Dan A

Typically a Value Investor but now also looking at growth stocks for mid to LT hold. Experienced I-Banker, PE and Credit Investor

[Conor Kenny @conorfkenny]

Crypto staking company KR1 is planning to list on the London Stock Exchange Main Market, according to the FT. 🚀

This move would make it one of the first pure-play digital asset firms on the LSE's main board, signaling London's growing embrace of crypto.

#KR1 #LSE #CryptoStaking #LondonFinance

[SCHD STAN | Craig @SCHDETF]

🚨 New $SCHD video from Jeff Teeples — packed with insights on Q3 dividend update, long-term growth, and a killer retirement scenario. 👇

[RAH @RAH00084]

Now abundantly clearly why #AVCT is so relaxed: non-dilutive funding via license deal(s).

Multiple options on table.

As there should be based on 3.5 years of data and 70+ patients dosed.

[Myles McNulty @MylesMcNulty]

New data from Avacta's Phase 1a trial for #AVA6000, specifically focusing on 10 patients with salivary gland cancer ('SGC'):

- Only 1 out of 10 patients experienced tumour progression - equating to a 90% disease control rate in this set of patients.
- 5 out of 10 patients experienced tumour shrinkage (1 partial, 4 minor).
- 6 patients remain on treatment.

These are P1a patients, and have been heavily pre-treated. This is vital to note, as pre-treated patients are usually much less responsive to further treatment.

Currently, "there is no standard of care for SGC once patients have developed distant metastasis, with a five year survival rate of approximately 43%."

It's also crucial to remember that - especially when used as a monotherapy - it is extremely rare for standard doxorubicin to yield complete responses for patients. Rather, it is used predominantly for disease control.

So, to summarize: even in extremely sick patients with advanced stage SGC, and who have very little (if any) treatment options available remaining to them, AVA6000 has prevented disease progression in 90% of cases.

In contrast, in treatment-naive patients with earlier stage SGC, there currently exists no standard-of-care.

Results should improve significantly for AVA6000, when used as a first-line therapy for those patients with earlier stage SGC.

It's now patently obvious (at least to me!) that AVA6000 is on for accelerated approval for the treatment of SGC.

And that's just the beginning for AVA6000. The Phase 1b commencing now is also running cohorts for triple negative breast cancer and soft tissue sarcoma.

If pre | CISION can transform the treatability of a certain cancer by modifying a chemotherapy that gained marketing authorization from the FDA over a half-century ago, just how much is it going to transform the wider oncology landscape when used to modify the most potent warheads on the market right now, such as exatecan (eyes on #AVA6103!!!) and MMAE?

Avacta is in possession of Paul Ehrlich's Magic Bullet.

[Myles McNulty @MylesMcNulty]

This is possibly the most consequential RNS that @avacta #AVCT has ever put out.

"Our first program, AVA6000, demonstrates a four- to six-fold increase in the therapeutic index in the clinic and in preclinical models.... We are now seeing a 75-fold increase in therapeutic index with our recently announced exatecan program, AVA6103 in preclinical models, suggesting that AVA6103 could have an unprecedented safety profile in the clinic."

- the maximum tolerated dose of pre|CISION exatecan (AVA6103) observed is 75 times that of conventional exatecan in a daily dosing regimen;

- up to 50-fold higher warhead concentrations in the tumor versus plasma in a patient-derived xenograft model;

- AVA6103 inhibits tumor growth, with complete responses noted in a preclinical treated model (N.B. multiple CRs!).

This drug will obliterate the existing competition in the ADC space (notably, the currently market-leading Enhurtu and Trodelvy ADCs that use Top-1 inhibitors). And I don't mean just surpass; but properly obliterate.

The company has nailed the science and the platform now. It can be used to harness immensely toxic warheads - the most potent in existence; and can be used to target as much as three quarters of all cancer cases worldwide.

A truly transformational development in the field of oncology.

The UK market may not see it immediately (especially given immediate-term Budget concerns and silly games over the HCI bond), but the world of Big Pharma will.

I am convinced that Avacta will be acquired within 12 months now - possibly much sooner.

[Myles McNulty @MylesMcNulty]

The first two drugs of #AVCT's new pipeline revealed this morning. The more advanced is #AVA6103, a peptide-drug conjugate that uses the uber powerful exatecan as its warhead. Potential indications for this new PDC are: breast, lung, pancreatic and gastric cancers. Huge, intensely competitive markets.

The market leading antibody-drug conjugate, Enhertu (co-owned by Daiichi Sankyo and AstraZeneca), uses a derivative of exatecan (deruxtecan) as its warhead.

