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Wow...
Seeing as they and BMY have given up, or had to give up on ICI's for SCLC, there is a treatment void for that indication, which a different kind of immunotherapy could eventually fill...
Just goes to show that ORR (tumor measurement) is often a flawed surrogate for survival benefit.
'Voluntary withdrawal' Hmmm.
That goes to show that you can be published in an alternative open access journal like the JTM and get good national mainstream publicity.
I don't get all this desire or need to be published in a so-called top flight journal. What purpose does it serve? The downside of making such a submission is effectively you show your hand to the entire industry for a couple of months before actual publication. Everyone knows what you've got...
If you ask me my opinion on the issue, I'll tell you...!
Not King's, to be completely accurate.
CCGTT, on the other side of the river. Who do have the requisite Specials licence.
But I agree that there is no evidence of Sawston having been licenced yet.
I didn't say I was enthusiastic about the prospect. I simply quoted Citywire.
I didn't offer an opinion on the issue, other than to suggest that it was a strange turn of events!
He (with Acacia) has to attract an influx of institutional money before he can invest it anywhere anyway.
Acacia might be riding a current reputation for spotting realizable value in biotech assets, but Woodford isn't!
Woody: "I'll be back..."
"Woodford makes dramatic comeback with Jersey fund launch. The disgraced manager has reunited with right-hand man Craig Newman and US investor Acacia Research for a biotech fund aimed only at institutional investors."
'Neil Woodford is making a dramatic return to investment management with a new fund, less than 16 months after his previous firm collapsed in a spectacular fall from grace.
The disgraced manager has reunited with right-hand man Craig Newman to set up Woodford Capital Management Partners, which will partner with US-based Acacia Research, to launch a Jersey-based biotechnology fund.
‘We’re going to rebuild the Woodford investment operation under a new brand,’ Woodford told the Telegraph in an interview at the weekend.
‘I didn’t want what happened to me in 2019 to be the epitaph of my career, I didn’t want it to be the full stop. I’m not trying to rebuild an ego, I just felt I wanted to continue to do the things that I believe in.’
The new fund will only be available to institutional investors and will hold a number of stocks previously owned by the failed LF Woodford Equity Income fund.
Woodford’s empire collapsed in October 2019 after he was ignominiously sacked from his flagship Woodford Equity Income fund by administrators Link Fund Solutions.
This followed a run of poor performance after a string of bets on illiquid, unlisted companies turned sour, leaving investors unable to withdraw their money for months. At the time of gating, £3.6bn of investor cash was trapped in the fund.
‘I’m very sorry for what I did wrong,’ he told the Telegraph. ‘What I was responsible for was two years of underperformance – I was the fund manager, the investment strategy was mine, I owned it, and it delivered a period of underperformance.’
He remains angry with Link for suspending the fund in June 2019 ahead of his sacking, claiming performance would have turned around if he’d been given more time.
‘I can’t be sorry for the things I didn’t do. I didn’t make the decision to suspend the fund, I didn’t make the decision to liquidate the fund. As history will now show, those decisions were incredibly damaging to investors, and they were not mine. They were Link’s decisions,’ he said.
Woodford highlighted the subsequent performance of several of his former fund’s holdings.
Synairgen’s share price more than quadrupled in one day after the Southampton-based biotech company found a potential Covid-19 treatment, and Oxford Nanopore surged on developing a rapid Covid-19 test.
Another holding, Kymab, was bought by Sanofi in a $1.45bn (£1.08bn) deal in January, months after Link had sold the position for a third of its current valuation.
Link also came under fire last June for selling a portfolio of up to 19 quoted and unquoted healthcare stocks to Acacia Research, the company Woodford is working with on his new venture, in a £224m deal.
Acacia went on to flip some of these stocks, making a £113m profit in just five months.
The remaining stocks held by Acacia will form the cornerstone of Woodford’s new fund. This portfolio will only be offered to institutional investors, with Woodford saying he now accepts that unlisted stocks are unsuitable for retail funds.
It remains to be seen how much money Woodford’s new venture will raise, but the fallout from the collapse of Woodford Investment Management will continue to be felt for some time.'
https://citywire.co.uk/wealth-manager/news/woodford-makes-dramatic-comeback-with-jersey-fund-launch/a1465595?ref=wealth_manager_all_stories_list
I expect he still believes in the investment case for NWBO!
Would make for an interesting twist in the tale...
