Member Info for M.McNulty

Robbie, it is nothing like a death spiral agreement.

It is a conventional loan for £2m, with a 2-year term, paying a 5% coupon.

The only addendum is that Cotec can simply choose to be paid back in shares, at a fixed price of 27p per share (which happens to be a 130% premium to the current mid-price of 11.75p), rather than be paid back in cash. That would equate to 7,407,407 shares, excluding any potential rolled-up interest.

I was sure I saw a post by RAH over the weekend on TMAC - perhaps it's been deleted.

Anyway, I think the gist of the question was: would an exquisitely specific pre CISION prodrug, to an extent negate the need for the development of TMAC molecules?

My answer to that would be, Certainly not.

In the best case scenario, that both platforms were to become a resounding success, then:

Pre CISION prodrugs I believe would be considered as, and used for, first line of defence against many cancer types. They’d replace standard chemotherapies used around the world today.

TMAC molecules would be a significantly more expensive treatment (incorporating the Affimer / mAb; the linker; and the warhead). However, their efficacy is likely to be superior to pre CISION prodrugs.

I have tried to explain as best I can in layman’s terms, exactly how TMAC molecules work, on pp.24-26 here:

aimchaos.files.wordpress.com/2022/04/avacta-group-precision-platform-3.pdf

In short, the prodrugs are purely chemotherapy (albeit very targeted).

The TMAC molecules on the other hand, have three weapons in their arsenal. Not only do they have the chemotherapy aspect (or something similar, in the warhead), but they also catalyse white blood cells to attack the tumour, as well as support those white blood cells via the immunotherapy component of the molecule (e.g. an Affimer blockading PD-1 or PD-L1). This ‘triple threat’ of the TMAC molecule, theoretically should produce even better anti-tumour activity than the likes of AVA6000.

The early pre-clinical data for the first two TMAC molecules have been incredible. See slide 20 below. Over half the animals experienced complete tumour regression; and, what’s more subsequent immunity to rechallenge. It would be foolish to use that word that everyone prays for, at this extremely early stage – but if those pre-clinical results can be built on and one day brought into man… Well. Who knows. TMACs could certainly be up there with the most potent oncology drugs ever developed, at the minimum.

avacta.com/wp-content/uploads/2021/11/IWC-2021-Avacta-Presentation.pdf

It’s important to note also that some tumours simply do not respond to chemotherapy treatment. Circling back to RAH’s question, that is the USP of TMAC molecules, and why the platform would still have a place (if Avacta can get it to work in man), regardless of the prior success of pre CISION. A cancer therapy that combines chemotherapy and immunotherapy in a singe molecule… It is quite incredible to contemplate.

I asked at the AGM if a data room for AVA6000 was open to possible licensees and/or suitors.

Whilst AS would not confirm whether actual talks were ongoing with any third parties, he did acknowledge that, yes, of course the data room could ("theoretically speaking" was the term used, if I recall correctly!) be open to any serious parties, under NDA.

"An opinion is that it would not be allowed to continue if it just went in and came out the other end untouched."

I am also of this opinion. Why?

clinicaltrials.gov/ct2/show/NCT04969835

Secondary Outcome Measures:

3) Elimination half-life (t1/2) of AVA6000 & Doxorubicin

4) Renal clearance (CLr) of AVA6000 & Doxorubicin

At the end of the AGM presentation, when I was questioning him, AS acknowledged that the Secondary Outcome Measures in the trial (i.e. focus on Activation at TME (essentially, Efficacy)) are critical – in reality, as important as the Primary Outcome Measures (Safety and Tolerability). As such, if NONE of the SOMs were being met throughout C1 (and subsequently, C2), it would have been pointless for the SDMC to continue the trial.

Now, I note that it's not down in black and white anywhere that achieving the SOMs is "critical" to trial progression... But, 1) I trust AS' word; and 2) I like to think I have a bit of common sense. In reality, activation in TME is as important as safety and tolerability, even in P1a (i.e. proof of concept). The SOMs are, in truth, POMs – and I think the SDMC will be treating them as such.

"What we anticipate is that very shortly we'll see dose escalation into Cohort 3" - AS, early on in his presentation last week at the AGM.

Quite a strong statement. There have been constant slippages, and it's likely there'll be more going forward - but those words do at least suggest that the last patient of C2 is very close to completion.

I'd go further than Timster - I think that the next Dose Escalation RNS will not only stabilize the SP, but provide a real boost, as the wider market (that only reads the RNSs, and hasn’t followed the story closely like us shareholders) will get excited and throw some new buyers in.

My bet is that there'll be an RNS at 7.00am on Thursday.

