Member Info for opti_mystic

Understood BV but again capping groups and linkers are not new technology either, are well understood and I don't expect there to be any problems with those elements either. I agree with you that given everything we have seen from CC and others, as far as it's possible to know, what they know looks good.

Exactly BV, this is what I have been saying here for a while, we already know most of it works and we know the payloads work. I refer you to my post of 10th March. 50% of drugs fail because the payload doesn't work. That risk is eliminated here. 30% fail because of safety issues. The whole point of Avacta's tech is to concentrate the payload in the tumour, also proven. The only remaining element is the slow release mechanism. CC said in her recent interview that they would add indications (they've recently added two) to the trial if the were seeing activity or if they were getting through the dose escalations. Being as they've added two at least one of those has to true, which indicates to me the slow release probably works. This platform is sginifcantly de-risked with a chance of success of more than 80% imo but is being priced as if it has a 10% chance of success and all the market ever seems to think about is the next raise. Hardly surprising, even our own broker wouldn't value us properly!

If 6103 works as desgined its status as the world's best chemo is assured imo. The tumour:plasma ratio pre-clinical in mouse models was already 99:1. We know from AVA6000 that ratio drastically improved when the drug entered the clinic. But even if 6103 does not improve that ratio,it is still very much good enough, it is till going to be cleaving at the tumour site, utilizing the bystander effect, with a much more potent TopoI than Enhertu the world best selling ADC, that is also more permeable into a tumour with more resistance to being pumped out, whilst drastically reducing the time the chemo is present systemically and therefore it is most likely considerably safer. The chemo in Enhertu, Deruxtecan, is detectable at low levels in the blood for weeks. Exatecan from 6103 disaapears completely in a few hours (2-6). If bathing the tumour in chemo is great for efficacy because it's time that matters not just concentration, then the same will also be true for safety, and 6103 reduces the time of systemic toxicity from weeks to a few hours. The level of toxicity is also low and falls rapidly. Add to that Enhertu's tumour:plasma ratio is about 10-1 and broadly Avacta's 6103 is ten times better, the drug has to be both more efficacious and considerably safer.

Obviously the AIM market must know this because the price today has risen one pence! Sure there's a long amount of time to go before all this is confirmed with patient outcomes, but those outcomes will be assured if the data we have been provided so far continues to translate in patients. You don't add two more indications if the very early data is not what you'd expected/hoped it would be. And as has been said here already, that Tempus information would have been available to them before the clinical trial began. Therefore adding those two indications is a sign of confidence and will increase the potential market and therefore the eventual buyout price.

All this means that patients on this trial have the best possible chance any patient has ever had, and that's a cause for celebration for them, their families and humanity.

I've no idea one4one. It would depend on which inhibitor it was and what they were targeting which would depend upon who the partner is. Plenty of potential though. I only mentioned it as from memory I think CC did at some point. I am hoping for an Astra Zeneca tie up so we could use ATRi and PARPi to broaden the scope. I would hope to include prostate cancers though as men have not great options for that and looks a fit. Probably 3 or 4 good potential indications but I think Avacta gets taken over before those trials begin.

They'll be no takeover until there is more data. It's just too soon for that for both parties. There is much greater value once 6103 is proven, a platofrm is more valuable than a single drug. What Avacta have is less of a drug and more of a delivery system that increases exposure of the tumour to the active element and drastically reduces systemic toxicity whilst being able to target 90% of solid tumour. If 90% of all cancers are solid tumours and Avacta can target 90% of those that is 81% of all cancers potentially at least. That's is a very large potential market. I'm looking forward to science day as I wondering what's next? Pathway inhibitors?

I agree B2, it's not chance CC discussed that in her recent interview. Taken with previous messaging like saying we can attach our peptide to virtually anything, and wanting to reveal one new drug per year it seems covering all potential cancer bases is the best way to develop the portfolio of assets. Bearing in mind Keytruda is off patent in two and a half years, it makes sense to prepare! This technology has a long way to run and I'm sure CC and the team will be thinking strategically for our best advantage.

I agree Alde, and also there is always the chance of a better deal even if one is tentatively lined up, so no point in closing off any potential parners.

Well I thought she'd risen quite a long while ago! But great recognition and very well deserved.

Originally 19/21 complete responses updated to 22 of 24 complete responses one of the other two showed tumour shrinkage of around 70% from memory.

Please don't Ice, engagement is his succour, his oxygen, his objective. He has to say complete nonsense to provoke a response that his objective, don't play his game.

Yes I've noticed that, a very narrow spread.

Avacta went from 40 molecules to 500 molecules in no time, why? When patents are applied for, BP want to know there's virtually no space for 'me too' applications from other companies before they spend big bucks. If there's a chance of that the price goes down. Those 500 molecules are there to protect the IP and obtain maximum value for shareholders. The purpose of those 500 molecules is to take up all that space leaving no options for similar patent applications. Key staff retention would also be on the agenda. That's why we've seen well deserved promotions. 6103 is a work of art. They should hang a picture of the molecule with the patent in the Tate Modern.

