Hi Doc:
Your response to Sentiment is appreciated as an indirect response to my post.
Perhaps, I have not been entirely clear about my concerns. I am rather confident that NWBO has enough for approval, EVEN if it misses the primary/secondary endpoints. That is my opinion. It is not shared, for example, by my investment advisor or others who I know and are fellow investors. Most of Wall Street has a limited and superficial attention span. In-depth research on the science behind NWBO's trial has not generally been done. Even Wall Street analysts who have followed NWBO(for example, Carol Werther) did not exhibit any in-depth knowledge about the science. Accordingly, NWBO has not only been ignored by mainstream Wall Street but has been pilloried by naysayers preying upon a small company with relatively complex(to limited attention-quick buck Wall Street)bio-technology.
On the other hand, I am concerned about the share price upon top line announcement, if the primary/secondary endpoints are not met, as I have previously explained.
Why do I believe DC VAX L will ultimately be approved? As you might have gathered, I am a rather unsophisticated(as compared to others on this board and, of course, experts in the field) simple thinker when it comes to things bio-technical. I try to dumb things down for ease of my understanding. As Einstein once said...."if you cannot explain general relativity to a child, then you have not understood it..." Anyway, here goes:
As a patient, I would be concerned about the 6 following factors if I were to pursue DC VAX L therapy:
1. How long can I live?
2. What would be my quality of life?
3. How safe is it and what are the side effects?
4. How easy is it to be administered?
5. How expensive is it and will it be covered by insurance?
6. Are there other and better alternatives?
I think with its more flexible regulatory approach, the FDA will follow the above considerations in reaching any approval determinations, including an assessment of manufacturing preparedness.
What we know from the blended results published in the JTM and updated thereafter are the following:
1. The ITT(minus 38 patients)categorised the trial patient population as methylated(M+) and non-methylated(M-). From the blended data, the M+ population appears to have fared extremely well(even when adjusted for randomisation) with a delta of 13 months from historical SOC to blended results. It is reasonable to expect that the treatment arm may fare even better. The M+ population was approximately 44% of the total characterised patient population(293 patients). M- also appears to have fared rather well with a delta of 7 months from historical to blended results although OS36 month survival was only 14.3% blended.
Furthermore, both the principal investigators in the US and UK(Drs. Liau and Ashkans respectively) have commented that patients seem to be living longer and that the therapy works, to a greater or lesser degree, throughout the entire spectrum of cancers that characterise stage IV glioblastoma. Furthermore, Drs. Liau and Prins have found that MES, largely M- and much more aggressive, responded particularly well to SOC and thus DC VAX L because it was more immunogenic. Both MES and M+ would comprise a patient population of over 60% where DC VAX L is suggestively more effective.
It should also be noted that tumours cannot be simply characterised as 100% MES or classical, etc. These tumours are striated and very heterogenous and mutative. Tumour composition will be different intra-inter tumour for any particular patient. There will likely not be facile determination that the tumour is this or that type. This is a highly individualised approach. Accordingly, I believe that if approval issues for DC VAX L, it will be broad and not narrowed to a particular molecular, M+/M- or other sub-group. Rather than imposing a regulatory fiat, the FDA will most likely leave it up to the patients and physicians treating them to make the decision whether to use DC VAX L for a particular cancer. As a practical matter, physicians will be able to prescribe off-label anyway although insurance coverage may not be available.
It bodes well that 69 physician/scientist authors signed on and thus endorsed the JTM article. NWBO's SAB is composed of prestigious physicians who would not risk their reputations. There have been technical papers in support of the science, i.e., Dr. Carlo Rago, who has also placed his money where his mouth is. Those naysayer professionals have never offered a scientific rebuttal of the science. The best they could offer is that the publication of blended data is pre-mature. Rather, we should wait for unblinded results.
Accordingly, bottom line, it appears that DC VAX L enhances survival across the board and suggestively, in a significant sub-goup or groups, that survival extension may be significant.
While it is true that we need to await for top-line results, it appears strongly suggestive that the response to the first concern is quite positive. A patient has a good chance of living longer and perhaps in at least a significant minority of cases achieve an effective long lasting remission.
