Iksuda receives US FDA IND clearance for IKS04

Newcastle, UK, 30 July 2026: Iksuda Therapeutics (Iksuda), the developer of class leading, antibody drug conjugates (ADCs), today announces that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for IKS04, a CA242-directed ADC, enabling assessment in a Phase 1 trial in patients with gastrointestinal (GI) cancers.

 

CA242 is a tumour-specific glycotope which is strongly expressed in a variety of GI cancers including the majority of colorectal (CRC), gastric, pancreatic and biliary tract cancers, and around half of bladder, endometrial and lung cancers, with limited expression in normal tissue.

Previous efforts to target CA242 with ADCs carrying tubulin inhibitor payloads have shown limited clinical efficacy, likely due to inherent resistance of GI cancers to this payload mechanism. In addition, there has been limited success to date with ADCs for the treatment of GI cancers such as those of the colon and stomach with topoisomerase I inhibitors, regardless of the target. There is a need for potent ADCs with differentiated cell-killing mechanisms and directed towards novel targets to enable higher efficacy and to overcome resistance.

IKS04 is a novel CA242-targeting ADC comprising an anti-CA242 humanized antibody and a highly potent pyrrolobenzodiazepine (PBD) prodrug payload. Typically, the use of potent payloads such as PBDs can limit the maximum tolerated dose of ADCs due to systemic adverse events, which in turn limits tumour tissue penetration and efficacy, particularly for high-expression targets such as CA242. This can create an antigen barrier that prevents the drug from penetrating deep into the solid tumour. 

Thus, in a first for the ADC field, IKS04 will be co-administered with the unconjugated antibody to tackle the challenge of solid tumour penetration for high potency payloads. This innovative dosing approach is akin to a dosing regimen that is already used in radioimmunotherapy. 

 

Preclinical studies have demonstrated potent activity across a range of GI cancers alongside a favorable therapeutic index - the widest preclinical therapeutic index of any PBD-containing ADC for solid tumors. Anti-cancer activity was further enhanced in high-expressing models by co-administration of IKS04 with the anti-CA242 antibody, validating the IKS04 Regimen. 

The concept behind IKS04, including its clinical dosing regimen, is consistent with Iksuda’s general ADC-design approach: selecting the most clinically relevant combination of antibody, conjugation chemistry, linker and payload mechanism to deliver optimal therapeutic index for target and indication. IKS04, like all Iksuda’s ADC programs, incorporates pro-drug technology with tumor-selective activation and release of payload through glucuronide triggers.

This design concept, which drives improved tolerability over traditional linkers, has now been clinically validated in Iksuda’s in-clinic ADC programs IKS014, (a HER2-directed ADC containing MMAF), and IKS03, Iksuda’s CD19-directed ADC which also contains the PBD prodrug used in IKS04, and is currently in phase 1 clinical development for B-cell malignancies.

This IND clearance for IKS04 and the IKS04 Regimen, is another important step for Iksuda and further validation of our approach to designing and developing innovative ADCs with the optimal clinical calibration for a given target and indication. IKS04 will be Iksuda’s third ADC to enter clinical development, a significant milestone for the company, with IKS014 and IKS03 both currently progressing through Phase 1 studies. This demonstrates the value of our expanding, innovative platforms, and further de-risks the clinical advancement of our novel antibodies, linkers and payloads. We look forward to progressing IKS04 into Phase 1 studies for GI cancers, an area of high unmet need with limited effective treatment options

David Simpson CEO

IKS04 is directed at a novel target in difficult-to-treat GI cancers. The co-administration regimen and PBD payload are a distinctive approach, and the clinical program will investigate whether they can thereby deliver a better balance of efficacy and tolerability. I am excited to see if this approach helps patients as IKS04 progresses through clinical development

Dr. Leon Pappas Investigator, Massachusetts General Hospital

For further information please contact:

 

David Simpson

CEO Iksuda Therapeutics

 Tel; +44 (0) 191 6031680

FTI consulting (Financial Media and IR)

Simon Conway/ Rob Winder/ Amy Byrne

Tel; +44 (0) 020 3727 1000

[email protected]

 

About IKS04

IKS04 is a first-in-class CA242-targeting ADC comprising an anti-CA242 humanized antibody and a highly potent pyrrolobenzodiazepine (PBD) prodrug payload, incorporating LigaChem Bio’s ADC platform technology and which is associated with tumour-selective activation and release of payload and drives improved tolerability over traditional linker formats. IKS04 is IKSUDA’s third ADC program to enter the clinic. 

 

 

About Iksuda Therapeutics

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