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2 weeks to ESMO and Dr Tap’s poster presentation – AVA6000 p1a.

Shortly followed by AACR and (maybe?) a significant pipeline update – wonder what (note – “AVA7100 Third Gen pre|CISION® FAP Affimer® (AffDC). Warhead not disclosed”)? Partner ‘warhead’?

January 15 2026 is the ‘long stop date’ – by which time we need to have done some kind of ‘deal’ (“partnership or other agreements in respect of its pharmaceutical products”), had a “strategic investment”, or another equity raise.

‘Yearly high’ is really quite low, £285m mcap for (IMO) multi-£bn asset.

Seems like some decent buys last week, trend line up, much further to go.

GLA

WHO knows wo we are and what we’ve got (from Grok, via StarlinX) …

“Significance of the INN 'Faridoxorubicin' Assignment to Avacta's AVA6000”.

“The assignment of the International Nonproprietary Name (INN) "faridoxorubicin" by the World Health Organization (WHO) to Avacta's AVA6000 is a key regulatory and developmental milestone for this investigational oncology drug. INNs are standardized, globally recognized generic names for pharmaceutical substances, designed to promote clear communication among healthcare professionals, regulators, and patients while minimizing confusion with brand names or trademarks. Receiving an INN signals that the drug has advanced sufficiently in development to warrant an official nomenclature, often after preclinical and early clinical data demonstrate promise. For AVA6000, this occurred amid positive Phase 1 trial results, positioning it for potential further advancement toward approval.”

“Prefix: 'Fari-' – A distinctive, invented syllable selected to ensure uniqueness and avoid confusion with existing drugs. In this case, it likely derives from "FAP-activated release in the tumor microenvironment" or a similar descriptor of AVA6000's FAP-cleavable mechanism. WHO prefixes are chosen for phonetic appeal, global pronounceability, and non-conflicting similarity to other INNs (e.g., avoiding overlap with "faricimab," an unrelated bispecific antibody). No established WHO stem corresponds to "fari-"; it's a custom prefix tailored to this prodrug.”

GLA

What I don’t really ‘get’ is why ProteinQure got FDA Fast Track before a patient had been dosed?

https://www.proteinqure.com/proteinqure-receives-regulatory-clearance-to-initiate-phase-i-trial-for-pq203-in-the-u-s-and-canada-granted-fda-fast-track-designation/?utm_source=chatgpt.com

“TORONTO, Ontario, Aug 7, 2025 – ProteinQure Inc., a leader in computational protein drug discovery, today announced it has received regulatory clearance from both the U.S. Food and Drug Administration (FDA) and Health Canada to initiate a Phase I clinical trial evaluating the safety, pharmacokinetics, pharmacodynamics and anti-cancer activity of its lead candidate, PQ203. The FDA has also granted PQ203 Fast Track designation for patients with triple negative breast cancer, recognizing the therapy’s potential to address a serious unmet medical need.”

First patient dosed announced Sep 17 2025.

Now I know different target - SORT1 (vs. FAPα), and different warhead - MMAE (vs. Dox), and targeting diseased tissue (vs. TME). But we have 4 years of patient data, across various Sarcoma types, SGC and TNBC. So why no FDA Fast Track for Avacta?

Anyone ‘shed any light’ on this?

GLA

@BV, ProteinQure think they have a PDC ...

https://www.proteinqure.com/science/

A good question though, is how 'precise' is the targeting?

GLA

I think that this is quite interesting, if not a ‘wake up’ call (courtesy Marty McFly) …

https://x.com/Blueberrymgmnt/status/1969369312449196345

https://www.businesswire.com/news/home/20250917696518/en/ProteinQure-Announces-First-Patient-Dosed-in-Phase-I-Clinical-Trial-of-PQ203-in-Advanced-Metastatic-Cancer

A few (key?) abstracts …

“ProteinQure, a Toronto-based biotech company pioneering computational peptide drug discovery, today announced the successful dosing of the first patient in its Phase I clinical trial evaluating PQ203 – a novel, rationally designed peptide therapeutic for advanced metastatic solid tumors.”

“PQ203 is the company’s first internally owned AI designed peptide therapeutic entering the clinic 3 years after the program was started.”

Note – ‘AI designed’.

“PQ203 is composed of a peptide targeting the Sortilin receptor conjugated to the cytotoxic agent MMAE. The Sortilin receptor is expressed in a high percentage of diseased tissue from Triple Negative Breast Cancer (TNBC) patients. ProteinQure has generated data that PQ203 exhibits potent efficacy in a patient-derived xenograft (PDX) model resistant to Sacituzumab Govitecan (Trodelvy™), an antibody drug conjugate that is the standard of care for metastatic TNBC.”

Note – PDC, targets SORT1 receptor in TNBC diseased tissue (vs. FAPα in CAFS / TME), MMAE payload (vs. Dox for AVA6000).

