Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Not wrong. Believe what you like. I don’t care.
The clock started on March 7, 2024.
His mind is in a foogie because he is 88. Just look at his handle. LOL.
Skitahoe:
I am certainly no expert, but the proliferation of educated T-cells is definitely an important part of the significant effects of DC VAX L. However, it is not the whole story. Of particular importance are the issues of T- cell exhaustion and the immunosuppressive environment. We know that with the mesenchymal signature, the vaccine is more effective because there is a greater residue of T cells upon which an attack on the tumor(s) can be mounted and that the tumor micro environment is less suppressive. Hence a so called “hot” tumor. Cold tumors have a smaller surfeit of T-cells upon which to build and the micro environment is much more suppressive. As a mono therapy, DC VAX L has achieved significant results although less dramatically in unmethylated signatures. Accordingly, with a cocktail approach, adding adjuvants such as poly ICLC, a myeloid inhibitor as well as a CI such as Keytruda, in combination with the keystone DC VAX L, goes a long way in significantly addressing these issues contributing to dramatically increased overall survival, and in a significant number of cases even a possible cure if I may dare to say so, and with an enhanced quality of life. I think this Is truly amazing.
GLTU.
I would agree with this, especially due to Orphan status which facilitates/encourages interaction and guidance with/from the FDA. Rolling application makes sense.
What a beautiful woman both inside an out!
Do not forget that Stupp, himself, stated that Optune long term survival data could not be relied upon because there was no follow up. So, there’s that.
Do not forget that Stupp, himself, stated that Optune long term survival data could not be relied upon because there was no follow up. So, there’s that.
Kabunushi-san:
I agree 100% with your recommendation. I am voting YES to increase authorized shares and NO to the bonuses.
Best regards,
Doc Logic
The lack of formal FDA guidance and delay is a real and foreseeable issue. Regulators often times move slow as molasses.
I am certain that NWBO’s regulatory counsel has made NWBO management well aware of this and a possible issue wrt a US journal willing to publish upon condition and when formal guidelines issue from the FDA wrt ECAs.
Accordingly, in an abundance of caution, I believe that in order to avoid this possible issue and hold up, NWBO in collaboration with the authors and strong support from Dr Ashkans opted to go with a UK journal. JMHO.
Biosect:
Just an excellent cogent recap and important post to read for any long having doubts and insecurities.
Thanks for all that you do.
Regards,
U
Biosect
It should be noted that guidance and confirming with the FDA is especially the case due to designated Orphan status.
Regards,
U
Meirluc
Absolutely agree and could not have articulated any better.
Meirluc
As I have pointed out in a recent post, even Dr. Stupp is on record as saying that the long term results presented by NVCR cannot be relied upon because there was no follow up. That means their 13% OS at 60 months cannot be relied upon. As you know, Dr. Stupp was a PI for the Optune trial and was an author of the clinical results in a prestigious journal. He made that statement during a presentation in, I believe, October, 2021 if memory serves.
Dr Stupp also served/serves as a consultant to NWBO and may be included as one of the 70 authors of the upcoming journal article. FWIW.
AEK,
I believe that under the PIM designation, all malignant glios are covered including lesser stage tumors. Hence, I believe that the MAA would be an all inclusive application, covering n and r GBM.
Hoffman
It is dynamic (partially) as you assert. I inquired and discussed possible purchase of Cs with LG. Price depends on market SP but then temporarily fixed for sale and subscription agreement. The fixed price is adjusted to the then prevailing market price allowing for a very small discount. This common share “price” is then worked back to derive the preferred C price which in my case was $16 per share. Different investors had different prices depending upon timing and there was some limited leeway for negotiations, however, there was a rather tight spread.
I declined purchase as for me, the discount was not enough. I was not buying enough volume to make company share purchases worthwhile as opposed to market purchases. Further, I did not like the restrictive holding period to conversion and how conversion to common would be guaranteed without increased shelf. I did not discuss these “demerits” as far as I was concerned because the whole deal was not appealing to me.
I heard from LG that there was interest and purchases of the Cs and that I could buy as many as I wanted. Although I am an accredited investor and have participated in previous raises, I did not find the C investment compelling enough in my particular case. And LG knew I would not sign up for millions of shares so I suppose, tongue in cheek, he offered “all I could want”. He did appeal that purchases would “help the company”.
To each his own.
It should be noted that even Roger Stupp officially stated in a presentation made in October, 2020, if I recall the approximate date correctly, that long term data provided in connection with Optune could not be relied upon because no follow up had been done. Accordingly, and in other words, Optune’s long term “data” could not be relied upon.
