While it is true that today’s journals require that study details be published on clinicaltrials, I am not certain at all that you would need to reference more than one site. European posting may suffice as properly reported since it is the latest.

My guess is that posting passes the bar

They are just inverting the typical US based company launch plan. It has been done successfully before. Just check out FOLD. The market has currently discounted their Pompe treatment and pipeline due to a modest mixed result which actually is in their favor as far as mixed results go.

Anyway my point, a one drug company with that launch pattern and $250M is worth $2.5B MC. That analogy applies fairly consistently. We all know DCVAX EU plus will generate well above that revenue.

Dendreaming these days away!

Fact: Germany (defacto EMEA) and UK have approved the new enpoints
Fact: EU plus accounts for 35-45% global revenue for most globalized products
Fact: NWBO submitted finalized SAP to all 4 RAs
Fact: NWBO has built manufacturing capacity through partnerships in US, UK and Germany
Fact: FDA has opened regulatory pathways for the current endpoints
Fact: FDA has proven responsive to patient demand, especially where safety is reasonable
Fact: FDA generally listens to expert advisory opinion (individuals w/o industry conflicts)

We dont even need FDA to justify current prices as a 40-80% discount to inherent value. But I have a lot of confidence FDA does not want wealthy US citizens traveling to private Canadian hospitals for too long, ethically questionable.

Sarepta would never have been approved in Duchene based on their regulatory package. To this day, no one can tell you if Exondis 51 works, but patients demanded the option. Safety was not in question so FDA acted in patient interest.

You should watch the FDA public comment session on Tysabri’s return to market after a clear link to a deadly outcome. Most agree that the patients brought the drug back to market regardless of what the company did to understand safety and build a model REMS. FDA acted on patient demand based on experience of both disease and efficacy. Patients spoke and FDA listened.

When I start to get nervous, I remind myself that the UK and German regulatory agencies approved the new endpoints (let’s not forget our friends to the North). Anyone that does not consider these a slam dunk is not living in reality.

Even if FDA issues a CRL, this gives us inherent value throughout Europe. Germany, Switzerland and the Nordics alone are worthy of a single digit Billion market cap for the SOC in GBM. When label expansion studies begin, and the market realizes how quickly these will flow in, I rest easy at $1.43. IMHO the risk at this price is extremely Low, and those of us who sit long understand the potential reward.

Probabilities...it all comes down to probabilities

GGB - I rarely post these days but I have to say that I love your reply!

Having worked directly with practicing physicians for more than 25 years, I can say this with certainty. Physicians and other providers don’t give a damn about what major institutions or anyone else associated with Wall Street thinks about a drug. Most all of them are motivated by what treatment will provide the best risk-benefit outcome for my patients. BP can accelerate adoption, to a very small degree slow the uptake of a new competitor option, and even get the opportunity to hear BP point of view, but BP is not effective at stopping progress once FDA approved. The only time I have seen better options for patients not get eventually adopted is when there is a clear financial disincentive for the physician or institution to adopt progress and that progress can be debated (e.g. a drug that requires an oncologist to give their patient to nuclear medicine when they have other effective options themselves).

Not every capitalist thinks like the power brokers. Most do the right thing.

The opportunity to stop DCVAX was to starve NWBO financially, but LP got us to the finish line. This drug will get adopted and once oncologists from other sub specialties see the data, they will race to get in line to have the first IND trial in their population. Immunotherapies are getting new indications monthly these days

Every day, week, month we wait, the stock price keeps going up $0.012, $0.06, and $0.25 respectively...at least since August. I think I can wait around a couple more months at this rate.

We have a saying in the industry... time is money.

When your products have a finite patent life and competition can drastically reduce revenue, every day you are not on the market is lost revenue. Since this is a condition where patients die, there is no future opportunity to recover this revenue. It is truly lost . This is not cold, it is just truth.

In the case of Nov 18 through summer 2020, the time there was not lost as it led to a change in SAP that drastically improves approval potential. This could have a huge positive impact on revenue. The problem now is that the company has no Public explanation that supports further patience on top line results. That does not mean that one does not exist, they just haven’t given reason. I know all about the publication yada yada. In and of itself, this is not a good rationale as most every other drug releases data and often even receives approval before study publication because time is money.

Troc, didn’t the warrant expiration get extended in exchange for the agreement to lock down those shares until November 1st? I fail to see what was gained by the company or for the general shareholder by performing this change. Either management truly felt they would have TLD well in advance of Nov 1, or they wanted to gift friendlies extra time to convert warrants. It baffles me why this maneuver was executed.

Uranium, the abstract deadline for late breakers is different than that of general presentations. As I recall the deadline for late breakers was 11/19, but I could be wrong about the exact date. I haven’t checked for some time and it may no longer be posted on the site.

It is pretty amazing that DI was able to speak with you at all. He once again confirmed the quiet period which is now in place over two weeks. This bodes very well for a positive result pending. You have to read into the “put 2 & 2 together comment” bit it sounds positive to me as well.

