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Just to be clear (amongst all I've written), this work was done under a grant from Avacta so the results are NOT independent verification.

Now the interesting parts...

This Avacta grant was for testing faridox in a combination therapy. As we all know, research takes time and this would have been set up quite some time ago. Avacta has moved on to dual warhead therapies as a step up from combination therapies so I part think but largely hope that this project was insigated AFTER the dual payload patent was written and that the patent covers, inter alia, a doxorubicin plus elimusertib (BAY-1895344) dual warhead as the combination of the two has now been shown in the public domain to be efficacious.

Additionally, a very interesting question is whether Bayer have been involved in this project in the background along the lines of "You, Avacta, pay for the basic proof of concept work and we'll take it from there" with a combination or dual warhead therapy. It is, afterall, the Bayer drug that is unproven. 😂

Here you are LDA...

Presenter/Authors: Lisa Pickard1, Ekta Paranjape1, Brian Cunningham2, Udai Banerji2

1The Institute of Cancer Research, London, United Kingdom,

2The Institute of Cancer Research, London, London, United Kingdom

https://www.icr.ac.uk/research-and-discoveries/find-a-researcher/test-researcher-profile-detail/dr-lisa-pickard

https://www.icr.ac.uk/research-and-discoveries/find-a-researcher/test-researcher-profile-detail/ekta-paranjape

As we know, Udai Banerji is at the Royal Marsden, home to part of the ICR, so Brian Cunningham will be as well – there is a subtle difference in ICR sites (1 and 2) not fully distinguished in the author affiliations.

https://en.wikipedia.org/wiki/Institute_of_Cancer_Research

I think the important parts of the rather confusing details given below are:

"Employment. U. Banerji, Verastem Oncology ), Other, Academic clinical trial grant. Avacta Therapeutics )." and the other two instances of "Avacta Therapeutics )."

I think these signify that Prof Banerji is in receipt of a grant from Avacta that covers the work of two ICR staff with the third, Cunningham, maybe working directly for Prof Banerji, but this is guesswork as I'm on a fiddly and slow mobile rather than my laptop so my patience to fully investigate is consequently short. Anyway, let's see how LSE strings out the Disclosures section...

Disclosures:

     L. Pickard,

    Avacta Therapeutics ).

    The Institute of Cancer Research Employment.

    E. Paranjape,

    Avacta Therapeutics ).

    The Institute of Cancer Research Employment.

    B. Cunningham,

    The Institute of Cancer Research Employment.

    U. Banerji,

    Verastem Oncology ), Other, Academic clinical trial grant.

    Avacta Therapeutics ).

    Chugai Pharmaceutical Company Ltd Other, Remunerated Consultant.

    Carrick Therapeutics Other, Advisory Board.

    PharmEnable Therapeutics Other, Advisory Board.

    Ellipses Pharmaceuticals Other, Advisory Board.

    Amalus Therapeutics Other, Advisory Board.

    Dania Therapeutics Other, Advisory Board.

    Pegascy Group Other, Advisory Board.

    DeuterOncology Advisory Board.

    The Institute of Cancer Research Employment

Look at the presenters' affiliations

Clinical trials of Bayer's ATR inhibitor, BAY 1895344: https://clinicaltrials.gov/search?term=bay%201895344

Third abstract (Wed, 22 April): https://www.abstractsonline.com/pp8/#!/21436/presentation/3456

Background: This study shows single agent and combinatorial activity of AVA6000 (Faridoxorubicin, FAP-Dox), in pancreatic cancer and liposarcoma, cancer associated fibroblast co-culture models. Fibroblast activation protein (FAP) is a transmembrane serine protease and present in cancer associated fibroblasts and some cancer cells. AVA6000 is a FAP cleavable peptide drug conjugate comprised of doxorubicin and a dipeptide that is selectively cleaved by FAP to release active doxorubicin within the tumour microenvironment. We aimed to study a) FAP-specific release of doxorubicin b) combinatorial activity of AVA6000 with DNA damage repair inhibitors, in preclinical models.

Methods: Cancer cells, labelled with GFP, were co-cultured with pancreatic stellate cells (PSCs) showing features of myofibroblastic cancer associated fibroblasts (such as alpha smooth muscle antigen expression) which expressed FAP. Cancer cell growth was quantified by counting the number of GFP labelled cancer cells per well, with cancer cells alone (i.e. no CAFs) used as controls. In addition, we studied the effects of the FAP inhibitor Talabostat (PT100) in reversing the effects of AVA6000 in co-culture conditions. Further, we tested the effects of the combination of an ATR inhibitor BAY1895344 in combination with AVA6000 in the coculture system.

