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Now, I have a different view on this from Toukmoron's backward look at life. Previous incumbent or new role, this indicates that Avacta's clinical trials have only just begun.

OK Toukankahmoron, I'll bite.

What hype did Alan put out about AffiDx?

No lurking in the wings. Limelight's on you now. Go for it!

Why worry about the SP falling? Nothing has changed since the last RNS. Unresearched weak hands selling, informed LTHs buying more at these unexpected prices. What's not to like?

I wouldn't read too much into this. It'll be their marketted anticancers and any that are about to be approved.

Yes, I think that's it JT. A matter of rate, overload and leakage.

I like pizza and could happily eat a delivered pizza a day for a week, but dump 7 or 20 or 50 pizzas at my door and nearly all of them will be going in the bin!

This raises an interesting possibility for variations to the AVA6000 trial...

So stated a few days ago, we don't know how long the IV infusions are - the concentration and rate of infusion. Avacta should have a good handle by now on the PK, with graphs and everything. They should be beginning to understand the rate at which FAP can cleave AVA6000. Could longer, more dilute infusions increase the amount of doxorubicin cleaved in the TME and getting into the cancer cells? What's the optimal rate? Questions they want answers to.

Good point!

Well I was answering the "where did the dox go if no side effects were observed ?" question.

Yes, certainly, if the injected polymer has dispersed and been elinimated, then there would be nothing available to bind the prodrug.

The procedure is this:

A formulation consisting of SQL70, a prodrug-activating biomaterial, and SQP33, a prodrug of the anthracycline antineoplastic antibiotic doxorubicin, with potential antineoplastic activity. Upon administration of SQ3370, which consists of the injection of SQL70 at the tumor site followed by the intravenous administration of SQ3370, the prodrug SQP33 binds to, through an as of yet not identifiable mechanism, to SQL70 at the tumor site. After binding, doxorubicin is released over a period of days, intercalates into DNA and interacts with topoisomerase II. This leads to an inhibition of DNA replication and repair, and prevents RNA and protein synthesis.

And with timings:

Participants will receive 10 or 20 mL of SQL70 biopolymer injected intratumorally on Day 1 of each 21-day cycle into a single lesion and then receive escalating doses of SQP33 protodrug administered IV from Day 1 through Day 5 (5 doses) of each 21-day cycle.

Anyway, there's no comparison to AVA6000 - and they don't have ODD!!

It wasn't doxorubicin that was infused, it was 'protodoxorubicin' - prodoxorubicin to you and me.

I should think that if it wasn't in the unbiopsied parts of the tumours, it was excreted unchanged - i.e. inactive.

I see what you did there mowzer

Can see why this platform is so hit and miss: the procedure is manual, complicated and long:
https://www.cancer.gov/publications/dictionaries/cancer-drug/def/doxorubicin-prodrug-prodrug-activating-biomaterial-sq3370

Whereas the AVA6000 procedure is just an intravenous infusion...
¯\_(?)_/¯

Very interesting. Thanks.

Here's some good background about Shasqi, its platform and SQ3370.

https://en.m.wikipedia.org/wiki/Shasqi

The Wiki entry states "Shasqi has presented interim Phase 1 results for SQ3370 in advanced solid tumors showing the total dose of doxorubicin administered to the tumor site was 12 times the conventional dose, without the myelosuppression and cardiac toxicity expected from those dose levels.[27]"

However, whilst informative, and one can see the parallels with the way our trial is being conducted, I can't see that "12 times the conventional dose" explicitly laid out in the cited reference: https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.3085?role=tab

Is that your opinion foxhat, or are you quoting from something you've read that you're not going to tell us about?

Yes that's J&J (Janssen in Europe), about the biggest pharma company in the world. They also do diagnostics. And baby powder.

I get the impression Alan didn't expect it to work so well in terms of cardiotoxicity and the other side effects - did we honestly ever think it would be otherwise?!

That means very highly targetted as doxorubicin has been found in the biopsies - did we ever think it would be otherwise?!

And that means multiple concentrations of standard doxorubicin in the tumour - did we ever think it would be otherwise?!

Sixty day review FDA before decision for both Fast Track and Breakthrough Therapy.

Accelerated Approval and Priority Review are other FDA programmes to speed up approvals.

https://www.fda.gov/patients/learn-about-drug-and-device-approvals/fast-track-breakthrough-therapy-accelerated-approval-priority-review

Good theory.

https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy

Would be fabulous if true.

Bid now at 151 :\

It would mean contracting the work out, as now, as it will be for nearly all aspects of taking this to market.

Phrmaceutical grade AVA6000, GMP-accredited formulating facility, stability testing. This would surey be started for late clinical trial phases to obviate any unnecessary delays, including finding mass production slots.

Ooh look! Another deadline being set!

clarification, not classification

From the RNS:

"On the basis of the very favourable safety profile of AVA6000 in the study to date, the Safety Data Monitoring Committee (SDMC) has recommended continuation to higher dose cohorts with the aim of identifying a maximum tolerated dose (MTD) necessary to inform the dosing levels for the phase 1b and future studies."

If it were solely up to the SDMC, they would have selected a new dose level when taking the decision to continue Phase 1a. As it was, they "recommended" continuation. I'm sure they'll have decided what options they want for future dosing, e.g. increase by 60 but by 40 is OK. I can only see the delay being because some authority needs to be consulted for approval. For example the Ethics Committee need time to go through the data and no doubt will want classification and more details about certain aspects. That will all take time and is beyond Avacta's control. Or it could possibly be the regulatory authority, the MHRA, even the FDA if doxorubicin-breaking changes are being asked for in studies in the US, need to be consulted or to give permission.

That 5140 structure is just embarrassing.