2. Administration of DC VAX L would likely ease the side effects of rad/chemo and inducing cell memory to mitigate recurrence and lessening the dosages and length of time on SOC or at some point avoiding the rad/chem part altogether.
3. Safety and side effects are of relatively little to no concern.
4. Ease of treatment is obvious
5. If approved, very likely to be covered by insurance and pricing, when compared to other less effective and/or tolerated treatments, is extremely competitive. Nicely set up for NICE(pun intended).
6. Currently, the helmet seems to be a viable alternative. However, it is more expensive and lacks sufficient long-tail data(no QALY). If DC VAX L is at least comparable in performance at the front end(and blended results appear to be so; treatment results would likely be superior) but is better at the back-end(long tail), it would appear that DC VAX L is the preferred alternative and would have orphan status to boot.
It is obvious that NWBO has been investing and gearing up for commercial manufacturing capabilities and upon RA approvals will have the capacity to meet at least initial commercial demand. I don't expect this aspect to be a regulatory hurdle for NWBO. They have been at it a long time.
Accordingly, I believe that the odds of FDA approval(most important in my view of the 4 jurisdictions) are extremely high regardless of whether the primary/secondary endpoints are met.
Having said all that, I believe the case for the share price appreciation upon top line announcement is decidedly different and depends upon meeting endpoints. Wall Street at large, as I have stated herein above, his a limited attention span. It follows popular trends. Other therapies which are decidedly limited in their efficacy, highly toxic and dangerous have garnered the interest of Wall Street and the companies possessing these drugs have seen their market values reach incredible levels. Why is it that these therapies are embraced by Wall Street with all their warts and liabilities whereas promising therapies that are safe, show promising albeit blended data results, go after an extremely broad market(solid tumours both operative and non-operative), have an ease of patient administration, possess manufacturing preparedness, have a platform pipeline(DC VAX L and D) for many indications rather than a "pill per indication pipeline" and is relatively cheaper than most other like therapies are not only shunned but pilloried?
However, and unfortunately, it is what it is. Thus, failure to meet primary/secondary endpoints constitutes a technical "failure" in the trial. The loud chorus of naysayers will latch onto this "failure" and accentuate the negatives over any positives. How will NWBO respond? Most probably by silence as has been the case up to now. NWBO does not want to jeopardise the FDA approval process through any defence and thus, until approvals, it will elect to stay silent just as before. The market needs to be spoon-fed on the value of NWBO. It will not come to any realisation of its value on its own any time soon. The market will only hear the incessant chanting of failure though only technical and of little approval consequence when measured as against the evaluative criteria indicated herein above. The share price will be battered if the end points are not achieved simply because Wall Street will not believe anything else. It will be a Johnny come lately, if at all, when it ultimately begins to realise that DC VAX L/D is a new paradigm in treating disease through the enhanced invocation of the immune system. This is not hard to understand, but for some reason, Wall Street doesn't understand or does but the forces that be are against a little company's engine that could but now can't because it has run out of gas.
Has the share price been priced for failure? No, I don't think so. If it were, the price would likely be a couple of cents or $0.00. It is now priced at "highly doubtful that the trial will succeed" price level. If the primary/secondary endpoints are not met, then the "highly doubtful......." level will give way to a sharply lower level..
I have to believe that NWBO management realises all this and is working very hard and deliberately to pull out all the stops for share price appreciation. It is possible that although the primary/secondary endpoints are not unequivocally met, that the share price could still rise. But they would need to hit some grand slam home runs in milestone/long tail, etc. that overwhelmingly drown out the technical failures. This is why, IMHO, there is no rush to unblinding. NWBO management is deliberately taking its time to get its ducks in order. But, at the same time, it can't take too long(much past ASCO) to announce top line. The share price will be very fragile and no doubt, NWBO is now between a rock and a hard place. While PFS may be "fluid" as Flipper claims, still, to my mind, failure to provide blended data on PFS, the need for adjudication and otherwise overall silence seems to indicate some jeopardy that this lowered endpoint may not be achieved. JMHO.
GLTA
AI
