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^So why has the price collapsed?

I would suggest that many people expected clarity on future financing, principally through a deal, and this wasn't forthcoming.

Given the price has done over 100% in a few months, a lot of people must have been sat on substantial profits which they crystallised. I joined the bloodbath and sold a bunch as it went down. I've bought it all back at a lower price - as I think the investment proposition is continuing to strengthen. Given we appear to have bottomed out, I imagine others have done the same.

So all in all, I don't the price is really reflective of the science, but the nature of AIM. I guess we will find out!

Chat GPT Prompt for anyone interested:

"the experimental drug AVA-6000 is currently in clinical trials. The molecule contains a linker which renders it inert until it is cleaved by FAP in the tumour microenviroment. Once cleaved, the molecule releases the linker and Doxorubicin into the tumour. Analyse the chemical structure of the Doxorubicin in AVA-6000 once released and compare this to the chemical structure of standard Doxorubicin: what are the differences, if any? And what could the pharmacokinetic effects of these differences be?"

"developing the previous answer, would the Pharmacokinetics of AVA-6000 result in lower efficacy of free Doxorubicin on tumours? For example, does AVA-6000 clear from the body faster than conventional Doxorubicin, ultimately reducing efficacy?"

Wyn,

Hope you are well. Having read this board since 2020 I actually rate your posts (boo, hiss) because I agree it's interesting to think about counterfactuals (eg. why is the price 60p on good data?).

However, an alternative reading of the points you have raised would be:

- Dr. Tap, a leading expert on Sarcoma, gave a good explanation of the disease a few years ago in a company science presser. He stated that you cannot really cure Sarcomas, you can only aim to halt progression. Sarcomas generally don't respond well to Cytotoxic therapies and, in the case of SGC, response rates are modest and usually transient.

- In this context, a 90%+ PFS is an exceptionally good result: while the responses are generally minor in terms of tumour shrinkage, the fact they have doubled the PFS rate with many patients still on drug (so potential for further uplift) is very encouraging.

- As you highlight, there is no standard of care for SGC. With the results they are achieving, AVA-6000 will become the SoC. To me, the focus on this indication speaks to an evolving regulatory strategy where, based on trial results, they are taking the path of least resistance to rapid/accelerated approval to get to market.

- CC has affirmed this herself in recent pressers; stating that going into other indications (eg Breast STS) will require Phase 3 trials which demonstrate an improvement on the SoC. These are expensive and are a longer route to market.

- Given the companies poor cash position and historic mismanagement of its financing (the bond), it would make sense to take the path of least resistance; especially as once on the market, it can be prescribed 'off label' for other indications.

- In light of the above, my sense from CC's recent pressers is that the strategy is probably to get AVA-6000 out ASAP via SGC and carve out deals for other indications, using the proceeds to fund the more valuable Exetecan compounds through their trials. This would be a prudent way of funding development without diluting everyone to death.

- So has the drug underperformed? I wondered if your argument here had any merit, especially given their more recent focus on half-life extension technologies. I wondered if the adaption of Doxorubicin resulted in lower efficacy through the change in its Pharmacokinetics. Not being a chemist, I asked chat GPT (I have copied the prompts below - its worth looking yourself as the response is interesting), but it's final summary is:

The pharmacokinetics of AVA-6000 do not inherently reduce the efficacy of doxorubicin in tumours, despite faster systemic clearance. This is because:

AVA-6000 uncouples tumour exposure from plasma exposure

Efficacy depends on local activation and intracellular persistence, not circulation time

Reduced off-target exposure allows greater dose intensity and cumulative exposure

The released doxorubicin is chemically identical and pharmacodynamically intact

Agree Livedata - the city has always been one step ahead on this share (like with every placing...) - turns out the money people talk.

I suspect the moment Richard Hughes saw what was under the hood internally and went out to raise funds, the city boys started talking again. He hangs out with major players, so no doubt a few hints have been dropped to get them to part with funds. And then they'll drop some hints to their friends and so on... It's been a few months since he came on board and started talking to them all about the co, one could imagine there's a bit of a buzz now the strategy looks about to deliver.

Either way, 5m before 10am feels unlikely to be just retail...

Was NT on IG/Hl this am for a good ten mins for a few thusands, so someones buying in bulk...

Seems like MM's want stock as well; spread is very tight and I can sell my holding at the ask, so feels likes an order being filled...

@Thornogson:

"No clear alternative treatment so Orphan Drug Status and fast track FDA approval etc more likely."