Acacia made a ton by buying his old holdings on the cheap.
I see another of his past holdings, Prothena, is up 45% on the day..
It's very curious. Several overlapping authors.
Same injection schedule. Same two adjuvants, both administered after the end of the 0, 14, 28 day shots. Both did gene expression profiling. Both used flow cytometry.
Too many similarities for me.
So I still reckon it's the same study. Just that two different author groups interpreted and reported the results in different ways.
I could be wrong. But we need to see dates of recruitment period, where recruited, sponsor etc, to see if these are two different studies or not. And how many got the Poly ICLC in each study, if they are different.
If they were all recruited at UCLA and in the same time period, then it has to be one and the same.
We need to see the full report of that AANS abstract and then compare with the other full report.
You may be right.
But I still kinda think they are one and the same study.
If anyone can find a write-up of another 23-patient study, I'd be happy to be wrong.
You're correct that all 23 in the study report I referenced, had GBM.
But in the trial listing mentioned in that study report, they took Stage 3 or Stage 4 gliomas.
It started out as a P1 and then morphed into the P2.
Brad was one of these patients.
https://clinicaltrials.gov/ct2/show/NCT00068510
Long time-servers will remember about 6 years ago, when we debated about why they didn't use either adjuvant in the P3.
Seem to remember Pyrrh going on about it....
So I still reckon it was all one and the same study. Starting out as a P1 and morphing into a P2 that focussed on Stage 4 GBM.
There is a good reason why the P3 didn't use an adjuvant.
They wanted to prove efficacy of L without an adjuvant.
Otherwise, any subsequent regulatory submission would have to be for L plus the adjuvant.
Ah; the much-referred to 23-patient Phase 2 study, which was used to demonstrate the use and possible additional survival benefit of either of the two adjuvants.
The same study was also used to demonstrate the non stat-sig additional benefit accrued by mesenchymal patients.
I'm pretty sure this is all one and the same study (though if anyone can demonstrate otherwise, I'd be happy to accept..)
8 of the 23 were rGBM rather than ndGBM.
So you have lots of variables and very small numbers, so there really isn't much in the way of statistical significance that can be attached to the outcomes (though your quote did claim one stat sig outcome). Additionally, some got post-vacc TMZ, some didn't, some got Bev and others didn't.
That's why personally I don't conclude that use of an adjuvant necessarily confers additional survival advantage (nor do I discount the possibility), and similarly, I don't conclude that L definitely works better with mesenchymal, though again, I don't discount it either.
Full study report is here:-
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071163/
(Table 1 gives patient characteristics of each and every one of the 23, whether or not they got one of the adjuvants, which gene expression profile they were, and what additional treatments they received. So you can dive into the individual outcomes of each patient and draw the conclusions that you think are valid and worth making.)
Ah, I see.
Didn't have access to full article.
So they have a load of vaccine that needs using up quickly.
I wonder why the initial enthusiasm has diminished?
Could it be something to do with their Jan mortality stats?
Mr Shorty doesn't like it, when a group of buyers play their game in reverse.
So they resort to getting the brokers to stop play.
https://www.zerohedge.com/markets/7087-billion-reasons-why-exchanges-betrayed-retail-customers
Yes, the philanthropath has a lot to answer for...
Thanks. Been following my own advice on that front for the last 7 or 8 months.
Vit C, Vit D, Zinc, washed down with something refreshing.
Maybe Public Health will catch up with that advice at some point...
All kindly enquiries, I trust?
A OK thanks.
Just had other fish to fry, and there really has been remarkably little happening in NWBO land (unless I missed it..) for the last couple of months.
FWIW (not a lot), I think it's more likely to go up 50% in the next month than go down 50%.
On that unscientific basis, I judge it as a 'hold'!
Perhaps they have such momentous news to deliver, they don't want to do it at a naff virtual conference, and are waiting for a proper conference with attendance in person.
That shouldn't be too long...
Should it??
OK, Tryn; at the risk of making myself look extremely silly, I'll bite:
Up 5-10% in the first few minutes. And up 18.4% (or thereabouts) on the day, to close out at $2.72 (or thereabouts..)
And if I'm miles out, I might then have to become a mod for the day, in order to delete this post.
Hey Abeta. No it's not an entirely accurate interpretation.
It would be if the trial started exactly 5yrs ago, and everybody was randomised on Day 1!
