Stock of Interest (NWBO): Potentially Lose $0.5 or Gain $30 or More in Near Future

本帖由 GlobeCitizen2016-09-25 发布。版面名称:投资理财

  1. GlobeCitizen

    GlobeCitizen 新手上路 ID:110879

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  2. As a starter, you can find a lot of information here: http://investorshub.advfn.com/NorthWest-Biotherapeutics-NWBO-3441/

    And here about the company: http://www.nwbio.com/

    I am long the stock with well over six figure dollar amount invested in this company hoping to see a disruptive and revolutionized cancer treating vaccine platform be materialized for the good of mankind while reaping handsomely my investment gain .

    A story today: http://www.infocusmagazine.ca/2016/surviving-the-storm/

    Disclaimer:

    All stock recommendations and comments are the opinion of writer.

    Investors should be cautious about any and all stock recommendations and should consider the source of any advice on stock selection. Various factors, including personal ownership, may influence or factor into a stock analysis or opinion.

    All investors are advised to conduct their own independent research into individual stocks before making a purchase decision. In addition, investors are advised that past stock performance is not indicative of future price action.

    You should be aware of the risks involved in stock investing, and you use the material contained herein at your own risk.

    In general and accordingly, it's your own responsibility for any action you make take, not that of the writer.
     
  3. GlobeCitizen

    GlobeCitizen 新手上路 ID:110879

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    Below are two interesting comments taken from nwbo Investorshub message board:

    " Dan88 Saturday, 07/09/16 11:36:54 AM
    Re: None
    Post # of 74519

    The current development regarding FDA's order to stop Juno's pivotal P2 trial due to deaths of patients has a very significant meaning regarding the future landscape of cancer treatments:

    Cart-t as a group may have run into corner as the investment world finally comes to a long overdue conclusion: this class of treatment is dangerous, cumbersome and costly, and its benefit/risk ratio is so unfavorable.

    CI as a class has shown some success with very limited treatable patient population due to its nature.

    Increasingly, more and more people will realize DCVax as a therapeutic cancer vaccine platform will emerge as a new and broader blockbuster cancer treatment class due to its pristine safety profile and potential significant efficacy; with combinations with CIs, the platform may be potentially a cure for some cancer indications.

    At this point of time, anyone who is debating on the purpose of debating is obviously naive or up to something that a normal investor will not do. So please stop engaging in such distractions, either from an old topic which has been discussed before with no new meaning but endless new speculation; something to do with fine prints pulled out from company's sec filing which have been covered in the previous discussions; and any other FUD such as tailored, sometime out of context copies and pastes of some selected FDA documents, and ambiguous subjects such as comparing a "lackluster device" to a potential blockbuster cancer vaccine treatment in any angle negative or ambiguous possible, etc.

    The bottom line is if DCVax-L or D is proved to be better than any existing treatment in any indication in terms of safety and efficacy, it will be approved by FDA; even if L or D might be shown similar in efficacy and/or even safety to that of any existing treatment, it will still be approved by FDA as an alternative which can applied for specific patient populations.

    While one may get carried away from a useless debate, he or she must always remember that at $0.5 a piece per share, basically the market has priced the company a failed company, the L trial a failed trial, LP a failed ceo, and all long investors failed hairballs, and nothing less.

    Don't tell me the company will go bankrupt if you are genuine and have a bit biotech experience, only if LP had nefarious motive if you believe. A company like nwbo will not go bankrupt at foreseeable future, though it is a likelihood that the company will survive simply by diluting its existing share holders.

    Nonetheless, as long as the potentials of D still exist, as long as there is still likelihood that L may still be used in combinations with other agents such as CIs even if L is proven a failure in brain cancer indication, a market cap of around $100 million will be normal, which will give you roughly $1 per share of stock price.

    Not saying the company has not filed a BLA (rolling application or not), not saying the company has not sought AA, but what I am saying is the current situation indicated by share price has totally denied any possibility of those and regarded the company a failed company with a failed L trial.

    It is then a natural, logic, reasonable and certain conclusion as long as investment is concerned: buy nwbo shares as many as and as much as one can afford at this option price.

    It is either $0.5 loss or $30 gain or $300 gain.

    It is my strong belief that there will be a major short covering coming within the next few weeks judged by current ultra-low share price (it should have never been at such a low price, no reasons, absolutely not), the closeness to a major revealing of many optional developments in the company, and the current on-going change of tide shifted from cart-t and/or CI toward DC-based therapeutic cancer vaccine treatment (cure) (note: it is my speculation)as well as the general trend of money inflow to biotech, which is on going.

