Expert Financial Analysis and Reporting

Purpose of Report:

At ASCO, Northwest sponsored a meeting attended by investigators in the phase 3 trial and other oncologists not involved in the trial. During the meeting, five patients gave testimonials on the spectacular outcomes that they had achieved due to treatment with DCVax-L. Four of these patients were treated in compassionate use programs and one was from Linda Liau’s phase 1/2 program at UCLA. As my wife and I listened to their stories, she started crying and my eyes welled up. Other people I have talked to had the same reaction. I urge everyone to take the time to view the presentation. I have also transcribed in this report the most important parts of the presentations made about these patients.

 

Patient Outcomes for Two Critically Ill GBM Patients who were Surgically Resected Three Times

The case histories of a 60 year old man from Canada and a young mother from the UK were very striking to me. Both had an aggressive, rapidly progressing form of glioblastoma multiforme (GBM). They had relapsed not after one surgical resection, received a second surgical resection and relapsed again and then relapsed after a third. Not many GBM patients have a second surgical resection, because relapse is an indication of an aggressive, probably untreatable cancer. Three resections are extremely rare as it is obvious that the cancer is extremely aggressive and most oncologists would not recommend this. In fact, in both of these cases, the treating physicians recommended against the surgery.

Both patients were told that they had failed all treatment options and had weeks or months to live. Generally, GBM patients who are resected for a second time have six to nine months to live and as I just said, third resections are almost never done. The third resections for these patients were only done because the family insisted. Families of both patients were told that they had no other drug treatment options. However, internet searches turned up information on DCVax-L and they were fortunate to get into the DCVax-L compassionate use program. Both patients were far too sick to be eligible for the DCVax-L phase 3 program.

The 60 year old man had terrible risk factors. Not only had he received three surgical resection, but he was also old and could only be partially resected. Physicians told him he had only weeks to live. He received DCVax-L after the third surgery in October of 2015 and is alive and doing well today-three years later. It was emphasized that he suffered no discernible side effects from DCVax-L treatment.

The second patient was a young mother who also had a very aggressive cancer. She had a third resection in October of 2015 and was told there was nothing else physicians could do for her. They gave her three to six months to live, but her husband was dogged in an effort to find something and through an internet search, he found DCVax-L and she was treated in a compassionate use program. Three year later, she is without cancer, is a mother to her child and has a job. She is leading a normal life. It was emphasized that DCVax-L had no side effects.

These cases are so striking because these were two of the sickest GBM patients one can imagine. It is without question the case that their life saving outcomes were due to DCVax-L. They had failed all possible surgical and drug treatments and were told they were soon going to die. It is invariably the case that if a drug works in advanced, refractory cancers, it will probably work better in newly diagnosed cases. This firmly establishes that DCVax-L can produce dramatic therapeutic benefits in some very advanced GBM patients. This is important from a regulatory standpoint in that these jaw dropping outcomes will be looked at alongside the results of the phase 3 trial.

The families and friends of both patients found DCVax-L through an internet search. I think that families and friends of most newly diagnosed and also relapsed GBM patients will do the same and quickly come to this video.  With the new Right to Try law allowing access to unapproved drugs, it will certainly be the case that Northwest will be deluged with requests to receive DCVax-L. The lack of side effects will be extremely important for patients considering accessing the drug through Right to Try.

Striking Results in Metastatic Merkel’s Cell Carcinoma Patient

The third patient from Florida was not a GBM patient; she suffered from Merkel’s cell carcinoma. Among cancers, metastatic melanoma (a skin cancer) is considered one of the worst cancers you can have. Metastatic Merkel’s cell carcinoma (also a skin cancer) is considered to be even worse. There are no effective drug treatments. The patient in this case was diagnosed with metastatic Merkel’s cell carcinoma and told she had only months to live.

A physician friend of hers was aware of DCVax-L and put her in touch with Northwest and she was treated in a compassionate use program about five to six years ago (from her speech, it is not clear exactly how long ago she was treated). She reports that she is leading a normal life with no evidence of cancer. She emphasized that she had no side effects from DCVax-L. It is extremely likely that many (most) Merkel’s cell patients will be eager to gain access to DCVax-L under Right to Try.

This case is important because it shows that DCVax-L can be effective in cancers other than GBM. The mechanism of action is applicable to all solid tumors that can be surgically resected. In previous reports, I have calculated that the worldwide addressable market for newly diagnosed GBM is $5.8 billion. If DCVax-L is effective in other solid tumors, its addressable market is vastly larger.

Two Other Cases of Long Term Survival for GBM Patients

The other two cases were patients with GBM who had spectacular outcomes, although somewhat less so than the three case I have just discussed. One case was that of a young California man who was diagnosed with GBM and who was treated by Linda Liau in the phase 1/2 trials of DCVax-L. He is alive 15 years after DCVax-L treatment. He is a father, teacher and coach who is living a normal life.  He also emphasized the lack of side effects.

