Cytospire Therapeutics has raised an oversubscribed £61 million ($83 million) series A round, as investors place early bets on its ambition to rewire T-cell engagement for solid tumours through a pan-gamma delta approach.The London-based biotech said proceeds will help take its lead programme, CYT X300, through IND-enabling work and into the clinic, with a first-in-human study planned in 2027. The funding is expected to carry the asset to clinical proof-of-concept.The round was led by 4BIO Capital and includes new backers such as Servier Ventures — the firm's first investment since launching earlier this year — alongside Sound Bioventures, the British Business Bank and Criteria Bio Ventures. Existing investors Abingworth and LifeArc Ventures also participated; the latter had backed Cytospire as early as 2023 alongside Abingworth and 4BIO, before the company formally launched in 2024.Cytospire is betting that its approach to immune cell engagers can overcome some of the hurdles of traditional T-cell engager therapies, particularly in solid tumours.Engager class constraints"Immune cell engagers are an important type of cancer immunotherapy, but we know that there are significant limitations from both an efficacy and safety perspective with conventional CD3 T-cell engagers," said CEO Natalie Mount.Over the past decade, CD3 T-cell engagers have been approved for blood cancers and some rarer tumour types such as small-cell lung cancer and uveal melanoma, but their use against solid tumours remains limited. Core challenges are a lack of tumour-specific targets as well as side effects, including healthy tissue damage and dose-limiting cytokine release syndrome (CRS) that has halted development of several CD3 engager candidates."We are building on the growing body of translational and clinical data showing gamma delta T cells are critical components of the anti-cancer immune response, with biology ideally suited to novel cell engagers," Mount said.'Full horsepower' of mechanismMount told FirstWord that the biotech's approach engages all gamma delta T-cell subsets — Vδ1, Vδ2 and Vδ3 — tapping into a larger pool of effector cells than subset-specific engagers. Its engagers also have the ability to proliferate, further boosting effector cell populations. Moreover, by activating both blood resident (Vδ2) and tissue-resident (Vδ1 and Vδ3) populations, the strategy is designed to "maximise the full horsepower" of the gamma delta T-cell mechanism.The approach is also intended to address patient-to-patient variability in the composition of gamma delta T-cells in their tumours, something subset-specific approaches are limited by.Meanwhile, the company contends that broader engagement doesn't necessarily come at the expense of safety. "All subsets of gamma delta T-cells have the ability to discriminate between tumour and healthy cells, and their natural biology is expected to yield a low propensity for on-target, off-tumour toxicity and CRS," Mount said. "In addition…our data, including initial [non-human primate] data, indicates we should have a favourable tolerability profile."Cytospire's planned study will test CYT X300 in EGFR-positive solid tumours, such as colorectal, head and neck, and non–small-cell lung.
