Member Info for LiveLongnProsper

Prompted by @JStonker [sic!], from SpacetwiX …

https://avacta.com/precision/

Have we moved from preCISION™ to pre|CISION® ?

“The superscript R in a circle, ®, is the registered trademark symbol. It indicates that a trademark or service mark has been registered with a national trademark office, such as the United States Patent and Trademark Office (USPTO)” . Courtesy Google AI.

GLA

Science day – more pipeline detail (what is the AVA7100 ‘warhead’)?

New CFO – with US capital markets experience?

AVA6000 – update on expansion cohorts, full data readout of results to date.

NASDAQ – IPO (with strategic investor taking stake?), RTO / SPAC (how to fund?), etc.?

DX sale – no great hurry (as becoming more cash generative), Coris / Launch together or in parts, what Affimer rights included, etc.?

Licencing / Partnering – what has ‘busy’ Simon Bennett been doing?

Brilliant science – please keep it up, now (at least after science day) for some commercials.

GLA

(no doubt have even ‘more’ that not mentioned abiove)

Poster presentations on Thursday 24 Oct …

https://cm.eortc.org/cmPortal/Searchable/ena2024/config/Normal#!sessiondetails/0000110530_0

“185: The novel peptide drug conjugate AVA6103 is a FAP-enabled preCISION™ medicine which targets Topoisomerase I to the tumor microenvironment via FAP cleavage - Francis Wilson, United Kingdom”

“172: Affimer® Drug Conjugates (AffDC) targeting Fibroblast Activation Protein-α deliver highly toxic warheads to the tumor microenvironment by leveraging the preCISION™ release mechanism - David Jones, United Kingdom”. (Presumably AVA7103?).

Perhaps, also see ..?

“171: Preclinical characterization of NaPi2b-PL2202, a novel exatecan-based antibody drug conjugate”. This from ADC Therapeutics.

NaPi2b is a protein with high levels of expression in Ovarian, NSCLC, Endometrial and (to a lesser extent) in Thyroid cancers. (Note - these cancers also express FAP in the TME).

So we have ADC Therapeutics presenting their pre-clinical ADC delivering Exatecan to Ovarian, NSLC and Endometrial cancers targeting NaPi2b , and Avacta’s pre-clinical PDC AVA6103 (see pipeline) delivering Exatecan to gastric, TNBC, SCLC and pancreatic cancers.

ADC Therapeutics presentation …

https://s24.q4cdn.com/575174480/files/doc_presentations/2024/Sep/18/cantor-presentation-09-17-24.pdf

Takeaways – multiple targets for their ADC pipeline (not including FAP?), clear focus on tumour types, some numbers around the target market, big focus on Exatecan (slide 19), etc.

Financially ADC Therapeutics (vs Avacta) have cash to early 2026, a slightly higher mcap, much higher debt, revenue just starting up, but a much higher cash burn.

Where are ADC Therapeutics based in the UK - Imperial College White City Campus (just for info).

GLA

Does look very interesting. Not sure (yet?) about the pure R&D possibilities - given that we are about using pre|CISION™

for vastly improved targeting of pre-existing 'warheads' (so far, anyway). However, checkout the Tempus 'Time' service to match patients to suitable trials. We could be using this now for the AVA6000 'expansion' phase.

GLA

Just to add, my question …

“Is there a commercial / collaboration agreement between Avacta and Astra Zeneca?”

ChatGPT[4] said:

“As of the latest available public information, there is no confirmed commercial or collaboration agreement between Avacta and AstraZeneca. While both companies are actively involved in developing cancer therapies, including targeted and precision medicine approaches, no formal partnership or collaboration has been officially announced in relation to their respective platforms or drug candidates.

Both Avacta and AstraZeneca are leading players in the oncology field, particularly with Avacta's development of FAP-targeted therapies and AstraZeneca's portfolio in immunotherapy and ADCs like Enhertu (trastuzumab deruxtecan). However, any partnership or collaboration between the two would likely be announced via press releases or regulatory filings.”