    Because unless shorts have bullets penetrated their heads making them totally blinded, a major short covering must be and will be coming, even if I prefer it not! "

    -------------------------------

    " Dan88 Monday, 08/08/16 05:01:06 PM
    Re: None
    Post # of 74520

    I try to be polite today so Outside Lane won't find any reason to delete my post:

    Since I don't want to tangle with any persons I deem to have no genuine intention or interests in this company, I would just like to point out one of the earliest speculations on the reason for the temporary patient screening halt in case people have forgot it:

    DMC contacted FDA reporting extremely low event rate, which is much lower than expected;

    FDA reviewed the information submitted by DMC and asked the company to halt screening for additional patients upon further notice while it conducts an investigation on what has really been going on and asking the company for some information ("certain information from the trial");

    Confirmed the abnormally low event rate for OS, FDA takes its time waiting for more patient accruals (OS events) so that it can draw a reasonable conclusion with certainty;

    The abnormally low event rate suggests patients in overall or in average live longer, much longer than would have been expected (recall LL's words?), which would be unethical to continue to enroll any additional patients since some patients would be put into the control, which would be likely inferior to the treatment arm;

    In the meantime, the company cannot do anything but wait for FDA's decision. It cannot say the reason either because if it does, any patients already in the trial would have the right to ask whether they have been in the control arm, and if yes, they would have the right to ask for immediate access to DCVax-L vaccine. As a result, the trial would be ruined (or compromised)!

    Any direct hint on the issuance of partial halt by the FDA would invite more questions as why, when exactly, etc., and the company may have to answer, which is exactly what the company won't do.

    And this may be exactly why there has never been a definite information on the reason regarding to the current ongoing partial halt for additional screening, kind of "intentionally making some murky water" at the ire of investors.

    The speculation above is today still one of the most reasonable theories on the reason of the halt, and yet some people are more than willing to forget it.

    It explains why it has taken so long and it still seems to be no end of it.

    Patience, ladies and gentlemen. It is out of control of anyone including FDA.

    God willing, let patients live much longer than would be expected."
     
  4. JSH

    JSH 资深会员 ID:85917

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    lz 上文学城的大千论坛吧,绝对会一呼百应的,在cfc里发股文是浪费你的才气。
     
  5. GlobeCitizen

    GlobeCitizen 新手上路 ID:110879

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    Thanks JSH. I have rarely posted in cfc, and has no intention to post anything in Wenxuecheng. I am actually relieved that not many cfcers have shown interests. Best wishes.
     
  6. GlobeCitizen

    GlobeCitizen 新手上路 ID:110879

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    Basically the company is developing two classes of DC based therapeutic cancer vaccines called DCVax-L and DCVax-D with the former intended for all types of operable solid cancers and the later for all types of inoperable solid cancers. DCVax-L is used in a pivotal P3 trial for newly diagnosed brain cancer. It has been partially halted for additional patient enrollment since last summer for reason the company has elected not to reveal. Instead, it hinted it was nothing untoward while criticized certain bloggers who have turned a good news into a bad one. According to https://clinicaltrials.gov/ct2/results?term=dcvax&Search=Search and company's sec filing, etc., the DCVax-L P3 trial could reach its primary event number of 248 PFS any day now, meaning there may be a binary event coming soon. If that is true, there will be significant price movement in either way.

    In addition, the company has recently released some news regarding its DCVax-D program. Below I attached an email received from Les Goldman, senior VP of the company a couple of days ago:

    Enjoy.

    "
    September 29, 2016
    NASDAQ:NWBO

    Dear XX,

    Attached please find a copy of this morning’s release describing a poster presentation by our CTO, Dr. Marnix Bosch, with further information about our DCVax®-Direct Phase I Trial, at the Second Annual CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference in New York.

    Of particular interest is the description of an approach comparing estimated individual-patient life expectancies with the actual survival results to date in those patients in the DCVax-Direct Trial.

    Following Dr. Bosch’s presentation of part of this information at a cancer vaccine conference last week, certain commentators incorrectly claimed that individual DCVax-Direct patients were being compared with general information on types of cancers or medians of groups of patients. That was not the case.

    We believe the approach of looking at estimated expected survival vs. actual survival on an individual patient basis is particularly useful in exploratory trials, such as our DCVax-Direct Trial, which cover a wide range of patients and disease situations. We invite you to take a look and judge for yourself.

    We believe the individual patient survival results to date are quite encouraging across a broad range of cancers, especially in the top 20% of patients and the top 30% of patients in our DCVax-Direct Trial. We look forward to putting this information to good use in our Phase II trials of DCVax-Direct.

    Thank you for your ongoing interest and support.

    All the best,

    [​IMG][​IMG]
    [​IMG] [​IMG]
    Leslie J. Goldman
    Senior Vice President for Business Development
    [​IMG]
    [​IMG]



    For immediate release

    NW Bio Presents Further DCVax®-Direct Phase I Trial Information

    On Individual Patient Survival At NY Cancer Immunotherapy Conference

    ETHESDA, MD, September 29, 2016 – Northwest Biotherapeutics (NASDAQ: NWBO) (“NW Bio”), a U.S. biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, announced that Dr. Marnix Bosch, Chief Technical Officer of NW Bio, presented additional information relating to the DCVax®-Direct Phase I Trial in a poster presentation at the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival, being held from September 25th through September 28th in New York City.
    Dr. Bosch’s New York presentation, as well as his presentation at a cancer vaccines conference in London last week, included information about estimated life expectancies for individual patients (not for types of cancers or medians of groups of patients) based on a system developed and published by Dr. Jennifer Wheler at MD Anderson Cancer Center. The Wheler system was based upon clinical experience with 1,181 patients with diverse cancers at the MD Anderson Phase I Cancer Clinic (where most of the DCVax-Direct Trial was conducted). Wheler validated and enhanced (with additional risk factors) a system for prediction of individual-patient life expectancies previously developed by the Royal Marsden Hospital in the UK and well established in the field.

