Announcement • Apr 10
Coiled Therapeutics plc Provides Clinical Trial Update on AO-252 Coiled Therapeutics plc provided an update on its clinical trial (NCT06136884) evaluating AO-252, a first-in-class TACC3 inhibitor. The transition to a Twice-Daily ("BID") dosing regimen (Cohort 4b) has delivered an 80% Clinical Benefit Rate ("CBR"), a significant improvement over the 40% CBR observed in the Once-Daily ("QD") cohort. A particularly notable result has been observed in a leiomyosarcoma patient, who achieved Stable Disease after just two cycles of AO-252, despite having received nine prior lines of therapy. 80% of evaluable patients in the BID cohort achieved tumour stabilisation or regression, with treatment durations exceeding six months. This substantially outperforms the two to three month benchmark typically seen with salvage therapy in this heavily pre-treated population. AO-252 continues to demonstrate excellent tolerability with no serious adverse events observed to date. The Maximum Tolerated Dose ("MTD") has not yet been reached, allowing for continued dose escalation to optimise therapeutic impact. Following encouraging signals, the Company is accelerating the transition to targeted dose expansion cohorts in ovarian and prostate cancers, with an enrolment target of 40 patients by Third Quarter 2026. Emerging data confirms AO-252's unique dual-action profile, combining direct cytotoxicity with immune-system activation via the cGAS/STING pathway. On track to complete dose escalation in First Half 2026, with a next-generation formulation to optimise dosing/efficacy and combination therapy protocols scheduled for mid-2026. The ongoing Phase I/II open-label dose escalation study of AO-252 in patients with advanced solid tumours has enrolled 31 patients to date, of whom 25 are evaluable for safety and dose-limiting toxicity ("DLT") assessment and 21 are evaluable for efficacy. Dose escalation remains on track for completion in First Half 2026. The transition to a BID dosing regimen in Cohort 4b has produced a clinically meaningful step-change in disease control. An 80% CBR has been observed in Cohort 4b, compared to 40% in the QD Cohort 4a, reflecting the importance of sustained drug exposure at therapeutic levels. Four out of five evaluable patients in Cohort 4b demonstrated tumour stabilisation or regression. Notably, treatment duration in this cohort has exceeded six months, substantially longer than the two to three months typically achieved with salvage therapy in these heavily pretreated populations (median of five prior lines of therapy). AO-252 appears to possess meaningful immune-modulatory activity, consistent with its known ability to stimulate the cGAS/STING pathway and activate dendritic cells and M1 macrophages. This positions AO-252 as a potentially rare small molecule capable of directly activating the immune system in addition to its direct anti-tumour cytotoxic effects. The Company believes this immune-modulatory property could significantly enhance AO-252's utility in combination regimens, including with immuno-oncology agents, and broadens its differentiated therapeutic profile and commercial appeal. Analysis of clinical pharmacokinetic data has identified distinct drug exposure variances between male and female patients. This finding is being incorporated into refined dose modelling to ensure optimal efficacy and safety parameters as the programme advances. A dedicated sub-arm of Cohort 4b is currently evaluating the impact of food on AO-252 absorption, with efficacy and pharmacokinetic data expected in late Second Quarter 2026. In parallel, a next-generation formulation of AO-252 is on track for introduction in mid-2026. The refined formulation is designed to further improve drug exposure to attain maximal efficacy and duration of therapy. Leveraging AO-252's immune-modulatory backbone and its demonstrated synergy with immuno-oncology and antibody-drug conjugate agents in preclinical studies, the Company is actively developing a combination therapy protocol. Study initiation is targeted for Third Quarter 2026, with a view to exploring AO-252's potential in multi-agent oncology regimens. The Company is preparing to transition from the current broad dose escalation strategy to targeted dose expansion cohorts focused primarily on ovarian and prostate cancer indications where early clinical signals have been particularly encouraging and where commercial interest from large pharmaceutical companies is strong. The Company is targeting enrolment of 40 patients by Third Quarter 2026. Strategic engagement with Key Opinion Leaders (KOLs) continues to refine the clinical development strategy, ensuring that study design and patient selection remain aligned with the emerging scientific understanding of AO-252's unique mechanism of action. Key milestones for 2026 are summarised below: First Half 2026: Completion of Phase I dose escalation; preliminary proof-of-concept safety and efficacy data from dose escalation phase. Late Second Quarter 2026: Food-effect sub-arm data from Cohort 4b pharmacokinetic study. Mid-2026: Introduction of refined next-generation formulation of AO-252. Third Quarter 2026: Initiation of combination therapy protocol study; 40-patient enrolment target reached. Second Half 2026: Comprehensive expansion cohort efficacy and safety data readouts in ovarian and prostate cancer; potential Phase II registrational trial planning and commercial discussions. 
