Member Info for MB53

My understanding is that the FDA can Fast Track any drugs which are showing very significant advantages over existing therapies. Orphan Drug status is specifically designed to encourage the development of drugs for rare conditions by providing financial and patent benefits. AVA6000 has Orphan Drug Status for Soft Tissue Sarcomas which are a relatively rare cancer. It is also a cancer for which Doxorubicin is pretty much the only treatment. If AVA6000 turns out to be much better than Doxorubicin in the Phase 1b study, then my money is on it being fast tracked before Phase 2 starts/completes.

Many thanks, BV - glad to know my reasoning stands up to peer review!

I am re-posting the weekend conversation as I would welcome more views on a significant topic.

AVA6000 has been shown to be a better drug than straight Doxorubicin both in its safety and tolerability profile and potentially (to be confirmed) its efficacy. At some point (and this may be as early as during the Phase 1b trial) the clinicians will be faced with the ethical dilemma of whether they continue to give straight Dox (with all its drawbacks) or offer patients AVA6000 which would give a better outcome with fewer side effects. I think this will drive the FDA to fast track AVA6000 sooner rather than later. I am sure that Dr Tap will not be happy treating his patients with straight Dox once the impact of AVA6000 has been demonstrated in Soft Tissue Sarcoma.

Beinthelead: Easy MB - trials will work that out. Agreed, in concept, and I’m sure that’s why P1b has been designed to give us as much data as possible, to reach that moral conclusion.

MB53: I agree - the trials will sort this out. The P1b trial design compares AVA6000 to straight Dox. If AVA6000 is shown to be so much better during the trial, it will be a very uncomfortable and potentially unethical decision for the clinicians to continue treating patients with an inferior drug (straight Dox). This is problematic as Dox is the main treatment for STS. If the difference becomes rapidly apparent during the trial, they could even suspend the Dox arm of the trial. It does happen.

Buena Vista: If the trial drug is shown to be clearly superior to the standard of care therapy then patients will be switched. This is normal ethical practice.

MB53: My point exactly. But unfortunately for the patients, this is an experimental and unlicensed drug. So for pateints to receive AVA6000 outside the trial,it will have to be fast tracked ASAP and Avacta will have to be ready to ramp up production. I think this could all happen quicker than we think.

My point exactly. But unfortunately for the patients, this is an experimental and unlicensed drug. So it will have to be fast tracked ASAP and Avacta will have to be ready to ramp up production. I think this could all happen quicker than we think.

I agree - the trials will sort this out. The P1b trial design compares AVA6000 to straight Dox. If AVA6000 is shown to be so much better during the trial, it will be a very uncomfortable and potentially unethical decision for the clinicians to continue treating patients with an inferior drug (straight Dox). If the difference becomes rapidly apparent during the trial they could even suspend the Dox arm of the trial. It does happen.

AVA6000 has been shown to be a better drug than straight Doxorubicin both in its safety and tolerability profile and potentially (to be confirmed) its efficacy. At some point (and this may be as early as during the Phase 1b trial) the clinicians will be faced with the ethical dilemma of whether they continue to give straight Dox (with all its drawbacks) or offer patients AVA6000 which would give a better outcome with fewer side effects. I think this will drive the FDA to fast track AVA6000 sooner rather than later. I am sure that Dr Tap will not be happy treating his patients with straight Dox once the impact of AVA6000 has been demonstrated in Soft Tissue Sarcoma.

Only a couple of hours left to post (promised to post on website within 24 hrs of SD).

What ever way you look at it, this is completely mind blowing! Better than anyone hoped for. Is that the sound of stampeding Big Pharma I hear?!!

Thought I might get some sensible responses to what was a perfectly reasonable potential roadmap for AVA6000. Unfortunately that was not the case. Doesn’t anyone have a view?

What is the reason that Soft Tissue Sarcoma (STS) was specifically mentioned in the RNS? There was no reason to do so unless they are indicating that SMS is the main focus for future development.
Avacta already have an IND for AVA6000 in the US and have Orphan Drug Status designation from the FDA for STS. We have Dr William Tap Chief, Sarcoma Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York presenting today.
Once Avacta have determined the MTD (or RTD) in Phase 1a, it is likely that Phase 1b and Phase 2 trials will have very substantial US involvement focusing particularly on STS. Phase 1b and Phase 2 trials will be subject to fewer delays than the P1A trial as they are predominantly about recruitment and collection of data (ie not multiple cohorts). Promising results from the STS trials could lead to Fast Track Approval by the FDA and AVA6000 coming to market. I think Avacta see this as the quickest way to get the drug on the market possibly as soon as 2025.