    A fundamental purpose of early stage exploratory trials, such as the DCVax-Direct Phase I trial, is to evaluate both product characteristics and patient characteristics – and especially to identify which patients show the best responses to the experimental product. Such evaluations enable later stage trials to be designed with more precision, to focus on the patients who are the best fit for the experimental product and to potentially best demonstrate the performance of the experimental product.

    Exploratory trials typically involve diverse patient populations, as did the DCVax-Direct Phase I Trial. In evaluating the results of such trials, it is especially helpful to be able to identify life expectancies for individual patients, and compare those expectations to the actual results obtained in those individual patients. Patient-specific assessments are still estimates, but are more precise than general assessments relating to types of cancer or medians of groups of patients. Patient-specific assessments also can be more relevant, taking account of diversity among the patients.

    The DCVax-Direct Phase I Trial included more than a dozen different types of cancers, as well as sub-types (e.g., several different types of sarcoma), patients with varying numbers of inoperable and locally advanced or metastatic tumors, and varying numbers and types of prior treatment regimens that had all failed. This diversity enabled demonstration, in a wide range of settings, of the safety and feasibility of DCVax-Direct (including feasibility of the novel intra-tumoral injections) as well as an initial signal or indication of potential results.

    As explained in Dr. Bosch’s poster presentation, under the Wheler methodology individual life expectancy is determined through measurements of 5 key risk factors: serum albumin, serum LDH, number of metastases, GI tumor, and ECOG (Eastern Cooperative Oncology Group) performance status. The expected survival is 24.0, 15.2, 8.4, 6.2 or 4.1 months for patients with 0, 1, 2, 3 or 4-5 of the above risk factors, respectively.

    Dr. Bosch’s New York and London presentations applied the Wheler system to determine estimated individual-patient life expectancies, and compare those to the actual clinical results in each patient in the top 30% of patients in the DCVax-Direct Phase I Trial. Dr. Bosch’s poster will be available on the Company’s website starting today.

    The top 20% of the patients in the DCVax-Direct Phase I Trial have each exceeded 2 years of survival so far, and are still alive. The longest survivor to date has reached nearly 3 years.

    The top 30% of the patients in the DCVax-Direct Phase I Trial (including pancreatic, melanoma, lung, ovarian, sarcoma and other cancers) have average actual individual survival to date of 26.7 months, compared with average expected individual survival of 12.3 months.

    The Wheler system for assessing individual patient life expectancies can be found at Wheler, et al.; Survival of 1,181 Patients in a Phase I Clinic: The MD Anderson Clinical Center for Targeted Therapy Experience. Clin. Cancer Res. 2012 May 15; 18(10): 2922–2929.

    Dr. Bosch’s presentation also included assessments of dendritic cell quality and their relationship with patient outcomes, such as stabilization of disease and overall survival. The encouraging survival results correlate with underlying mechanisms of action and cellular and immune profiles, including phenotype analyses, and relative production of a wide range of cytokines by the dendritic cells. Additional positive observations include T-cell infiltration, and PD-L1 expression, with 64% of the patients evaluable for PD-L1 checkpoint expression (14 of 22) showing either de novo or significantly increased expression of PD-L1 following DCVax-Direct treatment, indicating potential for combination of DCVax-Direct and checkpoint inhibitors. Such information will also be helpful in shaping later stage trials.

    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 the United States and Europe. The Company has a broad platform technology for DCVax dendritic cell-based vaccines. The Company’s lead program is a 348-patient Phase III trial in newly diagnosed Glioblastoma multiforme (GBM), which is on a partial clinical hold in regard to new screening of patients. GBM is the most aggressive and lethal form of brain cancer, and is an “orphan disease.” The Company is under way with a 60-patient Phase I/II trial with DCVax-Direct for all types of inoperable solid tumors cancers. It has completed enrollment in the Phase I portion of the trial. The Company previously conducted a Phase I/II trial with DCVax-L for metastatic ovarian cancer together with the University of Pennsylvania. The Company previously received clearance from the FDA for a 612-patient Phase III trial in prostate cancer. In Germany, the Company has received approval of a 5-year Hospital Exemption for the treatment of all gliomas (primary brain cancers) outside the clinical trial.

    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. Actual results may differ materially from those projected in any forward-looking statement. Specifically, there are a number of important factors that could cause actual results to differ materially from those anticipated, such as risks and uncertainties related to the actions and decisions of Nasdaq, the Company’s ongoing ability to raise additional capital, risks related to the Company’s ability to enroll patients in its clinical trials and complete the trials on a timely basis, uncertainties about the clinical trials process including the actions and decisions of the FDA and other regulators, 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 and Cognate’s abilities to carry out the intended manufacturing and expansions contemplated in the Cognate Agreements, risks related to the Company’s ability to carry out the Hospital Exemption program and risks related to possible reimbursement and pricing. Additional information on these and other factors, including Risk Factors, which could affect the Company’s results, is included in its Securities and Exchange Commission (“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. You should not place undue reliance on any forward-looking statements. 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
    202-841-7909
    lgoldman@nwbio.com

    "
     
  7. GlobeCitizen

    GlobeCitizen 新手上路 ID:110879

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    A video of Dr. Linda Liau's lecture uploaded in Feb 2016 is provided below. She is a Chinese American, a top 1% neurosurgeon in the US and the world. She is the principal investigator for DCVax-L trial, and has been a neurosurgeon with UCLA for a long time.