My bet is that it'll be a general business update, with a primary focus on trial progress. Whilst data will not be discussed at all, the Co could provide assurances to the market in the RNS (through various means) that all is going well in the trial (see my previous post for those potential various means).

This will ensure that no new information is released / discussed at the AGM.

Chief ramper here, completely at ease. I’m flattered that you think I can control the share price of a £300m mkt cap company.

But why are we rampers needed now? The share price is only belatedly catching up with wider market moves of the past two weeks - having held up so surprisingly well until yesterday. Yesterday and today have just been a race for those wanting to reduce risk across the board, and also probably as a result of a number of players being overextended on leverage in spreadbet accounts.

There is very little to say until next Thursday, when I’m confident there'll be an update, either via a general business update or an AGM statement (or both). We know that they're not going to discuss any data until completion of P1a, but what I am hopeful they will do (and what they're allowed to do) is give very approximate guidance as they have done previously, e.g. "We continue to be pleased with the data"; "the data remains consistent"; "patients recruitment / patient withdrawals from trial will push out completion to later in Q3, but we're nevertheless delighted with progress"; etc. etc. If they can say, “we’ve received biopsies and whilst we cannot comment on the specifics of the data now, we’re VERY pleased” – then I think that’ll settle the market and set up the SP for a glorious run into P1a readout (whether that’s in July or September, I don’t think the market will care!).

Shorting into Thursday seems a tad silly, given that there’s a possibility that they could infer that dox activation the TME is indeed occurring.

N.B. I reiterate ‘possibility’. The above is based on my own conviction that pre CISION is working in man (which is based on there having been no recent P1a update – if things had gone badly, we would know immediately). Complete guess on my part – but the Board isn’t stupid (regardless of what some here may think). I’m sure they’re well aware of how important the next update is, in context of the extreme fragility of the wider markets at present. They can’t talk about specific data, but they could indicate that all is going well, and leave us to make our own deductions on whether dox activation at TME is occurring.

A long one - but a very fair assumption to make and with excellent rationale - so very worthwhile, Fardistanthills! Thank you.

You could certainly be close to the truth. Whatever the case, I am 95% sure we get a 6K P1a update before the AGM next week (most likely, morning of). After all, the BoD is going to have a load of PIs asking them tricky questions, face to face.

For me, the most encouraging aspect of the progress to date has been AS repeatedly stating that were something untoward to occur, Avacta would report it to the market without delay. It is not a blinded study; there is no placebo. Thus very poor data would cause, at the least, a pause in the trial - which would be reported to the market.

Moreover, the effects of chemotherapy can normally be measured in a matter of hours (unlike immunotherapies such as Keytruda, which may take a couple of months or more for effects to be known). Mgmt will know the effects of AVA6K - and yet the trial goes on still.

And further to this point - the biopsies. These were being lined up two months ago, with the assays for analysing them already having been put in place. I would suggest that they've received the results from multiple biopsies by now. Yet the trial continues. Again, if there had been zero sign of activation of dox at the TME in those first biopsies, given that it's not a blinded study / there's no placebo, it would be reasonable to assume that the trial would have been paused.

As long as they say, in an RNS prior to the AGM, that they continue to be happy with progress and that the data remains consistent, I will be delighted, and easily stomach a wait to end Q3 for the completion of P1a (if indeed there is a wait).

But hopefully you are correct, Fardistanthills, and they remain on track to finish in a matter of weeks and not months.

The family is over 100% up on the majority of their AVCT purchases, in just 2 years - they’re delighted.

Epic response EGTP!

A handful of months to wait now. Little point me commenting now, until the company breaks its silence.

Evidently, management is more than happy with its cash balance and how the AVA6000 trial and development of the pre CISION platform are going. As frustrating as it is for us shareholders, clearly management is unconcerned with share price fluctuations, and believes that the science will very shortly do the talking.

As EGTP so eloquently stated, Avacta could be "on the verge of re-writing science for the better".

For me this is a once in a lifetime investment.

In the meantime, I am short-term trading the volatility in the markets - and don't feel the need to comment on Avacta so frequently at this point in time.

Given that he's up 197% on his entry into Avacta, and 990% up on his entry into Audioboom, I'd suggest she thinks he's pretty epic.

Oh do grow up, please.

It's not fun for any shareholder, to have the shares as illiquid as they have been for so long. I have 10.5 million shares and warrants in Tally. I would dearly like to have the option of selling them - but have you seen me come on here and whinge?

Complaining on public forums does no favours for anyone. On the contrary, it can do a huge amount of damage to existing holders. Potential investors in the IPO may happen to look in here: if they see a big crowd of angry existing holders, they’ll think twice about investing for fear of the immediate sell off on Day 1 of listing.