I am not sure when we will get results released, but so many signs are pointing to it being a positive announcement when it comes.

Sorry BSB, but in the US it is the responsibility of the sponsor to update the clinicaltrials.gov website, not the FDA. Europe runs thiis differently.

Sojourner, you are one of the few posters that I read religiously. I find your analysis to be balanced and insightful. I guess people get upset when they make bad decisions and want to blame others. Maybe they should read more closely. As an example with this chart you said

Might not is implicit, but people tend to read and hear only what they want, not what is there.

VuBru, I would temper your expectations around the publication timing. Every drug that I have launched took several months to get the data published. Journals don’t move that quickly to complete peer review, editing and eventual publication. I have launched nine drugs, four of them major advances/blockbusters, one of which was called the greatest medical achievement in history by the editor of JAMA. The quickest I have seen is six months, but generally closer to ten.

I hear you, flipper. I pulled out a very expensive wine that I had racked since 2007 and celebrated. Today felt like we broke through a barrier and really good things are yet to come.

Typically companies provide a summary of what will/has been presented, but there are a lot of details that get left out. The company will not be able to stream it as it is a plenary session at the SNO conference. If you want to see it, you will have to buck up and register for SNO. I just checked and it is $795 for two more weeks then $845. I am an allied health professional, so it looks like I may be able to register for much less. I’ll have to look into it.

My guess is that someone here will register and take copious notes. Hopefully they snag a few screen shots of the KM curves too.

1.2B

Hspooner, thank you for reposting IkeEsq’s recap of the 2019 ASM. Soooo many great nuggets there...about partnering, about combo trials, etc. Here is a part that is really relevant today considering the EMEA trial site updatE and corresponding EMEA SAP approval.

Thanks TCP. That’s more like a hunk of bread than a breadcrumb. I agree with Doc, if we don’t hear anything by Tuesday at the latest, there is a very good chance they are sitting on positive data. BTW - I’m pretty certain the SEC rule applies to any day of the week, not just weekdays. So Saturday and Sunday count.

He bought multiple times. As I recall he bought at $7, 5, 3, and 1. Unfortunately, I joined him in the open market.

If the quiet period was true and it was because they have seen TLD, then the 4 day notification period for bad news ends today. Monday could be another good day to kick off a great week.

We doubled in one week. I’d say this was a good week!

Has anyone confirmed or contested whether the company is in a self-imposed quiet period? I think the first report of this was Tuesday, correct.

At what price?

Wise move to add stability and cash to get them through to the finish line. I think they could have waited a little longer and gotten a slightly better price, but this is certainly the best stock sale we’ve seen in years.

You are all over the map bruh.

First you say that IAs don’t spend alpha, then you retrace and say they only spend a small, insignificant alpha=0.005. When playing for billions, and spend saved could be billions earned.

Now your saying the focus is on the third and forth secondary endpoints. I thought you said they are sequentially analyzed. Are you suggesting that the primary and first 2 secondaries are a slam dunk? Or are you backing away from sequential analysis?

I find it hard to believe but it sounds like you are saying we have a winner, and just how big a winner depends on the 4th and 5th endpoints analyzed. Glad to hear you have come around to the bright side of things lately.

Smiths got a few things wrong. Nowhere in the revised EMEA posting does median overall survival appear (mOS). What it say is OS. This is very likely to mean the Hazards Ratio for OS and not mOS or it would have been specified as such. Also he neglects to point out that the primary and first secondary endpoints are being evaluated versus contemporaneous controls. The piece is a bit sloppy.

Are you suggesting putting limit sell orders at very high prices to lock down shares? I’m not following

That $2.01 M in stock is now worth $6.6 M, assuming they were not given a discount to the market which they probably were. The $0.67 M could be worth $2 M, depending on how the deal was structured. Looks to me like the Flashworks folks saw some great potential by taking more stock than cash.

Hi Abeta,

I think you should convert the raw numbers into percents on your plots. It will be closer to a KM curve. If you can figure out the area under each curve, then you could calculate a poor man’s HR. Not the real thing, but useful to see anyway.

24 was said and done by NOV 2018 and it something near 151 (46.4% of 325 - hard to tell whether there are 6 or 7 LTFU because of image acuity, but this is how the math works best)

36 will be 92 (28.3% of 325)

60 will be 68 (20.9% of 325)

Meirluc, I am enjoying this conversation!

The main reason is that this KM curve is changing shape rather significantly as the back half of patients work through time, even more so for the back 1/3. Recall that KM estimate for 3 year survival jumped from 24.2% to 28.2% between MAR 17 and NOV 18. This is a pretty big move in KM curves. Since there is a huge group of survivors 48 in the last 108 this is going to cause a giant leap in 5 year KM prediction as they pass through 5 years.



That is the trouble with the tail end of KM curves. The data moves around a lot when there are relatively few remaining at risk (only about 30 at 5 years) but gets more steady as the numbers grow (Will be more than twice that in the end). Yes, the 5year survival number is going to blow the roof off historical data, especially in those randomized to treatment initially.