    Enjoy and GL!
     
  8. GlobeCitizen

    GlobeCitizen 新手上路 ID:110879

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    Neil Woodford filed an empty Form 4 yesterday after market: http://secfilings.nasdaq.com/filingFrameset.asp?FilingID=11622205&RcvdDate=10/4/2016&CoName=NORTHWEST BIOTHERAPEUTICS INC&FormType=4&View=html

    He is known as England's Warren Buffet, but he is much younger and energetic. Recently he has showed his willingness for risk taking. It is believed that he has single handedly made the stock price appreciated from around $3 to around $12 in a few months last year by throwghing his financial back, and has then also almost single handedly destroyed the share price down to today's $0.5 by playing into the hand of the short wolfpack through asking an investigation into various anonymous accusations against the company by the short wolfpack.

    Since then, his huge holding, at a time accounted for about 30% of the company's shares has fallen a whopping 95% in value. He has said as recently as last week, he has not bought or sold any of his shares of the company.

    成也萧何,败也萧何!

    Now with the filing mentioned above, it suggests he is no longer an "active" insider and has been exempted from anything subjected to Section 16 in the security act.

    It further suggests he may have prepared for taking further actions as the L trial is near completion for the first time since he played into the hand of wolfpack.

    Or it is just a formality filing in case he misses anything in his annual Form 5.

    Best wishes!


     
  9. Doubleedgesoft

    Doubleedgesoft 新手上路 ID:163649

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    渥村的股友根本看不懂生化股,抄什么呀?
     
  10. GlobeCitizen

    GlobeCitizen 新手上路 ID:110879

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    Larry Smith, a known biotech analyst has an interesting analyst report on the recently released DCVax-D data and also touched about the reason why the share price has been so low, etc. Enjoy reading below (btw, he is the guy who coins the term wolfpack for the first time in regards to the concerted short attack on nwbo):

    https://smithonstocks.com/northwest...ect-is-encouraging-nwbo-speculative-buy-0-43/
    "
    Expert Financial Analysis and Reporting
    Northwest Biotherapeutics: Recent Data Update on Phase 1/2 Trial of DCVax Direct is Encouraging (NWBO, Speculative Buy, $0.43)
    Posted by Larry Smith on Oct 9, 2016 • (0)

    Key Points:

    • Data for DCVax Direct recently was updated for its phase 1/2 trial in 40 patients having 13 different types of inoperable solid tumors. A scientific paper showed that the top 12 patients (30%) experienced overall survival of 22 months or longer.
    • This was an open label trial without a control group as is the case in almost all phase 1/2 trials. Results were compared to an algorithm (the Wheler system) developed by M.D. Anderson in 2012 that uses risk factors to predict survival of any individual patient based on certain risk factors. These can then be used to compare predicted life expectancy for each patient against the actual survival time. The average survival time predicted by Wheler for the top 12 patients is 12.3 months. With DCVax Direct treatment, they survived an average of 26.7 months and 8 are still alive. This suggest a remarkable doubling in average life expectancy by 14.4 months.
    • This very long duration of response in about 30% of patients is impressive and compares very well with results that have been seen in trials of other immune therapies. For example, the hugely successful checkpoint modulators, Opdivo and Keytruda, as monotherapy have been shown to produce such long durations of response in about 15% to 20% of late stage non-small cell lung cancer patients and 25% to 30% of late stage melanoma patients,. These patients were generally earlier stage than those treated with DCVax Direct. This has electrified the cancer treating community.
    • Another example is Kite’s highly touted CAR-T therapy (KTE-C19) which just reported interim phase 2 results in 51 r/r DLBCL patients. In those patients, 33% remained in complete response (CR) at three months. There can be no determination at this early date as to how these CRs may translate into length of survival. However, it is highly unlikely that all of the patients (33% of those treated) who achieved a complete response will survive two years. Kite is hailing these results as a medical breakthrough and states that they will support filing a BLA by year-end 2016.
    • The Kite data and Northwest data deal with very different drugs in very different cancers; both use open label designs (no control group). I fully recognize the huge disparities in types of cancer patients treated, but the results have some similarity in that they treat very advanced cancer patients for whom there are no effective, remaining treatment options. To me at this point in time, results seem more promising for DCVax Direct or at the worst as promising and yet Kite has a $3 billion market capitalization and Northwest has $59 million. Go figure.
    • This phase 1/2 data fully supports advancing DCVax-Direct into phase 2 trials. I had been expecting phase 2 trials with DCVax-Direct in two or three different inoperable solid tumors to begin in in early 2016. I discuss the reasons for the delay in this report.
    • I note that Opdivo and Keytruda have been approved based on phase 2 data from open label trials in certain aggressive cancers that had no effective treatment options. Also, Kite is planning to file a BLA on interim phase 2 data. If NWBO achieves outcomes that suggest durable cancer responses in perhaps 15% to 20% of patients in one or more of its trials, DCVax Direct might also be approved based on phase 2 data.
    • DCVax Direct has one major advantage over Opdivo, Keytruda and KTE-C19. It has a very mild side effect profile while those three drugs have serious grade 3 and 4 toxicities and KTE-C19 has been linked to deaths in the ZUMA-1 trial. The principal side effects of DCVax Direct are injection site reaction and grade and 1 and 2 fevers that can be treated with Tylenol. Remember that FDA decisions weigh risk to the patient as heavily as benefit in their regulatory decisions.
    • I am by no means claiming that this data establishes that DCVax Direct is effective and will gain approval. However, I think that any objective observer would find the data encouraging and intriguing, especially when analyzed against the Wheler algorithm. It certainly warrants further investigation in phase 2 trials.
    Other Investment Issues

