Avacta Therapeutics Presents Preclinical and Translational Data from pre

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28-04-2025

FAP-EXd (AVA6103) demonstrates tumor growth inhibition and durable complete responses in multiple therapy-resistant preclinical models
LONDON and PHILADELPHIA, April 28, 2025 (GLOBE NEWSWIRE) -- Avacta Therapeutics (AIM: AVCT), a life sciences company developing next generation peptide drug conjugates (PDC) targeting powerful anti-tumor payloads directly to the tumor, today announced preclinical results from its second pre|CISION® candidate FAP-EXd (AVA6103) and new analyses around the potential of the pre|CISION® platform at the American Association for Cancer Research (AACR) Annual Meeting in Chicago, IL.
The pre|CISION® programs are designed to target fibroblast activation protein-alpha (FAPα), the protease that forms the basis of the platform. FAP is consistently overexpressed across a broad range of solid tumors and enriched at the tumor-stroma interface, making it an ideal target for tumor-localized drug activation. Avacta's proprietary pre|CISION® chemistry leverages this tumor-specific biology to activate potent drugs selectively at the tumor site, enhancing efficacy while minimizing systemic toxicity.
"The encouraging results we are showcasing at this year's AACR Annual Meeting highlight the versatility of our pre|CISION® platform,' said Michelle Morrow, CSO of Avacta Therapeutics. 'Our data presented today demonstrate that the platform can deliver potent payloads like exatecan with remarkable tumor selectivity and our novel sustained release mechanism. Together, these programs reinforce the broad potential of our pipeline to transform outcomes for patients and generate long-term value for shareholders.'
AVA6103 (FAP-EXd) Preclinical Candidate Highlights (Abstract 3139, 28 April 2025)
Avacta presented preclinical data from its second clinical candidate, AVA6103, a novel FAP-activated pre|CISION® PDC delivering the topoisomerase I inhibitor exatecan directly to the tumor-stroma interface. This mechanism minimizes systemic toxicity while ensuring precise delivery of the cytotoxic agent directly to the tumor with a sustained release mechanism that optimizes the pharmacokinetics of the released payload. Importantly, despite a very short half-life of 9 hours with conventional exatecan, FAP-EXd (AVA6103) is capable of delivering high tumor concentration vs. plasma with exposures of more than 60 hours projected with a single dose. Additionally, FAP-EXd's bystander effect enables exatecan to induce cytotoxicity in surrounding FAP-negative cancer cells, enhancing its therapeutic impact.
The compound has demonstrated significant tumor growth inhibition and durable complete responses in multiple patient-derived xenograft models, including those that are resistant to topoisomerase I inhibition. These results reinforce the potential of FAP-EXd to deliver effective, targeted treatment with minimal off-target effects. The investigational new drug (IND) submission is anticipated in December 2025 and initiation of the first-in-human study in the first quarter of 2026.
Abstract Number and Title: #3139: The novel PDC AVA6103 is a FAP-enabled pre|CISION® medicine which targets exatecan, a topoisomerase I inhibitor, to the tumor microenvironment following FAP cleavage· Session Category: Experimental and Molecular Therapeutics· Session Title: Therapeutic Approach to Attack the Tumor Microenvironment· Session Date and Time: Monday, April 28, 2025, 2:00 - 5:00 p.m. CT
FAP Targeting Approach with pre|CISION® medicines (Abstract 2699, 28 April 2025)
FAP is overexpressed across a wide range of solid tumors, with estimated frequency of over 90% of patients with evidence of FAP expression. This expression is spatially enriched at the tumor-stroma interface, demonstrating the effective nature of the pre|CISION® mechanism to deliver highly potent payloads directly to the tumor. Given the broad expression of FAP in human solid tumors and correlation of the protein and RNA levels of FAP, an AI-based approach to this target was employed with the Avacta strategic collaboration with Tempus.
Avacta's work with Tempus has demonstrated several key aspects of the pre|CISION® platform, namely (1) FAP expression remains consistent across lines of therapy and in pre- and post-tumor samples, and (2) co-expression of genes associated with sensitivity to the payload and FAP identify the optimal patient populations for pre|CISION® medicines including FAP-EXd. These data reinforce the potential of Avacta's pre|CISION® platform to deliver potent therapies across multiple solid tumor indications with broad clinical utility.
Abstract Number and Title: #2699: Investigating fibroblast activation protein alpha (FAPα) as a therapeutic target for delivery of pre|CISION® cancer medicines: Expression, spatial localization and functional insights· Session Category: Tumor Biology· Session Title: Targeting the Tumor Microenvironment: A Brave New World· Session Date and Time: Monday, April 28, 2025, 2:00 - 5:00 p.m. CT
For further information from Avacta, please contact:
Avacta Group plcMichael Vinegrad, Group CommunicationsDirector
avacta.com
Peel Hunt (Nomad and Broker)James Steel / Chris Golden
www.peelhunt.com
Panmure Liberum (Joint Broker)Emma Earl / Will Goode / Mark Rogers
www.panmureliberum.com
ICR HealthcareMary-Jane Elliott / Jessica Hodgson / Stephanie Cuthbert
[e-mail]
Investor ContactRenee Leck THRUST Strategic Communications
[e-mail]
Media ContactCarly ScadutoCarly Scaduto Consulting
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About Avacta - avacta.com
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 warhead delivery system based on a tumor-specific protease (fibroblast activation protein or FAP) that is designed to concentrate highly potent warheads 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.
About the pre|CISION® PlatformThe 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.