Member Info for opti_mystic

With RH on the BoD there is zero chance of Avacta being sold on the cheap. They have to put serious offers to shareholders but I guess it depends how serious is defined. Offering half what the company is worth is not a serious offer in my view. They could down tools today and sell the IP and they'd get a lot more than the current market cap.

Oh yea of little faith. £10 is my absolute bare minimum from when I first invested. Due to progress on a number of fronts that has gone up. Somewhat disappointed that people would sell so cheaply. Hopefully the BoD know what the company is worth and will not put to shareholders derisory offers that significantly under values the company.

Ice, I usually agree with you on most things but I'm having second thoughts about 6k being sold off, mostly because I think it is worth an awful lot more than people actually realise. As I posted yesterday, the market just got A LOT bigger. It will be in and of itself a blockbuster drug whose value and broad applicability anywhere Dox is used is being massively under estimated in my opinion. It good to see that finally, the joke that is AIM, recognised positive data/information as good for the share price, but even so, having read around here and elsewhere I don't think 'the penny has dropped' so to speak. Obviously I'd like full value if we do a deal, as I am sure would you.

As has been alluded to here and elsewhere if you're an oncologist, once Faridox is approved, it makes no real sense to prescribe Doxorubicin when you could prescribe essentially ultra safe, no lifetime limit, probably more efficacious 'Doxorubicin' that is Faridox. That off label use and the fact that you can continue to use it beyond the former lifetime accumulative allowance in and of itself increases the market size for Doxorubicin replacement Faridox. If you google the market size for Doxorubicin you get a figure of around, ball park number here obviously, but let's just say $1 billion. The exact value isn't important as the principle here remains whatever the actual market size is now.

So here's what I think everyone has missed that is relevant to the foregoing. Doxorubicin is out of patent and again a quick google search says it costs roughly up to about $4,000. What chance do you think that Faridox an in patent revolutionary new drug sells for the exact same price? Didn't they say it was going to sell for around £100,000 per cycle. The exact numbers don't matter so much as the principle that where Dox is used Faridox could and probably should replace it and that means the market is WAY bigger than $1 billion.

Food for thought in negotiations and the company's strategy on licensing it now or waiting for the takeover and the true value of the asset.

Wmsjames: I agree with the vast majority of what you've written over the last day or two but I differ on efficacy of phase 2. Because the actual chemo we use is not new, either in 6k or 6103, if we can get it to the tumour in much larger quantities then efficacy is guaranteed in my opinion. Dox does what Dox does when it interacts with the cancer tumour. We know the efficacy profile of straight Dox but we are putting much, much more of it in the tumour so it follows that it cannot possibly less efficacious it will probably be more efficacious, but it will certainly be safer with fewer and less serious side effects simply because we're putting more of it where it is intended to go and therefore less of it being off target.

For me safety is everything if it's safer it is also likely to be more efficacious because much more of the chemo is delivered to the tumour. If it's safe it works! We have had confirmed by the regulator what I've been saying for a long time, it is very safe when compared to straight Dox. If straight Dox works 6k will most probably work better in terms of both safety and efficacy, one begets the other.

In view of this, I see the assets as being further along the trial journey than most people appreciate. Typically phase 1 trials establish safety, phase 2 establish efficacy. What I am saying because of how this works if it's safe, efficacy is guaranteed. Yes we'll need to do the trials to prove it for regulators, but it cannot possibly be not efficacious if as a result of the phase 1 trials we're putting many times more chemo in the tumour for a chemo we know works in both cases (6k and 6103).

Very obviously the ones that respond to Dox.

A lifetime limit the FDA first implemented in 1974. News so significant Thorn deleted his account. 😂😂

The significance of today's RNS is safety is everything for Avacta. We already know Dox works, it is used many more cancer indications than we have the money to fund trials in. All Avacta are doing to eliminating many of the problems of Dox those being side effects some of which result in cessation of treatment even if it works. This news today is imho likely to result in the FDA approving in due course Faridox for use wherever Dox is currently approved in ANY cancer indication where it is used. That list is much longer than the current list of indications we're targeting. Efficacy of Dox is known, same for Exatecan. Once safety can be established and is clearly improving on just Dox, the efficacy will be at least as good if not better because it will extend lives because it can be dosed for longer and at higher levels. The same will apply to 6103 FapExd. Once later this year we know it's safe we will also know it's efficacious. Yes the trials will have to proceed but at that point the outcome is inevitable. If 6103 is proven to work and therefore be safe, a TO follows like night follows day imo. TNBC data lands in June at the latest, by July /August they will know if 6103 is doing its thing. If it is it's game over.

