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Another take on the ‘ticking’ clock, from the Dec 13 2023 presentation ...

“AVA6000 phase 1 (ALS-6000-101) data cutoff 27 November 2023”.

“1 Cohorts 5, 6 and 7 have all patients ongoing at the time of the data cutoff, thus safety findings in these cohorts will continue to mature”.

“Disease surveillance every 6 weeks”. We now have 6 more weeks trial data.

GLA

Indeed, should be a ‘paradigm shifting’ year for Avacta.

Guess we’re all reasonably current with the ‘state of play’ as regards AVA6000 and the wider Pre|CISIONTM platform. At least as ‘(partly) revealed’ in December 2023. I.e. ‘it works’ ™.

Trials (seem to be going well), Regulators (we are talking to them), Data (more to come), IP (new patents?), Partners / Commercials (discussions ongoing, accelerating), etc. All good (hopefully great).

Now what about Affimers?

Last update from AffyXell in June 2023 with second milestone and increased equity stake. Still showing as ‘Discovery’ in their pipeline …

http://www.affyxell.com/en/pipeline/pipeline.php

LG Chem have LR19128 at pre-clinical in their pipeline of Oncology products …

https://www.lgchem.com/company/company-information/business-domain/biology

Presumably this is relates to “Avacta’s Affimer® PD-L1 inhibitor with Affimer XT™ serum half-life extension for a range of indications.” As per license renewal update on 30 June 2022. So what has happened in the last 18 months?

Meanwhile we seem to be progressing well with AVA032 - as per the poster below from November 2023 (AffyXell also involved in this) …

https://avacta.com/wp-content/uploads/2023/11/PEGS-Europe-2023-poster.pdf

But AVA032 now not showing on the Avacta site pipeline page (why?) …

https://avacta.com/therapeutics/pipeline/

AVA028 and AVA021 both showing as pre-clinical, but no updates.

Seems like there should be a lot of news to come on the Affimer front?

GLA

Pre|CISIONTM works. Not just AVA6000, but also for (at least in pre-clinical) AVA3996/2727D.

We continue to capture data on FAP cleavage (Tumour dox vs plasma dox for e.g.) and what is excreted from the body. Looks to me like most other measures are about Doxorubicin (albeit with the benefit of pre|CISIONTM delivery to the Tumour and (pretty much) nowhere else in the body.

So we are trialling Doxorubicin at higher doses than have ever been possible before due to side effects – particularly cardiotoxicity

This paper from 2017 recommends that “Doxorubicin should remain the standard first-line treatment for most patients with advanced soft-tissue sarcoma.”…

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/pdf/main.pdf

Noting that “Doxorubicin has been used as first-line treatment for locally advanced or metastatic soft-tissue sarcoma for more than 40 years.”

Is there something obvious that will supplant Doxorubicin that has been identified in the last few years, this ESMO article for 2 years ago suggests not really …

https://dailyreporter.esmo.org/esmo-sarcoma-gist-virtual-symposium-2022/news/single-agent-doxorubicin-is-it-still-the-standard-first-line-therapy-for-all-soft-tissue-sarcoma-subtypes

So why not just ‘do’ Dox much (much, much) better. Like without significant side effects, like in much higher targeted doses? My view is that the Phase 1:Arm 2 trial is about proving this, and achieving one of the designated FDA options below for AVA6000 …

https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track

Earlier this year someone (who should know) said “a doxorubicin [i.e. AVA6000] better than ‘standard doxorubicin’ overnight becomes ‘the standard of care …”

No wonder Sir Al wants to keep AVA6000 ‘in-house’. While the wider pre|CISIONTM platform is open for licensing deals.

GLA

In my post a few days I suggested that the PONT Biopharma PNT2002 (PSMA targeted radioligand) trial readout was “positive”. Just ‘stepping back’ a little, on further reading, while the headline Progression Free Survival (PFS) was 9.5 months compared to the control arm (treated with ARPI) at 6.0 months, the Overall Survival (OS) results were declared “immature” with a Hazard Ratio (HR) of 1.11 – which I interpret (please DYOR) as higher risk than the control? Full results in 2024. Also, it seems they are already working on (what looks like) the successor to PNT2002 with PNT2001?

This probably explains why the POINT sp has dropped from more than $14 to the Lilly offer price of $12.5. With ~49m shares traded in the last 3 days since the trial results were released, and with Lilly previously declaring 20% shareholding, it looks like the acquisition will now go through?

Radio Ligand Therapy (RLT) is really hard. Radioisotopes are not inert – you can’t turn radioactivity off (unlike AVA6000 where Doxorubicin is rendered inert until FAP triggered cleavage at the TME), so targeting is critical. Not to mention the supply-chain challenges of radioisotopes.

Looks like Lilly are just very keen to acquire a stake in the RLT market to try and keep up with Novartis – only $1.4bn.

So what value a platform that could deliver – established chemo warheads, (potentially) other cytotoxic payloads (e.g.MMAE), and (potentially) radioligands to FAP expressing tumours?

GLA

@Almostrich, great posts. @PL75, just seen your reply, I am slower typist, not a plagiarist!

A (open) question regarding BP in the context of your suggestion that – “It’s unlikely that any BP would commit to a license deal prior to completion of the bi-weekly study.”

It seems to me that we are now ‘stress testing’ Doxorubicin at higher doses than have ever been possible before due to side effects – particularly cardiotoxicity, without the (‘paradigm shifting’) benefit of pre|CISIONTM delivery. Dox has been in use for decades.

