\nCA242-directed ADC approved for assessment in Phase 1 trials in patients with GI cancers<\/i><\/p>
\nThe \u2018IKS04 Regimen\u2019 is an innovative dosing approach for an ADC which is employed to overcome the challenge of solid tumour penetration for high-potency payloads<\/i><\/p>
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.<\/p>
\nCA242 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.<\/p>
\nPrevious 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.<\/p>
\nIKS04 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.<\/p>
\nThus, 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.<\/p>
\nPreclinical 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.<\/p>
\nThe concept behind IKS04, including its clinical dosing regimen, is consistent with Iksuda\u2019s 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\u2019s 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\u2019s in-clinic ADC programs IKS014, (a HER2-directed ADC containing MMAF), and IKS03, Iksuda\u2019s CD19-directed ADC which also contains the PBD prodrug used in IKS04, and is currently in phase 1 clinical development for B-cell malignancies.<\/p>
\nDr. Dave Simpson, Chief Executive Officer, Iksuda Therapeutics, commented:\n
\nLeon Pappas (Massachusetts General Hospital), Investigator, added:\n
\nAbout IKS04<\/b><\/p>
\nIKS04 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\u2019s 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\u2019s third ADC program to enter the clinic.<\/p>
\nAbout Iksuda Therapeutics<\/b>: www.iksuda.com<\/a><\/p> \nIksuda 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\u2019s 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\u00ae<\/sup> platform. The early pipeline incorporates Iksuda\u2019s proprietary, first-in-class protein alkylating payload class, \u2018ProAlk\u2122. The Company\u2019s 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.<\/p> \nIksuda Therapeutics<\/b>