Member Info for LiveLongnProsper

Interesting to see some II activity – SINT trades so far …

2025-11-14T08:22:13Z GBp 79.25 50000 39,625 Off-book SINT

2025-11-14T09:11:47Z GBp 77.5 100000 77,500 Off-book SINT

2025-11-14T10:01:41Z GBp 77.5 100000 77,500 Off-book SINT

2025-11-14T11:12:57Z GBp 77.5 115000 89,125 Off-book SINT

2025-11-14T11:21:58Z GBp 77.75 15000 11,662.5 Off-book SINT

2025-11-14T11:21:58Z GBp 77.75 15000 11,662.5 Off-book SINT

2025-11-14T11:39:00Z GBp 77.623 365000 283,313 Off-book SINT

2025-11-14T11:39:00Z GBp 77.74 365000 283,751 Off-book SINT

GLA

@Bosi, Great spot, a few more details here (note the high prevelance of side-effects) …

https://investors.gilead.com/news/news-details/2025/Gilead-Provides-Update-on-Phase-3-ASCENT-07-Study/default.aspx

While HR+ / HER2-negative is not TNBC, both cancers express FAP, particularly in the TME (CAF’s).

Comparison chemotherapy treatments ‘included’ capecitabine, paclitaxel and nab-paclitaxel – Dox not specifically mentioned, though approved and often used in combo with the aforementioned.

Lots of research to do here (as always), but will add Gilead (Trodelvy® - Sacituzumab Govitecan) to my previously noted list of likely ‘interested’ in Avacta BP’s ..

AZN, Pfizer, Merck, and Roche / Genetech have products approved or in development based on ADCs with both MMAEs and DDRs (PARP / ATR inhibitors), also GSK without the MMAEs.

Also, AZN / Daiichi Sankyo have Enhertu (Trastuzumab Deruxtecan or T-DXd) – Deruxtecan being an Exatecan derivative.

And, Merck have Keytruda (Pembrolizumab), another kind of immunotherapy (PD-1 inhibitor).

Then there is GSK with DDR’s, but not MMAE’s, but do have Blenrep (Belantamab Mafodotin) that uses an MMAF (an MMAE derivative).

Plus, we have Novartis, who are targeting FAP with their RLT products, but don’t have ADCs.

GLA

ps, there's Lilly as well - are they doing anything with CanSEEK?

Woops - AVA6103

Just to help focus the research and highlight the likely value of any potential ‘buy out’, in the context of the recent ‘dual payload’ presentation, perhaps worth considering what these (ADC ‘heavy’) BP’s might be thinking through ..?

AZN, Pfizer, Merck, and Roche / Genetech have products approved or in development based on ADCs with both MMAEs and DDRs (PARP / ATR inhibitors), and GSK without the MMAEs.

Also, AZN / Daiichi Sankyo have Enhertu (Trastuzumab Deruxtecan or T-DXd) – Deruxtecan being an Exatecan (think AVA8103) derivative.

And, Merck have Keytruda (Pembrolizumab), another kind of immunotherapy (PD-1 inhibitor) .

Back to GSK - with DDR’s, but not MMAE’s, but they do have Blenrep (Belantamab Mafodotin), and that uses an MMAF (an MMAE derivative).

Plus, we have Novartis, who are targeting FAP with their RLT products, but don’t have ADCs.

There are more.

My guess (but please DYOR), these folks are probably quite interested in Avacta.

GLA

Updated today …

https://clinicaltrials.gov/study/NCT04969835?tab=history&a=10#version-content-panel

Dates …

Primary Completion - 2026-03-15 [Estimated]

Study Completion - 2026-08-15 [Estimated]

Conditions (not sure if updated?) …

Salivary Gland Tumor, Urothelial Carcinoma, Ovarian Carcinoma, Breast Cancer, Soft Tissue Sarcoma

Anything else?

GLA

Much positivity here and on SpacetwiX regarding the revolutionary science – which I share, and looking forward to tomorrow’s presentation.

But what about that commercial ‘event’?

Advice to BP – multi €$£bn’s now, or multi-10’s of €$£bn’s later?

Think about it, but not for long, time to commit?

GLA

@BV, “.. strongly suggests that funding of one sort or another is coming ...er, shortly.”

Exactly, one would certainly expect some kind of commercial ‘event’ very ‘shortly’.

Richard Hughes has helped the short-term financing enormously (twice), baton was then passed to David Byant – now being helped by Yulii Bogatyrenko, and we know Simon Bennett has been ‘busy’. Come on then guys – follow the ‘play book’.

I thought this picture was quite interesting, albeit a little out-of-date – courtesy Sean Dent via my SpaceLinX terminal …

https://x.com/SeanDentBsc/status/1981300296052588885/photo/1

Not only ‘gaps’ to fill, but existing products to complement and (maybe) ‘dual up’.

(‘Usual suspects’ - Novartis, Pfizer, Merck, AZN/DS, Roche/Genetech, Lilly, and maybe AbbVie or even GSK?)

GLA

Interesting.

Novartis gets heavily into rare muscular diseases etc., including a bunch of AOC's (yep, not ADC's).

