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I listened briefly and it appears to focus on individualised treatements, i.e., treating each patient differently, rather than targetted to the tumour treatments.

That's TMAC. Still some years away, I'm afraid, but incredible potential.

For the forseeable, the next step will be to bring Precision versions of many chemotherapies and treatments. Next up, Precision Velcade. Would be amazing to hear that the next drug in the Precision pipeline has entered pre-clinical studies (i.e., as Precision Velcade did in January, 2022).

So far each cohort has taken ~6 months, which appears to be longer than expected by Avacta. Fingers crossed that if DE2 happens, C2 will be significantly shorter.

@BITL - I don't think it was ever planned to release PK data in Q4 2021. This was mentioned in presentation slides as "Initial PK data", which was to inform the selection of the next precision product. The release of P1a data was always scheduled for mid-2022, although now that seems to have slipped by a few months.

DLT = dose limiting toxicity
MTD = maximum tolerated dose.

The above links by gmcc definitely point in this direction....

Was any more info on this given at the in person AGM? I had assumed that this referred to a new way to use the radiotracer (used in PET scans) that was based on the same basic principle as Precision, i.e., a radiotracer with a linker that makes it unable to enter cells until it is cleaved by FAP in the tumour microenvironment.

PET scans are amazing, but they can cause severe damage around the body, including an increased rate of future cancer. So if Avacta could use Precision to develop a safe(r) type of PET scan, that would be revolutionary.

In some ways, this is similar to the treatment with radionucleids by Point.

Hi BITL, thanks for your post, it's a good chance to go back and see the score. Indeed, as you (and others below) have pointed out, it is not as clear as I thought (i.e., whether or not ava6k will require a Phase 3).

In the presentation on 12 Feb 2020, AS states (around 1:50) that Phase 2 will be the pivotal trial and Phase 3 will using ava6k in addition to a checkpoint inhibitor, i.e., a combination of drugs. In clinical research a "pivotal trial" is "a clinical study seeking to demonstrate the efficacy of a new drug in order to obtain its marketing approval by regulatory authorities".

But just to muddy the waters, in the graphics of the above presentation, it says that Phase 3 will be the pivotal trial. So it's not entirely clear whether Phase 3 is needed for regulatory approval.

Thanks ES, a great summary of the timeline so far. A few of the trolls this weekend brought back the old nugget, that 90% of new drugs fail during clinical studies. While true, it is misleading to apply this blindly and assume that it also applies to ava6k. Why?

-It is a prodrug, not a new drug. The profile of the drug (dox) is extremely well known, so what the clinical trial is testing is the delivery mechanism, not the effectiveness of the drug. Note, on this point, that for such a trial, Phase 3 is not required.

-One of the main reasons for new oncology treatments to fail is that the toxicity of the treatment is too high. At least one dose escalation (by 50%!) has already occurred. This shows, at least at near the standard dosing amount (i.e., cohort 1) toxicity wasn't a limiting factor.

-Most importantly, it is not a blind study. The Avacta board have access to the data as the trial goes on. AS and others have mentioned multiple times that they are 'very pleased' with the data, that the data is 'remarkably consistent', and that the board is 'very confident in the short and long term prospects of the therapeutic division'. If the data wasn't looking good (either bad or even just so-so), the board would not be calling attention to the read out again and again. They would try to distract with other 'upcoming products'.

-The Therapeutics division of Avacta will live and die by the sucess/failure of the Precision platform (as it also covers half of TMAC). If ava6k fails, I would expect this division to close. Not only are they not keeping their head down, they recently moved the division to a more expensive location and are currently advertising new positions. Not the actions of a group whose future is uncertain.

Of course, we won't know it works until the official RNS. But not all trials are equal and given the above, it seems clear to me that the 90% failure rate often touted simply doesn't apply here.

Hints that another (UK) hospital is recruiting.
https://twitter.com/JR97793957/status/1537112642787106821
No es malo...

In the April 6th presentation, AS stated that they were halfway through cohort 2 (i.e., DE1). In the same presentation (and also updated on the clinical trials website on the same day) he said that The Beatson Hospital in Glasgow was 'now open and screening patients'.

One may then ask, what was the Beatson screening patients for? Cohort 2 was already under way ("halfway through"). The only possibility is for Cohort 3 (and beyond).

In the same presentation, AS said "we expect to go through 3, probably 4, cohorts" and that the Phase 1a would provide results in Q2 or possibly early Q3. That timeline hasn't slipped.

To me, this is pretty clear evidence that DE2 and possibly DE3 must have already happened.

I disagree a bit Timster. Yes, the board's job is to always be positive and build up investor confidence. But they wouldn't be likely to point to a specific near-term event, to draw significant attention to it, if it was likely to be a negative event. Rather, if ava6k wasn't looking good, they would be highlighting other aspects of the company, i.e., diagnostics, collaborations, etc.

Put another way, why build up a specific event if that event is going to destroy the stock price? Better to draw attention away and play down its significance.

