Replies to post #45874 on NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

Ready. Current situation from my perspective. IMHO.

From most likely to least likely. (For simplicity, I am primarily only answering this with regard to FDA considerations -- assume that global regulatory progress is happening in parallel.)

Scenario 1: They already have 1st interim results, they have filed an AA/BLA application (Mid September) through rolling review, they are awaiting a 74 day response, and they will announce filing acceptance soon. Under this scenario AA could occur any time between now and the end of February if rolling/priority review.

Scenario 2: Same as situation 1, but they filed the AA/BLA documents late, so any regulatory acceptance of filing will be later in this year. Consequently, any 60-74 day FDA response would likely not occur until January regarding filing acceptance. Similarly, move AA out to March/April if rolling/priority review.

Scenario 3: Same as situation 1, but the trial remains blinded and no regulatory response is announced until 3 to 5 months after full enrollment.** (By full enrollment, I mean complete enrollment, which I believe has already occurred, whether it reached 348 or something close to that number.) At 3 to 5 months, the confirmation trial on secondary endpoints will conclude and the trial would be fully approved. **The 3 to 5 month wait after complete enrollment would not be from thin air but rather the amount of time necessary after full enrollment to reach top line results set out by Linda Powers as far back as December 2014. I believe we fell off that schedule then returned to it when the German and Canadian large hospitals enrolled at a great rate -- as articulated/anticipated by Dr. Bosch to poster betweenthelines back in 2014. Under this scenario, full approval could be anywhere between February and May 2015.

Scenario 4: The blind is already off the trial, full approval is being sought through rolling/priority review, and it will be completely submitted later than the approximate September 4, 2015 date we heard about. Say late October to early November. If this were the option, there is no question it would be the highest priority for the FDA, and although the submission might be later, full approval could happen head spinningly fast -- like before February.

Scenario 5: The Tariquidar parallel -- In other words, no interim has occurred yet and they will wait until 3 months after complete enrollment to conduct an interim analysis. That seems hard to believe, because of the document submissions recently required by protocol during the suspension.

Scenario 6: They have not reached the 1st interim analysis. That seems even harder to fathom for reasons most are already familiar with -- it would results high above long expectations, IMHO.

Scenario 7: I really don't see safety or futility at this point, and I find them the least likely possibilities.


Outside these scenarios, I've discussed with sentiment the possibility that there may a desire by all regulators, Celldex and NWBO to await the second interim results from Celldex. Not out of niceties, but out of necessity to determine labeling and manufacturing considerations for both companies.

Consider,

Scenario A: If Celldex 2nd interim results are better in NWBO's egfrIII subclass ( I peronally don't think they will be), NWBO would want to know that slightly ahead of approval v. slightly after approval, instead of being blindsided by results that would change their labeling, manufacturing forecasts and regulatory consideration throughout the USA, Germany, Great Britain and Europe. If Celledex results in that subclass came out afterward it might also have a predictable but otherwise unavoidable hit on share price. This is also of Benefit to Celldex for obvious reasons.

Scenario B: If Celldex's 2nd interim either is a continue, futility, or simply poorer results than NWBO's egfrIII subclass, it would help NWBO to know this slightly before approval because it means a complete/full launch, it means complete labeling, etc. For Celldex, it would simply mean they take their remaining marbles and go home.


For regulators, it would greatly improve their ability to provide the public the correct information right off the bat.

Why silence then? Well in the meantime NWBO results continue to mature, and if they are still blinded, with the exception of an interim result, the long tail appreciation correlated with DCVax-L can only improve.

So under that rather bizarre side twist, what do we know about Celldex's 2nd interim?

1. 75% events (deaths) will occur before the end of the year.
2. 50% events (deaths) occurred by June earlier this year.
3. Those numbers do not bode well for CLDX if you scratch everything out on the back of a napkin.
4. CLDX should give the interim analysis DMC recommendation by mid January or sooner.

(I only briefly edited this. Now back to the game)