Still leaves a massive gap in their Oncology pipeline - all RLT, negligible ADC's.

And, despite spending $12bn, still leaves them with acquisition headroom.

So, now we know about MMAE's and PARP/ATR, the other suspects seem to be the 'usual suspects', i.e. Pfizer, Merck, AZN/DS, Roche/Genetech, Lilly, and maybe AbbVie or even GSK?

I'm still looking for that first big commercial (in some form) deal.

GLA

Https://x.com/coughlin582/status/1982141044805259516

Unbadged backpacks - sneaky BP folks.

GLA

Looks brilliant, maybe revolutionary. Quick thoughts re the ‘with whom’ (not revealed).

MMAE and ATR / PARP inhibitors (DDR) could be pointing to …

Pfizer – MMAE (from Seagen acquisition) plus DDR developments in own pipeline?

AZN / Daiichi Sankyo – AZN have ATR and PARP combo’s in pipeline, plus Enhertu (trastuzumab deruxtecan) with DS?

Or Avacta have just taken some ‘stuff’ from sample libraries and done a proof of concept to entice / invite / encourage interest?

Please do something (big) commercial Avacta.

GLA

@BV, Good point re size of mAb’s. So maybe could be something like (say) ADC Therapeutics pyrrolobenzodiazepine (PBD – interfere with DNA repair) dimer warhead? Haven’t we worked with them in the past? Or maybe an RLT – Lilly, Novartis (again)?

Probably find out this evening?

GLA

We know that pre|CISION® technology enables the targeted delivery of warheads to the tumour microenvironment (TME) via fibroblast activation protein α (FAP) cleavage.

For AVA6103, Exatecan induces DNA damage (to tumour cells) and apoptosis through topoisomerase I inhibition, therby creating a pro-immunogenic TME, making it an ideal partner for immunotherapy warheads.

‘Dual warhead’ sounds like a great idea then (and we know CC uses combo’s in the clinic).

So, for the other warhead, and assuming a partner product (not Affimer – AVA7100), which one? A few ideas from a ‘friend’…

Merck - Pembrolizumab (Keytruda®; anti-PD-1 mAb)?

BMS - Nivolumab (Opdivo®; anti-PD-1) or Relatlimab (anti-LAG-3)?

Roche/Genentech - Atezolizumab (Tecentriq®; anti-PD-L1) or Simlukafusp alfa (FAP-IL2v immunocytokine?

AZN - Durvalumab (Imfinzi®; anti-PD-L1) or MEDI5395 (FAP-IL2v variant)?

Novartis - Ociperlimab (anti-TIGIT mAb) or STING agonists (e.g., ADU-S100 from Aduro)?

Overall, taking into account various patent ‘cliffs’, pipeline ‘gaps’, technical synergies, commercial 'sense', etc., etc., my ‘friend’ thinks Novartis is a good fit, closely followed by BMS and AZN. But what does he (?), she (?), it (?), know?

Going to be an interesting few days.

GLA

Good post from Myles, point is straightforward …

https://x.com/MylesMcNulty/status/1980600995521401129

PDCs are superior to ADCs (at least in the ‘market’ Avacta are focused on).

Will BP be prepared to switch to PDCs (or dual strategy with ADCs)?

Which BP’s are not too heavily into ADCs? Here are a couple for starters …

Novartis – more or less nothing in ADC space, but trying to target FAP for RLTs.

Merck – Keytruda (Pembrolizumab) is a mAb (as opposed to an ADC).

Also, Merck are (or at least were?) working with Daiichi Sankyo on Patritumab Deruxtecan (Exatecan derivative) for NSCLC …

https://www.biopharmadive.com/news/merck-daiichi-withdraw-fda-application-lung-cancer-patritumab-deruxtecan/749243/

AACR could be quite interesting. Let’s see if we get a ‘partner’ for AVA6207.

GLA

XOFF, so possibly spread betters 'managing' their positions?

Anyone with insight on IG, Spreadex, et al positions just now?

GLA

More AZN / Daiichi Sankyo presentations …

https://x.com/stellanewslife/status/1979616249262043200

Enhertu - T-DXd (an Exatecan derivative), as previously noted.

Datroway - datopotamab deruxtecan (or Dato-DXd), TROP2 targeted ADC. TROP2 protein expressed on cancer cell surface. Note – TNBC high FAP (in CAFs) and high TROP2 (just one of many potentially complimentary examples?).

Imfinzi – immunotherapy, but often used in combo with chemo (could be opportunity in PDAC, NSCLC, TNBC?).

GLA

Underway, here’s a starter for 10 …

https://x.com/SuyogCancer/status/1979321455230992851

Destiny trial update – so that’s AZN / Daiichi Sanyo Enhertu (T-DXd – an Exatecan derivative), with a comparison against T-DM1 (taken to be Kadcyla from Genentech / Roche?).

AZN / DS no doubt very interested in AVA6103 – maybe combo’s as well?

Expect Dr Tap will do a great job on AVA6000 and look forward to seeing the poster.

Looks like the ‘real deal’ could be AACR with pipeline update and an actual commercial, err, ‘deal’?

