REG - Avacta Group PLC - Avacta presents preclinical data at AACR-NCI-EORTC

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RNS Number : 8541E  Avacta Group PLC  27 October 2025

 

 

 

Avacta presents first preclinical data from dual payload pre|CISION(®)
medicines at the 2025 AACR-NCI-EORTC International Conference on Molecular
Targets
(https://www.aacr.org/meeting/aacr-nci-eortc-international-conference-on-molecular-targets-and-cancer-therapeutics-2025/)

 

First-in-class dual payload peptide drug conjugate delivers two complementary
therapies from a single molecule with potential to overcome resistance and
maximize tumor control

 

 

LONDON and PHILADELPHIA - October 27, 2025 - Avacta Therapeutics (AIM: AVCT,
'Avacta', 'the Company'), a clinical stage biopharmaceutical company
developing pre|CISION(®), a tumor-activated oncology delivery platform,
announces it presented preclinical data demonstrating its novel first-in-class
dual payload pre|CISION(®) technology (AVA6207) at the AACR-NCI-EORTC
International Conference on Molecular Targets and Cancer Therapeutics on
October 25, 2025 in Boston, Massachusetts.

The data presented showcase the Company's innovative approach to delivering
two distinct therapeutic payloads simultaneously to the tumor microenvironment
(TME) through a single fibroblast activation protein (FAP)-mediated cleavage
event. Avacta is the first company to develop dual payload peptide drug
conjugates (PDCs), circumventing resistance mechanisms that cancer cells
develop against single-drug therapies while maximizing therapeutic effect
through targeted combination delivery. This approach has the potential to
address several critical challenges in cancer therapy.

 

The Company's dual payload pipeline currently comprises two strategic
approaches: combination of microtubule inhibition and topoisomerase I
inhibition (MMAE and exatecan), representing two distinct anti-cancer
mechanisms with established clinical activity; and DNA damage response (DDR)
agents (ATR or PARP inhibitors) combined with exatecan, where inhibition of
DNA repair potentiates the cytotoxic effect of exatecan.

 

Christina Coughlin, M.D., Ph.D., Chief Executive Officer of Avacta, commented:

"The first dual payload peptide drug conjugate marks an important step forward
in oncology therapy, significantly extending the potential of our
pre|CISION(®) platform by implementing combination cancer therapy in a single
small molecule medicine. The synergistic enhancement in anti-tumor activity
observed with our exatecan-DDR inhibitor combinations highlights the potential
of targeting the tumor with a potent cytotoxic drug while attacking the known
resistance mechanisms. We believe this technology has the potential to
markedly improve outcomes for cancer patients, particularly those with
highly-resistant tumors.

"The pre|CISION(®) platform has been validated by compelling clinical data
with faridoxorubicin (AVA6000, FAP-Dox), demonstrating a tumor-to-plasma
payload concentration of 100:1 and a significant reduction in off-target
toxicities despite dosing up to approximately 4x the dose of conventional
doxorubicin. The new dual payload intellectual property extends the platform
to release two drugs from one pre|CISION(®) molecule, targeting
highly-resistant cancers by addressing key resistance mechanisms."

 

 

 

Key Preclinical Findings:

The pre|CISION(®) dual payload technology demonstrated robust FAP-selective
delivery and potent anti-tumor activity across multiple complementary payload
combinations:

·      Validated dual payload release mechanism: Biologic and
biochemical analyses confirmed simultaneous release of two independent
payloads from a single FAP cleavage event. Modifications to the
self-immolative linkers enabled tunable payload delivery kinetics, providing
flexibility to optimize therapeutic profiles for different payload
combinations. Strategic modifications of linker and capping group structures
enabled optimization of compound activity.

·      FAP-selective tumor cell killing with maintained potency: Dual
payload compounds achieved potent cytotoxic activity comparable to free
payloads in the presence of FAP (IC50 values of 2-9 nM), while demonstrating
minimal activity without FAP (IC50 >100 nM), confirming excellent tumor
selectivity in 2D and 3D tumor spheroid models over the course of seven days.

