Doc,

Other possible discoveries:

1) The reason for the lift on the hold
2) The improvement in the process of manufacturing
3) something about umbilical chords
4) A picture taken between a survivor and CEOs of different companies
5) Sicker patients enrolling in the “back half” of the trial

At least we can play the guessing game to entertain ourselves while we wait :)

Dr Bala,

It is important to understand that those figures you gave out are not for treatment but for the whole ITT blended group.

Treatment group should be much better

Hi Dr Bala,

These are the survival numbers for blended blinded. I was particularly interested in the control group only.

Any thoughts are appreciated

Doc,

This is an estimate for where I have the Control group (yearly survival %):
1y- 78%
2y-37%
3y-19%
4y-10%
5y-7%

Does this match closely to what you’re anticipating?

Also, is what you “discovered” related to imaging and CD8 TILs by chance?

Doc,

Through your DD, what’s your thoughts on how the crossover group will do in comparison to historical SOC? 10%, 20% better?

It will be interesting to see the TIL activity of that group

Ahhh yes, very good

Doc, I hope you’re right because that’s one thing negative forces won’t be able to spin.

Even without an immediate partner, once the OS data is known it will be a ticking time bomb for shorts to cover and BP to partner or BO

To be honest that graph would be quite remarkable for SOC to not be separated from TX group for the first couple years. The blended, updated data demonstrates a 89.3% (1 year), 46.4% (2 year) survival compared to historical survival of 65% and 31% respectively.

Those numbers represent a ~37% and ~48% improvement than what would be expected based on decades of survival statistics. AND that represents blinded, blended data....

Oh boy, we’re almost there and soon enough we will no longer have to guess

The Dr obviously made an error and has recognized that he messed up.

Have to thank AVII for bringing even more confidence to this board.

In this video she mentions that she thinks since nearly 90% got the vaccine, this likely turned into a very large single arm trial.

Does anyone think this will be true?

I would assume many two arm oncology trials also have high rates of crossover as well.

Instead of making it into a single arm trial, couldn’t they compare early vs late and then also include a KM curve that adjust for crossover effect?

The basis of the article is that PD-L1 inhibitors such atezolizumab (in this study) may work significantly better in patients with a high DC signature before treatment. Aka- Dendritic cells make PD-L1 inh. more effective.

Examples of drugs that target
PD-L1 :
Keytruda (Merck)
Opdivo (BMS)
Tecentriq (Roche)

Great find Hyperopia :)

Again, beautiful work done by you and the Mrs! I bet the results we get will be even slightly better for MOS and significantly better for 3-4-5 year survival!
Permanent beach season is around the corner

Excited to see Mr & Mrs Alphapuppys OS model soon. Maybe tonight?

Awesome! No problem, just wanted the modeling as accurate as possible. Hopefully there isn’t too much of a change in results after correcting. Your hard work is incredibly appreciated btw

Alpha-

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1507-6


Thanks again!

You’re the man! How much does the modeling change if you correct the 111 number for the 99 that we’re actually in the SOC arm? Thank you

Alphapuppy- You are one of the posters that I enjoy the intelligent analysis and input you provide. Fantastic work.

I was wondering in your modeling, if there was a way to play with the control numbers. For instance, is there a way to adjust the control group in order to see what a 15-20% improvement would yield for a curve and Values?

Don’t bother if it’s too much work, just curious from a conservative analysis. Regardless, thank you for all that you’ve provided! Your impact is tremendous!

6/15

1,3,6,8,19

My ASM Questions:

1) For NWBO going forward, what is the biggest challenge or obstacle in the next 6 months
2) Following TLD, will be you working to get the data from the trial into a journal this year?
3) In the last year, what was the accomplishments that warranted bonuses for executives?
4) “What in Gods name is happening to this company?” -My Fiancé

I’d love to say it’s almost beach season.... but we will have to wait a bit for that :)

Hang in there Longs, it’s not supposed to be easy

If this were to be the case, then your saying they deliver TLD or any other type of sp significantly moving news afterwards?

Interesting..

What to talk about at the ASM then?

Hi Doc,

I’ve been doing some reading on the different trial designs, specifically with crossover built in. Are you familiar with the Keynote-024 trial?

Essentially Merck designed this trial for patients with NSCLC who progressed to have the option to crossover. Patients were assigned to either The treatment group (Keytruda) or control group (Chemo).

In order to account for crossover confoundment they used three crossover adjustment analysis methods:
1) simplified two stage method 2) rank preserving structural failure time and 3) inverse probability of censoring weighting

Long story short, after using these statistical methods they were able to adjust the control arm OS KM curve.