But as soon as you realise the possibility that someone who was randomised 8yrs ago could have survived 5yrs prior to dying three years ago, then you will know why!
Regards.
Kab. I hate to say this, but they were planning to, or at least considering, a reverse split to stay on Nasdaq.
But, in the event, they decided to jump ship before they were pushed off Nasdaq.
PR from 7 Dec 2016:-
Every year you survive, you have a better chance of surviving a further two years (or indeed just 1 additional year), so it is not the way you have reckoned.
Have a look at Table 2 on this link:-
https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.27590
Chances of surviving an additional 2yrs:-
If you make it to 1yr, then chance of surviving additional 2yrs is 20.6%
If you make it to 2yrs, it is 38.1%
If you make it to 3yrs, it is 57.3%
If you make it to 4yrs, it is 64.2%
You can see from this trawl of US registries from 10-15 years ago, that if you made it to 3yrs you had a 57.3% chance of making it 5yrs, with a fairly wide confidence interval. 57.3% of 28.2% gives you 16.1%
But things have moved on a bit since then, and our trial population has slightly better prognosis than patients from a large database and we know there is a very good long tail, so I think entire ITT OS60 of 18-22% is reasonable, with treatment doing that bit better.
Still pondering my final treatment OS60 estimate, but it has to be somewhere in the 21-24% range, I think.
And the EF-14 control arm contemporaneous comparator was 5%.....
Your 25.4% OS36 figure came from JTM in 2017.
The updated 2018 figure for the same metric was 28.2%.
Using fairly established conditional survival calculations, OS60 for the entire ITT would likely be in the region of 18-22%.
One would expect the treatment arm to definitely achieve 20%.
With the actual figure being somewhere between 20-25%.
I agree 30% is unrealistic.
'Both barrels' not a high hurdle at all, seeing as it employed both sides of the pond, I believe.
About equally easy to clear as managing to surpass an EF-14 control arm..
Lol.
Not sure about hangers and hoods though. Braces and bonnets?
I await your Maverickesque post..
Never mind Ex.
Help is at hand.
What are hangers?
That's the whole point. And as long as nobody knows whether certain proprietary manufacturing techniques are used or needed, then nobody knows what they need to do to replicate the process!
Who is going to invest a few billion and a decade of time and probably fall by the wayside along the way anyway?
It is inordinately difficult for a rival to get where NWBO are by plagiarising techniques and processes, patents or no patents.
Aivita lack the secret sauce, I believe..
Theirs is all autologous, using PBMC-derived DC precursors, plus an autologous self-replicating cancer cell line rather than a lysate. And by using a simple cell line, they will likely fail to pick up all the antigens.
https://aivitabiomedical.com/news/aivita-biomedical-provides-update-of-ongoing-phase-2-glioblastoma-trial-from-year-end-survival-analysis/
It is inordinately difficult for a rival to get where NWBO are by plagiarising and replicating, patents or no patents.
The copycats are not really copycats, imo. And they all appear to lack that certain Je ne sais quoi...
And as for a generic?
Not a chance ever.
The issue is not a source of concern to me at all.
The rGBM comparison is a helluva lot messier, it has to be said.
Because there isn't an SOC as such. You've got Bevacizumab or no Bevacizumab, Chemo or rad re-challenge or no re-challenge, repeat surgery or no repeat surgery.
And that also applies to our trial.
Some of our crossovers, as well as getting DCVax-L, got Bev, some didn't, a small number had second surgery, most didn't.
So a like for like comparison between our crossovers and control patients from other trials is very muddy.
If one thinks that that secondary endpoint is there to try and garner upfront approval for (operable) rGBM, as well as the ndGBM approval, then the evidential comparison (a very complicated comparison) for rGBM might not pass muster.
But that doesn't really matter a great deal, imo, because there is surely some scope for rGBM off-label use, and the formal label extension would probably come a year or two down the line anyway.
The problem will be gearing up Sawston just to meet ndGBM demand.
And fulfilling all the heavy CMC requirements and documentations which are essential for any regulatory submission.
Nope, I don't think you need patient records.
You get your Stat guys to do the work, by fully surveying the field of all comparators, drawing on meta-analyses, assigning a weighting factor to all well-known prognostic factors, make use of existing predictive nomograms, and do a bit of weighting accordingly.
It's a lot of legwork, but quite doable, imo.
