Bluelion123

UK based private investor in small/mid-cap listed equities

[⛏🅾️Ⓜ️💣 @tom_the_bomb__]

What a wonderful comment to hear from @coughlin582 @avacta.

35 of 38 #AVCT AVA6000 SGC patients have seen their disease either stabilise or respond.

The market remains focused on when median PFS will be reached.

For patients and their families, the question is much simpler = is the treatment working?

The emerging data suggests it very much is.

[Bluelion123 @79Jadds]

@Towlie1981 @avacta I get that & your not wrong. everyone has their own method. I was a bit disturbed by a Mail on Sunday int with Nick Leeson which said the only share price he checks everyday is @AVCT. Easy money i guess.just wish there were more LT holders in the market. At least you keep 80% inv

[TVR5 @TVR5AVCT]

@coughlin582 of @avacta therapeutics is the obvious choice @bradloncar.

#AVCT

[Bluelion123 @79Jadds]

@GBPolitcs Amazing Dads

[Bluelion123 @79Jadds]

@baroninvestment What are your thoughts re ECO? Guyana, Namibia & South Africa all now looking like near term drills largely free carry. Obvs gone up from the lows quite a bit. Nice explorer play imo

[Richard Hughes @hughesy0707]

Retention of 100% of our pipeline remains overwhelmingly in the best interests of #AVCT shareholders, for now. 💰 Delighted to have subscribed to the placing with credit to the team at Zeus for all their efforts. Looking forward to 2026! 🧨

[Bluelion123 @79Jadds]

@glr_1990 Because they had them leaked to them at 4pm the previous day! 😁

[Christina Coughlin @coughlin582]

Delighted to be at #BiotechWeekBoston connecting with industry and highlighting the great progress preCISION continues to make in clinic. #AVCT @avacta
#LetsDoThis
#PeptidesCreateHope
#HopeWithoutCompromise

[RAH @RAH00084]

That’s a very solid #AVCT RNS:

- P1a complete
- Dose expansion (RDE) already underway
- Dx divestment incoming
- Pipeline release 30th October
- Cash £32.5m end June
- Financing strategy linked to listing on NASDAQ incoming

Do they have a plan? Sure reads like it!

[Cumulus @Cumulus51896691]

Who has been casting doubt ?

A well known group of trolls
Winnifrith and his myrmidons
A contrarian analyst
Various trading chancers
Those connected to the short

Draw your own conclusions

#avct

[Myles McNulty @MylesMcNulty]

Even though I should be well-used to the indifferent attitude of UK investors when It comes to valuable-but-pre-revenue companies (especially, biotech businesses!), I really am surprised that the recent news out of @avacta #AVCT hasn’t caused much more of a stir (and direct impact on the share price!).

No, I’m not referring to yesterday’s RNS, about Avacta’s attendance at major European cancer conference, ESMO, this coming Saturday, at which they will present updated data from the #AVA6000 Phase 1a trial.

I am talking about the as-yet-not-publicly-disclosed (at least by Avacta itself) information discovered by super-sleuth @sandyradders over the weekend (see link at bottom). At a certain cancer treatment symposium in Barcelona next month, in a proffered paper session Avacta is presenting a new pre | CISION molecule:

The novel peptide drug conjugate AVA6103 is a FAP-enabled preCISION medicine which targets Topoisomerase I to the tumor microenvironment via FAP cleavage

Firstly, this is a peptide drug conjugate (‘PDC’); and not an antibody-drug conjugate (‘ADC’). There is therefore unlikely to be a biologic component in #AVA6103. Biologics (i.e. monoclonal antibodies) are the most expensive components of ADCS; often rendering them prohibitively expensive, in fact. More on that later.

Secondly, the small molecule component (i.e. the inert synthetic warhead – the toxin that does the kill celling) of the AVA6103 PDC is a topoisomerase I inhibitor. Very simply, a TOP1 inhibitor is a cytotoxic agent that prevents DNA replication in cells, leading to cell death. TOP1 inhibitors are thus particularly effective as drugs used to treat cancer cells.

……

There are three (mainstream) TOP1 inhibitors that have gained marketing approval of some kind, as cancer treatments. The first two are irinotecan and topotecan. These are inert small molecules – and are considered conventional chemotherapies. Highly toxic, very nasty side effects. Both secured their first marketing approvals from the FDA in 1996. As the owner of irinotecan when under patent, Pfizer branded it Camptosar. Topotecan was branded Hycamtin by its owner, GSK.