GLA

Here we go ...

AVA6103 – Exatecan.

https://avacta.com/about/

GLA

'Small world'. Wonder what Darlene's up to just now?

GLA

@Bella, interesting. invoX (Sino Biopharm subsidiary) acquired F-star (Eliot’s old co.) in 2023.

invoX currently in phase 1 trials for “FS222, an investigational CD137/PD-L1 bispecific antibody, in patients with advanced solid tumours.”

https://invoxpharma.com/news/event/invox-pharma-presents-positive-clinical-data-from-phase-1-study-of-fs222-in-patients-with-advanced-solid-tumours-at-the-2024-asco/

So far, some signs of efficacy, however …

“Grade ≥ 3 TRAEs occurred in 36/100 subjects, with the most common including increases in aspartate aminotransferase and alanine aminotransferase, thrombocytopenia, neutropenia, and febrile neutropenia.”

Michelle Morrow will, no doubt, have a very good understanding of the above, not to mention, perhaps (?), some useful contacts in Sino Pharma.

Who knows £££ ex-Chin-ah (or is it Chi-nah)?

GLA

Just to add …

“Ten payloads have been FAP-enabled” with the slide showing MMAE.

Perhaps others include …

Enhertu (Trastuzumab Deruxtecan), Exatecan (Deruxtecan being a derivative), Trodelvy (Sacituzumab Govitecan) – plus several other products delivering SN-38, or even Keytruda (Pembolizumab)?

The list of possibilities is much more extensive, the potential is huge, looking forward to finding out more soon.

(For the above, and others, checkout the BP's, the revenue, and the patent status - all very interesting).

GLA

Suggest watching this …

https://avacta.com/research-development-spotlight-series-episode-5/

For the mention of ‘Ten Warheads’ skip to ~4:10.

Firstly, see the slide heading – “Computational Algorithms for pre|CISION Medicine Designs Are Based on Ten Warheads”. So that’s ’10 warheads’.

Then see the ‘tiered’ pipeline – Tier 3 (2-3), presumably we will hear about 2 of them on 24 Oct at EORTC.

Given that tier 1 indicates ~20-40 compounds, I suppose this means chemical variations of the ‘ten’?

Assuming the IP is ‘locked down’ with the appropriate patents I would expect to see the detail soon.

GLA

@Jenkoool’s poll on twiX suggests Exatecan from Daiichi Sankyo will be ‘the chosen warhead’ (presumably for AVA6103?) …

https://x.com/Jenkoool/status/1844279337320906979

I wonder if Enhertu (Trastuzumab Deruxtecan or T-DXd) might actually be the warhead?

Deruxtecan is a derivative of Exatecan for use in ADCs such as Enhertu.

Enhertu off patent November 4th. Revenue to AZN/Daiichi Sankyo ~$2.5bn+.

GLA

More patents further up the pipeline? Courtesy Marty McFly from twiX …

https://x.com/Blueberrymgmnt/status/1844467257864487369

TNFR2 expression indicates immune system suppression by cancer.

So, something like - deliver the cancer killing ‘warhead’ plus “TNFR2-binding Stefin A polypeptide variants” to modulate immune response (T-cells etc.) in favour of attacking cancer cells?

Does feel like we’re ‘on the cusp’.

GLA

EORTC – ““Thursday, October 24th, 09:00 - 17:30, Exhibition Hall, Session code:220, Session title:Antibody-drug conjugates, Session type:Poster Session”. Abstracts released on 9th Oct.

“185: The novel peptide drug conjugate AVA6103 is a FAP-enabled preCISION™ medicine which targets Topoisomerase I to the tumor microenvironment via FAP cleavage - Francis Wilson, United Kingdom”

“172: Affimer® Drug Conjugates (AffDC) targeting Fibroblast Activation Protein-α deliver highly toxic warheads to the tumor microenvironment by leveraging the preCISION™ release mechanism - David Jones, United Kingdom”

MMAE already on Avacta slides, other ‘opportunities’ that may be ‘alluded’ to ..?

