NorthWest Biotherapeutics Inc (NWBO)

[Michonne]

I have never heard of "an incredibly powerful but very safe therapy." If DC Vax is it would be the first ever in oncology. What challenges of design are you referring to?

Do you find that statistic impressive? It is not uncommon for even a stage IV cancer patient to be SD for 8 weeks, which even allows for 24% growth of the sum of all target lesions. That is why PFS6 is an important milestone, because that correlates with survival. There is no such thing as "PFS2."

You might find this helpful: http://cancerguide.org/stable_disease.html

Also they do not reveal when Method B patients were enrolled nor under which criteria, and the criteria did change in this trial at some point. What if most Method B patients simply had a better prognosis? In other words, slower progressing mets, stable mets, or even no mets at all (as some patients had no metastases in the trial)?

If they could show these SD patients at 8 weeks had fast progression prior to entering the study, and that that progression reversed or stopped, then that would indicate it was from therapy. But you or I cannot know the individual prognoses of these patients. And the slides do not tell us how many of those still alive are Method B or Method A patients, so we cannot tell which group was enrolled first. Though if I had to hazard a guess, I would say they chose not to reveal the breakdown among those alive (even though they broke down Method among the dead) because it would have shown Method B patients alive from 9 - 12 months and Method A patients alive from 13 - 18 months. That would make Method B appear less impressive, which was not their goal.

Sorry but I do not share the same evident trust you seem to have in this management team. I tend not to trust any salesman or saleswoman when they are talking about their "product." You are sure to get a glossy appraisal.

You also mention: "I anticipate the next whole group data we will hear about will be tumor response (S.D., P.R. and possibly C.R.). This will likely be after most pseudo-progression responses are resolved."

The problem with your take on this is that that isn't how tumor response is measured. Are you familiar with RECIST criteria? It is a measurement of what are called "target" and "non-target" lesions. Target lesions are defined as those > 1cm in diameter. Non-target are all else. Non-target are too difficult to measure, but their number and appearance are noted, as well as a guess on approximate size. In order for there to be a partial response (PR), the sum of the diameters of all target lesions must decrease a minimum of 30%. And also must do so without the emergence of any new lesions.

As an example, for a patient with 5 target lesions of 1cm, 3cm, 3cm, 4cm and 4cm, their sum is 15 cm. Somehow, somewhere, 5cm needs to be "shaved off" for that patient to be labeled "PR." All while no increase occurs in the number of non-target lesions.

I see that you think because sometimes the injected lesion swells only to then recede that that may continue and cause it to even shrink enough for a "PR." But hopefully now you understand that's a misunderstanding.

Likewise, if in our example one of the 4cm tumors was injected and swelled up to 6cm (a 50% increase) that patient would not be labeled "PD," even though PD only requires a 25% increase or greater, because their sum would go up only 13% (15cm to 17cm). So if a patient is PD in this study it is because Direct failed to thwart the other lesions from progressing, lesions that are normally distal (unless the patient is locally advanced and has no mets). And if the therapy cannot stall growth of other tumors, non-target and target, then it is basically useless (except in very rare instances, but there are other therapies that may be effective then, such as ablation or intralesional chemos).

This is also why my initial question is important. I want to know if any of you have seen or heard any PD or PFS data on these patients. You are the grass roots longs after all. My reasoning is because that would tell us if there is any beneficial effect of therapy. Seeing survival times does not tell us anything. They are inseparable from that patient's prognosis. And these small studies almost always pick patients with good prognoses. Also there is record showing they amended the protocol to become even more selective at some point during the study.

But, if one could show that Direct actually had an impact on PFS out to 6 months or so, then that is certainly a plus for the therapy. In other words, if a patient was enrolled as presenting "progressive disease" and not just presenting "stable disease," then became stable disease some months after initiating therapy, that would be compelling. PFS data would give us some idea of this.

So far as I can tell there are no PFS or PD data beyond 8 weeks. And so no way to tell if Direct has had any impact or not.

Appreciate any feedback.