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It depends on prospects I think. Autolus (AUTL) will submit a Biologics License Application (BLA) to the FDA for their obe-cel for leukaemia by year end and have just 1% of their public float shorted. SP rose sharply at the end of last week - the end of interest rise worries, I think.

Let's hope we are applying for Breakthrough therapy designation and having lots and lots of meetings with and guidance from the FDA to expedite the intended registrational Phase 2 trial! AS talking about planning for a pivotal trial means I think that we are.🤞

Very informative. Thanks for posting.

"Buenavista can correct me here: we might see the intra-tumour cell doxorubicin level rise so high, it stops / reduces the risk of multi drug resistance developing." Sorry, CTSFO, not my area of expertese. This article may shed light though:

"Why Do Cancer Treatments Stop Working? Overcoming Treatment Resistance " - https://www.cancer.gov/about-cancer/treatment/research/drug-combo-resistance

Extract in the 'Keeping Cancer Drugs inside Cells' section of the article: "One way cancer cells resist treatment is by expelling cancer drugs. For example, healthy cells have proteins known as transporters that pump out toxic agents. One such group of proteins, called the ATP-binding cassette (ABC) transporters, expels some chemotherapy drugs, including doxorubicin, and some targeted therapies, like imatinib (Gleevec®)."

It would seem that AVA3996 might help there! "The influence of proteasome inhibitor bortezamib on ABC transporters’ expression and activity in tumor cells" - https://link.springer.com/article/10.1134/S1990747810020145

Here's a review on doxorubicin resistance generally: "Mechanisms of doxorubicin resistance in hepatocellular carcinoma" - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792121/

Extract: "The mechanisms of this [doxorubicin] resistance include increased expression of multidrug resistance efflux pumps, alterations of the drug target, topoisomerase, and modulation of programmed cell death pathways. Many of these effects result from changes in miRNA expression and are particularly prominent in tumor cells with a stem cell phenotype."

So, my amateur thoughts on this: AVA6000 hitting the TME hard and fast and being able to infiltrate the stroma to get at all the tumour is probably as good as it gets with doxorubicin alone before the cancer has time to develop resistance. Would expect it to be even more effective in combination with drugs which inhibit the various modes of resistance.

"explore ... as"

The wording is ambiguous but the process says safety and tolerability, not efficacy, as backed up by the answers to Q2 & Q3 and use of the term "protocol amendment" rather than something implying a more radical change.

"Fortnightly as a first line treatment for STS, there's some pretty big inflection points coming there and relatively quickly once it is started."

I know everyone seems to have convinced themselves that the fortnightly Phase 1a will be as a first line treatment. I say not and that as a Phase 1a continuation it will be under the same conditions as the 3-weekly dosing, including non-STS patients.* See the answers to Questions 2 and 3 from September's interims:

https://www.investormeetcompany.com/investor/meeting/interim-results-209

* When you think about it, initial efficacy data for breast, ovarian, colorectal, etc cancers coming out of a Phase 1a safety and tolerabilty dose escalation study would be very powerful data of interest to pharma companies interested in licensing AVA6000 for those other cancer indications.

I've been listening lately to a few quarterly results presentations by clinical but premarket biotechs listed on Nasdaq. Their presentations are a world away from Avacta's. For a start, they are very technical, and the questions from the audience are from investment houses that really seem to understand the detail. Hopefully soon those investment houses will descend on Avacta. I would welcome quarterly results and business updates from Avacta. More chance of questions being answered.

There are no wonder drugs for STS that will appear out of the blue and blindside AVA6000 because AVA6000 is close to approval and there there are no others currently in clinical trials that are better and could get approved sooner - and we all know how long it takes to get a drug through trials and onto the market, even one based on a highly efficacious drug that has been around for half a century.

AVA3996 is in IND enabling studies, so is pre-clinical.

https://avacta.com/therapeutics/pipeline/

Avacta has reached the stage where they require a Chief Medical Officer, for the job the role fulfills but also for the kudos in the US.

Neil Bell had the title of Chief Development Officer, a role that had been fine until Avacta went into the clinic. He could not have been appointed as CMO because, as I understand it, he does not have a medical doctorate, which is required for the post of CMO and the legal responsibilitoes for clinical activities that go with that.

I do think however that he has a severe personal issue, quite possibly ill health, as he continues to be absent from LinkedIn.

We may never know ...unless we can get a delegation together for a 7:2. Or if AS ever answers all the Q&A questions.

@Timster, hence the QA'd data. Dual purpose. Well, required for the FDA (as AS said, the data have to be correct) and also for whatever other purpose Avacta want it for for the market and potential suitors.

That's an interesting take. What do you think the FDA base there decisions on then?

Let's see.

I would think the FDA would be reliant upon Avacta providing collated and summarised QA'd data at specific decision points. I doubt they have the resources to monitor all data from all clinical trials in real time.

The RNS will have highlights and summary and link to the full document with its figures, tables and graphs.

The same QA'd data will go to the FDA and appear as published data. But which will it go to first?

@gmcc, what data do you think the FDA have been seeing?

Cj62 🤡

Yes, the collated, QA'd data that is currently being prepared.

Here's a question for anyone who wants to have a stab at an answer.

What do you think the FDA will need in order to approve a Phase 1a fortnightly dosing study, initial dose and dose increase rules?