And the Optune study is more admissible than the others because it led to regulatory submissions and approvals. So the regulators have already scrutinised all the data and its 'quality', and green-lighted it. And it is really quite recent.
FDA said:-
So yes, they should major on EF-14, because the regulator has already defined it as 'a well-defined and conducted study'!
Oh the irony!
Not old enough.
They simply compare like for like.
EF-14 is broadly similar.
If one trial comparator has 36% meth and the other is 40%, then you just make a small statistical adjustment.
Likewise if a trial had a few biopsy only patients.
You can blend the two Opdivo trials, one of which was for meth the other unmeth, and make that another comparator.
Did Tocagen ever report on their ndGBM trial?
Yes. They are contemporaneous and comparable so they are valid.
Though minor statistical adjustments might be necessary to true out the comparisons due to slight differences in ITT's.
It's so ironic that the EF-14 control arm did so badly and that is going to be one of the main comparators.
Quite amusing, I have to say...
Branko's chart is clear and his milestone percentage estimates for L treatment are on the money, I believe.
Any SOC arm from any trial you like, is going to pale in comparison to L treatment.
And for good measure we will outpoint the Optune treatment figures anyway.
Well, this is what it says:-
And I take that to mean control subjects from our trial who progressed and then crossed over and received L, compared to recurrent patients from other comparable trials, (which may include rGBM trials).
And the measurement will be date of recurrence to date of death.
The thing about that, of course, is that the crossovers to L will be getting a vaccine made from the original tumor rather than the recurrent tumor, so may not do as well, because of possible tumor mutation. And we have no guide to that. (Though by now the Stats will know.)
I think this endpoint is really only about whether they have the data to justify straight away applying for L approval for rGBM as well as ndGBM.
It's like a bonus approval, if the data merits it.
Just the way I read it.
Evaluate. The way I read it, 2(ii) is adjudicated PFS, and 2(iii) is unadjudicated PFS.
If I am correct, that means that at least the one regulator has accepted adjudicated PFS as a legitimate endpoint, and the fact that it is ranked this way round (giving primacy of adjudicated over unadjudicated) is rather gratifying.
Adjudicated PFS is individual PFS as adjudicated by the expert panel that retrospectively re-appraises all recorded PFS events.
One assumes that the Panel have now completed that work. Not that we know that for sure. Maybe they have to convene once more, to review the last handful of PFS decisions.
But in basic terms, they are looking for incorrect PFS calls that were made on the basis of imaging, and which mistook observed enhancement on the scan as disease recurrence, when in fact it actually indicated pseudo-progression. So (for each subject) they look at the next few scans. And if the enhancement goes away in subsequent scans and the other clinical indicators serve to corroborate, then that original PFS call is struck.
And replaced by the later PFS date of actual confirmed progression (a scan followed by subsequent scans confirming real disease progression, along with other clinical indicators of recurrence). And clearly there will have been a few subjects who were given an incorrect original PFS call (because it was only pseudo-progression) and perhaps never subsequently progressed.
And the hypothesis is, that it would have been treatment arm patients who were much more likely to have been given an incorrect PFS call, because of the known phenomenon of various immunotherapies sometimes causing pseudo-progression.
So basically the whole concern about pseudo-progression mucking up the PFS comparison is removed, if adjudicated PFS is accepted as valid, and if it is accepted that it actually gives a more accurate clinical picture. In fact if one was to really push it, one might say that adjudicated PFS is actually the Gold Standard of PFS assessment, because it is the most clinically accurate.
I think 2(iii) remains there because it allows for reference comparisons between adjudicated and unadjudicated.
Not sure about 2(v). But it might simply be a T-cell infiltration comparison. Seeing as it is low down the pecking order of endpoints, it will mainly serve a corroborative purpose and as an indication of mechanism of action.
The other point of interest is that 2(i) is actually in effect a recurrent GBM endpoint. Comparing OS (from time of recurrence) in patients treated with DCVax-L, with OS of control patients from time of recurrence in comparable trials.
And if the data proves good enough (and that is not a given), then it opens the door for a possible approval for recurrent GBM as well as ndGBM.
Not a lot to dislike really...
My opinion.
Indeed. Because I think that the PEI in effect means the EMA, thus whole of EU, rather than just Germany.
Hope I've got that right...
Thanks Abeta. Let's hope that Anders got accurate info and the PEI version gets an update shortly to mirror the MHRA one.