Trinity Delta Dual payload pre|CISION unveiled at EORTC-NCI-AACR

Dual payload pre|CISION unveiled at EORTC-NCI-AACR

Lighthouse | 14 October 2025

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New data on a dual-payload peptide drug conjugate (PDC), to be presented at the 2025 EORTC-NCI-AACR Symposium, provide the first details on how the pre|CISION platform can deliver two diverse and complementary payloads directly to the tumour microenvironment (TME). The preclinical data show a dual payload on a single construct can be selectively targeted to the TME, where it is activated via fibroblast activation protein (FAP) cleavage into the active individual components through a controlled and sustained release. This highlights the versatility of the platform, and creates opportunities for novel combinations; for example, a potent cytotoxic for tumour killing could potentially be combined with, say, a DNA damage repair inhibitor to overcome resistance mechanisms.
It is pre|CISION’s selective activation at the tumour site that underpins the whole opportunity of minimising systemic toxicities and improving patient outcomes. Last year management presented data on FAP-EXd (AVA6103), the lead second-generation pre|CISION peptide drug conjugate, at EORTC-NCI-AACR. This targets delivery of exatecan, a potent topoisomerase I inhibitor, to the TME. Following cleavage by the FAP enzyme, it induces DNA damage and promotes cancer cell death. Here pre|CISION is employed to overcome exatecan’s severe dose limiting toxicities and short half-life by modifying its PK profile and improving tolerability via a fine-tuning of the FAP-targeted release in the TME.
The industry focus on dual-payload constructs stems from their potential to significantly improve cancer treatment by using a single drug to deliver two different actives to the TME. This dual-action approach can enhance efficacy and overcome resistance mechanisms that limit current treatments, as the tumour cell would need to resist both drugs simultaneously. Dual-payload ADCs have already demonstrated the potential to outperform single-drug ADCs in preclinical models and could lead to more effective therapies for a wider range of cancers, though they face complex production challenges. The appeal of pre|CISION’s approach lies in its efficacy, delivery, and, importantly, simpler assembly and manufacture.
We believe a new linker, with relevant IP, has been created that, following FAP cleavage, allows the two selected drugs to be released independently in a finely controlled manner. Details of the construct to be taken forward are not yet known but the obvious toxic payload would be exatecan, as its properties as FAP-EXd are already largely known, and it would likely be coupled with a resistance modifying component targeting DNA repair, such as ATRi or PARP.

Trinity Delta view: These preclinical data once again provide valuable insights into the versatility and broad potential of Avacta’s pre|CISION platform. The proof-of-concept of FAP-targeted biotherapeutics will be demonstrated through its lead clinical candidate, faridoxorubicin (FAP-Dox, previously AVA6000), but we believe this should be viewed as the first in a pipeline of novel therapeutics that can be selectively activated in the TME, thus reducing toxicity and improving patient outcomes. We view FAP-EXd (AVA6103) as the true value driver and believe its continued clinical development, and related data, over the next 24 months will provide the more material inflection points. Our Avacta valuation is £457m ($571m), or 111p/share.

Lighthouse

14 October 2025


Price	71.0p
Market Cap	£296.1m
Primary exchange	AIM
Sector	Healthcare
Company Code	AVCT

Corporate client	Yes

Company description

Avacta is a clinical stage biotech focused on the novel pre|CISION platform to generate peptide-drug conjugates to target delivery of toxic payloads into the tumour microenvironment, which has the potential to expand the reach and reduce the systemic toxicities of highly potent cancer therapeutics. Lead programme faridoxorubicin is in Phase Ib, and multiple next generation candidates are in preclinical development.

Analysts

Lala Gregorek
lgregorek@trinitydelta.org
+44 (0) 20 3637 5043

Philippa Gardner
pgardner@trinitydelta.org
+44 (0) 20 3637 5042

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