I hope that Avacta has got some hot corporate lawyers and a large legal budget because there is going to be a lot of work negotiating, drafting and agreeing all those Licensing deals!

It all depends what is being presented on the Science Day. They have already given us the headline findings re safety and tolerability and release in the TME. The SD may present the detail behind these findings without releasing anything new. After all this is about educating the fund managers re the science and promoting Avacta's huge therapeutic potential.

I think it highly unlikely that Avacta will issue a significant RNS before Science Day. If they are presenting to fund managers and analysts at the SD then they won't want to stimulate the SP unnecessarily. My bet is that there will be a couple of weeks grace after the SD to give the fund managers time to establish /adapt positions before we see anything significant. And who knows when the Licensing deal is going to hit the streets?

I think two things are going on here which is impacting the SP. The first is that most of the market do not understand the science or understand the enormous implications of the January RNS. Secondly, people think that if something is too good to be true, it probably isn’t true. Avacta’s achievements do appear too good to be true (a revolution in chemotherapy) but they are true! IMO it will take a Licensing agreement to demonstrate to the market that Big Pharma realise the enormous implications of the platform and are investing. A Licensing agreement is also likely to make Avacta into a profitable company. Both of these will lead to a substantial re-rating of the SP.

Or Novartis, or Astra Zeneca, or GSK +++++

With Takeda'a Velcade being off-patent and revenues falling and with the fantastic results demonstrating that Precision works, how long will it be until we hear that Takeda have entered into a Licensing deal with Avacta for AVA3996? I reckon VERY soon!!

Thank you for the useful comments. Everyone is hoping for a very positive RNS in early January and clearly we are all getting excited after such a long wait. The purpose of the original post was to suggest that there are a number of different sorts of update that we may recieve in early January and they are not necessarily of the all singing and dancing variety stating that AVA6000 is safe, tolerable and works. We must be prepared for some disappointment from the forthcoming RNS whilst hoping for the best. Whatever the nature of the RNS, we are all convinced that Avacta have a ground breaking drug in development and all the data will come out at some point in 2023. As ever, patience is the key.

Acacta stated in the last RNS that: “The Company will update the Market on progress in this study in early January 2023, in advance of the Science Day.” But what does this actually mean?
The fact that the KOLs in the field of Oncology are being invited to present at the Science Day on 23rd February 2023 suggests that they will have had access to the latest data from the AVA6000 study. Otherwise, what’s the point?
However, the question is - will they report all the latest data in the early January RNS? It seems to me that they have a number of options in how they update the Market.
1. Update on study is that the study has moved to a further cohort and dose escalation. Very happy with progress. Data to date to be released before the Science Day. Verdict: Possible but hopefully unlikely. Market will not be happy!
2. Update on study is that the primary objectives have been met – safety and tolerability of AVA6000 are acceptable. No efficacy data available. Treatment dose agreed and study moving into Phase 1b. More comprehensive data from phase 1a to be published before the Science Day. Verdict: Very positive but not ideal. Even though very positive, it may not be enough to excite the Market.
3. Update on study is that the primary objectives have been met – safety and tolerability of AVA6000 are acceptable. Initial data from biopsies suggest that Doxyrubicin is being released into the tumour microenvironment. Treatment dose agreed and study moving into Phase 1b. More comprehensive data from phase 1a contained in annex to RNS. Verdict: This is what we all want to hear and I think that the Market will reflect the significance of the announcement.
I would be very interested to hear the views of others particularly those with a scientific background. Are there other permutations? Is my assessment of Market response reasonable?
Something to think about over the New Year weekend – Happy New Year to one and all and let’s hope Avacta rewards its long-suffering PIs in 2023 and provides hope for all cancer sufferers!

Thank you. The Science Day is about presenting the science behind the headline date which will hopefully be in the RNS. It cannot present any new market sensitive data. So presumably it is explaining to the fund managers and analysts the implications of the data and the potential for the future pipeline of drugs. There may well be a licensing deal announced before the Science Day as well.

There are potentially seven weeks between the update RNS and the Science Day. I am sure this must have been discussed at length but I have missed the posts. Could someone kindly outline the thoughts/consensus on why there is such a long gap?