The other patient was a middle aged woman from Hong Kong. She is alive 6 1/2 years after diagnosis. In her presentation she was passionate in how she has been able to live a normal life after being told at the time of diagnosis that she had 6 to 18 months to live. She found her way into the DCVax-L compassionate use program thanks to an internet search by her family. She emphasized the lack of side effects,

The ASCO Results Reinforce the Positive Results Just Reported for the Phase 3 Trial

Northwest Biotherapeutics had produced spectacular clinical data over the last week. In a recent report, I discussed the results of a manuscript dealing with blinded results from the phase 3 trial of DCVax-L in newly diagnosed GBM in my report. The manuscript indicated that patients in the trial were living meaningfully longer than would be expected with SOC and that this strongly suggested a clinically meaningful benefit from DCVax-L. The report was co-authored by 69 clinical investigators who participated in the trial.

One of the most informative statements about the interpretation of the phase 3 trial was from Dr. Keyoumers Ashkan, who is the chief investigator in the European segment of the trial. Dr. Ashkan is the clinical lead for neuro-oncology at King's College Hospital in the UK. He has an active research interest in brain tumors and movement disorders and heads the Neuroscience Clinical Trial Unit.  Dr. Ashkan is one of the most respected neurosurgeons in the UK and Kings College is the premier teaching hospital in the UK. For more background on Dr. Ashkan, click on this link. Dr, Ashkan summarized his view on the blinded results from the phase 3 trial as follows:

“The interim results of this phase 3 trial give new hope to the patients and clinicians battling with this terrible disease. Although definitive judgment needs to be reserved until the final data is available, the paper published today hints at a major breakthrough in the treatment of patients with glioblastoma.”

Investment Opinion

I am 98% certain that DCVax-L will be approved for the treatment of at least a sub-group of newly diagnosed GBM patients and more likely for all, probably in 2019. I am 99.9% certain that there will be enormous demand from both newly diagnosed and relapsed GBM patients to obtain access to DCVax-L under the Right to Try law that could lead to meaningful revenues in 2018 or 2019. The gating factors on use under Right to Try are the probability that most patients initially will have to pay out of pocket and the lack of manufacturing capacity. Patient demand will not be an issue and there is a high probability of meaningful revenues beginning in 2018 or 2019. Based on what I have seen so far, it is not hyperbole to say that DCVax-L could very well be a more significant advance in the treatment of cancer than checkpoint inhibitors (Opdivo and Keytruda) and the new CAR-T drugs (Kymriah and Yescarta). It promises to be effective against a wider number of cancers and has almost no side effects.

The stock was trading at $0.23 on the last trading day prior to the release of the manuscript on May 29. Now one week later, it is trading at $0.28. If anyone doubts that stock trading on small, emerging companies can be and often is rigged, you only need look to this stock behavior. The wolfpack and the market makers they conspire with can actually set the price of NWBO, at least for now. This is one of the largest criminal enterprises in the US affecting not just NWBO but many, many small companies.

The immediate intent of the wolfpack is to give the appearance that the spectacular clinical data is being received skeptically by investors and to discourage both current and potential shareholders. NWBO at the current price has a market capitalization of $122 million based on fully diluted shares as reported in the latest 10-Q and $230 million if every potential share equivalent were converted to common. In my opinion and based on my experience, if NWBO were a private company with the current clinical data and elected to come public, the offering would be priced at a market capitalization of $1.5 to $2.0 billion, would be quickly over-subscribed  and quickly rise to a substantial premium over the offering price.

The wolfpack is throwing everything including the kitchen sink, garbage disposal and baking ovens at the stock and at this point they are successful. Their goal is to force this financially distressed company into an equity offering at a sharp price discount and they may succeed. However, they have no chance of achieving what has been their prime goal of preventing the completion of the phase 3 trial and driving NWBO into bankruptcy. The clinical data is just too good to ignore and Right to Try could (will) provide meaningful near term results. NWBO may have to do another near term financing at the currently distressed price, but inevitably the magnitude of what is going on clinically and in Right to Try will overwhelm the wolfpack and allow the stock to reach a proper market valuation which I think could be at a minimum $1.7 billion. Assuming a doubling in the potential share count to 1.7 billion shares due to new offering the price could still reach $1.00 in 2019. I think it is more likely that the market capitalization could reach $2, $3 or $4 billion and to the extent that NWBO can gain access to sufficient capital to tide it over the next half year without issuing 850 million more shares, the upside would be more.