The App is working well; the Company needs to focus on driving organic growth now, which it is at last doing (after far too long a period, in my view!).

Railsbank, India and Finland are being liquidated and/or farmed-out; cash is being funnelled solely to refine and market the Tally App and business.

One key point to note: the recent director loan and placing. There are two very important positives for existing holders here, that emphasize CP’s commitment to making Tally a success story.

1) The loan itself is secured by both CP’s Tally shares (~£2m worth a 2p); and by CP’s own Railsbank shares. He has a little over 3.5 years to repay the £1.3m loan. If Tally is a flop and CP is unable to sell £1.3m of shares before October 2025 (either on a public market, or privately), CP will have to sell down his Railsbank shares to pay.

2) The interest repayment. At 2%, CP is paying £26k cash to the company each year – or £2,167 per month. For those thinking CP is draining shareholder assets, just consider that. Going off his 2021 salary of £124k pa, that would equate to 34% of his monthly take-home salary of £6,317.

One third of his salary – each month – being used for the privilege of buying £1.3m shares in unlisted Tally at 2.0p. And he’s guaranteed that he’ll use his Railsbank shares to pay for them, in the event of failure.

That screams ‘Commitment’, to me.

Hi Neutronic,

I think it highly unlikely that Avacta licenses out AVA6000 at this stage.

The large placing (and the LFT revenue that should recommence flowing in a month or two, I hope!) means that Avacta is not going to be held for ransom, in terms of having to raise cash in the near term.

Moreover, I believe that NASDAQ investors will much prefer the Company to have retained 100% of its most advanced drug (AVA6000) at the point it lists in the US (likely to be in H2, in my view).

As such, I think any licensing deal in the near term will be for 3996.

Now, it’s unusual for a pre-clinical candidate to be able to raise that sort of money upfront ($30m to $50m+). More commonly, it’d be 1/10th of that amount.

However, given that pre CISION is very clearly a delivery technology, I believe that – assuming 6000 data is great – management will have a much easier task in out licensing 3996 for (relative) big bucks, even BEFORE it enters the clinic.

Takeda is the most obvious potential farm-in partner.

Can Avacta raise $30m to $50m against 3996, at pre-clinical level? If 6000 data is knock-out, yes I think it’ll be possible.

IF management can pull it off, it’d give the Company much needed breathing space to relaunch MeduFlow with M19, and to start generating cash again to fund P2 for 6000, and start further pre-clinical development on other pre CISION prodrugs.

I suspect significant funds could come through licensing out AVA3996, even at preclinical level, going into P1 - on the back of excellent data from AVA6000.

Usually, only a few $ million could be raised at that stage, prior to human data. But given the "platform-delivery" nature of pre CISION, I think they could raise significantly more via farming out the drug.

As for AVA6000, I suspect that management will want to keep it fully owned, in-house. I believe NASDAQ investors would only be interested in funding (via NASDAQ IPO, if that were indeed to transpire) a 100%-owned asset.

Sorry Mr Ripley, just checked in here and saw your post! Had automatically blocked you on Twitter as assumed you were just another new handle of the trolls - unblocked now! Apologies about that.

Some critical milestones very close now for Avacta. Let’s hope they catalyse the share price rerating that I think most of us feel the company deserves..!

Hope everyone’s keeping well. The perpetual trolling is certainly annoying and beyond bizarre - but best just filter them and focus on the company’s progress, I’ve found.

If/when Affimers are proved safe in man, then (on top of a PD-L1 market challenging immunotherapy) Avacta could really push on with its Affimer-based bispecifics, and – the Holy Grail – TMAC platform.

If Affimers take 10% share of the antibody market (Diagnostics + Therapeutics) by 2030, then that’s $20bn pa (likely, $30bn+ by then) in revenues. Imagine the owner of the patent taking a mere 5% in royalties on those gross sales.

And then we get to pre CISION. No need to cover that now!

There will be many reading this post who have been investors for years, who perceived the MULTI-industry-changing potential of the Affimer and preCISION platforms long ago. I only acquired my major position in Nov/Dec 2019: I feel a relatively new LTH. I’m up a little shy of 600% from my initial entry of 17.2p, although down 40% or so on large top ups at just under 200p!

I haven’t sold any (alas, I can’t buy more as I’m much, much than 50% into Avacta now). I am convinced we’re in the low foothills of where Avacta could go in the coming decade. The important thing is that – due to our dearth of major instos at present – we retail investors need to stay united (at least, the majority of us do – unfortunately, we’re always going to have at least one or two resident trolls). I would be absolutely gutted if a £5 per share offer lands tomorrow, as I know many retail holders (not all, I know) would sell immediately at that.

