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If you are or were a warrant holder and you had any serious concerns about the data, wouldn’t you have taken the opportunity presented over the last 6 months to lock down profits.
The slow trickle of warrant execution certainly looks like a coordinated effort to support management’s cash flow needs.
There is currently about $500million in unexercised profit. No one seems too worried about losing that nest egg.
I am agreeing with you as was Lykiri from my read. That is all.
You seem to agree with each but use different language to express it.
The reporting bias in medicine has been clearly documented. Companies dont spend time, effort, and money to publish or attempt to publish negative trials. Journals don’t waste space accepting and publishing them. Most negative trial reporting ends at a scientific meeting.
If we are working to publish the data, it is positive.
Thank you to all board longs! The past day is filled with logical, fact-based comments that lend great confidence to this very long, long.
We are getting so close that I can smell salt in the air. I don’t live near an ocean so that must be blood in the water. We have had a number of tornados roll through in the past few weeks which is a clear reminder that it is always calmest before the storm, then winds start to pick up a little before the hammer drops from the sky in a torrent.
It has been a very calm summer for NWBO longs, but I sense a slight uptick in the wind. We are about to drop from the sky and rip shortie to threads.
One thing I like about Congresses are that they put a stake in the ground! We are just about 5 weeks away from the next stake. There are many opportunities with fluid dates circling around out there for significant news releases but ESMO is a hard stake in the ground at just about 5 week out..
Abstracts and late-breaking abstracts accepted as:
Mini Oral (suffix ‘MO’)
Friday, 17 September 2021
00:05 CEST (Central European Summer Time)
Abstracts and late-breaking abstracts accepted as:
Proffered Paper (suffix ‘O’)
EONS Proffered Paper (prefix ‘CN’)
Saturday, 18 September 2021
00:05 CEST (Central European Summer Time)
Abstracts and late-breaking abstracts selected for inclusion in the ESMO Press Programme (suffix ‘PR’)
Published according to a dedicated schedule to be made available by early September.
Totally agree! I see absolutely no benefit to long term shareholders by management providing any limited update that they possibly could before the grand finale. I am actually pleased by the silence which gives me a great sense of calm and certainty.
Good tidings to you biosect for keeping the faith and positive viewpoint active through the summer doldrums.
Very excited for September 9th…Gene therspy research day is just 4 weeks away,
Interesting thesis…Just curious, my friend, why do you hang around here?
What motivates you to devote so much time on a board for a company that you profess not to own?
No one has sold and moved on. Longs realize that we have a few more weeks of silence and have nothing new to say. Most everyone is tired of the same old same old song and dance of the shorts. No need to combat arguments that are so old and lame.
It is the last few weeks of summer. Stop watching the stock price and enjoy the outdoors.
When FDA approved Sarepta’s Exondys 51 there was outrage in the medical community at first. Shortly thoigh, they returned to agreement with their patients and families who pushed hard for the right to accept risk for the opportunity at a promising but unproven therapy. This process of FDA acknowledgement of patients’ rights conitued and recently culminated again with the approval of Aduhelm by Biogen. This time the outrage is from both physicians, institutions and congress who are investigating FDA. IMO these actions ignore patient demands whom FDA listened to and ultimately sided with over their advisors. Aduhelm has serious and potentially fatal outcomes, but patients want it anyway. FDA trusts Biogen perhaps more than any other company due to their volunteered REMS program for Tysabri and overall management of safety reporting for that drug which is seen as the bar for which others are measured. Key word in that was volunteered.
This tells me despite all of the signs and evidence that FDA has been involved with LP at each milestone beginning in the weeks up to the August 2015 halt in placebo use in the trial, IT DOES NOT MATTER. Regardless of how closely FDA has appeared to me to have ushered NWBO through a process, FDA WILL APROVE DCVAX-L for GBM, no qualifications on stage of disease.
If they do not deem the data fully sufficient which will not happen, they will listen to patient demands and in this case physician alignment and approve DCVAX-L period. End of story.
Looking forward to celebrating with longs this fall!