Note that the consensus forecast is for Enhertu to be generating global revenues in excess of $11bn per annum, by 2030.

Avacta clearly thinks that from the initial animal data that it has generated, AVA6103 could - at the very minimum - compete with Enhertu. More likely, it has demonstrated superior tumour-targetting ability, which one would expect(!) to result in superior efficacy.

No company has been able to harness the power of exatecan or deruxtecan without the use of a monoclonal antibody (for targetting to cell-surface antigens), in an ADC format.

To repeat, for those at the back: Avacta is now doing what no one else in the oncology world has been able to do.

It's not difficult to perceive how AVA6103 could mark a true step change in targeted oncology. And it's equally simple to understand why the likes of AstraZeneca and Daiichi - as well as all the other leading players in the ADC space - will now be on high alert.

Hugely looking forward to the unveiling of the initial pre-clinical data for AVA6103 (and #AVA7100) next week.

......

And on a "side-note", Avacta has also casually unveiled on its website that its first PDC, #AVA6000 (the pre | CSION form of doxorubicin), is now enrolling patients with triple negative breast cancer in its P1b study...! I shall repeat what I posted a couple of weeks ago:

"One of the three P1b cohorts (currently recruiting) is almost certainly to be for breast cancer. Assuming efficacy data is good, it'd be rather pointless doing a monotherapy P2 trial for that; but it would be of extremely high importance to do a P2 combo trial for 6K in replacing doxorubicin in the KEYNOTE-522 regimen (chemotherapy with Keytruda). Possible financing partners for that are somewhat obvious...!"
......

The future is very bright for Avacta.

[Avacta @avacta]

Today we announce the addition of two novel preclinical oncology assets, AVA6103 and AVA7100, to our pipeline of pre|CISION-enabled drug conjugates. https://t.co/KQFU7FpR2u #AVCT

[Dan A @DAKCapital]

Potential sale of diagnostic business & Nasdaq dual-listing. #AVCT

[Avacta @avacta]

Avacta today announces its unaudited interim results for the six months ending 30 June 2024 with recent progress against the Company’s 2024 stated goals. https://t.co/iGm4wd22bs #AVCT

[Christina Coughlin @coughlin582]

Buenos dias …. Thrilled to be here in Barcelona at #ESMO2024 for the #AVCT presentation. More to come today

[Dan A @DAKCapital]

@EndWokeness KK

[Myles McNulty @MylesMcNulty]

It's been a very quiet couple of months for Avacta (at least on the RNS front) following key management changes, but I believe that #AVCT is now on the cusp of a transformational few months (see @RAH00084's thread below, for likely major news items between now and Christmas).

The biblical share price rally that I have been harping on about for years is, I think, at last drawing near. Knockout data from the 3+ year #AVA6000 Phase 1 clinical trial will be the key catalyst, that could unlock so much for the company (commercial deals, corporate actions, expanded clinical activities). And that P1 study could officially be brought to a close, any day now.

The uber bull case is very simple: pre | CISION is the most targeted delivery platform for warheads designed to treat solid tumours, ever developed. As such, it represents one of the most important developments in oncology in years - many shareholders would in fact argue, ever.

The evidence for this is already coming to light from the AVA6000 P1a trial. See @jivetur88775834's post, also below. The first pre | CISION prodrug isn't just 20%, 50% even 100% more targeted than the leading antibody-drug conjugates on the market right now; it is many multiple times more targeted. The implications of this are absolutely staggering.

Clearly, most market participants do not yet believe this. It is, after all, a ludicrous claim to make. How could an AIM listed company have gotten hold of such a crucially important (and absurdly valuable!) platform?!

But as I've said, the evidence for this is already beginning to present itself. And it's not difficult to perceive what is going to happen when pre | CISION is used to modify much more modern and potent warheads than the half-century old doxorubicin, and moreover used in suitable patient populations.

Phase 1b/2 for AVA6000 will be kicking off between now and Christmas. This is the point at which multi billion $ takeovers become a very real possibility in targeted oncology (and there are plenty of examples of this occurring over the past five years).

In my view, it's simply a case of "When" for Avacta. The "If" part was removed quite a while ago now.

We (and Avacta's share price!) are in for in interesting few months.

Have a good weekend all! 🌞🍻

[Avacta @avacta]

Good to be featured by @joannemidas in MIDAS share tips 'companies working on future blockbuster treatments'. https://t.co/xpQoN0UDTX #AVCT

[RAH @RAH00084]

#AVCT finally hitting the mainstream.

[RAH @RAH00084]

If you can’t see where #AVCT is headed after digesting the latest written Q&A, you never will.

