Clinical Trial Update

Coiled Therapeutics PLC

08 April 2026

 

8 April 2026

Coiled Therapeutics plc

("Coiled Therapeutics" or the "Company")

Clinical Trial Update

Enhanced Efficacy Signal and Strategic Transition to Dose Expansion

Coiled Therapeutics plc (AIM: COIL), the clinical-stage oncology company developing precision medicines for hard-to-treat cancers, provides an update on its clinical trial (NCT06136884) evaluating AO-252, a first-in-class TACC3 inhibitor.  

Key Highlights

·      Superior Efficacy in BID Cohort: 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.

·      Durable Clinical Responses: 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.

·      Benign Safety Profile Maintained: 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.

·      Transition to dose expansion: 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 Q3 2026.

·      Highly differential Immune-Modulatory Potential: Emerging data confirms AO-252's unique dual-action profile, combining direct cytotoxicity with immune-system activation via the cGAS/STING pathway.

·      Operational Milestones: On track to complete dose escalation in H1 2026, with a next-generation formulation to optimise dosing/efficacy and combination therapy protocols scheduled for mid-2026.

Sridhar Vempati, Chief Executive Officer of Coiled Therapeutics, commented:

"Following our recent successful admission to AIM, we are pleased to share a meaningful clinical trial update that demonstrates real and tangible clinical progress with AO-252. The data from Cohort 4b is transformative, achieving an 80% Clinical Benefit Rate and durable responses in such a heavily pre-treated patient population validates our BID dosing strategy and underscores the potential of TACC3 as a high value target in oncology.

Furthermore, the emerging evidence of AO-252's immune-modulatory activity positions it as a rare small molecule capable of engaging both direct tumour killing and immune activation. This would place AO-252 among a rare class of small molecules capable of engaging both direct cytotoxic and immune-activating mechanisms, considerably expanding its potential therapeutic applications and combination strategies.

With dose escalation on track for completion in H1 2026 and multiple data readouts expected across the year, we believe 2026 will be a transformational year for Coiled Therapeutics with key data catalysts that will drive value. We look forward to updating shareholders as these milestones are achieved."

Phase I Clinical Trial Update

Enrolment and dose escalation

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. As previously guided, dose escalation remains on track for completion in H1 2026.

Efficacy: step-change with BID dosing

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).

Immune-modulatory activity

An important and differentiated scientific observation has emerged from both preclinical and emerging clinical data: 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.

Pharmacokinetics and formulation development

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 Q2 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.

Combination therapy development

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 Q3 2026, with a view to exploring AO-252's potential in multi-agent oncology regimens.

Outlook & Key Milestones

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 Q3 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:

·     H1 2026: Completion of Phase I dose escalation; preliminary proof-of-concept safety and efficacy data from dose escalation phase.

·     Late Q2 2026: Food-effect sub-arm data from Cohort 4b pharmacokinetic study.

·     Mid-2026: Introduction of refined next-generation formulation of AO-252.

·     Q3 2026: Initiation of combination therapy protocol study; 40-patient enrolment target reached.

·     H2 2026: Comprehensive expansion cohort efficacy and safety data readouts in ovarian and prostate cancer; potential Phase II registrational trial planning and commercial discussions.

Enquiries:

Coiled Therapeutics plc Sotirios Stergiopoulos (Chairman) Sridhar Vempati (CEO)	Via Burson Buchanan
SP Angel Corporate Finance LLP (Nominated Adviser and Joint Broker) David Hignell / Adam Cowl / Devik Mehta (Corporate Finance) Vadim Alexandre / Rob Rees (Corporate Broking)	[phone]
Shard Capital Partners LLP (Joint Broker) Damon Heath CPS Capital Group Pty Ltd (Joint Broker) Jason Peterson / David Valentino	[phone] [phone]
Burson Buchanan (Public Relations) Henry Harrison Topham / Jamie Hooper / Toto Berger	[phone]

About Coiled Therapeutics plc

Coiled Therapeutics (AIM: COIL) is an AIM-listed, clinical-stage biotechnology company focused on developing innovative precision oncology therapies. Its lead programme, AO-252, is a novel TACC3 inhibitor currently in Phase I clinical trials in the USA (trials ID: NCT06136884).  Coiled Therapeutics is actively enrolling patients to test for safety and efficacy in patients whose cancer has progressed on other treatments.   The Company is also assessing its STAT-6 siRNA programme for immunology indications. Coiled Therapeutics is supported by a leadership team with a proven track record in drug development and strategic backing from A2A Pharmaceuticals.

About AO-252

AO-252 is a first-in-class, orally administered, brain-penetrant small molecule inhibitor of Transforming Acidic Coiled-Coil containing protein 3 (TACC3). TACC3 is a validated oncology target that is frequently overexpressed in many aggressive, hard-to-treat solid tumours but is dispensable in normal adult cells, providing a wide therapeutic window.

By selectively disrupting cancer-critical protein-protein interactions at the TACC3 C-terminal domain, AO-252 induces mitotic and replication stress, impairs DNA damage repair, and triggers cancer cell death. Notably, AO-252 has demonstrated the ability to cross the blood-brain barrier, addressing a significant unmet medical need for the treatment of brain metastases.

The asset is currently in an ongoing Phase I open-label dose-escalation study and early clinical signals have shown encouraging anti-tumour activity and a benign safety profile, with the Company planning to initiate dose expansion cohorts in lead indications, including prostate and ovarian cancer, during 2026.

For more information, please visit: www.coiledplc.com

 

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