Thanks, Captain O.
13M in July breaks the recent trend and is a sizable chunck in basically one week of play.
What could they need an extra $3M for? Maybe general operations, maybe something else? This gets me a little bit excited.
New 8k regarding ongoing consulting relationship with former COO
https://investor.precisionbiosciences.com/node/8756/html
DW2, no matter how good you feel your data is, that has no value. What has value is the regulators perceiving your data as good, approving you to market it and the provider community agreeing afterwards. Even with good data and positive meetings, you cannot put words and perceptions in the regulators mouth about your drug until you have their approval to do so “IF” they choose to approve it.
“IF” is a required word. If a company choses not to say “IF” before approval they are misbranding their investigative product. This alone could cause delay, fines, or worse, not to mention lawsuits “IF” you screw something up along the way.
Thanks for posting this DD…very reassuring comments
My initial reaction to this debate is that since her schematic does not end with the YES box, we cannot make these conclusions as she is showing what happens when YES is achieved, we have evidence of benefit.
There is not much to say about what happens with a NO.
Except, then you get to thinking, well, what if some of them are YES and one or two are NO. Then, you really do need additional boxes to consider next steps in the process. In my experience, when she presents uncertain outcomes, she discusses possibilities plural. There is only one possibility displayed and discussed here. Her personality demonstrates that she has no problem speaking casually with certainty and conviction when things are known and she provides possible interpretations and interprets uncertainty with appropriate openness when that is the situation.
Ultimately, I do think this says something, and I don’t believe it was subconscious or an oversight to exclude other possible outcome scenarios. 2 YESs on Primary, and 2 NOs would be quite the scenario to consider for next steps. That is not where she keeps going. She is on to combination as next steps. She has been unblinded . Period, end of story.
She is not breaking any rules or leaking, she is just presenting the scientific process and state of affairs without giving away outcomes. But she has not considered failure and has defended the scientific model to her peers on multiple occassions. We have only seen the public ones.
Once a paper is written, edited by authors and submitted, you are in a waiting game with very little communication before the back and forth of questions and responses leading to publication.there isn’t much hard work left on that pathway for certain, as we saw in April and May that the model was already built. After that the stats are pretty quick. The very latest possibility for the pre-submission work to be completed, even given COVID, has now passed.
There is a clock. It is already ticking. We aren’t certain when that timer was started over the past 9 months or when a journal will end it, even which journal will end it. This notion that our ex-friend and other FUD try to push about never releasing results is pure and complete bunk. As this message is repeated, people should gain confidence knowing that those who spew pure garbage and do so repeatedly are either gravely misinformed or something a little more menacing.
Yet the clock is ticking. Tick tock tick tock my friends. Tick tock.
There will be results.
We have seen he statistical model.
We have been shown the SAP design.
We have seen blinded, blended results with projected long term outcomes at two different points.
We can compare these periods and assess differences that are known and anticipated.
TLD will be positive.
Likely the original OS randomized comparison (it never specified how as I understand it and it won’t be mOS) will also be positive which has be reinforced by the long term accumulation of data.
So back to this DI email and what he said. Nothing new, only reinforce what LP already told us more than once.
BUT, they can no longer be working hard on the publication. Hmmmm, what else could they be working on hard related to TLD?
Submission package is my guess. My guess too is that the first of three is US and news of this may come as early as month end but likely August-September as she will wait the 30 days for acceptance before a PR. Others believe UK is first. We will definitely hear about manufacturing approval by the same time frame.
What I do know is that manufacturing in US and Germany is ready, already. Expansion in both these regions is possible. Plans for UK readiness and expansion are also known.
All that remains is submissions and journal navigation. These have finite timelines.
Tick tock, tick tock, tick, tock, tick tock, tick tock, tick, tock ,tick tock.
Each time I hear that sound I know that I get closer to retirement.
Tick tock.