Says explicitly in the annual report that FDA has granted Orphan status for SGT - I almost posted at the time but I wasn't sure if this had already been announced.

In any case, they've been awarded it and clearly the pivot to SGT is because it's the fastest route to market via the Orhan/Fast Track pathway.

Once licensed, Consultant's can still prescribe off-label for STS - off-label use happens all the time - Avacta just won't be able to market it as an STS drug at this stage. So hardly either/or, and likely (IMHO) that if they can get to market in the first instance, they will rapidly start to eat into Dox's market share regardless of the indication they are approved in.

IMHO...

Trump is gutting the FDA, just look at the volume of new stories on this from yesterday alone. His FDA pick is skeptical of cancer research and yesterday laid off thousands of FDA employees. Our fast-track strategy hinges on FDA approval, so this is a headwind.

Elsewhere, Trump is cutting funding to the WHO, CDC and USAID - all of which would complicate disposal of the diagnostics business and may have slowed a sale.

Given Heights are vomiting shares into the market, these factors will have an outsize influence on Avacta.

But Diagnostics should be cash generative at this point and there should be sufficient cash to see Avacta out towards the end of this year, at which point more complete data sets should be available from the trial to support any partnership/licensing/approvals strategy.

Trump is like a cat with a laser pen, so while its health today in three months it will be something else, the situation will have clarified and markets will likely settle.

The board would be suicidal to raise at this point in time and have still have plenty of room for manoeuvre over the coming months provided the trial data continues to be solid.

Nonetheless, a painful hold ATM!

AVA6000 has led to 50% experiencing a partial response / 90% experiencing disease control.

This trial of "Cisplatin, doxorubicin and cyclophosphamide in advanced salivary gland carcinoma" achieved a response rate of 27% which "confirms that, at present, available drugs yield poor results, either as single agents or as combination therapy."

So looks like AVA6000 is a clear improvement on existing treatments.!

"Background

To evaluate the activity of CAP regimen in advanced salivary gland carcinomas.

Patients and methods

Twenty-two patients with advanced salivary gland carcinomas were treated according to the CAP regimen. All patients were previously treated with surgery and/or radiotherapy and/or chemotherapy. Seven patients had local or locoregional disease, nine patients had local and metastatic disease, six patients had metastatic disease only. The most common histologies were included.

Results

Of 22 patients, six achieved a partial response (27%, 95% CI: 11%–50%): no complete response was observed. Response duration ranged between 3 and 13 months (median seven months). The median survival time for the entire series was 21 months.

Conclusions

In this investigation, on 22 consecutive patients, CAP combination provided an overall response rate of 27%. This study confirms that, at present, available drugs yield poor results, either as single agents or as combination therapy.

https://www.sciencedirect.com/science/article/pii/S0923753419655419

Interesting Times article screen-grabbed on Twitter: https://x.com/baroninvestment/status/1845898585033826542

Proposal from two think tanks, inc Tony Blairs - which has purchase with Starmer - saying AIM is rubbish and should be merged with main market to attract fresh capital for start ups.

Realllllly. Oh wow

Maybe old news, but here's where he landed: https://spartabiodiscovery.com/about/

@BuenaVista - to investors, IMHO.

Perhaps they will reveal all in the coming days, perhaps we will get an in-depth explanation at the end of the month, perhaps you are right and the only people which matter are the big pharma executives they are currently negotiating £££BN deals with - but all of this is speculation.

But it strikes me as comms 101 that firing technically complex information - which requires specialist interpretation - into the stock market without the sort of accompanying narrative they would have given at the conference leaves it wide open to interpretation, risking adverse price movements.

Like it or not, Deutsch Bank are seen as a credible financial institution and their view will have an impact - 9 million shares have been dumped since yesterday and presumably these the questions around the data, the institutional view and the sell off have at least some relationship.

Maybe the Board are aware of looming news which makes this consideration irrelevant, but ensuring investor confidence in the data being presented strikes me as a key consideration for a company looking to build investor confidence for further fundraising. Hence I think they should clarify.

Equally, the Trinity Delta note is a much more robust (and positive) communication - albeit paid for by the company.

Not me - it's why I hold!

I fully understand this is a Phase 1 safety study and that clearly, AVA6000 is much safer than Doxorubicin - as otherwise the patients would be dead giving the dosing levels.

However, I don't think the data is straightforward as you make out, as if it was we would not be down 20% on it's release. Biotech as a whole is high risk precisely because it is not straightforward.

