NorthWest Biotherapeutics Inc (NWBO)

[Pyrrhonian]

-Confounded? Not after 6 months. If after 6 months the perceived regrowth disappears it was def psPD and not ePD shrinking from DCVax L. -pyrr

Wrong, by that point it could have been DCVax-Therapy. Immunotherapeutic effects are typically expected to kick in around 4 months should they occur. The 'Pyrr six month hurdle' is simply unscientific and unsound. -flip

No, intradermal DC vaccines really don't cause any inflammation of residual tumor or tumor resection sites in GBM, except in very rare instances. If they inject them intratumorally, maybe. Know why? Absence of cytokines. And as long as there is no massive lesion, partially matured DCs loaded with whole tumor lysate appear to be able to provoke a t-cell response which then induces apoptosis of cancer stem cells and other cancerous cells enough to at least slow down the process of progression and the formation of new lesions, or in some rare cases might prevent it all together. When the tumor is fully formed, however, the immunosuppressive microenvironment of the tumor is too much for the DC vacc to overcome.

Results: Dendritic cell vaccinations were not associated with any evidence of dose-limiting toxicity or serious adverse effects. One patient had an objective clinical response documented by magnetic resonance imaging. Six patients developed measurable systemic antitumor CTL responses. However, the induction of systemic effector cells did not necessarily translate into objective clinical responses or increased survival, particularly for patients with actively progressing tumors and/or those with tumors expressing high levels of transforming growth factor ß2 (TGF-ß2). Increased intratumoral infiltration by cytotoxic T cells was detected in four of eight patients who underwent reoperation after vaccination. The magnitude of the T-cell infiltration was inversely correlated with TGF-ß2 expression within the tumors and positively correlated with clinical survival (P = 0.047).

Conclusions: Together, our results suggest that the absence of bulky, actively progressing tumor, coupled with low TGF-ß2 expression, may identify a subgroup of glioma patients to target as potential responders in future clinical investigations of dendritic cell–based vaccines.

I've never been confident in DCs provoking the breakdown of established tumors esp via intranodal or intradermal injection. And especially not ePD (for inoperable GBM I would imagine DC vaccination would literally do nothing).

There's a reason why those patients are excluded from the trial.

-Those six studies where they get their 8-10 mOS of ePD from. When you actually look at the patients in those studies you find their prognosis was worse than those enrolled in the info arm, who had to pass Ph III criteria to even get that far. -pyrr

Wrong. -flip

No, I'm right. It's not very hard to go through the prognostic factors of each and find that those in the Ph III trial had a better prognosis simply because of the strict exclusion criteria. Even AVII get's it: http://investorsvillage.com/smbd.asp?mb=6543&mn=1845&pt=msg&mid=14810090

- [IMUC's trial] It did not fail for that reason. -pyrr

Yes, it did. Had they just used methylated and unmethylated HLA/A2 population combined in the phase II trial, it would have succeeded. But they went and used all newly diagnosed patients. Which was really cruel. In Phase III they will go back to using the antigen targeted subpopulation. If they get that far. The DCVax-L results could make IMUC's proposed trial economically difficult. Depends on how much information we get on subpopulations. Come on Pyrr, you know all this. -flip

No, they didn't go ahead and use "all ND-GBM patients. Which was really cruel.." Lol.. wow, look they are better at this than you flip. They have devoted their lives to the science and you in your arm chair telling them they're cruel is just ridiculous. They heavily pre-screened patients for the presence of one or more of their six antigens. Some 25% were enrolled who did not possessed them. I'm sure they had their reasons. 75% of the tx group did.

Post-hoc analysis caused the discovery of combined HLA/A1+ - HLA/A2+ methylated patients who also expressed more than 3/6 antigens as the best responders. Of course they cannot test in just these, it's far too small a demographic. They also saw 4 months diff between groups for all HLA/A1+ or HLA/A2+, methyl or non, who expressed at least 1/6 antigens. That's closer to 30% GBM pop.

My point though, which you continue to divert away from, is that in their Ph I, almost half of the patients lived beyond 5 years. For GBM, with a historical mOS of 14.6 months, wouldn't you say that's pretty freaking incredible?? Yeah, I would. But how was their market cap looking? Never got above $350mm.

No one will credit a tx for survival advantage regardless of how good their small patient pop Ph I single arm survival data look, even if almost half the patients quadruple the historical norm (as IMUC's did). Likewise, no one will credit Direct for the survival of patients beyond 2 years. They just won't. Neither the market nor the health community. Unless and until they can prove survival advantage in a randomized trial. So, there is now absolutely nothing that can come out of the Ph I Direct trial that will be pps moving. They needed ORR for that and they just couldn't get it.

Ph II? Maybe. I'd be more confident in that as a possibility if significant shrinkage was a regular occurrence, in at least the injected lesion, but it's not. Some shrinkage here and there. It's just not robust enough. And who knows if some necrosis is causing OS extension.

So, the market will not agree to a higher valuation of NWBO due to Direct data unless and until they can show ORR in the Ph II (probably over a year away for any of those data), or a PFS/OS advantage from a randomized, preferably placebo controlled trial.

-- Expanded access was only available from May 2014 on. However they gave ePD vaccine and monitored them from Jan 2013-May 2014. Where are their data?? Do you think it means nothing that psPD weren't treated along with them during that time and were instead randomized into their own cohort? I think it means a lot. Data from those ePD are probably much less than 15.3 months mOS. you have to hear what isn't said too. -pyrr

Be patient. This is latter data. The info arm covered more mature data. -flip

It's 12-28 months old. I think it's obvious why we aren't hearing about it buddy. It's probably not flattering.

But okay, let's wait another year and then see if they talk about it.

-I'm not sure what Woodford will do. I know he won't hold his shares if the Ph III fails though. And I just don't see him ceasing manipulative tactics to further derisk himself and his investors. If he can, why won't he? You think he cares about you? -pyrr

I know you think Woodford is not interested in building strong industries -- including in biotech. You can feel like that. I disagree. Keep on keeping on. -flip

Yeah, so, I didn't say that at all (classic strawman though). I said if he can make money while de-risking his investment along the way why wouldn't he? You have no idea who he is, or how he'll trade this going forward. For sure he's most interested in maximizing profits. I think he was seeking to elicit a short squeeze, and it somewhat worked. But probably not as he thought it would. It might have even annoyed him that he had to buy it up so much to keep it's head above $7.

-No poster at ASCO
-Just one repeat case study at AACR
-Repeat of info arm patients at AACR
-Some vague wording by Les that we'll hear about Direct patients sometime in spring or summer
-The data are certainly mature enough to divulge now, and MDA has no restrictions upon them to do so. At the very least if there were any partial responses they would be highlighted in a slide.
-The only catalysts I see left are EAMS and HE reimbursement #s. And for reasons I've already stated I don't think either will be strong pps movers.

Personally I think the pps here got a little ahead of itself. Manipulated movements, or pumps, usually do.