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Extremist, I hope things work out well and it’s nothing but a rocket shot to $50 billion market cap. Let’s just say I don’t think short arguments are going to stop, even in the face of positive top line results. Ultimately, positive results will carry the day, but between now and then, I personally expect more bumps in the road (sorry for mixed metaphors all you English majors out there!). Just my opinion.
Nope, but thanks for asking
You might want to check what happened with AMRN — it just happened. That was my mineral oil reference.
Idunno, let’s hope there is a repeat!
Thanks for posting this example— it’s exactly the kind of thing I asked about recently. Unfortunately there was radio silence (other than one generous PM). Understanding situations like this, and how they unfolded over time, might help us navigate the ups and downs that are still to come with NWBO.
Downs, you ask? Even if top line results are positive, there is still plenty of mineral oil to spread around — and that’s the best case scenario.
Got it - thanks! A noble impulse to round given a sensitivity to what the underlying data actually represents. One rarely comes across that in cancer research analysis.
Long ago, a friend who had access to a medical library made photocopies of articles for me. He was curious and actually read one of them. He was appalled by the dehumanizing language used by the researchers. “Cohorts” for groups of patients particularly stuck in his craw.
This tendency represents a danger that can have real world consequences for how doctors deal with patients. It’s definitely something for us to be vigilant about. Thanks for the reminder!
Sorry Basin, I knew I was replying to you but somehow addressed Doc — I knew I shouldn’t have started posting before finishing my first cup of coffee!! The old synapses weren’t warmed up and firing right.
Ex, I appreciate your attempt to establish the set of facts around the question. It’s good to start with what is known before speculating on what might be. This is probably a stupid question but have a set of facts that we could all agree on been established and listed somewhere back in the fog of time? Anything close to that? I’m not trying to give you an assignment, just wondering if it might exist or if you happen to have a particularly fact filled post handy.
Beartrap, one more thing regarding your son’s friend with the serious brain injury.
Stem cell treatments might make sense at some point to achieve some particular goal or effect in the course of his recovery. You might want to check out the Joe Rogan podcast that discusses the use of stem cells for healing many diseases. Go to YouTube and search for Joe Rogan and Mel Gibson, very worthwhile to see. If you have any questions as a result, we can discuss off-channel in the future. I’ve read the doctor’s book (the one meant for the general audience, not the one that presents all 800 scientific studies — $295 is a little pricey for me at the moment but I would love to read it). I’ve also followed the doctor’s work for a while. The stem cell company he helped found was bought out for a pittance several years ago and the technology seemingly buried by the acquirer. I follow the acquirer for multiple reasons and they’ve never mentioned the technology again. Pisses me off because it was one of the best stem cell lines.
Abeta, great idea to simplify the presentation of this analysis of the top 100 patients. I hope this bears some fruit. I’ve kind of thrown my hands up in despair of making sense of most posts on the topic, due in part to my own analytical shortcomings as much as to issues I have with the posts. And some of those issues are due to not having read the full history of the discussion which has been going on for years.
I do have one question — why don’t the number of patients in the last table equal 100 instead of 99?
Doc, good quote. I’ve heard that if anyone knew about overcompensation, it was Napoleon.
None of the above implies taking a side in the argument you’re having, just liked the quote because of the element of truth it contains, separate from the particular use you made of it. Certainly seems like it could apply to some opponents on both sides.
We now return to our regularly scheduled broadcast...
Correction to my prior post — I see you accurately quoted the study regarding tumor infiltration (and lack of survival) while I made a mistake on the tumor infiltration (but correctly quoted the lack of survival). At this point I’m more interested what you were asserting relative to preclinical studies and survival of our furry friends but certainly key details like tumor infiltration matter ultimately. I’m more interested in understanding what your larger point was and the level of seriousness you assigned to it.
It’s kind of difficult to discern what’s being claimed since I don’t have the reference and AVI hasn’t responded yet.
It seems good to take reasonable precautions if / when possible. The study in the article showed a presumably strong correlation between cell phone use and GBM specifically, not all brain cancers.
As a result, I did a quick search for more info and I briefly glanced through a very recent study that uses a classic causation model to assert just that, that there is evidence of causation. It was done in some Scandinavian country, which may be why we haven’t seen it here yet.
Since that’s a pretty strong, new claim, the study deserves more scrutiny that I can give it now. I’m content to have it register as “some anonymous horse on an internet message board made some wildass claim that he didn’t back up” at this point in time, even though I’m not making that particular claim — yet, if ever.
Hi AVII7, not sure how to interpret your use of the unreferenced mouse study that showed DC vaccination failed to cause infiltration of the tumor or extend the life of our heroic mouse friends.
Were you ironically flinging faulty data at those you said might use the Antonios study in a faulty way to claim it incorrectly supports the argument for DCVax?