Going after Trodelvy – AVA6000 can make a ‘dent’ here pending AVA6103 coming through.

FDA ‘Fast Track’ granted …!

https://www.proteinqure.com/proteinqure-receives-regulatory-clearance-to-initiate-phase-i-trial-for-pq203-in-the-u-s-and-canada-granted-fda-fast-track-designation/?utm_source=chatgpt.com

Get a move on Avacta, definetly a ‘wake up’ call here – AI designed PDC delivering MMAE, 1 patient dosed and already with FDA fast track, from a privately held company. Yes, we’ve got ~3 years head start on these guys, 4 years of patient data, and a platform with a much wider capability, but really Avacta – get on with it.

FDA ‘fast track’ (one of the variants) for AVA6000, plus AVA6103 IND please. Much hinted ar licence deal(s). Etc. Time for action.

CC presentation 30 Sept, ESMO 17-21 Oct. Expectations high.

GLA

Thanks to https://x.com/asininitybeyond for this ...

https://x.com/asininitybeyond/status/1968013379181875493

Quite significant I suspect – AVA6103 context. I dropped the Abstract on ChatGPT and asked a few questions. Refining the questions back-and-forth (so these not posted). On balance the responses very positive and favouring AVA6103. In summary, again from ChatGPT …

“With exatecan as the warhead and pre|CISION® FAP-cleavable activation, AVA6103 is well aligned to:

PDAC (pancreatic ductal adenocarcinoma) — top priority (high stromal FAP, dense stroma where peptide penetration helps, very high unmet need).

Colorectal cancer (CRC) — strong fit (topoisomerase-I agents already standard; local exatecan release could improve therapeutic index).

TNBC (triple-negative breast cancer) — attractive (Trodelvy validates Topo-I payload approach; FAP-high TNBC subgroups could benefit).

Selected NSCLC, gastric and other solid tumours — secondary opportunities with biomarker-driven selection.”

Further …

“Competitive differentiation vs FAP-ADC (exatecan ADC) — why AVA6103 could stand out

Tumour penetration: PDC (small) > ADC (large) in desmoplastic tumours (PDAC) — better stromal access and potential for more uniform TME coverage.

Controlled activation: pre|CISION® enzymatic cleavage by FAP localises release; ADC relies on internalization/hydrolysis which may be less efficient in CAFs or in non-internalizing contexts.

Manufacturing & cost: peptides/PDCs can be simpler and cheaper to make vs complex ADC conjugation and heavy biologics manufacturing.

Combination strategy: if AVA6103 demonstrates the same immune-remodelling at lower systemic exposure, it may have an improved therapeutic index for immunotherapy combos.”

Would encourage LTH’s to review the Abstract and, perhaps (?), speak with the AI of your choice.

GLA

Certainly seems to be some ESMO ‘activity’ in the next few days …

“Outcome notifications of pre-accepted, full LBAs are expected to be made available to first authors and submitters between 16 and 18 September 2025.”

“The presenting author or the designated replacement presenter must be registered by 1 October 2025.”

“Titles of accepted late-breaking abstracts are expected to be made available online in the “Programme” section, by 20 September 2025.”

Wonder if we hear anything directly from CC during this period (and before the results day)?

Way overdue updates since the last (one PR apart) data drop from April.

GLA

Next ‘update’ …?

From RNS 30 Jul – “… the Company will present an updated data analysis from the Phase 1a trial of FAP-Dox (AVA6000) at the 2025 European Society for Medical Oncology (ESMO) Congress, in Berlin, Germany, taking place from October 17-21, 2025 …”

“Avacta will hold an investor event shortly after the ESMO presentation. Further details will be made available nearer the time.”

From ESMO re deadline for Abstracts – “Late-breaking abstracts - 9 September 2025, 21:00 CEST”. So tomorrow (Tue 9 Sept) @ 20:00 UK time perhaps we find out a little more about …

https://cslide.ctimeetingtech.com/esmo2025/attendee/confcal_2/presentation/list?q=tap&c=s

Maybe some sort of ‘update’ on Wed morning? (Would be good to see some sort of 'cadence' in comm's develop).

GLA

Placeholder page just updated, news soon ..?

https://avacta.com/stage-products/ava7100/

GLA

Https://x.com/coughlin582/status/1963703146439705016

Just a 'flavor' [sic] eh?

GLA

Https://en.topdaily.kr/articles/8579

2 days ago - “LG Chem is restructuring its roadmap for its life sciences (pharmaceuticals and biotechnology) business.”

Reading down, a brief mention of LR19128, but nothing susbstantive.

“… and 'LR19128', currently under development based on Avacta's Affimer technology, also have anticancer indications.”

Looks like still in the pipeline? But needs a closer look.