Good coverage of the current state of affairs as far as stock price goes for Intellia. I the Motley Fool gives a balanced viewpoint with their bias included. We should be close behind them in ATTR. The status od DMD and other genes still seams to be a footrace. Mitochondrial disease are Precision’s
https://www.fool.com/investing/2021/07/04/2-reasons-to-buy-intellia-and-1-big-reason-why-i-w/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article
There is absolutely no relationship between CVM and NWBO other than a few people on this board own both and others on this board like to connect anything negative they can to NWBO.
CRISPR/Cas9 company Intellia and Regeneron report first in-human gene editing results in 6 ATTR patients showing positive safety and efficacy data. I had no idea that they were this far along. Pretty impressive.
https://ir.intelliatx.com/news-releases/news-release-details/intellia-and-regeneron-announce-landmark-clinical-data-showing
Ski-T, If you would like to diversify your rocket ships after the second stage booster goes off here, consider looking into Precision Bio and what I believe is their drastically superior gene editing technology. They are only priced at $650M with $200M in cash and a big daddy bank roll coming.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=164610061
Dendream
Just taking a quick look at where things were.
Avexis was a vector gene therapy company using AAV9 with 15 successfully treated human SMA babies, a few very early other MD vectors, and some preliminary CAR-T work. An inferior technology IMO with some questions of durability and long term safety. Novartis snatched them up for $8.7B.
https://www.fiercebiotech.com/biotech/novartis-inks-8-7b-avexis-buyout-to-build-gene-therapy-unit
Spark was a gene therapy company with a host of genetic eye disease vector gene therapies on market and in development with very limited revenuee from these conditions. Roche bought them for $4.3B.
https://www.fiercepharma.com/pharma/roche-to-wrap-up-4-3b-spark-deal-after-antitrust-ordeal-ends-ftc-thumbs-up
Astellas with early vector company Audentes $3B. https://www.fiercebiotech.com/biotech/astellas-inks-3b-audentes-buyout-to-expand-gene-therapy
All inferior technology for many reasons…Eli Lilly already thinks our first six genes are worth $2.6B plus royalties on sales. What is the whole platform and CAR-T program worth?
Great read Scotty! 199 patents with 65 pending. Damn they are good at lawyering.
Senti,
Can you remind me exactly when the clinicaltrials.gov website was updated with the JTM article?
Here is my take on the whole 12 month reporting thing. LP has been working with FDA throughout the conduct of this trial as of at least August 2015. At each breaking point when we were made to be excited that a milestone was confirmed, LP discussed options with FDA. At those times, FDA provided limited guidance with little assurances. Then the contemporaneous control arm idea came into play and the new SAP was drafted. Does anyone here believe that LP would not seek advice that is not only freely provided but also required upon formal request?
This time however, FDA responded with questions instead. How do you propose to handle this and that and this? Show me. Then a new SAP came into play and was shopped around. FDA now gives assurances without guarantees because that is not typically what they will do. Here LP asked, how do we handle this and that and this?
Being lawyers and all, and as far as I can tell darn nabbit good ones. My guestimate since watching about cerca 2013 is they are like 7-0 in court, 1-0-1 with SEC and pretty darn good in the patent arena. My guess too is that they know how to find themselves good attorneys and consultants when they need them. Like perhaps, Mr. Christian, as an example.
Any way to the point. One answer to her questions was…just post the results you have made public that is the data from that design that you have right now. If we accept your package, then we can talk about updating the design on the site.
Box checked
She talked at UCSF two weeks after that date but registration was cut off before I attempted. Per Dr. Bala and others, there were no new breaking news tidbits, but she did frame the discussion around endpoints differently giving some the impression she no longer questioned OS acceptability.
BBB,
Please click back to ATL post to see the data presented to date. The hybrid synthetic arm will be proportional to the DCVaX-L treated arm, so an adjustment needs to be made to the contemporaneous data. As they will be individually captured they will be adjusted back to the time of surgery, so a poor man’s adjustment of both proportion and timing should be made.
If you take the mean of means from the population of contemporaneous placebos and adjust to the proportion methylated vs unmethylated and adjust back to surgery on a group mean basis, you come up with 19.4 mo vs 23.1 mo combined. At p<=0.02 this trial was powered to show a 4 month difference in PFS. At p<=0.05 thie difference can be much smaller. If the populations are now one to one, this too drastically increases the power to detect a small difference.
