Iksuda Therapeutics, a developer of next-generation Antibody-Drug Conjugates (ADCs), has received clearance from the US Food and Drug Administration (FDA) for its Investigational New Drug (IND) application for IKS04, enabling the company to initiate a Phase 1 clinical trial in patients with gastrointestinal (GI) cancers.

The study will evaluate IKS04, a novel CA242-directed ADC, using an innovative dosing strategy known as the IKS04 Regimen, which combines the ADC with an unconjugated anti-CA242 antibody. This first-of-its-kind approach in the ADC field is designed to improve drug penetration into solid tumours while maintaining an acceptable safety profile.

CA242 is a tumour-specific glycotope that is highly expressed across a range of gastrointestinal malignancies, including most colorectal, gastric, pancreatic and biliary tract cancers, as well as a significant proportion of bladder, endometrial and lung cancers. Its limited presence in normal tissues makes it an attractive therapeutic target.

Despite advances in ADC development, gastrointestinal cancers have remained challenging to treat. Previous CA242-targeting ADCs employing tubulin inhibitor payloads have demonstrated limited efficacy, while ADCs using topoisomerase I inhibitors have also shown modest clinical success. These limitations underscore the need for more potent ADCs with differentiated mechanisms of action capable of overcoming tumour resistance.

IKS04 addresses this challenge by combining a humanised anti-CA242 antibody with a highly potent pyrrolobenzodiazepine (PBD) prodrug payload. To enhance tumour penetration and reduce the antigen barrier commonly associated with high-expression targets, the therapy will be administered alongside an unconjugated antibody, a strategy similar to dosing approaches already used in radioimmunotherapy.

Preclinical studies have demonstrated strong anti-tumour activity across multiple gastrointestinal cancer models while achieving one of the broadest therapeutic indices reported for PBD-based ADCs targeting solid tumours. The co-administration strategy further improved anti-cancer activity in high CA242-expressing models, supporting its advancement into clinical evaluation.

IKS04 also incorporates Iksuda's proprietary glucuronide-triggered prodrug technology, which enables tumour-selective payload activation to improve tolerability compared with conventional ADC linkers. The platform has already been clinically validated through the company's other investigational ADC programmes, IKS014, a HER2-directed ADC, and IKS03, a CD19-directed ADC currently undergoing Phase 1 evaluation for B-cell malignancies.

Commenting on the milestone, Dr Dave Simpson, Chief Executive Officer of Iksuda Therapeutics, said the IND clearance represents another significant step in validating the company's approach to designing ADCs tailored to specific targets and indications.

The Phase 1 study marks Iksuda's third ADC programme to enter clinical development, reinforcing the company's commitment to expanding innovative treatment options for patients with advanced gastrointestinal cancers, where effective therapies remain limited.