Dr. Stupp, as a PI in the Optune clinical trial, originally wrote the JA in NEJM as a lead author. Dr Stupp has since been a consultant for NWBO and has so acknowledged this relationship.
Reefrad:
Yes, I am very optimistic about the company’s future. As with some other investors, I am frustrated by the time it is taking to get out the JA and the overall quiet period/embargo. But I am satisfied with the overall progress made thus far.
I have a very sizable investment in NWBO and I continue to hold.
I made an inquiry in re the Cs and obtained the information I required in order to make an investment decision. I shared some of the information I obtained with the board FWIW.
Agreed.
Senti:
That may well be. However, the subscription agreement, which defines the t&c of the purchase of the securities, does not address this issue and much more guarantee that authorized shares will be available at the time of conversion, or ever.
Now to be precise, the subscription agreement I received is between me and NWBO. Other investors may have a different agreement where this issue is addressed and commitments may be negotiated such that in the event the covering authorized shares are not approved, options/shares held by management will cover the conversions and are pledged to do so in such an event.
Leverage in negotiations also depends upon who you are, how much you are investing, etc, etc…..
This raise was an initial tranche to fund the company which previously was partly funded by warrant conversions. It seems apparent that this source of funding has dried up.
FWIW.
Kabunushi-san:
You are correct. The subscription agreement so provides.
Nope. I am a small human.
Purchase of these securities is by inquiry. I made the inquiry directly with NWBO. I am a retail shareholder. The “Cs” were offered to me and I received a draft subscription agreement. The price was $16 per preferred share convertible into 25 common or $0.64/share. At the time of my inquiry the market price was about $0.68 so the “discount” was about 5% as the price was “fixed” the previous week..There was a three month holding period up to October 26, 2022. There was no guarantee that sufficient authorized shares would be available at the time of conversion, or for that matter, ever. There were no warrants attached. Nothing was stated as to whether the voting rights attached to the common were immediately available. When I inquired as to how many preferred I could buy, I was told “as many as you want.” The number of shares in my subscription agreement was left blank for me to fill in.
There is no doubt that NWBO has had discussions and guidance with and from the FDA. Especially since they have orphan designation which engenders such interactions and guidance from the FDA. There is no doubt in my mind that this relationship and now positive results from the trial has very favorably disposed the FDA towards an approval perhaps on or about the same time frame as the MHRA. I have to believe that with Dr. Ashkan’s known and vocal support, the MHRA, will act very expeditiously upon the submission of an application if it has not already been done so.
Dr. Bosch’s presentation was masterful and highly encouraging as they “have solved the three Ps “ After all, the manufacturing process is the product.
ASCO was not a nothing burger and these two superb presentations cast a wider net of information transfer of what we long term investors have already known. Highly encouraging to say the least.
I agree with your analysis. One thing that I have not been able to reconcile is the non-methylated presentation result as compared with the non-methylated interim blind/blended data.
As you know, in the JTM article, SOC mOS for non-methylated was 12.7 months and blended results as per the interim data was 19.8 months, which is a delta of 7 months. Adjusting for randomization, there still is a delta of 4 months. However, the presentation results show a negligible delta, if any at all, of any significance.
The 13% survival tail was less than the interim article would have suggested at or about 20% and not as robust due to the negligible, if any, efficacy wrt non-methylated.
I think NWBO needs to immediately contact the AACR with a letter setting out the facts, without threats, and asking for corrections and retractions as applicable and signed by the General Counsel.
That should get their attention and incentive to act expeditiously. . Hope that is what they are working on over the weekend. JMO.
IkeEsq:
I am compelled to say that this is an absolutely superb post. AF has unwittingly supported NWBO.
Kudos,
U
Dmb2:
I largely agree with the view that PFS is a surrogate and that it may not be a significant factor wrt RA approvals provided that other end points are met and that the tail is long and robust.
Having said that, even though PFS endpoints may not have been achieved/ may not be statistically significant, this does not mean that circumstances surrounding PFS analysis may not yield important information.
For example, it has been stated by Dr. Liau that patients appear to be living longer than expected. Accordingly, an important consideration to evaluate is the interval between PFS eventing and OS eventing.
In addition, it may be that even though patients progress, DCVAX L effectively slows the rate of progression as the vaccine’s effects become manifest as time unfolds. Immunological approaches require a longer time-frame within which to become more fully efficacious and manifest positive results.
Thus, while the endpoints, in and of themselves may not have been achieved or are otherwise not SS, the above described factors may provide strong support and dovetail with the indication that patients are indeed living longer due to the effects of DCVAX L when considering overall factors. All IMO.
