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

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  • A fellow investor and poster named Sentiment_Stocks in IHUB summed it up relatively good in her reply to Hungary hippo's question, "there seems to be excitement on this board..is there an approval coming or aticipated for a drug?..please help out a interested investor and what is the expected share price predictions if company is successful?

    Below is Sentiment_Stocks' reply [not the fact yet but pretty much mostly have speculated]:

    "Hungary hippo... the treatment involved with NWBO is a dendritic cell vaccine to treat all solid tumor cancers. They have been in a P3 trial (that evolved from a P2) trial for many, many years. The trial was due to end in 2014, but they instead expanded it. Then it was due to end in 2015, and instead, a screening halt was applied to it. The reason for the screening halt (which was lifted in Feb 2017) was never given but most think it was due, initially, to what appeared to be too many treatment patients eventing earlier than the the control arm patients. The ones that could see that would be the data monitoring committee (DMC) who could view the trial unblinded. Some think the DMC tried to halt the entire trial, but the company persevered claiming that all the patients were living longer, despite the early progression. One should note that the head of the DMC was also working on the scientific advisory board (SAB) of a competing dendritic cell company, and his brother was on the board of directors and SAB of the same company during the entire time, unbeknownst to anyone including NWBO. You can make of that what you will.

    Meantime, examining what would ultimately turn out to be pseudo progression (we think), and proving it, appears to have taken about two years, which was when the screening halt was lifted.

    Initially it was intended that the randomized trial would end with the primary end point, progression free survival (PFS), and that the company would ask for accelerated approval (AA) based on amazing results. Unfortunately, when one finds pseudo progression has "wreaked havoc" with your PFS results, that makes such an undertaking, well, next to impossible. So... the company opted to wait longer and let the overall all survival (OS) endpoint play out, since everyone was living longer than what is normally seen with GBM. There is also a cross over in this trial whereby when the control patient events, they can cross over to treatment. As a result, about 90% of the patients ended up on treatment.

    So... to your question, what is going on here? The trial is finally ended, all the patients have received all their treatments, there was a soft data lock done sometime in the Fall of 2018. Since then, the company has been assembling all the data with the intent to submit for a biologics license approval (BLA) for the treatment. First, though, and while they have been gathering and scrubbing the data (which is what you do in order to submit for a BLA and before you unblind a trial), they have also been finalizing their statistical analysis plan (SAP). Because they have never unblinded the data - remember only the DMC could do that - they can revise the trial as they progress as they are doing so based on a blinded viewpoint. So... when this SAP is completed, they will submit it to the FDA and 3 other regulatory agencies (UK, EU, Canada) for review and approval, or whatever it is that these regulatory agencies (RAs) do with the SAPs. Once the company has that approval or indication that the RAs are okay with the SAP in hand, and once all the data is scrubbed, the data is hard locked and the trial is unblinded.

    So... that time is what longs and bears are anticipating. We think the SAP has been, or is about to be submitted to the RAs. How long they will take is anyone's guess. Could they be anticipating this SAP because they've been working closely with the company as this immunotherapy trial in GBM (a disease for which there has been little if any progress in treatment for, like, ever?) draws to a close, and so an approval is as easy as 1, 2, 3, and it's done in a matter of days or weeks? Or could this be drawn out into a few months? Whatever the case, we know that the company has indicated that it is "pedal to the metal" time to get this to a hard data lock. We also know that the CEO, Linda Powers (LP) thinks ASCO in June is the best place in the world to announce anything, followed by SNO and AACR. So... my guess is they are trying to get everything done in time for ASCO, but they are at the mercy of Murphy's Law and life, so we as longs (and probably the company) don't know if the unblind will occur in time or not. Regardless, an unblind draws nigh, exactly when, no one knows.