Highly likely there will be bids within 12 months. A very good chance later this year. Why? Because Exatecan works. This is not in dispute. A modified and less potent version is in Enhertu a $5 billion p.a. drug right now. All BP is going to need to know are two things, does the 99-1 tumour: plasma ratio hold up? If yes or better=safety. Does the slow release mechanism works as described? If yes=efficacy. These outcomes are guaranteed and can be tested for before we see scans. The scan will confirm the inevitable outcome of a shrinking tumour, but BP won't need to see the scans to know tumours will shrink if those two things work, Exatecan is a beast. If 6103 tames the beast Avacta deliver 'safe' Exatecan in the same way it just delivered 'safe' Doxorubicin. It also delivers a proven scalable, cheap effective plug and play highly accurate delivery system of therapeutics to FAP positive tumours. Chemo, immunology , dual payload. It's a dream for BP with a patent cliff. It's dream for future patients with any cancer but especially those deemed hard to treat. It's an IP factory. It's a money factory.

I'll be raging if it goes for less than £15.

The pre-clinical mouse data for 6103 is pretty impressive. Not least because the tumours are said to be Topo I 'resistant'. There are two different ways such resistance may manifest itself. One is the stroma is simply impenetrable or virtually impenetrable. In these cases so little of the chemo hits the target as to render the chemo ineffective. The other is by way of DNA repair. Chemo is typically dosed on 2 or 3 weekly regimen. Mainly to allow the patient's body to have enough time and space between doses so that they can recover sufficiently from side effects and so that those do not become too cumulative.

6103 hits the tumour in minutes, even in the first type of chemo 'resistant' tumours. In our pre-clinical trials these would be both pancreatic and gastric tumours where the stroma is typically difficult to penetrate. Because Exatecan offer greater membrane diffusion and stays in the tissue for longer (resistant to MDR Efflux) it should do a better job than Enhertu where Enhertu is used (gastric and breast that are HER2 positive) but also other indications that are simply FAP positive.

Exatecan is simply more potent than Deruxtecan and any other Topo I inhibitor, many times more

The second type of resistance is simply DNA repair. In our trial that is the cervical and small cell lung cancer candidates. The expectation here is simply by dumping so much Exatecan in the tumour, the tumour is simply overwhelmed. As we know the blood plasma ratio at 99-1 is indicative of great safety and improved efficacy. If this improves from mice to humans as it did with AVA6000 then it may be possible to dose a more frequent regimen if this should be necessary. In any event with toxic cancer killing levels in minutes and extending for days the tumour will stand little chance. However the main thing that improves efficacy is bathing the tumour in Exatecan for many days thereby drastically extending the half life, that's the slow release mechanism.

The Enhertu comparison the company showed demonstrates its confidence. When Enhertu translated from mouse models to human trials, the complete responses reduced significantly. Currently the CRs are about 20% or less of their breast cancer patients. It was nigh on 100% in their mouse models. I expect our drug to have a higher level of complete responses with an improved safety profile in humans when compared to Enhertu.

Enhertu targets 15-20% of breast cancers we can target 90%. Enhertu is predicted to increase sales to in excess of $10 billion dollars by 2031. Estimates go as high as $14 billion. Our P1a does not include breast cancer. That can only be because AVA6000 targets TNBC and that is likely to be sold once the results are in. TNBC revenue predicted at $1.5 billion. You cannot sacrifice a 10-14 billion dollar drug market for a 1.5 billion dollar drug market. Therefore I expect our P2 to include breast cancer for 6103. I also expect Avacta to be bought before that trial begins.

CC has 3.6 million options, I think she'll be doing okay. The interesting bit of today " The Company considers that AVA6103 has the potential to validate its novel pre|CISION® sustained release mechanism thereby advancing the opportunity for a large number of oncology medicines to be available on the platform through the novel chemistry designs. The clinical trial of AVA6103 is structured to further validate the preclinical observations of the novel payload delivery kinetics." They seem pretty convinced it's a plug and play system and if they're correct it'll be very valuable. I'm looking forward to the preliminary data from 6103 but also I'm wondering what's next.

It's how these things work. You can believe whatever you want to Saint, and if you wish to be pedantic about then yes Avacta have not publicly stated explicitly that this is the case, but meanwhile back in the world we exist in, I don't need Avacta to confirm it to know that is how it goes and is very, very likely to be the case, because it's just what happens. Highly likely multiple parties have access to the data room and you don't get that without an NDA.

Of course Avacta have more than one company that has signed an NDA, that is so obvious it shouldn't need a discussion at this point.

@gemstar the way to think about it is the limit has been removed from the drug, not the condition, so there is no limit on TNBC or any of the conditions for which it might be used.

6103 goes into the first patient this month. It has three elements required for success. The FAP seeking element already proven in humans by the AVA6000. The chemo element, already proven by a slightly modified version in the hugely successful Enhertu. The third element is the slow release mechanism. This relates to the capping group and linker technology. These are not new although these particular ones have been invented by Avacta for the specific purpose required to extend the half life of the chemo used in 6103 Exatecan. Linkers and capping groups are widely used and quite robust. Given we invented the linker and capping group for the purpose and we had a choice of many other linkers and capping group we have also invented, I expect it to work, and really rather well. They will know in 6-8 weeks time.

Who would make an argument that BP are not interested in Avacta in view of the fact there has now literally been two presentations with "Avacta meets Novartis" in the metadata? Which company would not be interested in our technology? These are not serious arguments to be making a week or two before 6103 goes into its first patient. It's going to be a good year.