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CA242-directed ADC approved for assessment in Phase 1 trials in patients with GI cancers The ‘IKS04 Regimen’ is an innovative dosing approach for an ADC which is employed to overcome the challenge of solid tumour penetration for high-potency payloads NEWCASTLE, England--(BUSINESS WIRE)--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. ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); 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 favourable therapeutic index - the widest preclinical therapeutic index of any PBD-containing ADC for solid tumours. 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 tumour-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. Dr. Dave Simpson, Chief Executive Officer, Iksuda Therapeutics, commented: “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.” Leon Pappas (Massachusetts General Hospital), Investigator, added: "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." 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. Contacts Iksuda Therapeutics Dave Simpson, Chief Executive Officer Tel: +44 (0) 191 6031680 info@iksuda.com FTI Consulting (Financial Media and IR) Simon Conway / Rob Winder / Amy Byrne Tel: +44 (0) 020 3727 1000 Iksuda@fticonsulting.com

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.