Thank you. Post very seldom these days but occasionally read the board. Very busy running my business.
Keep well.
Regards,
U
The Pepsi guy was John Sculley. He was featured in a front page article in Fortune magazine wrt why CEOs fail and was part of a pantheon of failed executives e,g., Bob Stempel, Chainsaw Duncan, Bob Palmer, Mike Spindler( to whom I once reported at Apple), Gil Amelio who Steve Jobs pushed out, etc. Sculley was President of PepsiCo. before he joined Apple and was once a son-in-law of Don Kendall, CEO of Pepsi.
John Sculley was forced to resign by the BoD and Mike Markula replaced him with Mike Spindler. Mike was replaced by Gil Amelio who was a former CEO of National Semiconductor. Amelio invited Steve Jobs to consult for Apple and that was the beginning of his end. Steve came on board and got Apple to purchase NeXT OS for $498 million. Steve’s salary was $1.00 per year but he was “gifted” with a $98 million Gulf Stream. One of his first actions was to fire the entire board including Mike Markula who was an original investor along with Don Valentine. Revenge was sweet as Markula and the board supported Sculley and forced Jobs out of his company. Jobs then founded NeXT with funding from Ross Perot and of course, Pixar.
Sculley was involved in a scandalous business venture with Spectrum Technologies and was sued and counter sued. Case was quietly settled. Sculley went on to found his own consulting/venture capital firm, Sculley and Bros. He incubated a number of companies and was rather successful. Steve Jobs refused to speak with Sculley and never spoke to him again.
Inside story from an “insider”.
BB:
Please refer to my #425650:post where I said the same thing over a week ago. NHRA GMP cert is a precursor of NHRA marketing approval.
Iclight:
Coming from you that is high praise indeed.
Thank you very much and all the best.
Biosect:
Many thanks for your kind words. Your posts add so much to the board and your knowledge is astounding. I do not know your background but you write like a first rate litigation attorney. Very glad you are invested and I carefully follow your posts. Just a lot of logic and common sense.
Please keep posting.
Sincerely,
Umibe
Hi FeMike:
First, thank you for your comments. The points you make may well be valid.
However, my point was that I don’t agree with your statement that LP does not know what she is doing which is tantamount to calling her incompetent.
I don’t think any of us on this MB can conclude this. We do not sit where she does. We don’t have the facts she has. We don’t have her experience. We very likely don’t have her brain power. We certainly don’t have the phalanx of advisors she has. We don’t work at NWBO every day. We don’t have her resources. We don’t have the opportunity for collaborative decision making that she has. Accordingly, I think it quite unlikely that she is incompetent.
While I don’t like the deafening silence, missed guidelines, etc., this does not mean that well considered reasoning is lacking. Perhaps if I knew what she knows with benefit of her team of advisors, I would have made the same decisions. Who knows.
I don’t claim that she has not made mistakes. However, on the major strategic issues and decisions, these are assuredly well thought out and vetted with her counselors. In hindsight these decisions may not have been correct or even the best way to move forward, but they were well considered at the time and not incompetent decisions. To be sure not all company issues and operations involve such elaborate collaboration. Timeline guidance may have been one of them. I think that management wanted to throw shareholders a bone. I think counsel probably told them, OK, in the interest of investor relations but with all the caveats. However, continuing to miss the mark, probably they all came to the conclusion that due to external factors not under their control which significantly impacted their prognostications, they opted for silence and “don’t explain other than we are in a quiet period.”
LP has brought the company to where it is today on the brink of announcing what I think will be remarkable data and a new paradigm for SOC wrt the king of cancers. And she has done so in the face of daunting challenges where lesser resolute leaders may have given up. Has she made mistakes? Maybe. But incompetent? That is much too extreme a judgement. To repeat, we don’t sit where she does. Accordingly, the least we can say is to withhold judgement as, if and when she brings the company across the goal line. From what I see, overall, I give her the benefit of any doubt and firmly believe that her overall management will lead to success for patients and investors.
GLTU whatever you decide.
Could not agree more Iwasadiver. Thanks for all you do.
All the best,
Umibe
Thank you Mav. I appreciate your insights as well. Shame you are limited in your posts. Anyway, GLTU.
UMIBE
CT, thank you. My best to you and yours for the holidays.
Umibe
MID:
Well articulated. Good luck to us all. Best for the holidays.
Umibe
Thank you Kab. My best to you and yours for the holidays. Keep the faith. We are fine.
FeMike:
I think that you are wrong. The fact of the matter is that LP and LG are not making decisions in a vacuum. They are doing so on important strategic issues on a collaborative consensus basis with all the advisors they have.