(FYI - I’m not making claims about Antonios’ results other than PolyICLC looks like a good adjuvant for future DCVax use)
TIA
BTW am long ARMN and really glad they stuck with it — otherwise a life saving intervention would have been lost, for many decades no doubt. Seems like Fudstein was the chief fudspreader after the great data were released. The guy has a way with liquids.
Also long NWBO and grapefruit juice
Thanks Senti! The general drift of what you say makes sense but like you I’m not aware of the details of mutations in GBM. There is some work on inter and intratumoral mutational heterogeneity that I’m looking at in regards to the theoretical effectiveness of targeted therapies that might touch tangential on GBM but it’s not the main focus.
In any case, there is evidence of DCs being able to deal with neoantigens — which makes sense since that’s one of the key roles they play!
More to come, as they say.
Agree about the history of obfuscation on the dangers of things in the past and seemingly the present. Also agree that makes sense be a little skeptical of industry supported research as you suggest.
Hard to keep up on all this stuff. I did a quick search just now and found a couple of recent reviews of the literature that seem concerning— but don’t have time to dig into that at the moment. May pass some of that on at some point if it makes sense.
GLTY
I’m trying to picture this hollow tube thingy you used and I keep coming up with some kind of stethoscope. Not sure about those highs notes at the end of Barbers Adagio for Strings but it probably made Johnny Rotten palatable to women and canines
Thanks Mav, interesting stuff. Not sure of the pros/cons of the new legislation but worth getting up to speed on at some point. An interesting question from a patient perspective is “how do I choose which experimental drug to I try? Under what circumstances would it make sense?” No easy answers there.
Direct would be on my list depending on the circumstances.
Good ol stackoverflow, those guys have all the answers.
Too bad there isn’t a stackoverflow for cancer patients. I suppose it would degenerate fairly quickly — different domains, different forces at work. Not a bad idea if it could be made to work somehow.
Came across an article of general interest as a result of a hypothesis I had while checking a few things, mostly related to cancer mortality statistics and what they might say about the level of success we are having in “The War on Cancer” (horribly misleading metaphor from a patient perspective and how it affects treatment choices but that’s another topic).
I wondered if brain cancer incidence had actually been increasing because of cell phone use while the overall trend in mortality in all cancers the last 20 - 25 years or so had declined. (Incidence and mortality are influenced by different things but there was more stuff floating around in my head that made this thought relevant.) In England it has, at least for glioma:
https://www.telegraph.co.uk/science/2018/05/02/mobile-phone-cancer-warning-malignant-brain-tumours-double/
Really appreciate your taking the time to explain how things work.
Thanks!
Hi jammy, here’s some early evidence (2004) that whole tumor lysate primes DCs to generate tumor antigen specific T-cells in humans:
Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma.
https://www.ncbi.nlm.nih.gov/m/pubmed/15256471/
The antigens tested for in the study aren’t neoantigen, but are instead known tumor associated antigens. Is the assertion that DCs can’t identify neoantigens? Very unlikely since that’s its job, correct?
As you’ve suggested, DC vaccines could work through other mechanisms as well.
For instance, they also decreased Treg cell populations and decreased expression of CTLA-4 on peripheral blood T cells, after DC vaccination, which was correlated with longer survival in the phase 1 trial with glioblastoma patients (Liau and Prins). For those not up on the immune system components, DC Vax released two brakes on the immune system. And unlike ICIs, we get a two-for-one, without the added toxicity and potential of hyper-progression.
Monitoring of Regulatory T Cell Frequencies and Expression of CTLA-4 on T Cells, before and after DC Vaccination, Can Predict Survival in GBM Patients
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317661/#!po=0.724638
Liau and Prins milked that trial for some more data on mechanisms of efficacy—this time showing that DC vaccination increased the sensitivity of T-cells to cytokines in a way that increased clinical efficacy.
Cytokine responsiveness of CD8+ T cells is a reproducible biomarker for the clinical efficacy of dendritic cell vaccination in glioblastoma patients
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039989/
These are the kinds of effects that we would expect to see by recruiting the key component of the immune system in the treatment of cancer exposing it to the whole tumor lysate under the right conditions (which I know you know — just commenting for the skeptics )
Agreed. Is anyone aware of other companies that have been subjected to the same or greater level of sustained attack as NWBO? Have been meaning to ask this for a while — am interested in doing some analysis of these scenarios in my spare time.
BTW speaking of spare time:
Ex, I haven’t forgotten about following up on your reply regarding Coleys Toxins and it’s relationship to Chemo, the immune system, immuno-oncology and targeted therapies — still working through the complications/simplifications. I’m sure you can understand the complications, I’m just trying to avoid writing a book or three but am reading a book or three in the process.
Nassim Nicholas Taleb would suggest that looking at daily price fluctuations is pointless. Fooled by Randomness is a good read.
Very interesting - thanks!
Thanks for the link — I’ll check it out.
Regarding dendritic cell approaches to cancer. Just because it’s taken a long time to prove by the requirements imposed by the current drug approval process in no way means it’s obsolete in some way. The one doesn’t logically follow the other.