Results: The GI50 of AVA6000 in two pancreatic cancer cell lines ASPC-1 and Mia-Paca-2 in the co-culture system with PSCs was 58±21.4nM, (Stdev,n=3) and 66.5±16.3nM (Stdev, n=3). No GI50 was obtained in both cell lines at the highest concentration of AVA6000 studied in both cell lines (>100nM n=3) if PSCs were not included in the culture. In addition, we demonstrated that the FAP inhibitor talabostat at 100µM reversed any growth inhibition by AVA6000 (highest concentration of AVA6000 tested 100nM) confirming AVA6000 activation was FAP dependent. We further studied the growth inhibition of AVA6000 in the liposarcoma cell line SW872-GFP in co-culture with FAP expressing fibroblasts GI50 30.6±6.7 nM (StdevD, n=4). The GI50 of AVA6000 was not achieved in the absence of fibroblasts at >100nM and the FAP inhibitor talabostat reverses this growth inhibitor effect in the co-culture system. The combination of AVA6000 and BAY1895344 in the co-culture yielded a 2 fold shift in GI50.

Conclusions: AVA6000, is selectively activated by FAP expressing PSCs and is active in pancreatic and liposarcoma co-culture models. It also exhibits synergistic growth inhibition activity with ATR inhibitors in liposarcoma co-culture models. Clinical trials of AVA6000 are ongoing (NCT04969835).

Nope, here's the other abstract: https://www.abstractsonline.com/pp8/#!/21436/presentation/5743

5846 / 15 - AVA6103 is a FAP-enabled pre|CISION®peptide-drug conjugate delivering sustained release of exatecan in the tumor microenvironment with potent antitumor activity

AVA6103 is a novel peptide drug conjugate (PDC) based on proprietary pre|CISION® technology which incorporates a dipeptide that is specifically cleaved by Fibroblast Activation Protein α (FAP). FAP is a post-proline protease that is overexpressed on the surface of cancer associated fibroblasts (CAFs) in many solid tumors, and facilitates delivery of pre|CISION® medicines specifically to the tumor microenvironment (TME). AVA6103 consists of exatecan, a potent Topoisomerase I payload, covalently linked to a dipeptide containing a cleaving sequence (D-Ala-L-Pro), which is susceptible to hydrolysis by FAP but is resistant to hydrolysis by other mammalian proteases.

Exatecan has been investigated in the clinic, however, its utility is limited by dose-limiting toxicities. The exquisite selectivity of the pre|CISION® substrate for FAP results in release of exatecan payload selectively in the TME, greatly increasing the therapeutic window and hence reducing systemic exposure and associated toxicities.

AVA6103 is a pre|CISION-enabled PDC that demonstrates FAP-dependent release of exatecan and kills cancer cells via a bystander mechanism. In multiple in vivo efficacy studies utilizing diverse cell and patient-derived models, AVA6103 achieved complete regressions and sustained, durable responses which remained until study termination. Biomarker assessment indicated on-target activity of the exatecan payload.

The PK profile of AVA6103 and released-exatecan were assessed in tumor-bearing mice, showing that released-exatecan levels in the plasma were undetectable after 4 hours, whereas in the tumor, released-exatecan persisted throughout the 5-day observation period of the study, indicating the potential for AVA6103 to deliver sustained exatecan to the tumor whilst minimizing systemic exposure of exatecan below clinically toxic levels.

To gain a greater understanding of patient populations that may be sensitive to AVA6103, co-expression of FAP and SLFN11, a gene linked to sensitivity to topoisomerase inhibitors, were evaluated using Tempus AI’s LENS database. A positive correlation was observed between FAP and SLFN11 across multiple tumor types, further supporting the rationale for clinical development. Additional mechanistic studies demonstrated on-target activity and supported utility of AVA6103 in specific cancer indications to exploit genetic vulnerabilities.

This preclinical data package highlights the potential for AVA6103 to selectively target exatecan to the tumor microenvironment in a wide range of cancers. A Phase 1 dose escalation study designed to evaluate the safety, pharmacokinetics, and preliminary anti-tumor activity of AVA6103 in gastric, pancreatic, cervical and smal

Here's the other abstract: https://www.abstractsonline.com/pp8/#!/21436/presentation/5455

5656 / 26 - Characterization and translational development of novel pre|CISION® technology compounds delivering complementary dual payloads to the tumor microenvironment following FAP cleavage

