in packets of information. The brain is better able to process that rather than just having a post that just pukes out a very large amount of words.

So I don’t read your post because there’s no paragraphs.

[abc1212]

Pyrrhonian also posted this named 'SA article updated: let me know what you guys think.'

This highly positive report was in May 2014, before he changed sides and, imo, could no longer be trusted.

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=102224768
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In Our Lifetime: Northwest Bio's Race To Cure Cancer


It's the disease that affects everyone. Just how deadly is cancer? An estimated 14 million new cases were reported in 2012, and in that same year, 8.4 million deaths--an utterly unpalatable ratio. Even in the most developed countries with advanced medical practices and cancer treatment centers utilizing the latest advances--no matter the cost--of novel, recently approved cancer fighting therapies, the death rate over a ten year period is still in excess of 55%. Furthermore, it is estimated that the worldwide economic burden of this deadly disease is towering near $1 trillion a year (cancer even eclipses heart disease in this regard). It's just not working. Standard of care (SOC)--resection, followed by chemotherapy and/or radiation therapy--is failing miserably. Something must be done. And fast.

Enter immunotherapy. And in this field specifically, Northwest Biotherapeutics (NWBO).

NWBO has as their two leading therapies what are known as "dendritic cell vaccines;" one which utilizes the patient's own resected tumor (in operable cases) to trigger an immune response (called "DCVax-L"), and one which is directly injected into inoperable tumors (aptly called "DCVax-Direct") that can cause tumor necrosis (cell death).

DCVax-L is being developed to treat (for now) the most lethal form of brain cancer, glioblastoma multiform. In prior trials the vaccine was shown to outperform SOC by a wide margin, increasing patient's survival rates from 14 months with SOC to over 3 years on average with DCVax-L, with a number of patients surviving beyond the six year mark, and two surviving even beyond the 10 year mark. Unheard of in GBM. This is stunning in that for over 30 years now there have been no advances made in treating this disease. The therapy was developed over a number of years by Neurosurgeon Dr. Linda Liau of UCLA, and is currently being tested in a sponsored (by NWBO) double blind, placebo controlled Ph III trial. Given the blinded nature of the trial, there is little or no information released to the public about ongoing results. However, the trial is set to conclude by September of this year, with top line results due out early in 2015. There has been much validation accruing for this technology, when utilizing whole tumor lysate, as can be seen here:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2810429/

and here:

http://www.immunotherapyofcancer.org/content/pdf/2051-1426-2-10.pdf

What's very interesting at the moment (because ongoing results can be published) is NW's DCVax-Direct therapy. Currently in a Ph I/II open-label trial, this treatment utilizes "activated dendritic cells" (the master cells of the immune system--the "conductors," if you will) to infiltrate the tumor and initiate an immune response. This response causes the injected tumor firstly to be dissolved and meticulously removed (through cellular "clean-up" processes)--all without the "massive" tools of surgery (compared to cellular level functioning). Concurrently, the therapy elicits a systemic response that causes nearby, non-injected lesions to also recede. Further, it is theoretically possible (though difficult to test at the moment) that this systemic response may also extend beyond nearby tumors, and actually cause the immune system to seek out and destroy distant metastasized cells that have broken free in the body. These would inadvertently evolve to become tumors all their own eventually. This distant systemic effect could cause this treatment to even rival the functionality of chemotherapy.

It's notoriously difficult for any treatment to have an effect on a significant tumor mass, especially because of the thick wall of tissue surrounding each. Oftentimes treatments (chemotherapies in particular) are aimed at either cutting off the blood supply to these tumors, or hampering rapid cell division. Obviously these chemos cannot affect the cancer without also causing rampant destruction to the patient's own cells. This creates a bit of a race of its own: who will die first--the cancer or the patient?

Direct is different. Completely safe (non-toxic--virtually no side effects), it can be administered into any tumor microenvironment in the human body via injection using ultrasound guidance. That's right, anywhere, including in the brain, in the liver, in the pancreas, in the colon, in the lung--literally anywhere. The methods have evolved to perform this task quite well (unlike chemos themselves, which as a group haven't become much more effective today than thirty years ago). The methods of injection have especially advanced by way of treatments of Parkinson's disease. Now companies like NWBO can take advantage of this modern administration technology.