    The primary purpose of this report is to analyze the clinical trial data for DCVax Direct. However, I will first touch briefly on other key investment issues of the Company.

    The initial announcement of the screening halt in the DCVax-L trial in August 2015 marked the beginning of a sharp fall in the stock. Initially it had only minimal impact, but a series of other events, most of which (in my mind) were wolfpack orchestrated led to a steady, rapid and disastrous decline in the stock.

    Investors had initially expected a quick resolution to the screening halt, but disappointingly the Company has not yet offered an explanation for the screening halt nor has it provided any important updates on the trial other than several encouraging updates on the information arm relating to rapid progressors who were too sick to enroll in the trial, but received the exact same treatment as those in the trial. Based on company statements, I think that at least 300 (and possibly more) patients have been enrolled out of a planned 348. I think that results from this trial could be reported out by year end. See my report “My Hypothesis as to Why the Company Has Been Silent on Its Clinical Trial Programs and Why DCVax-L Might Succeed in its Phase 3 Trial” for a more detailed analysis. This report also includes a more detailed discussion relating to my speculative buy rating on the stock.

    Investors who have followed Northwest have watched an egregious short selling attack on the Company. I believe that the wolfpack (a group of hedge funds who work in coordination) have conspired to drive the stock price down. They have combined naked short selling with a propaganda campaign of immense breadth and sophistication, and have been successful in destroying the stock price. I won’t go through all of the large number of wolfpack tactics they have used but one that stands out was a report authored by anonymous hedge fund analysts who called themselves Phase V Research that was published on Seeking Alpha on October 29, 2015.

    Numerous allegations were raised in the Phase V report, one of the more important of which was self-dealing involving Northwest, its management and its contract manufacturer Cognate. The Company’s primary outside stockholder Neil Woodford drew attention to the Phase Five report and called for an investigation of the Company thereby delivering an accurate shot to his foot. His action was a major factor in the stock price decline. We are awaiting the release of an independent committee which was formed in January 2016 to examine in part a long list of charges made by Phase V as well as a number of other blogs attacking the Company. The wolfpack appears also to have worked closely with law firms who launched lawsuits that coordinated with the Phase V report and other negative blogs by other authors sympathetic with the wolfpack.

    Unrelated to the Phase V allegations, in April, 2016 NASDAQ cited NWBO for certain potential violations of stock issuance rules unique to NASDAQ. After ongoing discussions, in September, 2016 NWBO entered into a settlement agreement with Nasdaq that resulted in a change in status favorable to Northwest and its shareholders in regard to certain stock grants to Cognate, the Company’s contract manufacturer and affiliate.

    One of the positive repercussions of this settlement is that it would appear to an outside observer that in the process of reaching this settlement, NASDAQ examined much of the same information about the NWBO/Cognate relationship as was covered in the Phase V report, and disagreed with Phase V conclusions. The NASDAQ settlement also eliminated some of the key factors upon which the original Phase V questionable claims were based, in turn potentially gutting the various wolfpack sponsored lawsuits based on the Phase V allegations. While it is not possible for an outsider to know what the independent committee (which still has not reported) is considering, it seems reasonable that they would take time to assess the impact of any NASDAQ resolution on both the pending lawsuits and the Phase V Report before acting and this may be the reason for the long delay in publishing its report.

    I was expecting perhaps two or three phase 2 trials of DCVax Direct in two or three (inoperable) solid tumor types to begin in early 2016. As explained in this report, with favorable results these could be the basis for regulatory approval. I was also expecting a phase 2 trial of DCVax-L in combination with a checkpoint modulator (probably Opdivo) in recurrent glioblastoma to begin in the same time frame. Again success in the trial could be the basis for regulatory approval. Northwest has given no guidance on plans for these trials. The delays are almost certainly linked to the small management team of this small company nearly being overwhelmed in formulating responses to NASDAQ, the independent committee, the wolfpack lawsuits and the endless orchestrated articles and rumors.

    Northwest is also in a financially stressed condition and this may have played some role in the delay in starting the phase 2 trials. Northwest has now fought through and answered many of the issues raised by the wolfpack. I think that from a logistical standpoint, these phase 2 trials could start at any time, but there remains uncertainty as to how much funding will be needed, when it will be raised and how much dilution this may cause to current NWBO shareholders.

    Objectives of Phase 1/2 Trials; Putting the Results of the DCVax Direct Trial in Perspective?

