Avacta Group (AIM: AVCT) preCISION data signals tumor selectivity index emerging as the new ADC battleground

Avacta Therapeutics (AIM: AVCT) on May 6, 2026 disclosed comparative pharmacology data showing its preCISION tumor-activated payload platform delivering a tumor selectivity index roughly three times higher than Daiichi Sankyo and AstraZeneca’s Enhertu® and Datroway®, the two reference-standard antibody-drug conjugates currently driving the global ADC franchise. The framing of the announcement matters as much as the numbers themselves, because Avacta has publicly anchored its scientific positioning on a specific pharmacology metric, the tumor selectivity index defined as the area-under-the-curve ratio of payload exposure in tumor versus plasma, that until recently sat outside mainstream ADC commercial discourse. Avacta Group shares are trading at 77.14p on the London Stock Exchange, near the upper band of a 26.00p to 84.00p 52-week range that reflects a sharp 2026 recovery for the AIM-listed clinical-stage biotech. The Avacta Group AVCT disclosure lands at a moment when the ADC industry’s evaluation framework is quietly migrating from antibody specificity and linker chemistry toward the quantitative pharmacology of payload delivery, and the tumor selectivity index is becoming the metric on which next-generation conjugate platforms are competing. For executives tracking the ADC sector, the strategic question is no longer whether tumor-targeted delivery works but how it is being measured, compared, and defended in licensing negotiations.

Why is the tumor selectivity index becoming the central pharmacology metric in next-generation ADC development?

For roughly two decades the ADC conversation was dominated by three engineering questions: which tumor antigen the antibody targeted, how stable the linker was in circulation, and how potent the payload became once released inside the cancer cell. These remain critical, but they describe the construct rather than its behaviour in living tumors. The tumor selectivity index is a behavioural metric. It captures how much of the active payload reaches the tumor compartment relative to the systemic circulation over time, which is the parameter that ultimately determines the therapeutic window in cytotoxic oncology. A higher TSI means more drug where it should be and less drug where it causes toxicity, and it is increasingly being used by clinical-stage developers to differentiate platforms that share payload chemistry with approved ADCs.

Avacta Group AVCT has now reported a TSI of approximately three-fold higher for exatecan released from AVA6103 versus deruxtecan released from Enhertu® or Datroway® across a 14-day measurement window. The Company’s earlier February 2026 disclosure had already introduced the metric and the directional claim, and the May 6 update extended the comparator set to include Datroway alongside Enhertu, generalising the finding across two different antibody targets. The cleanness of the comparison is what gives the TSI framing its commercial weight. By holding the payload class constant, both deruxtecan and exatecan are topoisomerase I inhibitors derived from the camptothecin family, Avacta isolates the variable that matters for licensing conversations, which is the delivery mechanism rather than the cytotoxic chemistry. This is a notable departure from how earlier ADC differentiation arguments were constructed.

How does Avacta Group AVCT preCISION reframe ADC delivery from antigen specificity to stromal activation kinetics?

The mechanistic argument Avacta is pressing has implications well beyond a single comparison study. Antibody-drug conjugates rely on antibody binding to a tumor antigen, internalisation, and intracellular cleavage to release the payload. The kinetics of that process are governed by antigen density, internalisation rate, and lysosomal processing, and the resulting payload release happens inside the cancer cell. preCISION shifts the activation site to the tumor microenvironment by using fibroblast activation protein, an extracellular protease upregulated in the stroma of most solid tumors and largely absent in healthy tissue, as the cleavage trigger. Payload release becomes a function of stromal biology rather than antigen biology.

The pharmacology consequence Avacta is reporting is faster local concentration and tighter tumor confinement. Exatecan released from AVA6103 reaches peak tumor concentration in minutes, while deruxtecan released from Enhertu or Datroway reaches peak concentration after more than 24 hours. The maximal tumor concentration of free payload is more than a log higher with AVA6103. These kinetic differences feed directly into the TSI calculation because they expand the numerator of tumor exposure while shrinking the denominator of plasma exposure. The broader sector implication is that pharmacology kinetics, which were previously treated as engineering details inside ADC programmes, are emerging as the language in which differentiated platforms are now articulating their commercial case.

The published pharmacology literature on antibody-drug conjugates has long acknowledged that the therapeutic index of ADCs is constrained by the relatively narrow window between effective tumor concentrations and systemic toxicity. The peer-reviewed consensus is that strategies modulating the pharmacokinetics of individual ADC analytes at the site of efficacy and toxicity could materially improve the therapeutic index. Avacta’s preCISION pitch maps directly onto that consensus, and the TSI is the metric by which the improvement is being claimed.