This business could be worth many, many billions one day. A genuine household name. I cannot understand how many do not see this.

My point: let us try to unify, and block out the evil. Even since my last post a few hours ago, I’ve seen many green boxes pop up – and alas, people respond to the green boxes.

Positivity breeds positivity. Best not give the evil any breathing space.

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..........

I am part of a majority on the LSE Avacta bulletin board that is fed up with trolls. In unity with my fellow shareholders, I have filtered:

Ndn71 RorkesDrift coolfree wyndrum AgentB

I suggest that everyone reading this, who hasn't already filtered these names, clicks on 'Filters' and then copies and pastes in the entire line of Usernames mentioned above.

We as supportive shareholders of Avacta, will add further Usernames of other trolls to this list, if required. But: we will not let discussions over “troll-blocking” clog the bulletin board, needlessly.

I have taken it upon myself, in union with my fellow shareholders, to not respond AT ALL to the baiting of the trolls in response to this Signature.

To LSE admin reading this: I would rather be banned than continue to read the disgusting drivel and slander, on an hourly basis, from the trolls named above - that you have hitherto failed to police. Get a grip; do your job.

..........

Third party validation of the first CE Marked, Affimer-powered IVD product – putting it in the top tier of its antibody-based peers, globally – is a major milestone for the Affimer technology.

Developed in house, Avacta has complete control over the 2017 patented, Type 3 Affimer platform. It gives the Company global, exclusive ownership over optimal Affimers (that I believe are used in all current products under development and on the market, incl. the SARS-CoV-2 AffiDX) until 2037, with a potential 8 year extension.

Once this latest study is peer reviewed, I’m hopeful that the power of Affimers will continue to gain market recognition – and commercial traction.

The antibody market for both diagnostics and therapeutics must be closer to $200bn now, given that it was forecast (in 2019, PRIOR to the birth of the pandemic) to hit $130bn this year.

[And before any states, “Well, Avacta claims that the global LFT market is only worth <$6bn pa”, I will rebut with, “the research that the company quotes is patently wrong – given that a single LFT provider in a single nation alone (Innova in the UK) generated close to $6bn in 2021.” Totting up the twenty largest LFT providers worldwide, I am very confident that one will arrive at a number of well in excess of $25bn in 2021 alone.]

My belief is that the Affimer platform, in Diagnostics, will now snowball.

However, the greater prize that Affimers could provide lies beyond Diagnostics. AffiDX has just proved the Affimer platform to be best-in-class of the antibody/mimetic platforms in the Diagnostics industry; but the (start of the) true blue sky opportunity for Avacta COULD come through LG Chem challenging Keytruda / Opdivo / Libtayo with an Affimer-based PD-L1 immunotherapy for various cancers (mkt size currently $25bn-$30bn pa). LG Chem’s evident thesis is that an Affimer-based therapy would have better tumour tissue penetration than antibody-based therapies (as they’re smaller), but with XT serum half-life extension would lack the usual downside (that non- XT serum half-life extension, Affimer-based therapies might suffer) of being flushed faster than antibody-based therapies.

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During one small window, AffiDX BAMS could have become an absolute behemoth for Avacta.

The thesis was that it could have replaced PCR as the gold standard for SARS-CoV-2, worldwide.

Exquisite S/S, but without the amplification required by RT-PCR. Thus, in reality, making it the most accurate type of SARS-CoV-2 test 'in real time'.

Anyway, back to matters that count TODAY: the LFT is (and going forward, even more so will be) an infinitely larger market than PCR. Independent validation of the exceptionally high quality of the AffiDX will count for a lot, in commercial discussions.

Good days are coming for Avacta shareholders.

Good luck all.

Nota Bene: Egbert and NDN and Bishop and Coolfree is not a shareholder. It is an ignorant, despicable, vile and detestable person. Imagine being that loathed by everyone, and reveling in it. I suppose it's the downside of the internet. It can create monsters of men.

N.B.B. In fact, I propose that this BB, for every single message that anyone posts, copies and pastes the following elongated Signature to their own post, beneath their own content (including the line of dots above and below):

..........

I am part of a majority on the LSE Avacta bulletin board that is fed up with trolls. In unity with my fellow shareholders, I have filtered:

Ndn71 RorkesDrift coolfree wyndrum AgentB

I suggest that everyone reading this, who hasn't already filtered these names, clicks on 'Filters' and then copies and pastes in the above entire line of Usernames mentioned above.

