On April 24, 2025 Iksuda Therapeutics (Iksuda), the developer of class leading, clinically validated antibody drug conjugates (ADCs) reported that it will present three posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, Illinois (25-30 April) (Press release, Iksuda Therapeutics, APR 24, 2025, View Source [SID1234652126]). The posters cover the Company’s new payload class, the ProAlk series, its CA242-directed ADC, IKS04, being developed for the treatment of gastrointestinal (GI) cancers, and its proprietary PermaLink conjugation chemistry.
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Iksuda will introduce its new ProAlk payload class which has a novel protein alkylating mechanism and is incorporated in ADCs in a prodrug format for enhanced targeting precision. ProAlk is active across a broad range of tumours and has been designed for optimal ADC relevance. It is associated with potent bystander activity and is MDR-resistant. Its novel mechanism will help to address the growing and significant challenge of ADC sequencing, where differentiation from tubulin and topoisomerase I inhibitor payloads will become imperative. Iksuda is building a pipeline of ProAlk driven ADCs which incorporate its proprietary PermaLink conjugation chemistry for ADC stability and tumour-selective payload activation and release for enhanced precision and safety.
The Company will also present a poster on IKS04, its CA242-directed ADC for the treatment of GI cancers and which is in IND-enabling studies. IKS04 uses a pro-drug approach for the tumour-specific delivery of a highly potent pyrrolobenzodiazepine (PBD) payload, avoiding the typical toxicity profile seen in traditional PBD ADCs. In preclinical trials, IKS04 is associated with in vivo efficacy which is substantially improved over benchmark ADCs in all tumour models, and a superior therapeutic index over all other PBD-based solid tumour ADC programs. IKS04 will be administered via pre-administration of naked antibody – a novel dosing regimen in the ADC field – to overcome high expression abundance and enable higher tumour penetration and consistent levels of efficacy across tumours. IKS04 is expected to enter clinical development in GI cancers by the end of 2025.
In addition, Iksuda will highlight its proprietary PermaLink conjugation chemistry, which is used across its early-stage ADC platform alongside the Company’s glucuronide linker formats and novel ProAlk payload. PermaLink offers a simple, scalable and highly stable bioconjugation method as an alternative to maleimide-based conjugation, enabling highly stable ADCs with favourable anti-tumour activity and safety.
Dr Dave Simpson, Chief Executive Officer, Iksuda Therapeutics, said:
"These three poster presentations at AACR (Free AACR Whitepaper) demonstrate Iksuda’s leadership in ADC innovation as we unveil our novel ProAlk payload class, overcoming the challenges in ADC sequencing and which will drive Iksuda’s deepening pipeline. With two clinical-stage programs, a growing pipeline of class leading ADCs and our expanding, innovative platforms, we are strongly positioned to progress new and promising ADCs to deliver improved outcomes for patients living with cancer. We look forward to progressing IKS04 into clinical development for GI cancers later this year, an area of high unmet need with limited effective treatment options and poor five-year survival rates for the significant number of patients with advanced disease."
Poster Presentation details:
ProAlk
Abstract Title:
PA289, a prodrug linker-payload with a novel mechanism of action for the development of antibody drug conjugates
Session Title:
Antibody-Based Cancer Therapeutics 1
Date/Time:
April 28, 2025 9:00 AM – 12:00 PM
Location:
Poster Section 15
Poster Number:
1579/28
IKS04
Abstract Title:
IKS04, an antibody drug conjugate with a highly potent DNA crosslinker payload for the treatment of gastrointestinal cancers
Session Title:
Antibody-Based Cancer Therapeutics 2
Date/Time:
April 28, 2025 2:00 PM – 5:00 PM
Location:
Poster Section 15
Poster Number:
2885/24
PermaLink
Abstract Title:
PermaLink, a stable and scalable bioconjugation platform as an alternative to maleimide-based conjugation
Session Title:
Antibody-Based Cancer Therapeutics 1
Date/Time:
April 28, 2025 9:00 AM – 12:00 PM
Location:
Poster Section 15
Poster Number:
1570/19