Well, what exactly is this stuff they are injecting into these tumors? Why, your very own precisely matured DCs (dendritic cells), of course. They are harvested from your body, "activated" (proprietary company technology), and then injected 'direct-ly' into your tumor (should you be unfortunate enough to have one. Or several). In mouse studies using this tech, something incredible happened…

Not only did every one of these mice have their tumors shrink (necrosis/ dissolution), but to an incredible extent--80%-100% regression (this was over a short window of time--given more time, it is possible they would have all shown 100% regression). And then something even more profound occurred: researchers tried to re-graph these tumors back into their small bodies, but to no avail--they were immune.

Immunized to cancer. Like any good vaccine should do. Immunize you. We are all aware of "immune memory" in this regard. It's the reason for all of those annoying booster shots. But fortunately, that is the only pain they give you. And the pain they save you from? Well, that is hard to quantify.

Alright, a mouse study. Nice, but… It's a mouse study. Wait, there's more.

In a pilot study conducted in 2000 by Triozzi et al, they treated ten patients with metastatic breast and skin cancers with a similar (though less advanced) DC vaccine. He was limited by the administration technology of that time (even though not very long ago) to choose these more superficial cancers. Of course, in that these cancers were 'metastatic,' these patients also had tumors of the lung, liver, etc., but out of reach, unfortunately, to Triozzi's vaccine. However, in the tumors he treated, not only was a response seen in 100% of the patients (all ten patients showed tumor reduction), but some were observed to have an incredible response. One particular patient's injected melanoma tumor completely dissolved, along with all smaller tumor lesions within a 6 cm radius--even though the latter were not actually injected.

Encouraged by these results, Triozzi also looked to see if those distant, non-injected (because they, for him, were non-injectable) lung and liver tumors also receded. Unfortunately, after 8 weeks, it didn't appear they had.

Although incredible in itself, the Triozzi vaccine fell short in two ways; one, the DCs he utilized were not matured precisely to be able to take up and express dying tumor's antigens maximally. They also were not as able to travel to the lymph nodes to do their "bee dance"--in effect, communicating to the white blood cells where to go to fight. And two, he could not inject his vaccine anywhere deep within the human body.

Researchers sponsored by NWBO have solved both problems. Their vaccine utilizes precisely matured DCs that have maximal capacity in the human body. They can uptake antigens very effectively, and have the most capable transport abilities. It is similar to age and health restrictions in joining the armed forces. We send the healthiest, most physically able, youthful, select members of our society to defend our country. DCVax-Direct does the same. Oh, and this process is patented. No other company utilizing DCs can copy it.

There are online forums where those with terminal cancer go to discuss treatment options and support each other going through their hardship. If someone was stricken with this disease, and had possibly encountered a viable therapy that was effective for them, it seems likely some of them would find their way there to communicate this to others (as many do). Well, regarding the DCVax-Direct trial (still in its early stages), there was one recently. Here is his conveyance:

Quote:
Ever since going to Orlando Health I feel much better. My tumor in colon has begun to shrink in size and is no longer attached to abdominal wall. It is also beginning to move away from my bladder. The thickness of tumor in colon has also been reduced. Colon surgery will now be successful and it looks like I may be able to keep most of my urinary bladder and not have to worry about cancer in bladder reoccurring.


It certainly sounds genuine, and makes sense from a medical perspective. It also sounds like something someone who was treated and told what had occurred would say without having a medical background. Although this is not a documented result from a regulated clinical trial, and should not be given the same weight, it is a possible validation. And it seems logical that patients being treated and seeing their tumors dissolve to the point where surgery becomes possible (life saving--pass to "Go," collect $200) would come online to share their testimony.

However, there has recently been confirmation of this. On Thursday, May 15th, the Company released a case study from their DCVax-Direct trial documenting the incredible experience of another one of their patients:

Quote: The specific case study announced today involves a sarcoma patient with a large tumor mass and multiple inoperable metastatic tumors in the lung. This patient received the first 3 DCVax-Direct injections through the course of a month, starting in February. He received a fourth injection in early April and then was scanned for results in early May. At that time, this patient's MRI scan showed extensive necrosis and partial collapse of the injected large tumor mass, and a CT scan showed some early indication of shrinkage of one of the non-injected metastasized tumors. These results suggest both local and systemic effects of the DCVax-Direct treatment, as were seen in the pre-clinical studies.