From a theoretical perspective, given what we know about the role of DCs in the immune system, it seems like one of the best approaches to focus on to try to get to work.
JMO
Jondoeuk, you seem to be up on the neoantigen approach. How is this an improvement over all the prior tumor associated antigen vaccine approaches that have been used in the past?
BSB, great list - thanks for providing it. I’ve been thinking about finding this list and defining for myself what the term Big Pharma actually applies to as far as specific companies.
I would think that one could whittle the list down in terms of potential acquirers considerably by applying several filters.
Which BPs focus on both oncology and immunology? If they don’t do both, then I doubt they’re looking at a small company like NWBO which doesn’t bring enough expertise with them to really scale this technology up across the multiple indications (in terms of best indications in a medical sense and potential ROI,etc, not manufacturing) that are possible and which doesn’t have the broad immunological expertise to really help decide which other immune approaches might be best in combination. I know we could all offer some suggestions based on current ICIs that are being tested but that seems like a fly-by-the-seat of ones pants approach for a BP. I would think a BP would like to have that expertise available as part of what it does in its approach to the oncology market.
A second filter would be market cap. If you think NWBO is going to be bought out for X billion then I would think the buyer should be significantly bigger than that. Past BOs would give a good indication of what a realistic ratio of buyers to seller market cap might be.
There are probably other factors that would come into play but these two popped into my head immediately.
Just some food for thought.
Senti - I’m out of the loop on a lot of the speculation and dot-connecting that has gone on here for years so I hope this isn’t a stupid question — it seems like some people have suggested that Cofer Black was appointed to the BOD for the purpose of ferreting out the “wolf pack”. I somehow missed that fact over the last few years. What is the evidence for that? If so, wouldn’t he be honchoing that and not Les?
TIA
BTW, I don’t doubt that there are actors out there who are trying to screw NWBO over. Mr Fudstein is pretty obviously one and I’m sure he’s not acting on his own out of spite or a perverted sense of entertainment (though he does enjoy what he’s doing!) but beyond him, who the others might be, I would just be speculating if I offered any specifics - hence my use of “wolf pack”.
interesting that gold wasn’t mentioned in the article since Dalio values gold as a “hedge” and the Chinese and Russians have been stockpiling it like there is no tomorrow over the last 10 or so years.
Of course it’s a barbarous relic but still you’d think they’d mention it in a discussion of the reserve currency and the Chinese.
might read it tonight to help me sleep or in the morning to learn something. Probably both - thanks!!
It’s easier being in ATHX since I’m sitting on a nice gain — current position in NWBO is painful but if things go positively with the trial and FDA, it will be worth it, I believe. That’s a lot of IFs but it’s a grand slam or strikeout scenario for the most part. Not sure what I do if it’s a single!! Thinking about what that might mean before too much time passes since the 3-2 pitch may be upon us. Could be a balk! Jeez, who knew there were so many possibilities - lol!!
I was in MESO several years back and am contemplating a small position there. Would appreciate your thoughts there if you get a chance.
Saw you mentioned FATE in another post — I recently brought a small position there. I like that they’re working with Sloan-Kettering — great connection that puts you on the right side of things. Great pipeline too, though am concerned they will run into cash issues sooner than desirable — perhaps too many pokers in the fire. Athx had that problem in the past but they’re more focused now and have off-loaded some spend onto Healios.
GLTY
Thanks Pharmboy —That explains a lot! Not sure how I could have made that mistake — getting old or perhaps a sign I should cut back on the number of stocks I hold/follow — I’m running a frickin’ mutual fund over here.
Yep, Shaw is full of quotable quotes — quite a wit.
The fact that he had the quote on phagocytes in a play back in 1906 is pretty wild — and points to a level of understanding (or perhaps belief) that is more advanced than I was aware of for the time — part of what intrigues me about Coley’s work.
The “Drugs are a delusion” line is a little jarring to our ears and probably takes more context to understand accurately. JMO
Ex, your reply contains several points worth considering in depth — thanks for sharing them. A dialogue here would be an opportunity to understand some key issues around cancer treatment, both from a patient perspective and more indirectly as to how those issues might impact one’s investment thesis around a company such as NWBO. Sarcoma and DCVax-Direct being only one such touchpoint.
The recent advances in immuno-oncology are a key area of focus for me now, which is how I hit on Coley’s toxins once again. Presumably like you, when I saw references to Coley (in my past investigations of cancer treatments), I assumed his work went nowhere for good reason and skipped it — one only has so many hours in the day after all. I now believe there is more there than met my paradigm-blinded eye.
However, unpacking your comments on targeted therapies will probably be the most fruitful area of discussion, though the history of chemotherapy and immune therapy are certainly relevant — both as (potential) patients and as those interested in NWBO.
A lot of big topics - a couple of which I need to dig into further, as well as to figure out how to break down so things don’t spin off into the ether.
More to come