Both drugs were (and to a limited extent, still are) used as monotherapies and in combination therapies. Both are now off-patent, generic drugs (although both Pfizer and GSK still own the respective brand names).

It may be that Avacta is using one of these two drugs in its new PDC, AVA6103. After all, in presentations 2-3 years ago (all now removed from the Company’s website), irinotecan was explicitly referenced as a chemotherapy that could be modified with the pre | CISION platform.

Were this to be the case, AVA6103 would be not dissimilar to AVA6000 – a modified (supercharged!) version of an established drug that has been on the market and used by oncologists for 2-3 decades. Fast-track approval (as many Avacta shareholders believe is likely to be the case for AVA6000) would very much be on the cards.

……

Another possibility would be that the active metabolite of irinotecan – namely, SN-38 – could be used as the warhead in the pre | CISION PDC, AVA6103. SN-38 is significantly more potent than irinotecan, so much so in fact that it could not be used as a naked drug, due to it extreme toxicity.

There is already one ADC that uses SN-38 as its warhead, that has been granted marketing approval by the FDA. That ADC is Trodelvy, owned by Gilead Sciences. Trodelvy is currently used to treat certain cases of breast and bladder cancers.

In H1 of this year, Gilead failed two of its ongoing Phase 3 trials in certain cases of lung and bladder cancers. In one of the trials, deaths due to adverse events were in fact higher than those caused by conventional chemotherapy.

This was a big blow to Gilead, which had acquired Immunomedics – the inventor and developer of Trodelvy – in October 2020 for $21 billion in cash. At that point in time, Trodelvy had generated sales of approximately $20m, having been granted FDA approval for its first indication (“adult patients with metastatic triple-negative breast cancer who have received at least two prior therapies for metastatic disease”) in April 2020. The deal valued Immunomedics at over 5x analysts’ peak sales estimate of $4bn (which was supposed to have been reached nine years later, in 2029!). Trodelvy was the only approved drug / revenue generator in Immunomedics’ stable.

……

The third TOP1 inhibitor is exatecan. Exatecan was developed by Japanese major, Daiichi Sankyo, and remains under patent. Exatecan as a free drug has not been used as a monotherapy. It is multiple more times more potent than the earlier two TOP1 inhibitors, and thus would cause unacceptable side effects. Rather, Daiichi created a derivative of exatecan, named deruxtecan, to serve as a cytotoxic payload (i.e. the warhead) in its suite of ADCs under development.

Daiichi’s first TOP1 inhibitor-based ADC – Enhertu – has been marketed for several years now, and has secured approval for a growing number of indications. Daiichi and AstraZeneca have been working under a worldwide commercialization collaboration on the drug since 2019. Last year, Enhertu overtook Roche’s Kadcyla to become the world’s highest selling ADC, generating revenue of $2.6bn.

Daiichi’s second TOP1 inhibitor-based ADC is the not-yet-approved Dato-DXd (which could be a direct competitor to Trodelvy, as its mAb targets the same cancer cell surface antigen, namely TROP2). Daiichi and AstraZeneca are working under a similar collaboration for Dato-DXd, as they are for Enhertu. Yesterday, Daiichi posted some disappointing results for the drug’s first Phase 3 trial in lung cancer.

……

Now… Back to Avacta. In my view, AVA6103 – to be presented next month at a specialised cancer conference – is likely to be a PDC, similar to AVA6000, but with one of the following warheads (instead of doxorubicin):

i) irinotecan

ii) topotecan

iii) SN-38

iv) deruxtecan

Over the past several months management has made a big deal of the new (soon-to-be revealed) pipeline being very exciting (comprised of novel, highly potent molecules; boasting a range of modalities, etc.).

Moreover, management has seemingly shelved AVA3996, that was hitherto the first drug after AVA6000 in the pipeline, and which used another conventional chemotherapy, bortezomib, as its warhead.

Resultantly, my view is that AVA6103 will likely be a PDC containing the more novel SN-38 or deruxtecan, rather than the first-generation TOP1 inhibitors, irinotecan and topotecan.

