Excellent therapeutic profile with manageable and differentiated safety profile and promising anti-tumour activity in patients with a range of advanced HER-2-expressing solid tumours

Positive activity in a subset of HER2+ breast cancer patients previously treated with Enhertu (T-DXd)

Iksuda Therapeutics (Iksuda), the developer of class leading, antibody drug conjugates (ADCs), today announces the presentation of preliminary data from its Phase 1 study for its HER2-directed ADC, IKS014, which is being assessed in patients with advanced or metastatic HER2+, HER2-low and HER2-mutated solid tumours, at the San Antonio Breast Cancer Symposium (SABCS), December 8-11, 2026, San Antonio, Texas.

Additionally, the presentation includes a pooled analysis from dose escalation- and dose-expansion phases of the trial for a sub-set of HER2+ breast cancer patients who have previously received trastuzumab-deruxtecan (Enhertu/ ‘T-DXd’). This is an important patient population given the clinical challenges of ADC sequencing, and with T-DXd now approved as a front-line treatment in these patients.

As of April 2026, 105 patients with a variety of tumours were enrolled across Part I dose escalation and Part II dose expansion cohorts. Overall, 71 patients were enrolled in Part 1 dose escalation (DE) /enrichment cohorts and treated at doses from 40 – 120 mg/m²once every three weeks. A maximum tolerated dose (MTD) was not identified but a dose of 105 mg/m² was selected for further evaluation in expansion cohorts based on its promising efficacy across tumour types and a good, differentiated safety profile. 34 patients have been enrolled into Part II to date across 5 expansion cohorts (ECs), one of which (IIA) includes patients with HER2+ BC previously treated with T-DXd.

In the 105 patients, IKS014 has been shown to be well tolerated with a differentiated and manageable safety profile. Only 16 patients (15.2%) experienced Grade 3 treatment-related adverse events (TRAEs), of which seven patients (6.7%) experienced hypokalaemia as the most common event. Compared with other HER2-directed ADCs, there was a notable absence in the frequency of high-grade, pneumonitis/ILD, neutropenia, anaemia, fatigue, AST elevation and GI toxicities. The most common TRAEs were low-grade (G1 or G2) hypokalaemia (36%), dry eye (34%), keratitis (34%) and dry mouth (28%). No Grade 5 events or treatment-related serious adverse events were noted.

Pooled efficacy analysis consisted of 10 response-evaluable patients with advanced or metastatic HER2+ breast cancer previously treated with T-DXd, including four patients treated at ≥90 mg/m² in DE cohorts and six patients treated in the EC. Patients were heavily pre-treated, with a median number of regimens of 6 and a range of 2-12. The objective response rate was 50% (n=5/10), which consisted of confirmed and unconfirmed partial responses. Of particular note, PRs were observed in patients who had a best response of PD to prior T-DXd, and sustained responses were also observed, including in one patient with a response of over 18 months. Alongside the good safety profile, these efficacy results are highly encouraging.

As an evolving dataset, the final SABCS presentation will contain updated data.

The IIA EC will recruit 25 patients in total. Expansion Cohort IIA will continue to recruit patients with HER2+ BC previously treated with T-DXd, whilst patients with advanced or metastatic HER2-low BC, HER2+ gastric/ GEJ and oesophageal cancers, and HER2-mutated lung cancer will continue to be recruited to the additional expansion cohorts.

Dr. Dave Simpson, Chief Executive Officer, Iksuda Therapeutics, commented: “The data from our Phase 1 study of IKS014 is extremely exciting, with promising antitumor activity seen in patients with advanced HER2+ solid tumours across multiple histologies, alongside a differentiated and manageable safety profile. We are strongly encouraged by the efficacy in patients who have previously received T-DXd, a patient population with high unmet need, and we look forward to continuing with dose expansion and the enrolment of these patients.”

Dr. James O’Leary, Chief Medical Officer at Iksuda Therapeutics, added: “These data demonstrate the potential of IKS014 to address the high unmet need across various HER2-positive cancers, including for patients who have not responded to previous lines of treatment.”

The Phase 1 study (NCT05872295) is an open-label, multicentre trial of IKS014 in patients with HER2-expressing advanced solid tumours refractory to or progressing after standard therapies. Part I (Dose Escalation) will establish a recommended Expansion Dose and Part 2 (Dose Expansion) will further evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of IKS014 in five cohorts, including one for patients with HER2+ breast cancer who have previously been treated with T-DXd. IKS014 has been evaluated by a separate sponsor in trials conducted exclusively in China, including an ongoing Phase 3 trial in breast cancer.

Presentation details
Abstract number: 602
Presentation Number: PS3-1
Title: A Phase 1 study of IKS014 (caxmotabart entudotin) in patients with HER2+ solid tumours, and preliminary activity in breast cancer patients previously treated with trastuzumab deruxtecan
Presentation Date/Time: Wednesday, December 9, 2026, 7:00 AM - 8:30 AM CST
Location: 301 ABC

About IKS014

IKS014 is a potential best-in-class antibody drug conjugate, benefiting from tumour selective activation and release of the cytotoxic agent monomethyl auristatin F (MMAF). In preclinical trials, it displayed impressive activity in high- and low-HER2 expressing tumours with a favourable Therapeutic Index compared with other HER2-directed drugs. Iksuda gained exclusive world-wide rights (excluding Greater China and South Korea) to IKS014 from LigaChem Biosciences (https://iksuda.com/2022/01/iksuda-deepens-clinical-pipeline/).

About Iksuda Therapeutics: www.iksuda.com

Iksuda Therapeutics is a clinical stage, UK-based biotechnology company focussed on the development of class leading ADCs targeting difficult-to-treat haematological and solid tumours. Iksuda’s pipeline of ADCs is centred on a portfolio of prodrug ADCs which utilise tumour-selective release and activation of payloads, incorporating proprietary and in-licensed (from LigaChem Biosciences) prodrug and linker technologies in combination with stable conjugation chemistries including its proprietary PermaLink^®platform. The early pipeline incorporates Iksuda’s proprietary, first-in-class protein alkylating payload class, ProAlk™. The Company’s design concepts for ADCs are now clinically validated to significantly improve the therapeutic index of this important modality and improve the outcomes for patients living with cancer.

View source version on businesswire.com: https://www.businesswire.com/news/home/20261101790886/en/

For further information please contact:

Iksuda Therapeutics
Dave Simpson, Chief Executive Officer
Tel: +44 (0) 191 6031680
info@iksuda.com

FTI Consulting (Financial Media and IR)
Simon Conway / Natalie Garland-Collins / Amy Byrne
Tel: +44 (0) 020 3727 1000
Iksuda@fticonsulting.com

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