NorthWest Biotherapeutics Inc (NWBO)

[Evaluate]

www.cancercompass.com/message-board/message/all,72718,0.htm?mid=545515

I found various things of interest in the July 2013 letter from Carol Powers to m.Nabil, such as:

· we have to pay for the ENTIRE treatment cost (compassionate use)? or we can pay initial 1st year or some doses

The manufacturing process for the vaccine is called a “batch method” meaning the entire three years’ course of vaccine is produced at one time. As much vaccine as can be produced from the tumor lysate and the patient’s blood draw is produced, meaning some patients receive enough vaccine for several years (more than the clinical trial’s three year dosage schedule) and some patients only obtain enough vaccine for a few doses. The payment required is for the manufacture of the vaccine and it does not vary based upon how many doses are able to be produced. The accommodation that we have been able to grant is that, of the total $110,000 cost for the vaccine, $25,000 is due before the tumor tissue is delivered to the lab and the lysate production process begins. Once we confirm that sufficient lysate was able to be produced, then the remaining $85,000 is due before we schedule the specialized blood draw known as leukapheresis and before the vaccine is manufactured. Although the doses work out to be approximately $10,000 each (typically there are eleven doses given over the course of three years), the payment for the vaccine is due in full for the actual manufacture of the entire batch.

As a recap of our conversation, I would note that the vaccine is made from the patient’s tumor tissue (produced into a lysate which extracts the tumor’s unique biomarkers) and from the patient’s dendritic cells (isolated from a specialized blood draw). Each step involves an intensive laboratory process requiring an extraordinary level of expertise and extensive quality control testing to ensure both potency and purity. The production of the tumor lysate takes 8 to 10 days and then the quality control testing typically takes another few days.

Once the tumor lysate is made, your mother would then undergo a specialized blood draw called leukapheresis. The monocytes (precursors to the fully developed dendritic cells) are separated out, purified and matured in the lab. The blood from the leukapheresis must be processed within 20 hours after being drawn. It takes 8 days to produce the vaccine and then it is sent for quality control testing, an additional 35-40 days. The manufacturing process involves using the tumor lysate biomarkers to “educate” the dendritic cells to recognize the cancer cells. It is our expectation that, when the vaccine is administered, the patient's immune system is activated and responds to fight the cancer.

As you can tell, the length of time from the shipment of the tumor tissue to the administration of the first dose of vaccine is not short. As a result, several significant timing issues must be addressed. As I mentioned earlier, we always recommend that the patients follow their doctor's standard of care protocol. We will work within that protocol to make arrangements for the procedures that need to be done and the timing of the DCVax injections. In particular, there are challenging timing issues which arise in connection with both the leukapheresis and ongoing radiation.

Leukapheresis:
One concern that arises in connection with leukapheresis is the use of steroids. The primary goal of this part of our process is to ensure the blood cells are as plentiful and vigorous as possible. The administration of steroids affects the viability of the blood cells. With regard to steroids, “less is better” and no steroids in the ten days prior to the leukapheresis is best.

Radiation:
As I am sure you know, radiation plays havoc with a patient’s immune system. You indicated that your mother was beginning her standard of care protocol of chemo and radiation. It usually takes at least 4 weeks for the monocytes to recover after a series of radiation doses and, even then, the quantity and quality sometimes do not fully recover. That being said, we do have patients who have their leukapheresis about 10 days to 2 weeks after their radiation has been completed and the monocyte yield has been fine.

As I think I mentioned, the Specials program at King’s College in London is oversubscribed and is not an available access point for the DCVax-L vaccine at this time. That means the only access point for a compassionate use/private pay patient is through a clinic in Israel where we have a collaborative arrangement. The tumor tissue would be shipped to Israel and your mother would need to travel to Israel for the leukapheresis, where the vaccine would be made. Your mother would then need to return to Israel to receive the first dose of the vaccine.