I’ll go on record and predict 68 patients will make it to 5 years. I also think 6 will remain LTFU so that will come to a whopping 22.1% for the combined data, much higher for the early treatment folks.

1.12 on Good volume, but not crazy Volume yet. There is plenty of more upside prior to TLD as we get more attention.

You have to go back to the Neil Woodford buying spree to find $1 prices

Here is the EMEA link provided by ATLinsider

https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-001977-13/GB#summary

Please see posts by ATLinsider and Anders for the actual links and DD.

Basically, on Thursday EMEA updated their clinical trials website to show new trial endpoints for NWBO’s GBM study. The primary endpoint is now OS vs Contemporaneous controls. There are five secondary endpoints which include rGBM (aka crossovers) vs Contemporaneous controls, confirmed PFS vs in-study placebo group, PFS vs in-study placebo, OS vs in-study controls and I forget the last one. This was brought to us by ATL.

On Friday, Anders called EMEA and was told that in order to update the site EMEA has to approve of the change and they do the updating. It was further confirmed that they specifically approved NWBO Changes.

Flip, By placing the rGBM endpoint as the second secondary, it is my opinion that they are not using sequential analysis for the secondary endpoints. Of the five endpoints, the rGBM is the biggest question mark in my mind. They would not place cPFS or the IIT analysis after this one in a sequential process for risk of never getting to look at these other very important data.

Are you aware of what contemporaneous rGBM data sets exist? I haven’t done any investigating yet here.

I will have to read up on alpha spend to check what you are saying, but here are a few thoughts.

First, I am fairly certain that alpha is spent if interim efficacy analysis are performed. Each peak at the data spends alpha. Like 95% certain here.

Second, you are talking about sequential analysis of endpoints which is an assumption on your part just as lack of sequencing is an assumption on my part. As I understand it, if there is a lack of sequencing of secondary endpoints then all five are looked at simultaneously and the alpha is split between them. So, each of the secondary endpoints in this scenario would get 0.01 alpha. The advantage here is that if say number 3 is not significant, you still look at numbers 4 & 5, and success on 4 or 5 still counts. The disadvantage being you now technically have to hit a p value of 0.01 instead of 0.05 to be significant.

Third, if Any interim efficacy analysis were performed then there is no way the EMEA would allow for a change in endpoints. Therefore, no IA was performed. Period, end of discussion here. Now we know this to be fact. You don’t get to peak at an endpoint and then change it. So stop with your “why has LP evaded this question” BS because it is total BS. No interim efficacy analysis was ever performed.

Meirluc, I am tracking with you completely except that I think you are being overly conservative in your 5 year OS prediction.

Two things to consider... first since the top 100 median is KM derived, it comes at the point that half the KM percentile for the top 100 is crossed, not at the 50th patient. Here, I have to correct my prior math due to an adding/subtracting error. The KM % for the top 100 is actually 31.2% (100/(308+13)) not 33.9% (100/(308-13)) as I have previously reported out. Therefore, the median occurs when the KM curve crossed 15.6%. At that time about 190 patients were at risk so 30 were alive. When you do the math, you find that this new number agrees better with the estimated 50 because 15.6% of 324 (331-7 LTFU) is 50.5

Second, in Mar 17 only 44 patients had survived past 36 months. Then, 18 months later (54 months) 30 patients survived to 58.4 months or longer. So fewer than 1/3 (less than 31.8% actually = 14/44) died between 36 and 58.4 months. This cohort is 2/3rds Early treated and 1/3 delayed tx/placebo. Now for the final 108 there were actually 48 that made to or very near 36 months (87 in Nov 2018 minus 44 in 2017 plus the 5-6 that were hash marks just prior to 36 months) Since this cohort is 3/4 early treatment rather than 2/3 AND 45% of them versus the 22.9%, as you point out, survived to @36 months, then one should expect more than 75%, probably 80-85% will make it to 5 years. So 80% of 48 = 36 and 36+30=66. Plus there are a few extra that will come from the skipped cohort of 26 patients (331-7 LTFU - 108 - 190= 26) lets say just 2 -3 should come from this between cohort. So now you are talking a conservative 21% (68/324) Personally, I now think it may even hit 22% (71/324).

This is a lot of math to take in and follow, but if you track with me you will see that the long tail gets to be very, very fat.

Doc, there are many brilliant aspects to the new SAP endpoints, the fact that OS was elevated to primary, that rOS is the first secondary, that cPFS comes before straight PFS, that analysis was held off so long so as to strengthen the OS HR determinations, and not the least of which was that regulatory approval was sought before finalizing the SAP.

In the midst of this, I would like to add something that may be overlooked. The fact that LP preserved maximum Alpha by not doing any interim efficacy peaks (2 were planned) is what is allowing them to have 5 secondary endpoints. Brilliant! Absolutely foresighted brilliance.

I have my issues with how LP communicates information to her shareholders, but I take no issue whatsoever in how she has managed the trial. She has done so with more deliberate patience and trial intelligence than most BPs would have managed.