The blatant attempt of the wolfpack to delay or prevent the development of a highly promising drug like DCVax-L cries for a Congressional investigation. Their manipulation scheme is widely recognized by investors and companies. They are just so brazen that they think they can get away with this forever and so far they have been proven right. However, I think that the new wild card to be dealt to the wolfpack may be Donald Trump. If he is made aware of and persuaded about the wolfpack, he could see this manipulation scheme as blocking the intent of his Right to Try law of bringing promising new drugs more quickly to the market. We know what Trump can achieve when he becomes passionate about an issue. Let us hope that he chooses to jump into this.

Partial Transcripts from ASCO Presentations about Five Patients Treated with DCVax-L

Patient 1: Sixty year old Canadian man with GBM who had three surgical resections:

The patient’s daughter spoke about the experience of her father who was diagnosed with GBM in July 2014. The treatment then went as follows:

• He was surgically resected and started on radiation. He was able to tolerate radiation, but not chemotherapy.
• He had a recurrence in the spring of 2015 and was surgically resected in June 2015.
• The tumor recurred in October 2015 and a third resection was performed. Surgeons were able to resect 70% of the tumor mass, but 30% remained and it was a fast growing tumor.

Physicians told them that he likely had about two weeks to live as there were no viable treatment options. They contacted Northwest and because they the tumor tissue that had been preserved, NWBO could prepare the DCVax-L vaccine and begin treatment. Today, her father is nearly three years out from the last surgery. He continues to do well and he is continually improving in his speech and cognitive functions. Three brain surgeries produce a lot of trauma. His physical ability is also improving. They are obviously grateful to Northwest who has treated them as part of the family and been prompt to answer all of the family’s questions.

When her father was diagnosed he was over 60 and the surgeons were not able to completely resect the tumor. These are two prominent risk factors associated with shorter expected survival. His inability to tolerate chemo enormously increased the risk.

SmithOnStocks comment: I am very familiar with the publicly available data on DCVax-L, but this case was so striking that it caused my jaw to drop. This patient would not have qualified for the phase 3 trial in newly diagnosed GBM because of the risk factors. He had experienced not just one relapse, but three and had high risk factors. I suppose the hedge funds and their bloggers will say that this is just one case and argue that this was a spontaneous remission, not attributable to DCVax-L. This is a totally ridiculous argument based on the evidence, but they have made more ridiculous claims in the past.

This tested DCVax-L in recurrent GBM, which is a different disease state than newly diagnosed GBM and is much harder to treat. The results speak for themselves. The case is important in that it points to an expansion of the use of DCVax-L to recurrent GBM as well as newly diagnosed. One would also expect that if a cancer drug works well in recurrent stages of the cancer that it should work even better in earlier, newly diagnosed patients.

Patient 2: Young UK woman diagnosed with GBM who had three surgical resections

The speaker was from the UK and the husband of the patient. In 2013, three months after the birth of their son, his wife was diagnosed with GBM. Since then she has had three surgical resections, has received radiation and has several type of chemotherapy. In 2015, her physicians told them there was nothing else they could do. They told her there that she had three to six months left to live.

They refused to give up and through an internet search they discovered DCVax-L and she was able to receive treatment under the compassionate use program. Three years later she is alive and vibrant. She is working part time as an analyst at a bank and a mother to a five year old boy. Her husband described DCVax-L as miraculous. It has given his wife back her life. Every six months she receives an injection by taking a train to a physician’s office without her husband to receive another injection and then hops back on the train to come home.

The speaker said that his wife had experienced the terrible side effects of chemotherapy. He said, with DCVax-L there are no side effects. He said there is no more tumor. It is completely gone. He said that they had flown all the way from the UK to tell their story because they want every GBM patient to have the same experience as they had.

SmithOnStocks comment: Like patient #1 this was a recurrent GBM patient who had three surgical resections. Again, my jaw dropped. I think the really important aspect to this story is the absence of the tumor, her ability to live a normal life and the lack of side effect of DCVax-L.

Patient #3: Middle aged woman from Honk Kong with GBM

This patient was from Hong Kong and is six and one-half years post GBM diagnosis. The doctors told her that optimistically she might have 18 months to live, but it could be as little as 6 months. The physicians at the hospital didn’t have anything other than the standard options, but her husband and her friends wouldn’t accept this.

They came across DCVax-L though an internet search and following treatment with DCVax-L, she has had an MRI every six months. She is symptomless and there is no sign of a reoccurrence of cancer in her brain. This patient spoke at length about what it meant to her to get a reprieve from a death sentence and be able to watch her boys grow up. She emphasized that she looked good, was feeling good and living a normal life as before the GBM diagnosis. She did not have to suffer chemotherapy like side effects. She still takes the vaccine every six months. She wants other patients to have the experience that she had.