Which other clinical-stage developers are competing on tumor-activated or conditionally-released payload delivery?

Avacta is not alone in pursuing tumor-activated payload delivery, although it is among the most explicit in publishing comparative TSI data against approved ADCs. Bicycle Therapeutics has built a parallel platform around its Bicycle® Drug Conjugates, a class of small bicyclic peptide-payload constructs that the Company positions as an alternative to monoclonal antibody-driven delivery. Bicycle’s lead programme zelenectide pevedotin targets Nectin-4 and uses a valine-citrulline cleavable linker with an MMAE payload, and the Company has reported preclinical head-to-head comparisons against Nectin-4 ADCs claiming superior anti-tumor activity in xenograft models. Bicycle’s separate EphA2 programme nuzefatide has clinical data showing tumor MMAE concentrations approximately 10-fold higher than corresponding plasma levels at 24 hours post-infusion, which is a clinical-stage analog of the tumor-versus-plasma exposure argument Avacta is making in preclinical settings.

Beyond Bicycle and Avacta, the conditionally-activated payload field includes a growing set of next-generation ADC developers working on probody designs, masked antibodies, and protease-cleavable linker variants intended to confine payload release to the tumor microenvironment. The peer-reviewed literature on ADC pharmacology now routinely catalogues bispecific ADCs, immune-stimulatory payloads, AI-guided design, and nanotechnology-enhanced delivery as parallel strategies all pursuing the same underlying objective, which is widening the therapeutic index by improving tumor selectivity. The convergence of these approaches on a shared pharmacology vocabulary, anchored on tumor-versus-plasma exposure ratios, is what makes the TSI metric increasingly central. Whichever platform produces the most defensible TSI claim in clinical translation is likely to command the strongest licensing leverage.

What does the rise of tumor selectivity benchmarking mean for Daiichi Sankyo and AstraZeneca’s deruxtecan franchise?

Daiichi Sankyo and AstraZeneca have built the most commercially successful ADC franchise in oncology around deruxtecan as a payload, with Enhertu projected to reach approximately $4.6 billion in sales in Daiichi’s fiscal 2026 and Datroway recording an early launch trajectory described as smooth following its US approval in January 2025. Daiichi’s stated ambition, articulated by chief executive officer Hiroyuki Okuzawa at the J.P. Morgan Healthcare Conference, is to expand ADC reach from approximately 120,000 eligible patients in fiscal 2025 to 700,000 by fiscal 2030 across breast, gastric, lung, and HER2-positive solid tumor indications. That is the most aggressive ADC franchise expansion plan currently disclosed in the industry.

The TSI framing creates a long-dated strategic challenge for that franchise. Deruxtecan’s clinical efficacy is established and its commercial momentum is intact, but the safety signal that has constrained Enhertu’s expansion into earlier lines of therapy is interstitial lung disease, a deruxtecan-related toxicity that Daiichi’s own commercial team has identified as requiring careful physician education and site management. ILD is, in pharmacology terms, a manifestation of off-tumor payload exposure. A platform that can credibly claim multi-fold higher tumor selectivity is implicitly arguing that its delivery mechanism narrows the very exposure window that drives the ILD signal. Avacta has not made the ILD claim explicitly, but the pharmacology logic of the TSI argument leads in that direction, and large-pharma business development teams reading the data will draw the connection without prompting.

How might tumor selectivity benchmarking reshape ADC dealmaking and platform valuation?

The dealmaking implications of a TSI-led evaluation framework are substantial because they change what gets diligenced. Pfizer’s $43 billion acquisition of Seagen in 2023 was structured around an antibody-driven ADC platform with established clinical assets. The subsequent wave of ADC dealmaking, including the Merck and Daiichi Sankyo collaboration valued at up to $22 billion, has shifted toward milestone-heavy licensing structures that reward platform optionality rather than acquired revenue. The TSI framework reinforces that shift because it foregrounds platform pharmacology rather than asset-by-asset clinical readouts. A tumor-activated delivery platform with a defensible TSI advantage can in principle be applied across multiple payloads and indications, which is exactly the optionality structure that licensing-heavy deal models price.