GTAL
Let’s say your name is Linda, it is early February and you know that you did not make the ASCO deadline, a regulatory package won’t be ready, and your publication is close to or just submitted. You know this process could take 6-10 months. You have a self-imposed quiet period because you have been unblinded to certain aspects of the trial immediately and by now you have seen first pass results. Some here suggest this is just BS and the company controls the narrative. What do you do? Do you sit on your hands as some here would suggest and wait or punt? Do you answer questions posed by your shareholders? Do you provide updates through multiple channels to your shareholders?
Timeline of Events since FEB 2021: I am sure a few are missing
16 MAR 2021 Northwest Biotherapeutics Announces Development Completed for Initial Production Capacity of Sawston, UK Facility
Some time later the hiring of Canadian Kristen Powers, no relation, makes its way to shareholders that look for these things
12 APR 2021 primary investigator, Dr. Linda Liau presents the statistical modeling of a randomly captured, blindly treated and evaluated, placebo control cohort and the process for building a synthetic placebo group for GBM and rGBM trials.
12 MAY 2021 UK Manufacturing Facility & Phase III Trial Updates From Northwest Biotherapeutics
18 MAY 2021 NWBO holds Annual Shareholder Meeting where they respond to questions presented in writing by shareholders representing this board. In addition to discussing manufacturing advances in the UK, they answer a question related to patents received for DCVAX-Direct and its potential future excitedly, a few other things and most curiously respond to rumors of an ASCO presentation and TLD release. Expectations for timing of manufacturing approval in UK and recommitment to the publication process are transmitted to shareholders.
Dr. Linda’ Liau shows but does not discuss the statistical model for the DCVAX-L phase III trial comparison to the synthetic placebo arm of contemporaneous controls (mixed with non-crossover matched controls?).
19 MAY Linda Liau presents the statistical model after receiving an annual guest lecture award (20th recipient) and being lavished in praise by the Academic Leadership of Mt. Sinai (Upper East Side, Manhattan, NY, NY). She also presents glimpses of adaptive design combination trial work that is ongoing at UCLA using self manufactured DCVAX-L.
Some time later FDA approved two different phase III rGBM registratioal trials for two compounds using a hybrid synthetic control arm built from contemporaneous controls. Interestingly, no ndGBM trials are announced or planned for these products.
Also, Some time later news leaks out about the hiring of consultant for uplisting to the NASDAQ who joins an NYSE uplisting expert in advising NWBO management.
Since the September appearance of Linda Powers, more than 150M warrants have been exercised and the stock price has risen almost 5-fold. There is a narrative that management is failing shareholders, but these two facts say otherwise.
Dots Well connected hyperopia. That seems like less breadcrumbs and more like an established foot trail.
I do not anticipate much happening these next several weeks by way of press release or major release of some other kind, but once we get through the doldrums that are July vacation month a new cycle may begin. These dots all form a line that intersects the market around late August, early September. The publication/presentation pathway refered to in October landed new dots in April and May which seem to point around that timing with ESMO and typical review timelines for journals.
There could be a few bombshells like UK, EMEA, and/or FDA package acceptance or partnership dealings but I am not holding my breadth in July for anything like that. Personally, I am checking in on any news but devoting my interests elsewhere for 6-8 weeks. If that means the shorties occupy ihub-street so be it, I have no worries about my investment and have other interests to pursue at the moment.
I am thinking that they must have to test each ‘batch’ in some way to ensure successful manufacturing of the individual vaccine. Having this companion diagnostic would likely be required for approval of DCVax. Having it in place first would likely be needed before submission.
Another regulatory step…check
Thank you both for the added DD!
Here is the FDA draft guidance on Companion Diagnostics. I have not had time to read through it in detail, but this comes from the upfront. Interesting that this appears in late 2020 on CRLs site.
