Hi there friend @ydqcauThanks! And look - I agree - I don't...

Hi there friend @ydqcau

Thanks! And look - I agree - I don't think the 10 patient extension would not be enough to apply for Accelerated Approval on its own.

What I think they are aiming for is to get reasonable confirmation that the initial result for the two BC patients was not a statistical fluke, and confirmation that BC patients on Vaxinia perform well against the "Surrogate End Point" of tumour control - ie Stable Disease, Partial response (major shrinkage of tumours) or Complete Response (eradication of the tumours). And they want to do that as fast and cheaply as possible - which is the purpose of the 10 patient extension.

They can do that as part of the current dose escalation trial - once Optimum Biologic Dose has been determined.

That's why they expect to start the expansion in Q2, and they haven't started it yet. They are still determining the OBD. Once they have the OBD - the most effective dose level (above which there is no significant extra benefit) - they will know that they can start the 10 patient expansion with the best possible prospects of maximum success.

They don't have to whip up a whole new trial and trial protocol with all the FDA paperwork required to do that. They can do the 10 patient expansion pretty rapidly - and then consider the results.

If the tumour control results are as good as they hope - or even just a bit better than the current Standard Of Care - then they will know that they are looking at something much better than the SOC because the SOC is so toxic, expensive, hard to administer etc. We already know that Vaxinia beats the SOC hands down in those respects (assuming there is no nasty surprise at the high levels of Vaxinia dosage - but we are now at 3 x 10⁸ so I think they are pretty darn sure its's very very safe). With equivalent effectiveness - and very possibly far better effectiveness - we are on a big winner.

The FDA will then, I am sure, require a Registrational Study - but that would almost certainly be a Ph 2, not a Ph 3 - and yeah, maybe 50 or 60 patients - with a view to Accelerated Approval as soon as they can demonstrate/confirm real achievement against the "Surrogate End Point." ie. If they can demonstrate good results in terms of tumour control and tumour shrinkage, the FDA will accept that as being a high probability indicator of eventual improved Overall Survival (the usual "End Point" - without waiting for the trial to grind out for several years to get that OS data.

So then - bingo - Accelerated Approval. Vaxinia gets approved as a treatment for Biliary Cancer, with the approval to be reviewed subject to the ultimate OS data from the Ph 2, and maybe a follow up Ph 3. But meanwhile it would be "in the market" and starting to generate major revenue, either for IMU on its own or (much more likely) through a partnership deal with Big Pharma.

I'm sure IMU is doing this in close consultation with the FDA - which is the whole point of the Fast Track designation. The FDA will be supporting the 10 patient expansion as the quickest pathway to get to a limited Registrational Study.

I just rewatched the webinar with Leslie and Dr Paul Woodard where they talk about the Vaxinia results. Someone asked a question early in the Q and A about whether the Stable Disease or Partial Response patients might improve over time (the way the Complete Response patient did) with the SD patients reaching PR (or better) and the PRs becoming CR. Leslie missed answering that, so later in the webinar I put it back in as a follow up question. Dr W responded. He confirmed that yes - some of the patients who were SD and PR as of 31 October (and maybe some of the Progressive Disease patients) may indeed improve their results by the time another data cut is analysed, because of the whole "pseudo-progression thing." ie. in the short term their tumour may grow and look like Progressive Disease, or just look like Stable Disease, but really this is because they are being attacked by the immune system and are inflamed by that, and then later as the immune attack becomes successful, they shrink.

That was the answer I expected/hoped for.

What I didn't notice at the time was his follow up remark that "I should also say that we're continuing to enrol patients, so it's.. it's a moving target. We had 34 patients when we did this data cut; we have more now."

LC, Doc W and Dr Bradley Glover are all on screen at that point. All 3 nod. LC smiles pretty broadly and Doc W's mouth twitches.

Students of body language might be inclined to read something into that. Myself - if it was a card game - I'd be confident they know they have a good hand. I'm betting a good number of the new patients are showing SD, PR or better.

Normal caveats apply: I could be wrong; they could be great bluffers; we could all just simply be mistaken; the relatively low numbers to date may have generated a high rate of positive responses out of sheer chance.... etc etc.

But that's why IMU is currently 11c and speculative - with massive possible upside - and not a couple of bucks with confirmed results but far less chance of further capital gain.

Cheers

Dave