    With an unblind, we can see first, how the treatment arm compared to the control arm, despite the fact that both groups were, for the most part, on treatment. But one must bear in mind that the control arm did not cross over until after they'd progressed, so they will be at a disadvantage, unless you listen to the bears who likely think otherwise. Especially ex, who thinks the control patients are doing great (lol). There needs to be a separation between the two arms as that is what will determine whether the trial's statistical significance can be determined. The SAP should also delineate what the various pathways forward "anticipating" (not knowing) what is ultimately found when the data is unblinded. Different RAs may be more amenable to certain pathways versus other RAs.

    Finally, Novocure, with its FDA approved Optune helmet to treat GBM by wearing the device 22 hours a day (also a competitor), and with questionable results that DCVax-L with it's blinded data (combination of treatment and control) is already on par with, currently has a market cap of 4.23 billion. Of course, with a DCVax-L approval, Optune will not have that type of market cap, but analysts at most funds will quickly figure out that NWBO should have a market cap of at least that. And with every possible NWBO warrant on the books exercised, that would result in a share price of over $4.00."
     

    GlobeCitizen

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    courtesy of muro1 in IHUB:
    "
    Interesting $9B amount in Linda Liau MD, PhD, MBA's presentation title @ the Sway Minds Technology Summit: Great Ideas have the Power to Sway Minds May 9, 2019 | San Francisco, CA | 08:00am - 4:30pm May 9, 2019:

    15:30

    The $9B Question: Is the Cost of Drug Development Killing Us? Can Digital Health Save Us?"

    Linda M. Liau, MD, PhD, MBA Neurosurgeon and Professor of Neurosurgery at the David Geffen School of Medicine at UCLA

    Samuel R. Browd, MD, PhD Professor of Neurological Surgery

    John Norris, JD, MBA Former Principal Deputy Commissioner (COO) at the FDA

    Daniel Haders II, PhD Operating Partner at Sway Ventures

    Moderated by Bill Malloy Founding General Partner at Sway Ventures

    https://swayvc.com/sway-minds
    "
     

    GlobeCitizen

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    Immunotherapy and Clinical Trials for Brain Tumors | UCLA Neurosurgery
    At Min. 10:56, Dr. Linda Liau states, "But it's interesting. It's not just 3 year survival, it's 3 year... the majority of these people (3 year survivors - almost 30%) actually have PROGRESSION FREE SURVIVAL."
     

    GlobeCitizen

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    NW Bio Announces Settlement with Cognate BioServices Resolving Past Matters and Providing for Restart of DCVax®-Direct Production

    PR Newswire
    May 28, 2019

    Resolution and Reduction Of Past Billings & Pending Stock Issuances and New DCVax®-Direct Manufacturing Agreement" data-reactid="11">Resolution and Reduction Of Past Billings & Pending Stock Issuances and New DCVax®-Direct Manufacturing Agreement

    BETHESDA, Md., May 28, 2019 /PRNewswire/ -- Northwest Biotherapeutics (NWBO) ("NW Bio"), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, today announced that it has entered into a settlement agreement with Cognate BioServices, Inc., resolving past matters and providing for restart of DCVax®-Direct Production." data-reactid="12">BETHESDA, Md., May 28, 2019 /PRNewswire/ -- Northwest Biotherapeutics (NWBO) ("NW Bio"), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, today announced that it has entered into a settlement agreement with Cognate BioServices, Inc., resolving past matters and providing for restart of DCVax®-Direct Production.


    Northwest Biotherapeutics Logo. (PRNewsFoto/Northwest Biotherapeutics, Inc.)
    $2 million for partial payment of certain past obligations, restart of new manufacturing of DCVax-Direct, and revised product manufacturing fees which incorporate certain volume discounts." data-reactid="24">NW Bio and Cognate agreed upon revised market terms for a new Manufacturing Services Agreement for production of DCVax-Direct to be used by NW Bio in clinical trials. Production of DCVax-Direct is scheduled to start in 10 weeks. Other terms provide for a dedicated cleanroom suite, an upfront payment of $2 million for partial payment of certain past obligations, restart of new manufacturing of DCVax-Direct, and revised product manufacturing fees which incorporate certain volume discounts.