The proprietary pre|CISION® technology incorporates a peptidic substrate that is specifically cleaved by Fibroblast Activation Protein α (FAP). FAP is a post-proline protease that is overexpressed on the surface of cancer associated fibroblasts (CAFs) in many solid tumors, and facilitates delivery of pre|CISION® medicines specifically to the tumor microenvironment (TME). AVA6103 is a pre|CISION®-enabled exatecan candidate in clinical development. AVA6103 consists of exatecan, a potent Topoisomerase I (TOP1) inhibitor, covalently linked to a dipeptide containing a cleaving sequence (D-Ala-L-Pro), which is susceptible to hydrolysis by FAP but is resistant to hydrolysis by other mammalian proteases. The exquisite selectivity of the pre|CISION® substrate for FAP results in release of exatecan payload in the TME, greatly increasing the therapeutic window and hence reducing systemic exposure and associated toxicities. Drug combinations are commonly used in cancer therapy to improve outcomes and overcome resistance, therefore we engineered two complimentary payloads into a single pre|CISION® molecule. This may offer similar benefits whilst minimizing systemic toxicity. To create dual payload pre|CISION® Peptide-Drug Conjugates (PDCs), a series of compounds have been engineered with modifications in the capping-group and linker portions. Using structure-based drug design, clear structure-activity relationships have been established for affinity to, and susceptibility of linker cleavage by FAP and subsequent payload release. We now demonstrate how the use of the pre|CISION® technology platform has been widened to selectively control the release of multiple payloads from a single molecule via a FAP cleavable linker. This includes TOP1 inhibitors and DNA damage response inhibitors as the dual payloads. Selective payload release has been demonstrated in kinetic studies showing the ability to tune the rate of payload release and in cellular studies showing potent cytotoxicity and bystander activity in cell-based assays including tumor cell-fibroblast 3D co-culture models. Synergistic activity of two potentiating payloads and downstream pharmacodynamic markers for each payload have also been evaluated in cancer cell-lines with specific gene expression profiles. This has provided translational evidence for potential biomarkers and clinical indications. Delivery of payloads to mouse tumors in vivo has also been confirmed. We show the potential of the technology to deliver a therapeutically relevant combination of payloads specifically to the TME while reducing systemic dose-limiting toxicities. This broadens the utility of the pre|CISION® platform in the delivery of novel medic

Well, today...

"Today's recommendation from our system is to SELL. The BEARISH DESCENDING HAWK pattern has finally received confirmation because the prices crossed below the confirmation level at 70.50, and our valid average selling price now stands at 69.77. The previous BUY signal was issued on 11/03/2026, 6 days ago, when the stock price was 69.00. Since then, AVCT.L has risen by +1.12%."

In other news...

"You may find yourself emotionally challenged today by a strong force demanding your attention. Your hyperawareness to every situation might be driving you a bit crazy. Perhaps you just need to tone things down and relax. Enjoy rather than question the fun-loving energy of the day. The more you simply let loose and explore, the better off you'll be."

"likely", "unlikely", "due"

"I continue to be right"

Bigly self-unaware.😂😂😂

😂 'but I continue to be right...' ...is a very telling phrase.

What you see on LSE are only an assignment of buys and sells dependent on where the mid-price is.

Yeah, I'm sure Avacta would love to conclude the SGC part of the trial and put the results out there if only it weren't for that pesky PFS which just keeps being out of reach.

How did you know?!

AACR abstracts are out tomorrow - https://x.com/TVR5AVCT/status/2033488971750162622/photo/1

If previous years are anything to go by, I'd expect more AVA6207 preclinical data, further what was presented last October at AACR-NCI-EORTC, and more AVA6103 data, maybe some of the IND submission data such as the dog study.

It would also be nice to have an update on AVA7100 and/or a total surprise topic.

Oops! Not ESMO (that's in the Autumn), ASCO (American Society of Clinical Oncology). I should have followed LDA's link.

AACR is the American Association for Cancer Research and the presentations tend to be preclinical development and specialised topics such as the AI trial design and PK and antitumour activity that Avacta presented last year along with the AVA6103 preclinical data.

CC said updated AVA6000 data will be presented at a medical conference so I guess that will be at ESMO (European Society for Medical Oncology) at the end of May.

Yes Hammy, on 6 March:

"Simon Bennett has gone from the Executive Leadership Team on the Leadership page so I presume he is no longer acting as Chief Business Officer. However his email address is still being given as the contact on the Partnering and Pipeline pages."

I also suggested they use a dedicated Business Development mailbox but you can't tell Americans anything.

Complete incompetence. Pipeline page still has Simon Bennett as contact and email address and the email address link doesn't work and probably never did - it has a full stop at the end, thus invalidating it.

The Yulii Bogatyrenko email address is outside the avacta.com email domain. Do they really want a contract worker conducting business outside their oversight? Could they not create an in-house email address for him??

Today's announcement was 'open for recruiting' so you've still got a couple of days.