If it’s SN-38, I believe that Avacta could be the sole owner of AVA6103. SN-38 is only under patent (held by Gilead) as part of the whole ADC molecule, Trodelvy. As it’s derived from irinotecan, a generic drug, so SN-38 itself could be used off-patent. When combined with pre | CISION, however, it could/would be patented by Avacta as sole inventor/owner.

If it’s deruxtecan, then Avacta would have to have entered into some sort of partnership with Daiichi Sankyo (and possibly AstraZeneca). Consider this: in 2019 when the Enhurtu collaboration was formed, Astra paid Daiichi $1.35bn upfront, and committed to up to a further $5.55bn in contingent payments. And that was only for a 50% share of future sales in most markets. Enhertu was in multiple pivotal trials at the time of the deal, but hadn’t secured marketing approval from any governing body.

In 2020, the second collaboration between the two over Dato-DXd – which hadn’t even commenced clinical trials at the time – involved similar figures. In return for a 50% revenue share across most markets, Astra paid Daiichi $1bn upfront, and committed to up to a further $4bn in contingent payments.

……

Whether its SN-38 or deruxtecan, the key point is that through AVA6103, Avacta will at last be going tête-à-tête with the leading ADCs on the market. With the largest of the ADC players – Pfizer, Roche, Daiichi / AstraZeneca, Gilead.

Then it’s down to which is a more targeted delivery platform, and accordingly which can result in greater amount of active warhead reaching cancer cells before dose limiting toxicities are hit.

However, there is also an important second matter to consider: cost. Avacta’s TOP1 inhibitor-based PDC would not include a monoclonal antibody component, in contrast to the TOP1 inhibitor-based ADCs of Daiichi / Astra and Gilead. Earlier this year, the National Institute for Health and Care Excellence (‘NICE’) rejected Enhertu for use on the NHS in England, following a failure to agree a cost effective price with Daiichi and Astra.

PDCs should be substantially cheaper to manufacture than ADCs. This should expand their addressable market considerably, relative to ADCs.

It's also worth noting that in holding a proffered paper session at the EORTC-NCI-AACR symposium, it is probable that Avacta is already sitting on some in-vivo (i.e. early pre-clinical) data. This could plausibly be the early foundations for mounting a direct challenge on the ADC class, at least as it exists today.

Things are going to get hot at Avacta between now and the end of next month…!

https://t.co/1qqn1fhiw6

[Avacta @avacta]

Avacta to present updated clinical data on AVA6000 at the European Society for Medical Oncology (ESMO) Congress. https://t.co/kwlRFqW59o #AVCT

[Christina Coughlin @coughlin582]

My daughters have always called it “get home day”

Today I leave #AVCT filled with optimism. Reminded of a quote “never doubt that a small group of thoughtful, committed citizens can change the world. Indeed it is the only thing that ever has” 😊

Here’s to that team. #LetsDoThis

[Myles McNulty @MylesMcNulty]

Along with certain other shareholders, I've put in a considerable amount of effort this year (and last) into helping to reconfigure #AVCT's board composition, through activist measures.

I didn't think I could be any clearer: I believe @avacta has the most valuable oncology platform in the world - which could ultimately be worth tens, and likely hundreds, of billions of dollars, once it has received the necessary development capital (as well as human capital that can provide the requisite expertise and experience).

It's very unlikely I'll be selling out at an equity value of £250m, especially now that the platform has already been largely clinically derisked by the wildly successful three-year #AVA6000 P1a trial.

[Bluelion123 @79Jadds]

@theprince580591 #ECO

[Bluelion123 @79Jadds]

@Robin25461631 Was a bit surprised Gil never made more of the overlap onto Ecos block. Guess it would be irrelevant if Jethro and Joe worked out. Hope this is good news #ECO @gil_holzman

[Robin Mayes @Robin25461631]

ExxonMobil to expand oil production offshore Guyana with new multi-billion-dollar Hammerhead project. This v exciting for #eco $eog.v. Some of Hammerhead is in Orinduik……! https://t.co/aIC0KMYO4f

[Cumulus @Cumulus51896691]

A simple way of understandIng what is going on. Avacta have sacked their Southgate.

#AVCT

[Bluelion123 @79Jadds]

@nickkaulbach @JESKirrane @glr_1990 @asininitybeyond @coughlin582 Agree as long as the board is strengthened with another Exec to help the CEO through the murky depths of AIM. If a US listing is a possibility then even more need for experience, but not part time.