We can put that down to traders, who were sat on decent profits from 50p, bailing out to buy back lower again - which is clearly a much more successful way to make money on this stock than buying and holding (my so far failing strategy) - but I imagine DB have access to at least some level of expertise higher than that available to this BB, and so don't think their view can simply be dismissed out of hand.

FWIW I think theres a lot to be encouraged by in the data set which is why I still hold all my shares - but I still think the company needs to present their interpretation of these results rapidly to counteract the bearish view DB, and clearly the market, has taken.

Unless you're a cancer specialist, odd's on you have no idea how to interpret that data.

Mr Deutsch Bank may have an axe to grind, may have misinterpreted the findings of the data set - or may have applied his background in biotech (he appears to have a PhD in Neuroscience, but thats not cancer) to draw his conclusions. Unless you have a specialist background, it's difficult to really tell.

However, while the FAP-mid data doesn't look great, but from my limited understanding, Doxorubicin is not commonly used to treat the cancer types in this data set.

The FAP-high set looks much better, with both strong responses and multiple patients still on trial at data cut off. Here the indications are (nearly) all for Sarcomas, where Doxorubicin is a front-line treatment.

Crucially for me, back in the days of captain Al, Dr Tap explained at length that you can't really cure Sarcoma - you can only work to slow its progression and hold it at bay. So the fact that very few patients have seen progression - and the majority appear to be having an ongoing response - suggests efficacy is better than DB are making out, in this trial which is not designed to show efficacy (yet).

Nonetheless, one has to ask why the fairly advanced AVA-3996(?) has been canned given the capital investment in pre-clinical work. I wonder if, with only so much FAP to go around in many tumours, heavier warheads are needed to ensure efficacy. Perhaps it's simply that the evolution of the platform has yielded much better assets, but until the company reveals the pipeline it's impossible to say.

Ultimately, the scientific advisory board are experts and notionally independent of talking the companies book - IMHO the company needs to wheel them out to explain where we are and where we going fairly quickly.

@Sieveco, have a read of the Turner Pope note, especially pg 6 - is a lot clearer on strategy and timelines than they have previously been and is obviously coming from the company.

Suggest P1a ongoing as no MTD; P2 starting H2 2024 and taking 18 months.

Commercialisation starting in 2026, Phase three also in 2026 - so seems like they are aiming to get rapid approval for Orphan Use to get out there immediately, then use the P3 to target the entire Doxorobicin market

Doesn't answer all your points but hopefully helpful

https://mcusercontent.com/d9ebd7c1aa0f3dbc5fab42eca/files/0131e630-3c92-ac71-831a-e2175441110a/AvactaGroupplc_29_2_2024_FINAL_BG.01.pdf

I agree there's serious questions for the CEO and a need for senior leadership changes, but no-confing the CEO now will just destabilise the company and paralyse decision making for several months while they find a replacement, keeping the SP in the sewer while its fought out.

Al does need to move to a science focused role and step aside from running the business to make way for a more hardened pro. But for all the mistakes, even this morning the Mcap is £157 million, which isn't bad for a university professor with a passion for science.

That said, they do need to urgently explain what the f they are thinking and the status of the trial, especially wrt to strategy, as atm their credibility has evaporated IMO

Would someone with a subscription mind copy/pasting the article? Thanks!

Re lack of data: If I remember correctly, in previous presentations by Alistair at the start of the trial, they suggested they would not be able to release data from the trial until its conclusions, owing to 'ethics considerations' - he was quite forceful about it at the time.

Given the trial is being run and reviewed externally, I imagine they need sign off from the trial supervisors to release information. While the trial is running (and thus still recruiting patients?), I would suspect theres a lot of quite stringent ethics legislation in place - perhaps anyone who knows more can further clarify.

That said, the latest video says very clearly they have improved efficacy, which is the first time they have confirmed that I think. Given the current dosing levels, its obvious safety has been improved, so I think the signs are there if you look for them - just a waiting game now.

Fantastic news today which makes clear the platform is working as intended. After a long wait its truly amazing to see todays news - well done to everyone who has held this share for a while!

Out of curiosity, what do people suggest might be the next steps for the company?

Obviously, with the trial ongoing, there is a way to go before AVA 6000 is commercialised - though the FDA Orphan Drug pathway and availability outside of the trial suggests this might happen faster than one suspects.

However, do people think the public release of this data makes a licensing deal more likely - for example, regarding the Velcade asset?

Curious to hear peoples (speculative) thoughts!