SmithOnStocks comment: I would like to have known more about her treatment as with patient #1 and #2. The key takeaway is how long the patient has remained alive and how normal her life is. I think it is also important to note how aggressively her husband and friends searched to find DCVax-L. This was about six years ago and now there is much more information on the internet including her just given account. I think this speaks to how important the Right to Try law may be in leading to meaningful revenues for DCVax-L. With the manuscript and these testimonials, I think that many newly diagnosed and recurrent GBM patient will quickly become aware of DCVax-L. It is a “no brainer” to try to obtain DCVax-L under Right to Try given the promising efficacy results and lack of side effects..

Pateint #4: Florida woman with metastatic Merkel’s cell carcinoma

This patient was from Florida and started her speech by saying that she was a breast cancer survivor. She went through eight months of torture due to side effects of her treatment for breast cancer. She was nine years free of cancer when in roughly 2011 or 2012, she was diagnosed with Merkel’s cell carcinoma and her doctor said that no chemotherapy would work on this aggressive cancer.

Two years later the Markel’s cell had metastasized. She told her husband and friends that she would not go through chemo again and instead was prepared to leave the planet before doing chemo again. This was not easy for her as her son was in college and her husband and she were getting ready for retirement and had a wonderful life planned. One of her friend’s husbands was a doctor who knew about DCVax-L and she contacted Northwest Biotherapeutics. They quickly accepted her as a compassionate case. She went to Israel to be cured and was blessed with that experience. At the time, the DCVax-L trial in the US was on hold due to financial issues and she had to go to Israel for her treatment.

She now goes into the office every six months for an injection and then goes on her way. With chemo, it was a week or two week process after she got her chemo shot during which her normal life stopped. Now she is out and about after her shot, enjoying her friends and going out to dinner.

She is now six and one-half years out and cancer free. She had been told she had nine months to live. She said she feels so blessed to be able to speak about this product and now with Right to Try, hopes other patients can gain access before the drug is approved.

SmithOnStocks comment: Metastatic melanoma is an extremely aggressive cancer with very poor outcomes. Perhaps 15% to 20% of patients respond to a combination of Yervoy and Opdivo although the side effects are horrible. Metastatic Markel’s cell carcinoma is even more aggressive that metastatic melanoma and no drugs have shown effectiveness. The outcome with this patient was perhaps even more jaw dropping than the first two patients.

The major takeaway here is that DCVax-L is active in other solid tumors beyond GBM. This was a truly amazing result in a devastating cancer. I think that Northwest based on this could undertake a small, open label trial that could be potentially be registrational. I have seen companies raise significant amounts of money on the basis of showing an objective response in one Merkel’s cell patient treated out of 12. The other takeaway is consistent with what all patient say about this drug. It has no side effects and allows them to lead a normal life.

Patient #5 Young California man with GBM who participated in Linda Liau’s phase1/2 trial

He was an aquatic athlete who came from Huntington Beach California. He was an All American swimmer and All American water polo player. In 2003, he was in his lifeguard unit driving along the beach and had a major headache forcing him to go home sick. He went to a doctor who diagnosed it as a migraine and prescribed medicine that seemed to help but two days later he had another headache and was sent to a neurologist who ordered an EEG, lab work and then an MRI. The EEG showed that the left side of his brain was not working and that the MRI showed there was a golf ball sized tumor in his left frontal lobe.

That was 15 years ago. When he went to the doctor who did his first biopsy, he was told that the size and location of the tumor meant that surgery couldn’t be done. He decided to go another doctor to see if he could get surgery and to also see what drugs they might have to offer from a clinical trial. Luckily he found Dr. Linda Liau at UCLA and had a very successful surgery. He then started and finished radiation. At the time, temozolomide had not been approved for GBM. After a short time, he got his first shot of DCVax-L.  He was given chemo treatments (unspecified) and was taking DCVax-L injections in between. When he took a break from chemo to get his DCVax-L shot, the lack of side effects made him feel like he did not have cancer. After two years, he was free of all treatments except for DCVax-L booster shots. He said that then he decided to not live his life around cancer and live like a normal person.

He feels that he is so blessed and wants to share his experience. He hopes that all GBM patients have the opportunity to receive DCVax-L like him.  He urges everyone to let people know about DCVax-L.

SmithOnStocks Comment: This was one of the patients who was lucky to find and to be treated by Linda Liau in the phase 1/2 trial at UCLA. His prognostic factors were exceptional in that he was very young and very healthy, but this does in any way explain how he has survived for 15 years after receiving DCVax-L. I think that this is the longest that any patient has survived after receiving DCVax-L. He is a father, teacher and coach leading a normal life.

 

Tagged as 2018 Northwest Biotherapeutics presentation at ASCO, Manuscript on blinded data from phase 3 trial of DCVax-L, Northwest Biotherapeutics Inc. + Categorized as Company Reports, LinkedIn