179 If an IVD companion diagnostic is essential to assuring safety or effectiveness of the
180 therapeutic product, FDA generally will not approve the therapeutic product or new
181 indication for a therapeutic product if the IVD companion diagnostic does not already
182 have marketing authorization or will not receive contemporaneous marketing
183 authorization for use with that therapeutic product for that indication.
241 On the other hand, important safety or efficacy issues related to a particular subpopulation
242 identified by testing with an IVD may not arise until late in the course of therapeutic product
243 development. In such cases, approval of the therapeutic product could be delayed until an
244 appropriate IVD companion diagnostic receives marketing authorization. As described in the
245 guidance on “In Vitro Companion Diagnostic Devices,” in certain circumstances, FDA will
246 consider the timing of the therapeutic product approval after discussion with sponsors (see
247 also Section III.F.2. of this guidance).15
haTTR is a rare disease with currently two antisense treatment options from Alnylam (leader) and Ionis (alternative). These launched recently and adoption os as expected for a solid rare disease launch.
They come with their benefits and drawbacks which are now generating about $500M annual revenue with a 12% growth clip as these get adopted worldwide. There remains unmet medical need in this disease and there are advantages to a one and done approach. Solving how to price and recover gene editing value is another question.
https://investors.alnylam.com/press-release?id=25686
https://investor.precisionbiosciences.com/news-releases/news-release-details/new-preclinical-data-presented-2021-american-society-genetic
Some SPORE, and SPORE adjacent publications this past month focus on IDH mutations, identification and treatments in gliomas.
https://pubmed.ncbi.nlm.nih.gov/34121166/
https://pubmed.ncbi.nlm.nih.gov/33778493/
https://pubmed.ncbi.nlm.nih.gov/33691798/
https://pubmed.ncbi.nlm.nih.gov/34078652/
Most patterns have an explanation. The easiest answer isn’t always the right one, but it is the usual one. Usually, one who picks the easiest explanation is right.
A lot of people are excited about this Canadian hire, some are interested in this uplisting consultant addition, while others look to the CROs for clarity of process, some say DMC tells all, while others will tell you to just watch what is happening in Swanton, some question all of these but I do not question Linda Liau, Keymours Ashkan, nor their collaborators who seem to be rejoicing in a new day already.
There are those who point and say regulators, regulators, regulators and there are others that say ct.eu, MHRA, NICE, Franhaufer, Cognate/CRL forecasts, and halt in Placebo not study of drug. Some say look at the shares they have accumulated, look at the delays, look at the SEC and lawsuits, look at the potted plant. One must not forget about the potted plant. Look out for the potted plant. Others say yes, look at the shares we have accumulated, why did we accumulate?, look at the progress in manufacturing capacity, in resource management, in friendly warrants, in patents, in property, in publicity among key opinion leaders….KOLs….leading the opinion of their peers. Look at the statistical model and the beauty in its complexity. Look at the statistical comparisons, the sensitivity measures, the validation of data and process, look at the future of GBM research.
I say it rained this morning, heavy at times, and it was lovely. The flowers are blooming the breezes are blowing and the sun is coming out a wee bit later. This is a summer to enjoy for this book is already written. Some times the editorial process, the publication, the planning, the publicity, the timing, the unveiling, the revealing, the showmanship and the strategy not only take time, but are all that really matter in the end.
I can see the smile on Linda Liau’s face as she takes the first question which isn’t really a question it is a congratulations veiled as a question.
These Cure muscular dystrophy advocacy organizations are quite shrewd in investing research support with the dollars they raise through charitable giving. They will endorse technology in research support and clinical acceptance post safety and efficacy trials.
I love this podcast! Precisely the kind of affirmation I needed to start the day. Bioscientificaly unique advantages to ARCUS will likely have meaningfully differentiated outcomes in human practice. Precision Biosciences.
I am not sure why that question is relevant to our prior comments. LP and LL decided that OS was the endpoint that mattered in GBM and decided to go out to the very end to prove it conclusively (Early vs Late). Along the way, some believed the tea leaves pointed to a stopping point but were wrong. I myself have been wrong about timing multiple times.