Enhertu (Trastuzumab Deruxtecan) from Daiichi Sankyo and AstraZeneca, used in the treatment of HER2-positive breast cancer.

Trodelvy (Sacituzumab Govitecan) from Gilead Sciences, targets Trop-2 and delivers the topoisomerase I inhibitor SN-38, used for metastatic triple-negative breast cancer and others.

Keytruda (Pembrolizumab) from Merck & Co., patent Expiry 2028. annual revenue: ~$14.4 billion (2020), biological target: PD-1, cancers treated include NSCLC and head and neck squamous cell carcinoma, both with high FAPα expression.

Not exhaustive in the slightest, many more 'opportunities'.

Pipeline update (partial or full) before, or during, the above, more on ‘science day’?

GLA

Good thoughts raised by https://x.com/t0m_the_b0mb_ from twiX ...

https://x.com/t0m_the_b0mb_/status/1841924181048357314

What if pre|CISION™ ADC could be used to deliver Trastuzumab Deruxtecan (Enhertu) to FAP mid/high stromal cells, cleave, and release the Trastuzumab Deruxtecan ‘payload’ to HER2 expressing cancer cells? Potential for enhanced targeting with reduced side effects?

(Enhertu is an antibody-drug conjugate consisting of the mAb trastuzumab – targeting HER2 expression, covalently linked to the topoisomerase I inhibitor deruxtecan – which inhibits DNA replication).

As ttb notes, Enhertu is off patent next month. Enhertu revenue in 2023 ~$2.5bn and projected to grow.

Pipeline reveal (in whole or part) by Oct 9 EORTC abstract release day, or embargoed abstracts and Oct 24, or wait for ‘science day’?

GLA

Does look like the partners list has been deleted today, no doubt pending update with new entries?

Was …

Tufts (Professor William Bachovchin et al – apparently quite good with a chemistry set).

LG Chem (That well known Affimer – LR19128, still showing in pre-clinical - https://innovation.lgchem.com/ResearchDevelopment/Pipeline.do )

Daewoong / AffyXell (Immunomodulatory Affimers)

Lilly / Point (canSEEK™ or pre|CISION™ for certain, limited by licence, radioligands)

Looking forward to seeing (the preferably fee paying) the new entrants.

GLA

Contact form page changed (dunno what?) …

https://avacta.com/contact/

Web Dev guys fixing another broken link, or is there a hidden message about … ?

GLA

@B2, items172 and 185 below, looks like our guys ..?

https://cm.eortc.org/cmPortal/Searchable/ena2024/config/Normal#!sessiondetails/0000110530_0

Could be a 'spoof' I suppose (haha).

GLA

@B2, re point 3, AVA6103 and first AffDC presented on 24 Oct at EORTC, so expecting to see pipeline update before?

GLA

Thanks @gmcc and Marty, a bit more info (please DYOR) ..

A couple of examples of products using maleimide/cysteine conjugation for targeted drug delivery, particularly utilsed in antibody-drug conjugates (ADCs).

Kadcyla (Trastuzumab Emtansine) from Genentech/Roche, revenus ~$2bn 2022, approved for HER2-positive breast cancer. The antibody is conjugated to a cytotoxic agent via maleimide/cysteine bonds.

Trodelvy (Sacituzumab Govitecan) from Gilead, revenue ~$600m 2022, ADC targeting Trop-2 using a maleimide linker.

Both products leverage stable cysteine bonds for precise drug delivery. Indications for above 2 are FAP expressing.

Someone already mentioned that choice of new warheads (when revealed) should ‘stir up’ BP.

GLA

@PL75, agree. Let's see what 'filters' through IM.

GLA