I share your enthusiasm but I think it's even better than that! That was the market size when there was a cap on total accumulated dose and dosing had to stop. That has just been removed. Therefore the Dox market just got A LOT bigger.

It's worth noting that Faridox is most likely to become standard of care (SoC) for SGC a disease setting that literally has no SoC and that market is around £180 million per year. Our valuation is what £220 million today? Just that one thing is worth more than double today's 'valuation'. That attributes zero value to: other indications where Faridox may have a role such as TNBC or STS

The value of 6103 in 4 different indications

The value of 6207 the worlds first dual payload PDC

A platform to effectively target FAP, a target until now widely thought of as difficult to achieve

Affimer

The rest of the iceberg

Yes, I guess I should've mentioned the third way we get valued more accurately if we list on the Nasdaq too but I can't really see that happening this year by which time it may be all but too late.

My belief is the risk return profile is exceptionally good. The pathfinder has de-risked the first drug Faridox, because it is no longer a question of does the FAP seeking element work. On that journey we have discovered that the translation of data from lab mice to humans is exceptionally favourable moving the dial on tumour/blood plasma from a best of 15-1 in the lab to a median of 100-1 in humans. 6103s different chemistry means it lodges and stays in the tumour, resulting in a lab mice ratio of 99-1 already. No wonder the tumours were so responsive for 6103.

We have many, many other advantages over ADCs, the molecule size (less likely to be affected by the immune system), the bystander effect being leveraged, the tumour penetration is far better, the much more widely occurring bio-marker FAP being present in 90% of solid tumours, the fact the drug does not destroy the very target it is seeking to enable the release of the payload, unlike ADCs where this can happen and the fact that the bio-marker for ADCs are more prevalent elsewhere in the human body resulting in a far greater degree of off target toxicity mean a greater incidence of side effects and those side effects being more likely to be a grade 3 or 4 adverse event.

That's why I am invested here and will continue to be until the much fabled takeover. I don't much care about the noise of the share price and I have no expectation of the AIM market being able to price this company even vaguely accurately. I knew that when I bought it, otherwise I couldn't have bought it at the price I did. The share price was not and is not indicative of the future value of this company. People talk about the 'valuation' but the valuation is not connected in any way to the progress of the company. Have we seen a price rise off the back of the IND approval which means we will double the number of drugs in phase 1 trials? Will we when we dose? Will we if the initial results are positive (ie it works as designed) No we won't. There are only two ways the price rises, an actual commercial deal bringing both validation of the platform and money, or a takeover when it'll be too late to buy shares.

I think that's optimistic Lovable being as the initial doses will be very low. It is a safety trial initially remember, but the trial design (BOIN) will allow for dose escalation quite quickly and also potentially skipping from say dose level one to does level 3. I think more realistically summer months we may start to see some useful efficacy. What they will know sooner is are there any problems/does it works as expected and designed. If no bad news by May/June I think we're on a winner. I expect it to work.

Hi B2, yes DS is Daiichi Sankyo, they invented Exatecan in its original form but it is no longer under patent. It can therefore be obtained from a variety of sources now. However they did modify it slightly for the various ADC collaborations (Enhertu with Astra Zeneca) and therefore those variations are still in patent.

Avacta has a proven way of delivery much more drug to a tumour and it applies to 90% of solid tumours. 90% of all cancers are solid ergo it applies to 81% pf all cancers. Exatecan was too toxic in humans mainly because it was too indiscriminately delivered. It also has a short half life of only 9 hours. Avacta has solved both problems in the lab, it now bathes the tumour by a slow release mechanism for 5 day plus. It has a 99-1 ratio in mice. We know that for the first drug a maximum ratio of 15-1 in mice translated to a 100-1 median ratio in humans. 6103 does not have be better than in mice merely the same. I do expect the ratio to be better though. Direct benefit of low toxic side effects and brilliantly efficacious. 6207 has the potential to deliver 2 drugs simultaneously. The direction of travel for anti-cancer drugs is exactly this. Exatecan could be partnered with either a PARPi or an ATRi. Astra Zeneca JV'd with Merck for one of the only four approved PARPi Pfizer and GSK being two of the other three. Of the companies developing ATRi (none of these are yet approved) Astra Zeneca and Merck both have ATRi in various stages of development. In view of Merck's pending patent cliff with Keytruda (end of 2028) and Astra Zeneca most advanced development of and ATRi and a JV'd approved PARPi it is reasonable to consider the possibility of of a JV for 6207 or either one of these giants wanting to have a good look at our science and results. DS make Exatecan and they too have a relationship with these two so it's starts to look a virtuous circle of relationships.