GLA

Good spot @gmcc, apologies for repetition, but needs highlighting.

“About Avacta” followed by “About the pre|CISION® Platform” – increase in wording ‘precision’ and focus on ‘platform’ …

30 Sept RNS …

“Avacta Therapeutics is a clinical-stage life sciences company expanding the reach of highly potent cancer therapies with the pre|CISION® platform. pre|CISION® is a proprietary payload delivery system based on a tumor-specific protease (fibroblast activation protein or FAP) that is designed to concentrate highly potent payloads in the tumor microenvironment while sparing normal tissues. Our innovative pipeline consists of pre|CISION® peptide drug conjugates (PDC) or Affimer® drug conjugates (AffDC) that leverage the tumor-specific release mechanism, providing unique benefits over traditional antibody drug conjugates.”

“The pre|CISION® platform comprises an anticancer payload conjugated to a proprietary peptide that is a highly specific substrate for fibroblast activation protein (FAP) which is upregulated in most solid tumors compared with healthy tissues. The pre|CISION® platform harnesses this tumor specific protease to cleave pre|CISION® peptide drug conjugates and pre|CISION® antibody/Affimer® drug conjugates in the tumor microenvironment, thus releasing active payload in the tumor and reducing systemic exposure and toxicity, allowing dosing to be optimized to deliver the best outcomes for patients.”

13 Oct RNS …

“Avacta is a clinical stage life sciences company developing an innovative proprietary drug delivery peptide drug conjugate (PDC) platform, pre|CISION®. The pre|CISION® platform uniquely enables the repurposing of a range of oncology drugs as PDC payloads with the goal to significantly reduce toxicity and side effects for patients by concentrating the drug directly in the tumor.”

“The key aspect of pre|CISION® is its peptide drug conjugates (PDC) technology. The combination of the cancer drug and the proprietary cleavable peptide (the PDC) is inert and incapable of entering cells and killing them until the peptide is specifically released within the tumor. The active payload in the pre|CISION® PDC is released when the PDC comes into contact with the common tumor-associated protein, known as fibroblast activation protein (FAP), in the tumor. The release of the payload from the pre|CISION® product directly in the tumor results in higher concentration of the drug at the tumor and lower blood and healthy tissue levels than standard systemic administration, offering the potential to improve efficacy and patient tolerability.”

Significant shift in language and (implied, IMO) confidence.

GLA

LY4337713 is a radioligand (beta-emitter radioisotope) with targeting that binds to FAPα – but can’t see that Lilly have published the detail of the chemistry / biologics used for targeting. Could well be their own proprietary tech – possibly quinolone based? Pre-clinical, not yet recruiting.

Whereas, the pre|CISION® platform is a peptide drug conjugate (PDC) that masks a cytotoxic warhead from the immune system, cleaving via FAPα in the TME – well documented by Avacta. In phase 1, heading for phase 2, 4 years of data. i.e. ‘it works’™.

GLA

@Bella, I think they're mostly into the 'illumination' of FAP expressing sites that can be targeted by an actual RLT treatment (presumably also a chemo warhead though). In this respect I think that they have licensed some targeting tech to Novartis. Also seem to be in with GE Healthcare in big way. Catching up on my research here.

GLA

What do we think the next pipeline update (October mentioned) will be about then?

From the IM presentation …

~12:00, paraphrasing - ‘We’re excited to bring that one – a new way of leveraging our pre|CISION® platform and a whole new way of looking at it and using it in the clinic – very excited to bring that to you later in October …’.

Will it be - “AVA7100 Third Gen pre|CISION® FAP Affimer® (AffDC). Warhead not disclosed”)? Partner ‘warhead’?

Or maybe RLT – Can’t find any evidence that Lilly are doing anything with CanSEEK (please correct if you have info on this). Novartis (no ADC’s remember) are trying hard to target FAPα with radioligands.

Or even, perhaps, a ‘long-shot’ - remember the SOFIE collaboration, from 23 May 2024 – “This sub-study represents an ongoing collaboration between Avacta and SOFIE, in the use of [18F]FAPI-74 PET as a complementary diagnostic. [18F]FAPI-74 PET is currently in clinical development and for investigational use only.”

Well SOFIE are making progress with the above-mentioned Fluorine-based diagnostic …

https://sofie.com/2025/10/01/sofie-biosciences-prepares-launch-of-two-18ffapi-74-phase-3-studies-following-successful-fda-engagement/

But, getting to the point, here’s the ‘long-shot’, FAPα expression seems to be associated with several disease types …

https://sofie.com/pipeline/overview/

Reading down, perhaps part of the “new way” puzzle (?) – “FAP overexpression has been linked to non-malignant processes and disease, including wound healing, chronic inflammation, myocardial infarction, benign tumors and fibrosis. The FAP inhibitor family of compounds (FAPI) allows non-invasive visualization of this important target for oncology and non-oncology indications through binding to FAP with low nanomolar affinity. These compounds can be labeled with various isotopes, including Gallium-68 and Florine-18, for use in PET imaging.”

So FAP can be targeted, and ‘warheads’ dropped, to fix other (non-cancer) disease.

GLA