These encouraging results were further supported by tumor biopsies taken at the time of the most recent injection, which showed a high rate of tumor necrosis and appearance of T cells (immune cells) infiltrating into the injected tumor.



The remarkable trend continues. This would be the 11th patient officially treated (adding to the ten in the Triozzi pilot study) with a directly injected DC vaccine that has seen effectual results from this therapy--and now in terminal lung cancer at that, the number one cancer killer. The fact that this is one patient in the study does not mean it is a bizarre occurrence. Because of the three-tiered dosing schedule, necessary in these Ph I stage trials, many of the patients simply do not have mature enough data to report on. Given the small population of those in the trial with more mature results (perhaps 7-10 patients by now) and the extensive yet ultimately ineffectual SOC treatments each patient had received prior to enrollment in the DCVax-Direct trial, the probability of an effect of this magnitude being seen in even one patient from a mostly ineffective therapy, would be exceedingly small. If due to chance, it is akin to 36 people being dealt five cards each, turning over ten hands, and finding one of them is a royal straight flush.

The far more likely scenario is that, just as seen in the Triozzi study, 100% response rate will eventually be reported in the DCVax-Direct trial. What has not been seen to date with an intratumorally injected DC vaccine is zero response. In fact, as a broad category, intratumoral injection has always proved effective. The problem has been poor tolerability in using synthetic, toxic and therefore harmful substances, such as seen here. This is not the case with the abundantly homogeneous DC vaccines. Furthermore, intratumoral chemotherapy fails to solve the underlying problem: lack of immunity. The immune system will go on viewing those recently destroyed cancer cells as normal cells. DCVax, on the other hand, trains the body's immune system to see them, and their full array of biomarkers, as the enemy. This should cause regression of tumors to continue even in the eventual absence of injected vaccine (as already witnessed via the regression of non-injected tumors).

Northwest will be presenting these and more mature developments from their DCVax Direct trial in two weeks at ASCO. Between now and then they've stated they will release data and updates regarding progress in and around the trial itself--a literal PR campaign. This astounding case study is only the beginning. These updates could include:

-possible Breakthrough Therapy designation granted by FDA;

-enlargement of the trial to include a Ph IIb leg of 144 patients (the CEO's words at a recent conference), which would enable them to be able to petition FDA for Accelerated Approval;

-possible expansion of the trial oversees, thus seeking EMA approval in addition to FDA approval (more than doubling target patient populations);

-complete data on the first cohort of Ph I patients through three scheduled dosages;

-completed enrollment of Ph II leg of 24 patients.

Considering how quickly the primary endpoint of tumor response can be assessed (8 weeks), the trial could move very quickly towards completion (as opposed to over many years, like with most therapies), getting this non-toxic, apparently highly effective novel therapy to the patients who desperately need it. There would also be little hindrance to approval, such as an already approved therapy that DCVax-Direct must show superiority over. There literally are no approved therapies for these patients, only palliative care. The bar isn't only set low, it barely exists. Any measurable effectiveness will green-light this therapy for approval.

You see, patients with inoperable cancers all, always die. Not one survives inoperable lung cancer. No one survives inoperable secondary brain cancer. No one survives inoperable pancreatic cancer. And millions of cancer patients will unfortunately find their way into one of these terminally ill categories. DCVax-Direct is being used to treat the poorest prognosis, highest mortality cancer patient population. And what is utterly amazing--nearly incomprehensible--completely unprecedented--is that they might all survive.

What's difficult to conceive is a way in which this therapy will not work. Unlike with synthetic, highly targeted therapies (such as chemo), DCVax-Direct utilizes the patient's own immune system to attack cancer, which cannot escape its fate through mutations that slip away from overly targeted therapies. And Direct does so with cellular precision.

Could cancer truly be on the verge of defeat? Is it too soon to get one's hopes up? I posit it's not too soon. It's about damn time.

[CassieW]

TL;DR