Pre|CISIONTM works. So what’s holding up BP? Do we need to prove that it works with another ‘warhead’, e.g. AVA3996/2727D (AKA Bortezomib – as modified)? Pre-clinical suggests pre|CISIONTM works in the same way here. Is it simply now about a ‘stamp of approval’ – but just for safety and tolerability, or now efficacy as well?

As has been noted – the narrative is changing to emphasise the potential of the pre|CISIONTM platform, not just AVA6000.

I also mentioned earlier the huge potential for AVA6000 in combining chemotherapy with immunotherapy.

Personal view is that the Phase 1:Arm 2 trial is about achieving one of the designated FDA options below for AVA6000 …

https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track

Primarily for the benefit of patients.

Sir Al wants to keep AVA6000 ‘in-house’ (probably, maybe, unless a great deal comes along).

The wider pre|CISIONTM platform should now be available for licensing deals.

GLA

Also consider the huge potential for combining chemotherapy with immunotherapy – there are many trials ongoing. This paper explains the rationale …

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252089/

Doxorubicin specifically mentioned. Also note the importance of PD-1 and PD-L1 checkpoint inhibitors (then think AVA021 and AVA028).

GLA

Https://investor.lilly.com/news-releases/news-release-details/lilly-extends-tender-offer-acquire-point-biopharma-dec-22-2023

Eli Lilly being persistent - tender extended @ $12.50 until 22 December. They only have 22.8% so far. POINT holders will see the positive PNT2002 trial results now as well.

GLA

PNT2002 (PSMA targeted radioligand) readout positive …

https://pointbiopharma.com/press-releases/splash-topline-results

Lilly value Point at $12.50/share or ~$1.4bn, the market currently says more, Friday close @ $14.02. Let’s see what Lilly do now.

Oh, and the relevance is more than just CanSEEK™ (AKA pre | CISION™), both POINT and Avacta are all about 'targeted' therapy - one radioisotopes one chemotherapy (and potentially other molecules). The valuation differential is ridiculous.

GLA

On the one hand …

“Atlas Capital Markets (‘ACM’) provides creative solutions for those seeking capital.”

But given they have acquired 50m shares (5%) then perhaps they …

“… are comfortable purchasing an asset or equity or serving as a merchant partner in facilitating a transaction between two parties.”

GLA

Slide 7 – AVA6000 delivered to FAP expressing tumours and not FAP-negative cells.

Slide 16 – Dox ratio Tumour:Plasma – 33:1 (low dose AVA6000), 104:1 (mid dose AVA6000).

Slide 18 - pre|CISIONTM works.

Slide 13 – Cohort 7, 1 of 3 patients (so far reported, as 4 recruited) with grade 1 adverse event. “Minimal grade 3-4 events observed across all [7] cohorts vs. doxorubicin alone”.

Slide 11 – Phase 1:Arm 2 – we are testing Dox at dosage levels not previously possible (due to side effects – particularly cardiotoxicity) without pre|CISIONTM delivery of AVA6000.

pre|CISIONTM works.

We are testing Dox to the limit – via AVA6000 as ‘first line’ therapy.

(Note – presentation data cutoff was 27 November – already nearly 3 more weeks data available).

GLA

Https://twitter.com/AlastairSmith__/status/1736119410719330616

Sir Al very positive about things then.

GLA

Just to reinforce what has already been said …

Slide 12 - No. prior regimens, median (range) 3 (0-7)

Slide 13 - Cohort 7 385 mg/m2 N=3, Grade 1 1 (33), Grade 2-4 0

(Note – slide 11 N=4 for Cohort 7 – one patient not included in above?)

AVA6000 is ‘first line’ treatment for Cohort 7 (so far reported), no adverse events greater than grade 1 (so far reported).

When will BP move ?

GLA

27:27 " We do see similar curves for each of the dose levels and are happy to discuss those ...".

Discuss with who? Almost like an invitation to selected listeners, or were there others in the room'?

(Remember log scale on this slide).

GLA

Why are @Avacta tweeting this on #AVCT just after market close ...?

https://twitter.com/avacta/status/1735703512695148582

Am taking up the suggestion. Chris Coughlin is brilliant.

GLA

Paul and Justin on Vox ...

https://www.youtube.com/watch?v=GF2z8MRu1NQ

Avacta from ~45min. Paul @ ~49:50- "at least 50%" when discussing TD note. "Could be worth £13" - re-ramper eh?

GLA

Lance - plenty of examples, suggest a bit of research. Here's one to start with (albeit at a much earlier stage than Avacta) ..

https://www.fiercebiotech.com/biotech/lilly-links-european-adc-network-snagging-elahere-rival-acquiring-2nd-biotech-quick

Lilly buying the French ADC startup Mablink for their pre-clinical asset. What's particularly interesting about this is ...

"France-based Mablink is building a pipeline on PSARLink, a linker technology designed to reduce systemic toxicity and increase the amount of the therapeutic payload delivered to target cancer cells."

Now Avacta have proved, 'unequivocally', that they can do this.

GLA

AVA6000 is primary then.

GLA

Warren again ...

https://www.reuters.com/markets/deals/occidental-petroleum-buy-crownrock-12-bln-deal-2023-12-11/

“Occidental Petroleum to expand Permian ops with $12 billion deal for CrownRock”. (Texas shale).

Still lots of money around for deals then.

GLA

Might be £200 ex Chi-nah (or > ¥2000 inc), might not though?

(Would DYOR research).

GLA

Dec 4 RNS quite clear in relation to Wednesday ...

"Avacta's Chief Executive Officer, Alastair Smith, Chief Scientific Officer, Fiona McLaughlin and Consultant Chris Coughlin will present a detailed review of the AVA6000 clinical trial's Phase 1a data, followed by an investor Q&A."

GLA