Timing and outcome are not correlated. This means statistically, one does not generally run in sync with the other. Unlike GBM trial placebo groups where the correlation coefficient for the KM curves is remarkably similar. This should not be confused with concordance. There is not strong concordance between rare disease commercial success and accelerated approval or not. There is remarkable concordance with the placebo groups from similarly selected patient populations of other trials.
GBM is an orphan disease with a fatal outcome where little medical need has been addressed in decades. You gamble one way, I invest in the science.
Glad you enjoyed Flipper. Good luck and good fortune to you!
I play that song when I want to think about a loved one that I lost. It helps me remember to seize the day
Bio, we are aligned most everywhere on NWBO. Where we are not tends to be hairsplitting issues. I am busy with work but also kicking back and enjoying this summer as I am not worried at all by the silence from management. I fully believe they have us investors, GBM patients, and GBM providers in mind as they work through all that must be done to cement DCVAX as the SOC for GBM first, and later much broader application.
Cheers and good fortune to you!
Ahhh and you will wave your hands and speak of powering. This trial was powered to detect a very small difference at a p value of 0.02. Powering is a forward looking calculation which asks the question how many patients are required to predict the ability to detect a difference at a certain p value given a certain variance. If a study is powered to detect a two month difference at p=0.02 then it is also powered to detect a narrower difference at p=0.05.
You are correct, it is an assumption that the alpha was split with OS, Otherwise, the alternative is even less good for your side. If the endpoints are independently powered at full alpha, you have the ability to statistically measure a very tiny difference. Splitting the alpha up is the best case you could have hoped for.
This is a phase 3 registrational trial, EX. The alpha started at 0.05.
There is no question regarding the answer to this posed by you, LC. There is something in medicine called diagnosis by exclusion. When everything else can be ruled out, you are left with one answer to the diagnosis,. It is how one receives the diagnosis of ALS and many other neurological conditions.
The diagnosis here is simple and has not been disproven by anyone here, because all else can be excluded. What the DMC and FDA knew but did not explicitly tell LP and LL was that DCVAX was making all people live longer from the beginning and thus more deaths were occurring on Placebo from early on which was not just early on beacuase there were patients in trial for many years by June of 2015. Placebo deathrate outpaced treatment by a wide margin and therefore, termination of the trials were recommended (lets not forget the pseudoprogression trial) and ultimately placebo was terminated due to laws required by Geneva Convention. FDA and DMCs tend to stand firm on crimes against humanity.
Wallstreet, however, does not. Replace ‘violence’ with short interest in the attached. It is a brave man that puts his creation in the hands of another that can do it better than you.
A very good podcast on gene editing for DMD and other diseases. Good to hear Precision and Lilly on the same stage. This is going to be a very lucrative relationship. If you want to learn about DMD start from the beginning, or fast forward to 17 min for the companies.
https://soundcloud.com/user-457375319-637033873/s3-ep3-gene-editing-fighting-dmd-from-every-angle
When they amended the protocol to increase the size a bit and change the PFS trigger to 248, the also split the alpha between the primary PFS endpoint and the secondary OS enpoint. The study was now powered to detect a difference at 98% certainty (p=0.02) rather than the original 95% certainty (p=0.05). By doing so, they elevated the OS endpoint. There is your reason. Need I post the PR?
None of this need be done with an interim efficacy analysis. Everyone who bother to do basic DD knows that no interim efficacy analysis was ever performed.
Not even a nice try LC.
Reading the old comments everyone who trashed AF ultimately got it all wrong with Germany and the rest.
Do we know exactly when the DMC dissolved?
>>adamfeuerstein Comment
You don't resize a study without a reason. And the DCVax study wasn't just resized, it was radically altered by increasing by 125% the number of PFS events required for the final analysis. If you believe these changes were made without an interim analysis, you know nothing about clinical trial design and conduct and should not be invested in biotech or drug stocks.
NWBO issued two press releases in which it stated clearly, definitively, that an interim efficacy analysis was underway. It's been almost a year, where are the data?