The result was a movement towards what is typically seen with OS for control, moving the whole curve towards the left and the median OS from 14.2 to 8.7 months. Treatment saw a median OS of 30 months.

Anyway, I was curious if you or anyone on this board was aware of this crossover adjustment in this trial. The updated analysis was published January 2019 in the journal of clinical oncology .

TIA!

And also directly mentioned:

“The projected market values for Nivolumab, Tecentriq, DCVax-L, Imfinzi?”

https://www.prnewswire.com/news-releases/global-cancer-immunotherapy-market-is-forecast-to-hit-115-billion-by-2023---reportsnreports-300981446.html

Scotty didn’t you say data in January?

Doc, just curious as to your thoughts on what other indications Dcvax may be used for down the road?

-Alzheimer’s?
-HIV?
-Prophylactic use?

TIA
Happy Holidays to all!

I think a lot of what they are needing to discover from this trial is related to biomarkers. If the drug is working, how is it working? If patients are living longer, why are they living longer? Instead of just saying it targets all antigens, they will know which biomarkers may offer a more detailed MOA and better prognosis/predictability for treatment outcome. Of course IMO and I guess we will find out soon.

Regardless I feel like the industry has not only accepted immuno-oncology, but is racing at breakneck speed to discover treatments in the space and learn more about biomarker testing etc. All of these things are great for the future of patients and hopefully we will see dramatic improvements in cancer survival in the coming years.

Thanks to all who contribute here, hopefully we are close to the finish line of this marathon

What kind?

Well said. A little common sense goes a long way

Things that have been given to us recently:

Follow-up survival data from the Informational Arm patients who did not qualify for the Phase III trial are encouraging and appear consistent with the blinded interim data from the trial. In the group of 25 Informational Arm patients who had actual of apparent early tumor recurrence, the follow-up data showed that 40% of the patients lived for 3 years or more, 20% of the patients lived for 5 years or more, and 12% of the patients are still alive at 7 years.

The above was given to us by MB at ASCO. We know that these patients received DCVax-L early. This seems quite encouraging to me, unless I am missing something?

The updated improved data was given to us at SNO. I assume the data improved because more patients crossed the 3 year mark? The 3 year ITT blended survival of 28.2% is better than Optunes 26%

LL gave a presentation at UCLA in early March. In the presentation she mentioned that the majority of the 3 year survivors were progression free survivors. She mentioned that they were like Brad. Brad was treated with DCVax-L right? How many of these survivors at this time point would we typically expect to be PFS? Most of these “3 year survivors” had been on trial for longer than 3 years if I am correct?

LL mentioned that they compared the DCVax-L trial to other trials including Stupp and the prognostic factors were all very similar. I take this to mean that these patients were not a healthier group of patients to begin with. This has been a bear argument for some time now, which seems to be debunked.

I may be missing something, but from what I’ve read and seen, I feel as though the data will be quite good. I am also given common sense confidence by the 24/7 posters on the board that continually bash all things NWBO and yet have no stake in the game. They are here for a reason.

I read once that a patient investor is a wealthy investor… I guess time will tell :)

Not a chance pfs isn’t statistically significant.... IMO of course :)

Within the past month (more like 16 days), there have been 31 job postings on LinkedIn for Cognate

Hmmm

I think there had been some discussion on which countries the RAs would be from earlier on in the message board. Just to clarify :

“As soon as the SAP is finished (including review by advisers), it will be submitted to the regulatory agencies for each of the 4 countries where the trial was conducted, for their comment and buy-in”.

Happy fourth to my fellow Americans!

Bingo!

I am following you there Flip!

Just curious if you guys are taking into account what LL said:

“The majority of these 3 year survivors have pfs”

I would imagine when trying to estimate how many will live to 4-5-6 years, factoring in pfs the estimates could be higher since there would be a majority of these patients not contributing to the death rate due to gbm? Just a thought

Very odd and quite frustrating. You mentioned that you thought she might be sandbagging at UW. Why?

Woahhhh.... 28:00 minutes in-
LL- “the majority of patients actually did get the vaccine at some point, umm so the, so this actually probably turned, is going to turn out to be a very large single arm study that has a variable where some patients got the vaccine early and some patients got the vaccine late”

This is an unbelievable find

Larry’s numbers are off regarding how many initially received SOC + DCVax and how many just SOC...just FYI to anyone who reads his article

I am going to look for some examples of other small or clinical stage biotech/pharma companies that presented positive phase 3 data . I’d like to see the market reaction resulting in change in share price/market cap.

Does anyone have any examples off hand? I’d like to evaluate the immediate market reaction potential in order to prepare for what is to come. Thanks guys

Great post, I agree my friend

Agreed. I’ve been saying that for a while now. QALY points will help the approval process and allow for more room for treatment cost.