    The primary objectives of a phase 1 trial for a cancer drug are to: (1) evaluate the safety of the drug (or drug combination), (2) determine an optimal dose or dose range to produce a therapeutic effect, and (3) identify side effects at that dose range. Phase 1 trials typically enroll small numbers of patients with advanced cancer for which there are no effective treatments and in whom the disease is progressing (rapidly). Because of this, it is often difficult to gauge efficacy; also the mechanism of action of the drug may not directly address the cause of the cancer. Innumerable mutations occur in tumors so that effective treatment of one solid tumor might be totally ineffective in another. Even within a tumor type the mutations can be very different and respond differently or not at all to a drug.

    Investigators look for signals of efficacy in phase 1 trials, but because of the reasons just cited, there may be no clear sign of activity even for a drug that goes on to phase 2 and 3 trials and is ultimately shown to be effective. The hope is that lessons learned in phase 1 can provide the information to identify patients most likely to benefit and the therapeutic dose or dose range. The phase 1/2 trial of DCVax Direct combines objectives for phase 1 and 2 in one trial. I think that this provided a clear path forward to designing phase 2 trials

    Results from phase 2 trials in some cases are adequate to seek regulatory approval as we have seen in the case of the checkpoint modulators-Bristol-Myers Squibb’s Opdivo and Merck’s Keytruda. It is extremely interesting that Kite is guiding investors to expect approval of its CAR-T drug KTE-C19 on the basis of an interim look in a phase 2 trial, which is based on only 51 patients with r/r DLBCL. However, it is more often the case that the phase 2 trial is intended to further refine patient selection and dosage to design a phase 3 trial for regulatory approval.

    I think it is possible that relatively small phase 2 trials of DCVax Direct in inoperable solid tumors, if successful, might be the basis for regulatory approval. As I will discuss in this note, we have seen very promising signals of activity and remarkable safety. I had thought that phase 2 trials in two or three different types of solid tumors could have been started in late 2015 or 2016. The short selling attack and resultant financial distress have delayed the start of these phase 2 trials.

    Perspective on the Phase 1/2 Trial of DCVax Direct

    The 40 patients enrolled in this trial were suffering from 13 different types of inoperable solid tumors. Let me explain why these are the sickest of the sick cancer patients. If possible, in treating any type of cancer the desired first step is to surgically remove (resect) as much of the tumor as feasible to rid the body of as many cancer cells as possible. In many, many cases the complete removal of the cancer is not possible due to its location or because it may have metastasized from the primary site to organs throughout the body. Let me give you the example of pancreatic cancer which is widely recognized as being among the most deadly of cancers.

    The problem with pancreatic cancer is the inability to detect it at an early stage. The pancreas is deep within the abdominal cavity and unlike cancers such as breast, prostate or colon, there is no way to periodically check and to detect the cancer at an early stage and operate. By the time the cancer produces symptoms that lead to a diagnosis, it has often advanced to the stage 4 or the final metastatic stage and is inoperable. Also the anatomical position of the pancreas makes it difficult to operate without damaging surrounding vital organs.

    The DCVax Direct trial was meaningfully different in that 40 patients with 13 different solid tumor types were treated. Generally, phase 2 trials focus on patients with a particular type of tumor or even a particular mutation of that tumor type. The heterogeneity was highly unusual in a trial of this size (40 patients). An intriguing aspect of DCVax-Direct is that its mechanism of action makes it potentially effective against all solid tumors and their mutated sub-types; this is a huge addressable market. DCVax-Direct is also unique in that it has a relatively benign side effect profile which is virtually unprecedented for a cancer drug. The principal side effects are injection site reaction and grade and 1 and 2 fevers that can be treated with Tylenol.

    Interpreting Data from the Trial

    The heterogeneity of the cancers treated makes it difficult to evaluate the results. Subjects had a median of 3 tumor sites within a range of 1 to 5 and had received an average of 3.1 prior treatment regimens. There was no control group and with so few patients per tumor type, how can investors judge if results are promising? The first time I looked at the results, my impression was they appeared impressive as most key opinion leaders feel that in inoperative solid tumors, most patients die within six months to a year. However, without a control group this is speculative.

    Again let me turn to inoperable late stage pancreatic cancer to illustrate issues of patients treated in the trial. Stage 4 inoperable pancreatic cancer is treated with chemotherapy or perhaps just palliative care which involves pain relief and supportive nursing. The primary and most widely used chemotherapy agents are gemcitabine (Gemzar) and erlotinib (Erbitux). Other drugs like oxaliplatin, irinotecan, leucovorin, and fluorouracil (5-FU) are sometimes used. These chemotherapy regimens have low objective response rates and produce little increase in median overall survival.

    The pivotal trial of gemcitabine that led to its approval compared gemcitabine to 5-FU (essentially a palliative treatment) in stage 4 pancreatic cancer. The one year survival rate for gemcitabine was 18% versus 2% for 5-FU. A subsequent trial compared gemcitabine alone versus gemcitabine and erlotinib. The median overall survival for gemcitabine plus erlotinib was 6.2 months versus 6.9 months for gemcitabine alone. The one year survival rate for gemcitabine was 17% (in line with the earlier study) and was 23% for patients receiving erlotinib combined with gemcitabine. There have been numerous other combination regimens that have been tried but none have produced meaningful increases in median overall survival with acceptable side effects. I think that we can generally conclude that median overall survival is six months and about 20% of patients live for one year for this cancer type.