For clinical-stage developers like Avacta Group AVCT, the practical consequence is that the value proposition presented to potential partners increasingly rests on quantitative pharmacology benchmarks rather than purely qualitative platform descriptions. The Company’s decision to publish comparative TSI data against Enhertu and Datroway, and to indicate that the findings will be submitted for peer review and presented at academic meetings, fits the diligence pattern that licensing-stage acquirers expect. The risk is that preclinical TSI advantages do not always survive translation into human clinical data, and Daiichi Sankyo’s deruxtecan franchise has the benefit of years of real-world efficacy evidence that no preclinical pharmacology comparison can substitute for. The evaluation framework is shifting, but clinical proof remains the final arbiter.

What execution and translation risks define the TSI battleground for clinical-stage ADC challengers?

The principal translation risk is the gap between preclinical pharmacology in xenograft models and clinical pharmacology in human patients. Tumor selectivity indices generated in mouse models, even patient-derived xenograft models, do not always survive translation into the heterogeneous biology of human cancers. Patient tumor microenvironments vary significantly in fibroblast activation protein expression, stromal density, vascular access, and protease activity, all of which influence how a tumor-activated platform performs in practice. Avacta has indicated that AVA6103 is expected to enter Phase 1 clinical trials, and the clinical TSI data, when it emerges, will be the first real test of whether the preclinical advantage holds in human disease.

The second consideration is competitive intensity within the conditionally-activated delivery field itself. Bicycle Therapeutics has clinical-stage data showing tumor-versus-plasma payload ratios in patients, which is ahead of where Avacta currently sits on the clinical translation curve. Probody and masked-antibody platforms are advancing through earlier clinical phases at multiple developers. The TSI metric, having become the language of the competition, also raises the bar for what counts as a defensible advantage. A three-fold preclinical TSI claim is meaningful, but the commercial value depends on whether it survives clinical validation and whether peer platforms can match or exceed it. Capital is the third constraint. Clinical-stage biotechs developing platform technologies typically require sustained financing through to either a pivotal partnership or a clinical readout that supports licensing, and Avacta’s negative price-to-earnings ratio reflects its pre-revenue clinical-stage status. The investment case rests on the optionality embedded in the preCISION platform rather than near-term cash generation.

Key takeaways on what the rise of tumor selectivity benchmarking means for Avacta Group AVCT, its peers, and the antibody-drug conjugate industry

• Avacta Group AVCT has anchored its preCISION platform pitch on a roughly three-fold TSI advantage versus Enhertu and Datroway, the two reference-standard deruxtecan ADCs in the global oncology franchise driven by Daiichi Sankyo and AstraZeneca.
• The TSI framing represents a migration of the ADC evaluation framework away from antibody specificity and linker chemistry toward the quantitative pharmacology of payload delivery, with implications for how platforms are diligenced in licensing transactions.
• Bicycle Therapeutics is the closest comparator pursuing a similar tumor-versus-plasma exposure argument, with clinical data on its EphA2 and Nectin-4 programmes showing tumor payload concentrations approximately 10-fold higher than corresponding plasma levels in patients.
• Daiichi Sankyo’s projected $4.6 billion fiscal 2026 Enhertu sales and 700,000 eligible patient ambition for fiscal 2030 are not directly threatened by preclinical TSI claims, but the framing creates a long-dated strategic challenge that will compound if clinical translation supports the preclinical signal.
• The interstitial lung disease safety signal that has constrained Enhertu’s expansion into earlier lines of therapy is, in pharmacology terms, a manifestation of off-tumor payload exposure, which is the precise window that high-TSI platforms claim to narrow.
• The dealmaking shift from outright acquisitions like Pfizer’s $43 billion Seagen deal toward milestone-heavy licensing structures like the Merck and Daiichi Sankyo $22 billion collaboration aligns with a TSI-led evaluation framework that prices platform optionality across multiple payloads and indications.
• Avacta Group AVCT shares trading at 77.14p, near the upper band of a 26.00p to 84.00p 52-week range and a market capitalisation around £349 million, reflect a 2026 recovery that prices the optionality of TSI validation rather than near-term clinical cash flows.
• Translation risk remains the central execution challenge, because preclinical TSI advantages do not always survive into human clinical data, and Daiichi Sankyo’s deruxtecan franchise retains the benefit of established real-world efficacy that no pharmacology benchmark can substitute for.
• The competitive intensity within the conditionally-activated delivery field, including Bicycle Therapeutics, probody designs, and masked-antibody platforms, means the TSI bar is rising as the metric matures, and the platforms that produce defensible clinical TSI data first will capture the strongest licensing positions.
• Tumor selectivity index, defined as the AUC ratio of payload exposure in tumor versus plasma, is emerging as the central pharmacology metric on which next-generation ADC and tumor-activated delivery platforms are now competing for licensing leverage.