GLA

This does look like a ‘defining’ RNS to me. Some ‘conditionality’ …

“Upon the earlier of (i) the date on which the Company publishes the data readouts of its Phase 1b trials of FAP-Dox (AVA6000) in triple negative breast cancer and …” (Rather implies those ‘readouts’ will be quite good).

“Avacta completing a fundraise of, or receiving gross proceeds of at least £13,000,000 in aggregate on or prior to the Long Stop Date by way of:

Entering into any partnership or other agreements in respect of its pharmaceutical products; and/or

Any strategic investment into the Company; and/or; An equity fundraise”. (Thanks to Mr Hughes demonstrable, and most welcome, capability to deal with financing, we can focus on science and trial progress).

Some serious confidence (and reputations 'on the line') …

“The initial clinical activity observed in Phase 1b of the FAP-Dox trial is highly encouraging and has further increased our confidence in the utility of our pre|CISION® platform to transform how we treat cancer."

So what are BP thinking now ..?

What does it mean for our current products – many of which have upcoming patent expiry?

What does it mean for our pipeline investments – what chance some are already obsolete?

Have these guys really ‘cracked’ FAP-α targeting (4 years in the clinic now), is AVA6000 / FAP-Dox already demonstrating efficacy in TNBC and about become the new standard of care for SGC?

Have these guys really got a method of safely delivering Exatecan to the TME in large doses without significant side-effects (whether from mis-directed payload or platform interactions)?

BP thinking (?) – ‘crikey’ what are we going to do ..? (Or are one or more already ‘on with it'?).

Answer – buy, invest (license), try harder with own ‘stuff’, wait a bit longer to see if it really (like really, really) works, put head in sand ..?

Think it gets quite exciting in the run up to ESMO.

GLA

@Bella, yep could certainly add Pfizer to the list, J&J also with significant Dox product sales. Second point - seems many BPs trying to get Exatecan / derivatives working, but don't have the targeting capability of pre|CISION® , not to mention ADC side-effects. The risk to these BPs increases massively once AVA6103 is in humans. See if they wait to find out the results ...?

GLA

Strong negotiating position indeed, ‘confidence is high’ (guess ‘it works’™ then) …

“ … confidence in Avacta's ability to partner pre|CISION® across a number of modalities …The initial clinical activity observed in Phase 1b of the FAP-Dox trial is highly encouraging and has further increased our confidence in the utility of our pre|CISION® platform …”

So which prospective ‘partners’ (perhaps potential acquirers?) are in our data room ..?

My top 6 (alphabetic order) – AZN, Daiichi Sankyo, Gilead, Merck, Lilly, Novartis. Why ...?

AZN / Daiichi Sankyo – Enhertu (trastuzumab deruxtecan), Datroway (datopotamab deruxtecan) – part of DXd Topo-1 payload ‘family’, HER2 and Trop-2 targeted, approved.

Gilead - Trodelvy (sacituzumab govitecan) - ADC targeting Trop-2, delivering SN-38, approved.

AZN – AZD8205 (AZ0132 exatecan derivative) – phase 1/2.

Merck / Daiichi Sankyo – Ifinatamab deruxtecan – phase 2/3.

Lilly – LY4101174 and LY4170156 (exatecan ADCs) – phase 1.

Lilly - PNT6555 (177Lu-PNT2004) - FAP-α targeting radioligand (probably not CanSEEK?) – Phase 1.

Novartis - 177Lu-FAP-2286, 177Lu-FAPI-46, 90Y-FAPI-46 - FAP-α targeting radioligands – Phase 1/2.

Corrections, additions welcome.

GLA

From the Times (subscription required) …

https://www.thetimes.com/uk/healthcare/article/breast-cancer-drug-trodelvy-held-nhs-bw6m2zb7m#:~:text=The%20pharma%20giant%20Gilead%20Sciences,its%20citizens%20and%20its%20patients.

“‘Precious’ breast cancer drug withheld from NHS in price row - The pharma giant Gilead Sciences will not send Trodelvy for assessment by the UK drugs watchdog, claiming it can’t make enough profit in Britain”.

Won’t post a long ‘research’ note – but suggest anyone interested in the significance could do some AI research on Trodelvy (sacituzumab govitecan), an ADC targeting Trop-2 and delivering SN-38. Also look at Trodelvy’s rather ‘mixed’ track record in trials.

Just a few tips – AVA6000 is in P1b for indications including TNBC, AVA6103 delivers Exatecan which is a TOP-1 inhibitor (like SN-38, but more potent), PDC’s much cheaper and easier to manufacture than ADC’s, pre|CISION® platform superior targeting (for FAP, so far), minimal side-effects so far, etc., etc.

Seems like a massive opportunity for AVA6000 in the near-term (no doubt some early P1b data already available to some), and AVA6103 in the medium-term.