    There are other aspects beside the heterogeneity of patient selection that make the results of this trial difficult to interpret. Some are listed below:

    • Patients were scheduled to receive six injections over 32 weeks, but most patients actually received only 3 injections over 2 weeks, with some receiving a 4th injection at 8 weeks.
    • There was no retreatment.
    • Patients were only injected at one tumor site. It seems to me that injecting at multiple tumor sites, as is planned for phase 2, would result in a better effect.
    • Three different cell dose levels were studied so that the number of cells injected might have been sub-optimal in some patients.
    • Patients had varying risk factors such as performance status, and had undergone (and failed) varying prior treatment regimens with some patients having failed as many as 5 or 6 prior regimens.
    • All patients were late stage 3 or 4 status patients. Results in earlier stage cancers might have produced better outcomes.
    The following waterfall plot shows the outcomes in the 40 patients. Remember that in inoperable pancreatic that six months median overall survival is probably a reasonable expectation and that perhaps 20% of patients will be alive after one year. The best result in the trial was a pancreatic cancer patient who has survived 33 months. You can read about that patient in my report National Geographic Special Features DCVax Direct Treatment of Stage 4 Pancreatic Cancer Patient.



    [​IMG]



    From the above table it appears that 12 out of 40 patients (30%) had a dramatic result (and without retreatment). We have seen this type and level of response in other immune therapies like the checkpoint modulators Opdivo and Keytruda. As monotherapies, about 15% to 20% of non-small cell lung cancer and 25% to 30% of melanoma patients achieve long durations of response (long survival tails). The response increases with combinations, but toxicity does also.

    More recently the highly touted CAR-T therapy from Kite (KTE-C19) reported that in 51 r/r DLBCL patients treated that 33% remained in response at three months meaning that 67% had progressed. It is likely that the 33% result will drop over time (perhaps significantly). Kite is hailing these results as a medical breakthrough and promising that they will file a BLA based on these results. Investors seem to have bought in on this as reflected in its $3 billion market capitalization.

    Viewed against this backdrop, does the 30% of DCVax Direct patients remaining alive at about two years mean anything? I think so, but the hedge funds who are heavily short the stock put a negative spin on these results. They stress that there is no control data to compare against (which is almost always the case in phase 1 trials), and point out the small number of patients treated. They maintain that the long term survival just reflects outliers who are expected in any trial. While they are obviously putting the most negative spin possible on the results, an objective observer cannot categorically conclude or demonstrate that they are wrong.

    An Interesting Way of Comparing Reported to Expected Results

    In the latest paper on DCVax-Direct, a very interesting and more revealing way of interpreting the data was used. This was based on research done at the prestigious cancer center M.D, Anderson (who incidentally performed the DCVax-Direct phase 1/2 trial). In 2012, Wheler et al. provided a basis for determining life expectancies for an individual cancer patient. The Wheler system was based on examining a database of 1,181 patients who were treated at M.D. Anderson. NWBO applied the already established Wheler system to determine individual life expectancies for individual DCVax-Direct patients.

    Most clinical trials compare aggregated or median results in a group of treated patients versus a control group. This is difficult or not feasible in small trials. Hence, it can be argued that individual patient assessments with the Wheler method provide more specific information than median survival measures. This methodology can be especially useful in exploratory early stage trials such as the DCVax Direct trial. Using the Wheler method, individual life expectancies were determined for the top 30% of the patients in the DCVax-Direct phase 1 trial, who have lived ≥22 months to date.

    Here is how the Wheler system works. It assesses five risk factors for each patient: (1) serum albumin, (2) serum LDH, (3) number of metastases, (4) GI tumor, and (5) ECOG performance status. Scores for a particular DCVax Direct patient were determined using the Wheler system, and an individual life expectancy for that patient was determined. The Wheler system was based on scores in a data base of 1,181 diverse patients. Under the Wheler system, the expected median survival is 24.0, 15.2, 8.4, 6.2, and 4.1 months for patients with 1, 2, 3, 4 or 5 of the above risk factors, respectively. For example, a patient with five risk factors would be predicted to live 4.1 months.

    Using the Wheler algorithm as a gauge, these risk factors were assessed and reported on for the 12 patients achieving the best response in the DCVax Direct trial. The individual life expectancies predicted for these DCVax-Direct patients are plotted in the following waterfall plot as the shaded horizontal bars, while the actual survival is plotted as solid horizontal bars. The average expected survival for these 12 patients based on the Wheler algorithm was 12.3 months and the average actual survival time was 26.7 months, for a highly impressive difference of 14.4 months.



    [​IMG]



    F-Stein Weighs In on the Trial

    In his latest of what is now 30 negative blogs on Northwest, Adam F-stein decided to give all of us a lesson in interpreting clinical trial data in a blog called “Biotech School: How to Spot Hidden Danger Signs in Clinical Trial Data.” He modestly informs us that “Using Northwest Bio as an example, I'm going to teach you how to read clinical trial data to find red flags and bad stuff biotechs don't want you to know. These "results" -- I struggle to even call them that -- amount to meaningless hand-waving.”