FWIW:
-i don't think they are recruiting for Phase 1b yet. This is an inference and alternatively can simply be read as them outlaying the planned Phase 1a and 1b parts.
-in the Avacta timeline, Phase 1b wasn't expected to start until the end of Q3 or early Q4. There is usually a break between the end of P1a and the beginning of P1b in most studies.
-Each hospital has a specialisation, so a specific mention of sarcoma doesn't necesarily mean a change in phase.
-The patientwing site looks like a poor copy and paste job, so the fact that the primary endpoints aren't mentioned means little. Whether or not these end points were met in P1a doesn't mean that they wouldn't be used in P1b, i.e., they remain throughout the study.
-The clinical trials website is not updated regularly, so it is definitely possible that US sites are online, but haven't been announced yet.

I remain confident that the ava6k trail is going well and expect some amazing results in the next month or two. I'm also not opposed to 'connecting the dots' and I think a lot of clues are out there (selection of ava3996, DE, move to London, 'very consistent', etc). But in this case, I think people jumped the gun.

I have invested in (and follow) a number of other biotechs (e.g., crispr, moderna, gilead) and from those I can state that dose expansion to new cohorts are *not* normally communicated to investors. The fact that Avacta did announce DE in Feb is, in my view, likely due to the fact that they are a young biotech, and face an uphill battle to assure investors that all is well. Normally, you only hear anything at the end of each phase when results are announced.

Note that back in the Sept (21) update, AS stated that he expected to undergo multiple dose expansions before the end of the year. We heard in Feb., that the trial was going slower than planned due to covid delays. So according to the trial design, there is nothing to stop multiple DEs within a few months.

My (likely optimistic) view is that DE2 (cohort 3, C3) had already started or was planned the last time AS gave an interview, which could explain his "probably four cohorts" statement...as it would be strange to project 2 cohorts in the future. Would make much more sense if C3 was already underway.

Based on the above, I don't expect any updates to the ava6k trial before first read out, which I was very happy to see is still expected 'mid-year'.

RD - I don't think I understand your point. WIth ava6k, dox gets released in the tumour and gets processed (i.e., used) there. Little or none should escape into the system. So in an ideal word, the systemic exposure to dox, when using ava6k should be little to none. Of course, FAPa exists elsewhere in the body, so some dox will be released from ava6k throughout the body, but this is low. This will be the dox that goes around and kills healthy cells (i.e., cardiotoxicity). But the whole point of ava6k is that this should be as low as possible. In mouse models, for the same amount of dox in the heart, 18x more was in the tumour. A fantastic result, that may even be bettered in humans (as impled by AS as mice have more freely circulating FAPa than humans).

gmmc - in standard dox, all organs experience the same amount of dox. With ava6k, the tumour sees much more (~3x more than for the equivalent amount of straight dox) and the other tissues experience much less.

Yep, that's the mystery. Both Neil and Fiona explicitly mentioned the possibility of patients receiving more cycles of ava6k (relatively to dox by itself). If the cumulative max amount of dox is held constant, then this is impossible if the amount per cycle is increased (and we know that they have increased the dose at least once). AS also took pains to point out that the MTD for ava6k may be very different than dox on its own.

The clinicaltrails.gov site states that the patients will keep receiving treatment until some conditions are met, which includes "reaching maximum lifetime cumulative exposure to doxorubicin (or other anthracyclines)."

If the max cumulative exposure to dox is kept the same, then the comments by Neil and Fiona don't make sense. My guess that the max cumulative dose is calculated from the systemic amount of dox present (as estimated through urine and blood samples). For standard dox, this is directly related to the dose amount. However, for ava6k this is (hopefully) very different. i.e., very low systemic dox as all/most of it is restricted to the tumour.

If true, this would allow continued dosing well past the current cumulative limit.

As noted by another poster last week, it would be quite immoral to stop treatment (i.e., stop dosing) if the treatment is working (tumour reduction) with little or no side effects.

Hence, let's hope that the dosing continues...

Indeed Wress, nothing to do with affimers. It's great to hear how that 'is the future' of point (canSEEK), he seems genuinely excited about it. AS explains it much better though.

Sorry Hurst, but the panel discussion at ASCO on "Precision" has little or nothing to do with Avacta's "Precision platform". So no, Avacta's pre-clinical data will not be discussed or likely mentioned.

But indeed, we are waiting for the two US sites to come online soon, presumably to participate in the DE2 cohort and beyond. That will be very welcome news when it lands.

AS has also said, on multiple ocasions, that he is very pleased with the data so far, and that the data are 'very consistent'. Oh, and they have also said that they would chose the next drug in the precision pipeline once the data supported such a decision. So yes, they have access to the data.

Could be Mr. A. But if the technology wasn't working, you wouldn't hire people to replace those that have left.

In much the same way that you wouldn't move offices (especially to a much more expensive site) if you didn't see a bright future for that division. I could image that before last August, one could have argued that such a move was based on optimism, i.e., that the technology had a good potential. But after it has been in human, you know one way or the other if it is performing as designed.

Nice find! 5 research associate/research scientist positions. Would be strange to hire more staff if the technology underpinning the therapuetics pipeline wasn't performing.