LP is being counseled by extremely experienced and top advisors who can afford to be objective about the direction the company is taking.
For example, I can guarantee you that their outside counsel including Gibson Dunn for legal and regulatory matters are extremely experienced and have extensive networks. LP is not ignoring their advice on regulatory, legal and business matters, you can be sure. Firms of that caliber are very conservative and careful and their reputation is of the utmost importance. They don’t need NWBO’s business and if there is even a hint of impropriety they will investigate and withdraw if they have to. There is no question that she is collaborating with her SAB, independent consultants, Principal investigators and other experts where she is paying not insignificant sums for their input and advice. She would be foolish to make decisions in a vacuum. Further, LP and LG are not inexperienced themselves. So it is the ENTIRE TEAM that is contributing to the decisions made and not just LP and LG. Further, they are in possession of a lot more information than ordinary shareholders and denizens of MBs like iHub.
I am certain that their outside counsel has recommended that NWBO engage in silence rather than to give essentially meaningless updates on timelines and progress where at least some of it is completely out of their control. What is meaningful is TLD and much more importantly RA approvals. Short of that(pun intended) other information revelations will not move or sustain the needle much if at all. Until they are ready to reveal important information, it is better to be silent.
Naysayers FUD that management is hiding something, that if the trial were a remarkable success, the data would speak for itself and it is not necessary to tie TLD to a journal publication. And if the data were so remarkable, a top tier journal would have accepted an article by now or at least it would have been written and submitted for peer review and this announced by now in conjunction with TLD.
The fact of the matter is that it is not quite that simple. And NWBO is playing to three separate audiences: RAs, the medical community and Wall Street wrt MC. It would not be a surprise at all if NWBO missed the original primary PFS and secondary OS endpoints. In that respect, the naysayers could well claim that the trial failed. Within that context, LG has insisted in conversations with me and others I know that the “trial has not failed”. Even DI has indicated in certain conversations with MBers that if the trial had failed they would have had to reveal this and certainly by now.
What I believe is not adequately remembered or understood is that this is an adaptive trial. Further, the trial concerns an orphan disease. What the former means is that the trial can be modified within the context of advancing knowledge and techniques not known or reasonably foreseen at the time of original trial design provided that the trial remains blinded. This resulted in the modified SAP with the reordered and added end points. The orphan disease designation allows for and encourages the trial sponsor to engage and have easy access to the FDA for guidance. There can be little doubt that the resulting SAP was developed in accordance with FDA guidance. In fact, the guidelines developed by the FDA were drafted in connection with at least some input from these discussions and back and forth with the FDA. Support for these guidelines from members of the FDA were mentioned in recent Lancet publications. IMO, it is reasonably certain that the FDA at least implicitly if not tacitly agreed with the modified SAP and resulting endpoints especially considering the adoption of these endpoints by European RA counterparts. I think it is reasonable to conclude that the 4 involved RAs are in agreement with these endpoints regardless of whether the US clinical trials org was updated or not. Hence it is a true statement that even though the original endpoints may not have been achieved that this trial has not necessarily failed given the modified SAP. Admittedly, this does not mean that the trial absolutely succeeded but may be in a “grey area”. Accordingly, NWBO has not directly confirmed that the trial has been a success but rather nuanced that it has not failed at least wrt to the modified end points even though it may have failed to achieve the original endpoints.
I am reasonably certain that NWBO has succeeded in meeting the current OS endpoint as compared to synthetic external controls by a significant margin. In addition, NWBO has highly likely achieved the 6th endpoint(secondary) with respect to immune agent infiltration. At a minimum, NWBO has almost certainly achieved to meet two endpoints. In addition, NWBO will also be able to demonstrate a long and robust tail. All especially wrt the new definition of GBM. With the achievement of the foregoing, it is a reasonable certainty that at least the MHRA will relatively expeditiously extend marketing approval. This will get the ball rolling with the other RAs. I believe a precursor to MHRA marketing approval will be its preceding GMP approval for Sawston. The MHRA would not waste its time giving GMP approval for a “failed trial product.” Accordingly, marketing approval by the MHRA is very likely to follow suit. I think it likely that the MHRA(as well as the other RAs) has been given a peak at the results. The foregoing as a minimum and worst case scenario is almost certainly sufficient enough for approvals from all 4 RAs including the FDA which will not risk being an odd man out especially given its guidelines and FDA staff endorsements in recent articles. There is just too much pressure upon the FDA given almost certain approval by the MHRA, the Biden administration’s stance on cancer and familiarity especially wrt glioblastoma and the need for an alternative therapy that is reasonably efficacious and SAFE for patients afflicted by this disease. Further, the results of this trial will compare extremely favorably with Optune as we have seen with the blinded results comparisons and the divergence seen as one goes out beyond two years which is where Optune actual data stops.