Avacta is in an enviable position in global oncology. It has a tumour seeking technology that dispenses its toxic payload only where it is needed, in the tumour. Because of this fact, it has drastically reduced side effects. It can tune, where tuning maybe needed if the pk (half life) of any drug whose half life is too short, it can be extended by slowing down the rate at which the peptide is cleaved so that the duration of release is extended. In the case of 6103 this changes the therapeutic window of the delivered Exatecan from 9 hours to 5 days. Neat Doxorubicin has been used in cancer treatment on its own for 50 years. If it had a half life problem I think they would have noticed by now. As Christina noted, when they stop using it in breast cancer survival rates go down. If anyone on this board is embarrassing themselves with any further piffle about 6000 having a half life problem it is because they themselves live half a life and they therefore think everything else has a half life problem. It is FUD.

FUD thrives on engagement. It is the oxygen that gives it momentum to continually discuss the topic the FUDsters wish to be front and centre on the board. If you engage with them, you're helping them to achieve their desired outcome. The domination of the board with FUD. Discussing non-issues over and over again ad infinitum.

The company has the best cancer technology in the world for solid tumours. It is very broadly applicable and the future is incredibly bright. Time is that is required. The only share price I am interested in is the price agreed by the company with which ever BP offers the winning bid for the takeover. In the mean time I do not care what the market cap is or what the share price is. I bought it on the basis I did not think the SP was even vaguely reflective of the future value of the company. The tech has delivered in spades since then and the SP has not moved very much. AIM will not value it correctly BP will, it has demonstrating time and again it is incapable of it. Until that happy day that we receive a successful bid, who cares what the SP is?

Understood BV but even at 99-1 same as mice, it'll work and it is likely to be more imho.

The idea that certain people haven't been earning their corn is nonsense; you have absolutely no idea what they've been doing or what they have been tasked with doing so who are you to judge the success or otherwise of the work? Just because we do not know what discussions have been had and with whom does not mean no progress has been achieved. RH himself said at the AGM he's not interested until (in effect) 6103 human results are in later this year. They'll be lining up the requisite companies and keeping them informed of progress and taking them through the science etc. Just because we don't see it or hear about it doesn't mean it's not happening.

The science sounds amazing, remember the video in December? The animal models for 6k showed a broadly 4-1 up to as much as, at best, a 15-1 ratio tumour to plasma. That translated into a median of 100-1 in humans. With 6103 it's already 99-1 in animal models! So taking the worst case scenario of 15-1 and translating that across means broadly more than six times, so in the region of 600-1 tumour to plasma ratios. No wonder there's barely a trace of the Exatecan in the blood stream, all gone, undetectable in four hours. Explains why there are so many complete responses too. Bathing the tumour at those or even anything like those ratios for 5 days is going to work out pretty well I believe. Those of us that are invested know what we have.

These things take time. WE start doing next month most probably, the regimen of 2 and 3 weekly dosing. In animal models these complete responses were after on three doses. By April we will know if the patients have any significant side effects or if the doses can be increased. By June they'll be increased again if safe to do so. By late summer early Autumn we'll have a very good idea of what we have and BP probably before us. We might even get some insight in the late spring early summer if we're seeing significant tumour shrinkage with the lower/starting doses. Lots to look forward to this year.

I'm on 38, a new record!

@golfnut 🙏🙏🙏🙏Excellent explanation much better than mine but it will make no difference as Dan says, they want to not understand it, because they want it to be an issue even though it isn't.

@Nanomat I agree 2 years max. It's a nuclear bomb into a tumour. This short term share price stuff is noise and irrelevant to long term holders waiting for the magical red dot. That red dot is inevitable when 6103 replicates in humans. The ration for 6k was 4:1 in mice and then became 100:1 in humans. 6103 is 100:1 in mice what will it be in humans? It's going to blow the bloody doors off! 6k is about PFS and DCR, 6103 will be about complete responses.