·      Confirmed dual mechanism biomarker modulation: Target-specific
biomarkers for both payloads were modulated only in the presence of FAP.
FAP-Exd/MMAE compounds induced decreased TOP1 levels, DNA damage markers
(γH2AX, pCHK1), tubulin depolymerization, M-phase arrest, and characteristic
S-phase and G2/M cell cycle arrest patterns, confirming both mechanisms of
action were operational.

·      Enhanced synergistic activity addressing resistance mechanisms:
FAP-Exd/PARPi and FAP-Exd/ATRi compounds demonstrated 4-5 fold greater
FAP-dependent tumor cell killing compared to exatecan alone, directly
addressing the known DDR-mediated resistance pathway to topoisomerase I
inhibitors. FAP-dependent biomarker modulation confirmed payload release
(reduced TOP1, PAR, and pCHK1 levels) alongside elevated DNA damage and
apoptosis markers (γH2AX, cleaved PARP), with synergistically increased
γH2AX demonstrating enhanced therapeutic effect.

·      Validated bystander mechanism in physiologically relevant 3D
models: Tumor-fibroblast co-culture 3D spheroid studies confirmed that
FAP-positive cancer-associated fibroblasts mediate payload release, resulting
in concentration of both therapeutics in the TME and effective killing of
FAP-negative tumor cells. Activity was dependent on FAP presence, with minimal
effect in monocultures or upon FAP inhibition, validating the bystander
mechanism of action.

 

Dual payload cancer therapies represent a highly novel approach in oncology
with the first dual payload antibody drug conjugates (ADCs) emerging in recent
years. The pre|CISION(®) platform has four key advantages over traditional
ADC delivery, including tumor-specific payload release that avoids the
toxicities associated with nonspecific release, small molecule manufacturing,
better tumor penetration and bystander effect, along with a large addressable
market of 90% of solid tumors.

 

The poster presentation (Abstract #C123) titled "Discovery and
characterization of novel pre|CISION(®) technology compounds delivering
complementary dual payloads to the tumor microenvironment following FAP
cleavage" is available on the Company's website at www.avacta.com
(http://www.avacta.com) .

 

The Avacta team will deliver a presentation via Investor Meet Company to
review the published data upon their return from the Congress at 16:00 GMT on
Wednesday October 29, 2025.  Details for the webinar will be posted on the
Avacta home page and available through the Investor Meet Company platform.

 

-Ends-

 

For further information from Avacta, please contact:

 

 Avacta Group plc                                           https://avacta.com/ (https://avacta.com/)

 Christina Coughlin, Chief Executive Officer                via ICR Healthcare

 Peel Hunt (Nomad and Joint Broker)                         www.peelhunt.com (http://www.peelhunt.com)

 James Steel / Chris Golden

 Panmure Liberum (Joint Broker)                             www.panmureliberum.com (http://www.panmureliberum.com)

 Emma Earl / Will Goode / Mark Rogers

 Zeus (Joint Broker)                                        www.zeuscapital.co.uk (http://www.zeuscapital.co.uk)

 James Hornigold / George Duxberry

 Dominic King

 ICR Healthcare (Europe/UK media and investors)             avacta@icrhealthcare.com (mailto:avacta@icrhealthcare.com)

 Mary-Jane Elliott / Jessica Hodgson / Stephanie Cuthbert

 Investor Contact                                           renee@thrustsc.com (mailto:renee@thrustsc.com)

 Renee Leck

 THRUST Strategic Communications

 Media Contact                                              carly@thrustsc.com (mailto:carly@thrustsc.com)

 Carly Scaduto

 THRUST Strategic Communications

 

About pre|CISION(®)

 

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.

 

About Avacta - www.avacta.com (https://avacta.com/)

 

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.

 

 

 

 

 

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