As I opined hereinabove, I would not be surprised if NWBO failed to achieve the original primary and secondary endpoints, unadjudicated PFS and OS Tx as compared to control which includes crossover. I think these endpoints were reordered and included under FDA guidance with a recognition that these endpoints should not be ignored and swept under the rug so to speak even though there may be good reasons for possible failure given confoundment of pseudo progression which was not well understood and crossover which if not required by the FDA was at least tacitly agreed by them in recognition of the difficulty in attracting trial candidates as well as ethical considerations. In addition, confirmed PFS(cPFS) may not be statistically sufficient in that even though there may be some or even significant pseudo progression found, it is not possible to accurately ascertain how much longer, if at all, these pseudo progressors may have gone until an actual disease progression finally occurred.
In addition, while not a certainty, I believe that there is better than a 50% chance that the cross over arm as compared to external rGBM SOC could be statistically significant. This would be an extremely remarkable achievement and perhaps even more significant than achieving the primary OS end point for nGBM. This was not a trial geared for rGBM. There were an insignificant number of second resections where mutated antigens were not covered and provided a pathway for more virulent recurrence. However, a significant proportion of these recurrent tumors morph into the very aggressive mesenchymal type which is the sweet spot for DCVAX L. This would be a significant breakthrough for rGBM therapy significantly increasing efficacy in recurrence with safety. If the three foregoing end points were achieved, this would be a grand slam home run which even market naysayers would be hard pressed to refute. This would certainly call for expedited RA approvals. The original OS secondary endpoint would probably not demonstrate a statistically significant separation meaning that even delayed administration of the vaccine is efficacious and particularly in connection with aggressive recurrence. Accordingly, curve separation would be evident in this first secondary end point achievement.
Non achievement of the original PFS endpoint may certainly be evident due to confoundment of pseudo progression. Thus, PFS in this case may not be a good correlative or surrogate for the gold standard OS. It may be that there was no significant improvement in PFS over control but that does not necessarily mean that the vaccine is not effective with respect to PFS. It may be that although there is little to no difference between control and treatment eventing, never the less, DCVAX L slows the progression rate such that OS is prolonged and this might be demonstrated by the improved interval between PFS eventing and succeeding OS eventing. I specifically addressed this possibility with LG and he said that this plus other factors would be considered depending upon the results. So this possibility appears to be on the investigative table.
Hence, with very careful and detailed explanations backed by the data, what might be perceived by the market at first as overall lackluster results with non-achievement of original endpoints including adjudicated PFS, would be eventually reconsidered by the market as significant and remarkable results especially if the rGBM endpoint is met. Certainly the regulatory and medical communities would be quick to perceive a successful trial even if the worst case scenario mentioned above should occur. Market recognition would inevitably follow.
Accordingly, a peer reviewed top tier journal is required in order to provide explanations for what might be perceived at first blush as a mixed bag result, especially by the marketplace. After all, it will be very important for NWBO to gain market recognition for needed financing, without more toxic dilution, through a significant rise in the MC/SP. Therefore, it is absolutely essential that NWBO/PIs provide a carefully explained and supported publication through a high impact journal. That is a key part of their strategy and may be a reason for the length of time thus far taken for journal acceptance and publication. They need to get it right the first time. Such explanations, as suggested above as examples, will have important validation if published in a top tier journal. But they need to be carefully explained and wordsmithed and this takes time and input/reviewed by a number of interested parties.
My point in explaining all of the above is that this is overall a complex process not given to simple explanations that the data speaks for itself. Unfortunately in such a case, the numbers/ graphs are not the whole story. LP and LG are not making decisions in a vacuum considering all these complex parts and how they come together. It is a whole team including NWBO management and their entire hierarchy of consultants and advisors possessing information that we as retail shareholders are not privy to in making collaborative decisions. Even the FDA has provided guidance and input through the orphan status protocol. If one claims that LP does not know what she is doing, then I submit that it is not just her but her whole team. This is highly unlikely.
In the past, I was highly critical of management but I was certainly premature if not entirely wrong in my judgement. These are very smart and experienced teams including LP and LG. Read their backgrounds. Don’t know what they are doing? Not by a long shot in my book.
I strongly believe that the results will be understood by all constituencies as remarkable including the RAs, medical community and patients and ultimately, Wall Street. “Incompetent management” will have a lot to do with this success. JMHO.