    $10 million, with some amounts related to periods of inactivity being cancelled and with $1.1 million being deferred until 2020. In addition, 52 million shares of NW Bio's stock which NW Bio had previously agreed to issue to Cognate were reduced to 12 million shares. As part of this overall settlement, NW Bio also provided for additional consideration of $10 million that is only payable to Cognate after DCVax product approval in or outside of the U.S." data-reactid="25">Cognate billings to NW Bio for prior periods were reduced by approximately $10 million, with some amounts related to periods of inactivity being cancelled and with $1.1 million being deferred until 2020. In addition, 52 million shares of NW Bio's stock which NW Bio had previously agreed to issue to Cognate were reduced to 12 million shares. As part of this overall settlement, NW Bio also provided for additional consideration of $10 million that is only payable to Cognate after DCVax product approval in or outside of the U.S.

    In connection with the overall settlement, all past obligations of both Cognate and NW Bio were settled and all claims of both Cognate and NW Bio were released.

    Linda Powers, CEO of NW Bio, observed, "We are happy to have  resolved the past contractual issues and reached agreement on terms for a new manufacturing relationship with Cognate, putting us both in a position to move forward with a clean slate. We believe this is good for NW Bio and Cognate, good for our patients, and good for our shareholders. We greatly appreciate Cognate's belief in NW Bio and its DCVax technology, and we look forward to a strengthened and reinvigorated partnership with Cognate as we move forward on our exciting programs."" data-reactid="27">Linda Powers, CEO of NW Bio, observed, "We are happy to have resolved the past contractual issues and reached agreement on terms for a new manufacturing relationship with Cognate, putting us both in a position to move forward with a clean slate. We believe this is good for NW Bio and Cognate, good for our patients, and good for our shareholders. We greatly appreciate Cognate's belief in NW Bio and its DCVax technology, and we look forward to a strengthened and reinvigorated partnership with Cognate as we move forward on our exciting programs."

    About Northwest Biotherapeutics " data-reactid="28">About Northwest Biotherapeutics

    North America and Europe. The Company has broad platform technologies for DCVax® dendritic cell-based vaccines. The Company's lead program is a 331-patient Phase III trial of DCVax®-L for newly diagnosed Glioblastoma multiforme (GBM). GBM is the most aggressive and lethal form of brain cancer, and is an "orphan disease."  The Company is also pursuing a Phase I/II trial with DCVax®-Direct for all types of inoperable solid tumor cancers. It has completed the 40-patient Phase I portion of the trial, and is preparing for Phase II portions. The Company previously conducted a Phase I/II trial with DCVax®-L for metastatic ovarian cancer together with the University of Pennsylvania. " data-reactid="29">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 North America and Europe. The Company has broad platform technologies for DCVax® dendritic cell-based vaccines. The Company's lead program is a 331-patient Phase III trial of DCVax®-L for newly diagnosed Glioblastoma multiforme (GBM). GBM is the most aggressive and lethal form of brain cancer, and is an "orphan disease." The Company is also pursuing a Phase I/II trial with DCVax®-Direct for all types of inoperable solid tumor cancers. It has completed the 40-patient Phase I portion of the trial, and is preparing for Phase II portions. The Company previously conducted a Phase I/II trial with DCVax®-L for metastatic ovarian cancer together with the University of Pennsylvania.

    https://www.prnewswire.com/news-releases/nw-bio-announces-settlement-with-cognate-bioservices-resolving-past-matters-and-providing-for-restart-of-dcvax-direct-production-300857384.html
     

    GlobeCitizen

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    FWIW, below is a new video of Dr. Linda Liau's presentation.
    It seems she is more confident and smooth in her presentation which contains some new information.
     

    GlobeCitizen

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    It is share accumulation time for those who have done their DDs. After the company feels comfortable with the four RAs regarding its SAP, data lock and the subsequent analyses can happen very quickly. It will be a binary event, so invest accordingly.
     