In summary:

- yes, we’re already talking to the FDA about accelerated approval. Our P2 will be 80-100 patients. Big. And we’re still not worried about cash… why do you think that is?

- data is such we’re re-evaluating whether to go for more common indications in P2 (no doubt informed by the bi-weekly data). An expedited approach may also be possible here, depending on FDA discussions.

- we have 28.5 months of detailed data, we did not present it because we will seek further IP protections and present this rich data set at the major conferences in early 2024

And just in case you still don’t get we’re not worried about cash (because we will strike a deal):

“More broadly, our commercial strategy includes partnering of the pre|CISION platform to enable third parties to develop pre|CISION chemotherapies under license using their own proprietary cytotoxics. We believe that approach provides the best opportunity to maximise the benefits to our stakeholders”

And if you *still* don’t get it, they go again:

“Avacta therefore plans to take AVA6000 into phase 2 and will then consider partnering this asset to take it to market and to broaden its applications into other cancer indications.

There is potential to partner AVA3996 or any other undisclosed pipeline assets at a preclinical stage. More importantly in the short term is the potential to partner the pre|CISION platform.

This means potentially licensing the platform to a third party to use in combination with their own cytotoxic agent.

Such a licensing deal would be expected to be narrowly focused on a specific agent or agents. The clinical data published on December 13th 2023 plays a pivotal role in generating business development discussions and accelerating those that are ongoing.”

You’re going to wake up one morning very soon to Avacta having signed a license deal for preCISION.

I can’t quite believe the SP sits <200p, let alone below where it was before the trial began (124p) on this Q&A but there you go. It does.

The unadulterated madness of AIM.

[Myles McNulty @MylesMcNulty]

Phenomenal results (so far!) from @avacta's #AVA6000 Phase 1a trial.

These results genuinely set the ground for #AVCT to revolutionize the treatability of the majority of solid tumours. There is so much to cover (which I will do in a long note), but a key quote from the CEO is:

"Targeting potent therapies to the tumour, while limiting the systemic toxicity that often characterises these therapies, is one of the holy grails of cancer drug development....

...The potential of the pre|CISION platform to change the way in which potent cytotoxic drugs are delivered, improving cancer patients' quality of life and treatment outcomes, is truly remarkable."

The fact that multiple instances of highly encouraging efficacy data have been witnessed in this patient population - who are very sick, and heavily pre-treated, and whose tumours are often not treated with dox at all - makes it all the more remarkable.

I am quite sure that this is the firing gun for commercialization of the platform (licensing, collaborations) with Big Pharma.

Huge congratulations to the Avacta team. pre | CISION is going to change one of the most important industries on the planet.

[PMH Capital @CapitalPmh]

#AVCT

Excellent news &amp; very well done to the whole @avacta team &amp; CEO Alastair Smith.

You've certainly over-achieved wrt the Phase 1a clinical data for AVA6000. Indeed across just about every metric.

All the details here.

https://t.co/tuthdlwWA4

[Avacta @avacta]

Avacta is pleased to provide detailed pre-clinical, clinical and pharmacokinetic data from the Phase 1a dose escalation study of its lead pre|CISION programme, AVA6000, a tumour activated form of doxorubicin. https://t.co/OWNtJyHfvQ #AVCT

[Myles McNulty @MylesMcNulty]

Personal view is that, over the next two weeks, @avacta's #AVA6000 Phase 1a trial is covered by mainstream media - @BBCNews, @SkyNews, etc.

Stories of efficacy will drive #AVCT's share price now. This is what MSM wants to report on.

And astonishingly, despite the P1a trial's primary purpose being to evaluate the safety and tolerability of AVA6000, management has already reported that signs of efficacy (stable disease, even a case of significant tumour reduction) have been observed in the extremely sick patients taking part in the trial.

The world will very shortly find out that Avacta's pre | CISION platform is going to turn the cancer treatment industry on its head.

For investors going forward, the single most important aspects to remember are that pre | CISION prodrugs could possibly be used to treat a majority (say 65-70%, possibly as high as 80%) of all cancer cases; and that only Avacta can use the pre | CISION substrate to make or modify any drug for at least another decade (and then patent any and all of those modified drugs for a further 20+ years beyond that).

My own plan is to hold on for dear life to these shares, as I think volume and share price volatility could both absolutely explode in the coming weeks.

Hopefully, at long last many thousands more investors will start to appreciate just how gigantic AVCT can become in the pharma world.

[Avacta @avacta]

Shareholder update to review AVA6000 Phase 1a data. https://t.co/sksDrkGzGc #AVCT

[Elon Musk @elonmusk]

Cybertruck deliveries start on Thursday