Hi there @fourdollarsI'm having trouble making the reply...

Hi there @fourdollars

I'm having trouble making the reply function work. So - this post is a reply to your post at 15:46 today.

Thanks for your kind comment. I try to help and I enjoy participating in discussions here.

I do have a keen interest in IMU, like most of us here, and of course it is possible that my own heavy exposure to the stock influences me to be less critical than I should be. There will be opinions both ways on that, amongst the readers here, and everyone can make their own judgement - as they should.

From my personal perspective, I don't think my comments were either particularly optimistic or particularly pessimistic.

My key points were/are:

• We don't have enough data yet to know - so the real story here is a mystery
• If Her-vaxx is showing evidence of failure then the company is required to disclose that to the market. They haven't made any such disclosure so I draw the conclusion that the cancellation of the supply agreement is for other reasons

That second point could be construed as optimism. I would say, rather, that I have seen no evidence to date of IMU significantly failing in its duty of disclosure so, logically, it would seem unlikely that the current situation is such a failure.

My alternate suggestion is that the supply agreement is being cancelled for commercial reasons. I haven't speculated on what those might be. Some others have, and some of those speculations (eg "deal imminent") are certainly optimistic. The full range of possible commercial reasons is wide - some would be positive and some might be negative.

I'm just holding an open mind until they tell us more.

The original Her-vaxx trial - we are still waiting for final data on Overall Survival. If that data turns out to be excellent then they might still go for a registrational study. In the meantime they are not sitting on their hands - they are running extra trials to expand the range of possible applications in combination therapy, which seems to be sensible and in line with repeated statements by IMU (and others) that combination therapy is likely to be the way forward for Immunotherapy.

A small point - IMU did not "cancel the trial" and it was not "terminated early." The IDMC suggested that Imugene reduce the total enrolment, which would have the effect of shortening the study time, but the trial is certainly being completed in full for the patients they did enrol - which is why we don't have final data yet.

The IDMC recommendation on this gets a lot of comment here on HC but I think it is worth examining in more detail. The only definite knowledge we have on this - ie "officially released to the market" is in the Announcement of 23/11/20: https://hotcopper.com.au/threads/ann-imugene-her-vaxx-shows-positive-overall-survival-in-trial.5770964/

The relevant passages are:

"The Independent Data Monitoring Committee (IDMC) confirms a favourable survival outcome with no added toxicity for HER-Vaxx combined with SOC chemotherapy over chemotherapy alone and advises to lower the number of patients required for study completion."

Also: "the IDMC reported no safety concerns and viewed this preliminary data as strongly in favour of a HER-Vaxx survival effect"

And then:

"The IDMC provided guidance that it is scientifically and ethically appropriate to reduce the overall number of patients required to complete the study given the strong signal observed in the data."

The CEO's comment on this, included in the Announcement, is that: "I am excited that the interim analysis favoured the survival outcome for HER-Vaxx and the IDMC suggested to shorten the study by lowering the number of patients. "

Many posters here on HC interpret this as the IDMC saying that the study should be shortened "for ethical reasons." I do not interpret it quite the same way. The literal statement was that "it is scientifically and ethically appropriate to reduce the overall number of patients required to complete the study given the strong signal observed in the data." My interpretation: the "strong signal" is a reference to the "overall favourable survival outcome with no toxicity" and the IDMC is saying that scientifically the study has already shown that HER-vaxx is beneficial to survival, so they should just shorten it by restricting enrolments. That would have the effect of giving them final data earlier than would be the case if they enrolled the full original planned number. ie it would be "scientifically appropriate" to do so because additional enrolments are not required to prove effectiveness.

They also say it would be "ethically appropriate." Let's look at that:

A registrational trial would require a larger enrolment than was ever planned for the Phase 2 trial. By shortening the Phase 2 Imugene would be reducing the wait for a registrational trial to start - but it would still require them to wait for final data from their shortened Phase 2 trial. It's just that the wait time for that would be shorter than it would be if they enrolled more patients.

Yes - you are correct in saying "patients that could have been enrolled in the Phase 2 trial were denied this treatment" but when you ask "Where is the ethics in that?" I would suggest a simple answer:

In ethical terms the IDMC will be trying to achieve the greatest good for the greatest number. Yes for sure - by reducing the enrolment from the planned 68 to the 36 enrolled so far Imugene would be "denying" 32 hypothetical (not yet identified and enrolled) patients the opportunity to participate in the Ph 2 trial, of which probably half (16 hypothetical patients) would have otherwise ended up on the Her-vaxx arm of the trial.

However, by reducing the total time required for the trial Imugene would also be reducing the wait time for a much larger registrational trial - which might involve and provide benefit to hundreds of patients. If that registrational trial went ahead and was successful, then the IDMC recommendation to shorten the Phase 2 trial would have also reduced the total wait/delay time for the drug to go to market - and that reduced delay would benefit many many thousands of hypothetical patients. So yes - shortening the Phase 2 would disadvantage a potential 16 patients, but it would potentially advantage many many thousands of patients in the longer term - which would make it "ethically appropriate."

I think that's a fair interpretation of the 23 November Announcement.

Now back to today's Announcement, which has caused understandable disappointment:

I entirely understand why many here are unhappy about today's announcement. We were all expecting "good news" because we have become accustomed to good news. I remind myself, however, that I know of no company which has a record of unbroken "good news" announcements without a single "bad" price sensitive announcement.

In my opinion this one could be good or bad. The degree of "goodness" or "badness" could be mild or large. We just do not have sufficient information yet to know. Everything else is speculation.

And sure - of course - like yourself, @fourdollars , I would love to know all the facts right now.

Thanks again for your kind comment and - again - I'm not saying you are wrong. I'm just saying that you may be right, or the "boosters" may be right or (more probable in my view) the facts will turn out to be somewhere in between.

We will find out in due course.....

Cheers

Dave