    GlobeCitizen

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    Mahatma Gandhi: First they ignore you, then they laugh at you, then they fight you, then you win.
    I believe we are in the final stage of this process.

    BTW, Andrew Yang has changed the impression of Asians running for president or participating in politics. Regardless the result, he has raised the profile of Asians in American politics. Canadians have taken the note. Thank you Andrew.
     
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    GlobeCitizen

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    New this is a significant news:

    NW Bio Expands Senior Management Team With Dr. Kevin Duffy As Vice President, Medical Affairs & External CollaborationsPress Release | 09/04/2019
    NW Bio Expands Senior Management Team With Dr. Kevin Duffy As Vice President, Medical Affairs & External Collaborations
    Specialist in Immuno-Oncology; Previously Research Scientific Director In Merck's Keytruda® Program
    PR Newswire

    BETHESDA, Md., Sept. 4, 2019

    BETHESDA, Md., Sept. 4, 2019 /PRNewswire/ -- Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, today announced that it has expanded its senior management team with the addition of Dr. Kevin T. Duffy as Vice President, Medical Affairs and External Collaborations.



    Dr. Duffy is joining NW Bio from Merck, where he has served as Research Scientific Director in the Keytruda® (pembrolizumab) program during the last five years. Dr. Duffy's roles included scientific support and outreach to health care providers and national and regional scientific leaders in over 20 different solid tumors and hematologic malignancies (blood cancers and lymphomas) relating to Merck's clinical development and commercialization of Keytruda, as well as ongoing scientific support for Merck's Investigator-Initiated Study Program. He served as the national contact point between the scientific affairs team working with medical professionals in the field and the internal research and development team in Merck for the Keynote-024 study in first-line non-small cell lung cancer, the Keynote-522 and -756 studies in triple negative breast cancer and ER+/HER2- breast cancer, and the Keynote-641 study in metastatic prostate cancer.

    Dr. Duffy also served as Scientific Affairs Strategy and Training Lead in Merck's Global Center for Scientific Affairs for Merck's immuno-oncology franchise for hematologic malignancies. Dr. Duffy was the recipient of numerous achievement awards during his tenure at Merck.

    In his roles at Merck, Dr. Duffy has been involved in the Keytruda development program from its early days through its wide commercialization. He has gained extensive experience with clinical trial designs and strategies, clinical results and feedback from medical professionals. He has built a nationwide network with key opinion leaders in both the clinical and the scientific arenas.

    Prior to his time at Merck, Dr. Duffy served in Medical Affairs and Scientific Affairs positions in several pharmaceutical companies, including as a Regional Scientific Manager for oncology and cardiovascular therapeutics at AstraZeneca. Dr. Duffy has a Ph.D. in molecular pharmacology and structural biology, with a focus on oncology, as well as an MBA.

    Dr. Duffy commented, "My years at Merck, from inception of the Keytruda programs, have been exciting and invaluable. As I look forward now to the next wave of advances in immune therapies for cancer, I am excited about the potential of NW Bio's DCVax technologies to deliver new breakthroughs for patients. I hope to build on my experience in immuno-oncology and my network of relationships in the field to help NW Bio achieve this potential."

    Linda Powers, CEO of NW Bio, noted that "Dr. Duffy's experience with immune therapies for cancer and one of the most successful product development programs in the field will be an invaluable addition to our team. We at NW Bio could not be more excited about Dr. Duffy's choice to join us and help realize the broad potential of DCVax."
     

    GlobeCitizen

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    Quick note on Les' interview with The Big Biz Show
    Total 331 in which 31 never get the vaccine

    So ITT 300

    "We are getting the very near the end of it"

    Median OS of 331: close to 2 years (24 months from surgeries) compared to about 15 months for SOC

    Top 100 could live five years by average [should use the word median]

    So projected five years of OS: 50/300 = 17% blended, hopefully patients who received vaccine from the beginning show advantage over those who received vaccine later at crossover after progressions, and in this case the five year OS for those patients who received vaccine at the beginning should be above 17%. Could it be 20% or more. Keep in mind that for SOC this number is about 5%.
    The trial needs unblinding to see if there are indeed favorable differences between various groups of patients, in favor of those who received vaccine, and those who received earlier.

    upload_2019-10-3_18-28-4.png
     

    GlobeCitizen

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    "
    Over-thinking confuses and ultimately kills anything on its tacks!

