New targets and DNA modifying payload addition set to enhance ADC work at Iksuda
In April 2020, the UK biotechnology company licensed global development and commercialization rights for three ADC programs using LCB's ADC linker/toxin platform. Under this expanded deal, it has been granted rights for three additional targets, bringing its total number of potential ADC programs using LCB’s technologies to six.
Iksuda is also gaining access to that South Korean company’s “innovative” and recently discovered novel DNA-modifying payload, supplementing LCB’s proprietary tumor-activated DNA toxins that were included in last year’s deal.
When asked what difference those three additional targets will make to Iksuda’s pipeline, company CEO, Dave Simpson told BioPharma-Reporter: “Iksuda has been building an extensive, early stage antibody portfolio to further accelerate towards pre-clinical/clinical development which is now fully supported by the company’s current investment. Having access to an additional payload and the ability to nominate more targets (under the same terms) allows us to build further value using a payload mode of action that is well understood in a clinical setting.”
And in what way will this additional DNA-modifying payload innovative benefit Iksuda’s work?
“The mode of action for this payload is based on DNA alkylation rather than the DNA-crosslinking variant that are current used in the clinic and in our own IKS03 program.
“Historically DNA-crosslinkers have presented issues with long term toxicity and whilst the LCB prodrug platform has removed this as a potential risk, the ability to leverage an alternative, DNA activating mode of action which remains active in our target indications and removes this risk is a significant advantage in our development plans,” added Simpson.
Iksuda is focused on the development of ADCs targeting difficult-to-treat hematological and solid tumors; its pipeline of ADCs is centered on a portfolio of non-prodrug/prodrug DNA and protein alkylating payloads in combination with stable conjugation chemistries.
Its IKS03 is a CD19-targeted ADC candidate for B-cell cancers. It delivers a tumor-activated prodrug pyrrolobenzodiazepine (PBD) that was licensed from LCB. Preclinical testing on IKS03 demonstrated best-in-class efficacy (vs in-clinic and marketed CD19-targeted therapies) in in vivo xenograft models and significantly raised maximum tolerated dose (MTD) in non-human primate disease models, said the developer.
IND is planned for Q4 2021, with initial phase 1 patient data anticipated in Q3 2022.
The company recently completed a US$47m financing round, co-led by Celltrion, Mirae Asset Capital and its subsidiaries, along with Premier Partners to support the advancement of its lead ADC assets, including IKS03, and the expansion of its payload platform technologies.