    It is striking how venomous F-stein is in his attacks on the Company without even a faint attempt at objectivity. In this article he takes his usual tack of creating a strawman argument and then destroying it. He claims that the NWBO presentation compared an individual patient’s survival with the median survival for a whole group of patients or a whole category of cancer, and that is like comparing apples and oranges. In fact, NWBO compared individual patient life expectancies based on the Wheler system with individual patient actual survival to date – i.e., apples to apples. It was F-stein who tried to compare individual DCVax Direct patient survival times to median survival times for patients with diverse types of cancer, in his effort to discredit the data. In actual fact, the only one comparing apples to oranges was F-Stein.

    It is a waste of time refuting what is clearly another biased F-stein article with limited (if any) meaningful insights. However, I would point out that F-Stein seems to have not understood or given no credence (probably both) to the Wheler algorithm which is so useful in putting the DCVax-Direct results in perspective. Or perhaps, he holds M.D. Anderson research in contempt as he does me and anyone who thinks that the DCVax vaccines are something more than grapefruit juice. Because his article mirrors the negative spin of the shorts, it may be of interest to compare his article to mine.

    I am by no means claiming that this data establishes that DCVax Direct is effective and will gain approval. However, I think that any objective observer would find the data encouraging and intriguing, especially when analyzed against the Wheler algorithm. I am certain that if F-stein reads my article that he will respond with a personal attack against me that Clinton or Trump could not aspire to. I have become inured to his personal attacks."
     
  11. Doubleedgesoft

    Doubleedgesoft 新手上路 ID:163649

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    英语Perspective一词就是专属忽悠类,股价太低几乎等同太差,写再多文章吹嘘也没用!
     
  12. GlobeCitizen

    GlobeCitizen 新手上路 ID:110879

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    You may be right in that that most people would not buy a penny stock. Nonetheless, when the price is over $1, some people would be buying; when the price is over $5, institutions and ETFs would be buying or coming back (buying again). Then, it will be followed by a large number of sheep, the so-called the effect of herd mentality. This is true for both normal stocks and biotech stocks, but for some biotech stocks, particularly those which are in the development stages with blockbuster market potentials, they have their uniquenesses.

    For instance, it is often you would come across terms such as manipulation, FUD, naked shorting scheme, etc. associated with a biotech stock.

    By all means, a small biotech stock is not for the faint of heart!

    Best wishes!
     
  13. Doubleedgesoft

    Doubleedgesoft 新手上路 ID:163649

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    所有生化股我都研究过,其制药方向,進程,股价及持股等。如果纯粹从技术分析来说,价低几乎等同太差,抄股实质是风险控制,算法千变万化,但不离其宗。
     
  14. GlobeCitizen

    GlobeCitizen 新手上路 ID:110879

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    You are going circle. I think I have commented on your previous post which stated almost the same thing as the one you just posted.

    On the other hand, you may realize nobody has the time and capacity to have done DD on all biotech stocks (所有生化股). Northwest Biotherapeutics (NWBO) is not a drug development company. It is a therapeutic cancer vaccine developer on the cusp of a major shift towards approvals and full commercialization. As a matter of fact, the German regulatory authority has granted the company with a 5-year approval of DCVax-L to treat all kinds of brain cancers commercially under its Hospital Exemption Program. The initial 5-year term can be renewed after expiration.

    TA (技术分析) in most cases is not appropriate for a small biotech stock!

    From your statements, it seems you don't have a basic grasp on the biotech company specifically, and the biotech companies in general. I will excuse myself from replying to any such a post unless it is genuine in nature and fact-based.

    Time is invaluable and best wishes!
     
  15. Doubleedgesoft

    Doubleedgesoft 新手上路 ID:163649

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    誰关心德国?只有美国FDA 是关键。大大小小的生化公司就几百家,一天研究一家,二年也弄完了。TA 绝对有用,需要很好的数学和编程能力,再加上网络与实时糸统,太多的技术。本意是支持你一下,你误会了。
     
  16. GlobeCitizen

    GlobeCitizen 新手上路 ID:110879

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    [Added after initial post] My following comments are solely based on your initial comment which stated "誰关心德国?只有美国FDA 是关键 [end of post]." Since then you have added information which is full of fault and you once again headed back to a circle. For instance, there are roughly 3,000 biotech companies in US in 2016, not a few hundreds. No investors (even professional analysts) can follow hundreds of companies. A genius may have the capacity to follow several dozens of companies. That's it.

    I am not a salesman, and I don't care what readers think about my posts for which I just put out as information for those who may be interested. That's all.

    But, thank you for your support!

    [The initial post is below:]

    Exactly, see my subject line: "Stock of Interest (NWBO): Potentially Lose $0.5 or Gain $30 or More in Near Future"

    If FDA approves it, the share price would be skyrocketed. Now the one million dollar question is what the chance of that will be for DCVax-L of which the decision is approaching, and what the chance of further future approvals of DCVax-D by FDA will be?

    BTW, the German approval is a milestone and it should have mattered a lot to the company, but the reality is that approval has not yet been materialized commercially due to complexities in negotiating prices with more than several dozens of German insurance companies and hospitals individually.

    Best wishes!
     

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