    In Summer 2015, there was a planned interim analysis. As a result, DMC disbanded and Linda has since headed on a long road of regulatory pursuit for changing the primary endpoint from PFS to OS, all due to the messed up PFS data because of pseudo-progressing.

    Nobody knows and can be ascertain that PFS data would be eventually adjudicated correctly and nobody knows FDA would look at nwbo in the future with a change of smile.

    Soon, FDA refused Linda's request for endpoint change (the regulatory pursuit has been ongoing until a certain point, maybe when FDA lifted the partial halt). What happened next is the revelation of the partial halt for new screening -- the stock price collapsed and has never recover since. There have been endless dilutions!

    If nwbo were a big P, it will be highly likely FDA would approve the endpoint change, since OS is the golden standard and it is still today and will be in the future.

    So the reason for the partial halt could not be disclosed at that time and it continues, which could only be disclosed (and nobody will really care), if topline data is released and it's positive.

    So it's as clear as day that the only way for nwbo to exist as a successful company for years to come is to extend the trial as long as possible to catch the long tail -- a significant large number of patients (20 - 25 %) will live a long term, about and above five years, in a manner of statistically significance -- no companies, big or small have never ever approved a big fat long tail with the actual years and days patients have lived in the history! We are close to that revelation.

    Nonetheless PFS is still the Primary Endpoint and OS is still the Secondary Endpoint. Although if the long tail exists and it is statistically significant, meaning there are clear separations between the some comparable groups, and FDA will have to approve the vaccine because of that, the best interest for the company is that PFS endpoint is better approved statistically significant. Besides, nobody can guarantee that the long tail will be a clear cut without unblinding.

    All these have hinged on the SAP saga we have all experienced for so long! Despite that, I don't think the company will stretch any more longer as long as it receives the initial responses from four RAs; even if no response from say FDA, the company is ready to lock the data, unblind, analyze and publish topline data in the near future, by end of this year or the latest early next year. All my bet is on this, and I have bought a lot of more shares recently.

    With regards to the Q report: it tells us, the SAP draft was completed in the quarter (any day from July through September 2019), and the data scrubbing was almost complete with only "a small number" outstanding from a few hundreds of queries as we knew from the last time it was mentioned -- A small number, a few queries remains back before the end of September meaning database lock is ready at any time!

    Also bear in mind there are usually three factors a successful biotech company must have:

    1) we have a quality product (DCVax-L, suggested long tail without side effects) with real-world demands (in our case for GBM patients) -- this is the first thing a successful biotech company must have;

    2) we also have quality and accessible advisory board and committee (Linda is smart enough to use the experts opinions in a continued base) -- this is the second thing a successful biotech company must have; and

    3) A good relation with FDA -- this is the third thing a successful biotech company must have, which we are not sure at this point, but I do understand why Linda has traded anything and everything FDA so carefully.

    As for my investment in this company, the only part I don't like is the repeated dilutions of shares, and I am dumb enough to repeatedly add more shares, but I can only look in the future, and it will be bright!

    (I have no interests to post further).
    "
     

    GlobeCitizen

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    Smith's new analysis talking about endpoint changes, which does accommodate the lengthy process of SAP preparation. BTW and FYI, Smith is believed to have talked to the company often. Below is his new analysis: [to respect his work, I am not going to copy and paste his analysis so you have to click the link below if interested:

    https://smithonstocks.com/northwest-biotherapeutics-company-is-closing-in-on-unblinding-of-the-phase-3-trial-of-dcvax-l-in-gbm-that-could-lead-to-a-cascade-of-important-follow-on-events-nwbo-buy-0-22/
     
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