Gilead should certainly be interested – not to mention the healthcare ‘establishment’ (Streeting, NICE, NHS, FDA, RFK, et al).

GLA

@gracie12, largely agree.

At least Mr Hughes efforts have improved the sp to a slightly larger (small) fraction of the true value of the pre|CISION® platform, even if a few ‘HNWIs’ have made a few, too easily earned, ‘bucks’.

But yes, this is not sustainable, strategic finance is needed now – as it has been for a long time.

We approach a ‘confluence of events’ …

ESMO presentation of the ‘Phase I trial of FAP-Dox (AVA6000)’ by Dr William Tap – Oct 17.

Investor presentation shortly after the above (tba).

The next CLN due w/c 20 Oct.

The need to demonstrate ‘proper’, long-term, funding – by the above dates we will be well within 6 months of the acknowledged cash ‘runway’.

Progress update on IND for AVA6103 and FDA discussions re AVA6000 – surely must be made more widely available to patients soon?

Notwithstanding the ESMO presentation, a full and comprehensive update on trial and pipeline status – note, apart from the RNS 19 June re a PR in SGC (so CC could speak about it), there has been no comprehensive update since April data.

Looking forward to the ESMO update, but more so – a large strategic investment and / or license deal(s), or just acquisition, on strong data.

GLA

Courtesy https://x.com/111BEN_111/status/1950949620332282052 from twiX ...

Remember …

AZN / Daiichi Sankyo – Enhertu (Trastuzumab Deruxtecan) delivers an Exatecan derivative, targets HER2.

AVA6103 huge threat then ...?

Other ‘under threat’ examples, perhaps ...?

Novartis – no ADCs, have Pluvicto targeting PSMA and other RLTs trying to do FAP targeting and imaging – such as FAP-2286 and FAPI-46/74 (all acquisitions / licensed in).

Pfizer and J&J with significant Doxorubicin sales.

Merck – Keytruda (Pembrolizumab) a PD-1 inhibitor – remember the ‘Affimer® biotherapeutics: The next generation of cancer therapiesmmunotherapy’ poster from 2023 – AVA032 being a PD-L1 therapy. Immunotherapy mentioned by CC in recent interview.

And so on …

GLA

R&D video and new presentation pack still mostly based on April data (both excellent though).

Scene being set for next data release? Coris sale overdue. License deal(s) inbound?

Or is Avacta being ‘positioned’ for full acquisition?

GLA

Interesting @Yorkshire. Not a ‘million miles’ away. ADC targeting GPRC5D, a protein expressed in multiple myeloma (malignant plasma cells).

Sino Pharma getting in ahead of Meck and AZN – who already had licensing deals, and all for net $500m.

Our ‘package’ much more comprehensive – FAP targeting, multiple warheads (dox in trial), half-life management, no ADC issues, etc.

Now, how much inc. Chi-nah? Multiples of the above then ..?

GLA

@BV, thanks for the tip, trying again ...

ADC ‘hegemony coming to an end …?

@RAH’s poll on twiX asks a question that I’m sure most well researched LTH’s already know the answer to …

https://x.com/RAH00084/status/1944002353637572680

Nevertheless, I checked my undesratnding with ChatGPT and this was the (confirmatory) answer …

“Typical Numbers:

Lt 1% to approx 5% of the total administered ADC dose’s warhead payload actually reaches and is released within the tumor. For most FDA-approved ADCs (e.g., T-DM1, enfortumab vedotin, trastuzumab deruxtecan), sudies using radiolabeled or fluorescent-tagged warheads estimate: ~0.1% to 1% of the injected dose (ID) reaches each gram of tumor tissue. This can correspond to a few percent of the total warhead dose being delivered to all tumor lesions combined, especially in disseminated metastatic disease.”

And the AI’s concerns with ADCs continues …

“Why so little reaches the tumor?

Several limiting factors:

Systemic clearance – Much of the ADC is cleared or taken up by the liver, spleen, or other off-target tissues.

Tumor penetration – Large antibodies (~150 kDa) poorly penetrate dense tumor tissues.

Heterogeneous antigen expression – Some cells express the target, others don’t.

Endosomal trafficking inefficiency – Even in target cells, only some internalized ADCs release their payload effectively.

Warhead instability or premature cleavage – Some payloads are released in circulation or in non-target cells.”

ChatGPT then goes on, unprompted, to say …

“Implications

This inefficiency is why there’s so much interest in:

Smaller formats (e.g., antibody fragments, nanobodies, or peptides)

Prodrug systems (like Avacta’s FAP-activated tech)

Better linkers (cleaved more selectively in the tumor)

Higher DARs (drug-to-antibody ratios) while maintaining stability”

Yes, Avacta is the only company mentioned specifically (ansering this question at least) with an alternative to ADCs.

AI knows who we are, where we live, and what we’ve got. Major upheaval for BP coming, just a matter of tome …

GLA