We as supportive shareholders of Avacta, will add further Usernames of other trolls to this list, if required. But: we will not let discussions over “troll-blocking” clog the bulletin board, needlessly.

I have taken it upon myself, in union with my fellow shareholders, to not respond AT ALL to the bating of the trolls in response to this Signature.

To LSE admin reading this: I would rather be banned than continue to read the disgusting drivel and slander, on an hourly basis, from the trolls named above - that you have hitherto failed to police. Get a grip; do your job.

..........

I appreciate that this Signature will take up a fair bit of space, but if LSE admin aren't going to do anything, I suggest this BB polices itself. If anyone can think of a better way of doing it, I'm all ears.

In the meantime, what a tense but potentially glorious few months approach us!

So where is the discrepancy?

It is this: the trial can commence the (escalated) dosing of the next cohort, after the preceding cohort has completed SEVERAL cycles only. The trial need not wait on the full six cycles to have been completed.

If the first say 2-4 cycles have yielded very positive results, the next cohort can be launched.

I do not know what the exact number of cycles is (that need completing, prior to launch of the subsequent cohort), but I know it’s around 2-4.

The aforementioned timings fit with this. For example, taking my theoretical, perfect-timing scenario set out above: were the subsequent cohorts to commence 21 days after the THIRD dose day of the preceding cohort, and not after the sixth, then the final recovery day after the third dosing of the fourth cohort would be on 20/04/2022.

What does this mean for RIGHT NOW?

Well, the first patient of the first cohort is due to be dosed for the FIFTH time next week. Their THIRD dose occurred 36 days ago. It’s been over two weeks since the second cohort could have commenced, assuming that it would be permitted to start 21 days after the preceding cohort’s third dose.

If the second cohort has commenced, why hasn’t it been reported on? I’d suggested there’s still not enough data for the hospitals and Avacta to feel comfortable in doing so.

Perhaps they will wait for all three patients in C1 to completed their six cycles? Or wait for all three patients in C2 to have successfully gone through one or two cycles, without dose limiting toxicities (assuming, of course, pre CISION works in man!!!)?

If the second cohort HASN’T commenced, then why not? Perhaps it has taken longer to find the second and third patients, and they are not yet through the third cycle? Perhaps one of those first three experienced DLTs, and so a fourth patient had to be recruited?

My money is on C2 having commenced, or at the least – extremely close to commencing.

The opening of a third hospital on 19/10/2021 – a week after the FOURTH dosing of the first patient in C1 – would suggest that they’re looking aggressively for more patients than just 1-3 potential replacements for C1.

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Dose escalation. Has dosing of the second cohort already commenced?

My belief is that the first dose escalation has indeed already occurred. That is, to say, the second cohort of three new patients has already received its first dose of the next level up of pro-dox. If not, then I believe it is within the next week or so.

My rationale for this is based on the publicly stated trial format, coupled with the stated completion date of Phase 1a.

Firstly, the trial format:

First cohort, comprised of an initial three patients. Each patient to go through six cycles (and actually, possibly more), being dosed at 80mg/m2 once every three weeks.

Assuming no dose limiting toxicities in those first three patients, the second cohort of three patients would be dosed, at a higher dose (dose escalation to follow a modified Fibonacci series and guided by both safety data and PK data from Cohort 1). Each patient from the second cohort would be dosed (at least) six times, again at three week intervals.

And so on, with an estimated four cohorts in total.

Theoretically, taking no short-cuts, and in a perfect world (assuming that all three patients for each new cohort started on exactly the same day; that there was no lag between cohorts finishing and starting; and that each cohort DIDN’T require a fourth, fifth or sixth patient to step in), then:

First patient in C1 was dosed on 11/08/2021. Therefore sixth and final dose will be on 24/11/2021, and final recovery day on 14/12/2021.

First patient in C2 would then be dosed on 15/12/2021. Sixth and final dose would be on 30/03/2022, and final recovery day on 19/04/2022.

First patient in C3 would then be dosed on 20/04/2022. Sixth and final dose would be on 03/08/2022, and final recovery day on 23/08/2022.

First patient in C4 would then be dosed on 24/08/2022. Sixth and final dose would be on 07/12/2022, and final recovery day on 27/12/2022.

Meaning Phase 1a would end on 28/12/2022.

Evidently that is at least 6 months longer than what Avacta has guided – which was that Phase 1a would completed before end June 2022. That does not include delays between launching cohorts; nor does it include delays due to individual cohorts may having to ‘restart’ owing to any patient reaching a dose-limiting toxicity. Had they be included, we’d be looking at an end to Phase 1a around Q2 2023.

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