Leading ADC innovation
01 ADC design principles
The modular nature of the ADC modality provides an unparalleled opportunity for continued technologic improvement for next generation ADCS.
Every ADC needs careful & individual design consideration to achieve its optimal profile. Iksuda incorporates stable bioconjugation alongside glucuronide-driven tumor-selective payload activation technologies to enable the design of powerful differentiated ADCs for class leading efficacy & tolerability. We match payload MOA with clinical indications, based on our payload expertise, which is built from a deep research base spanning all known mechanisms. Importantly, we fine tune all components as required to optimize intracellular payload delivery, anti-cancer effect & ADC safety.
Iksuda’s proprietary ProAlk payload class has been designed to achieve a highly ADC-relevant profile. Its novel MoA helps to address ADC sequencing and drug resistance issues, whist it also delivers a powerful bystander effect. It is active across a broad range of tumors.
Through our design principles and a large toolbox of ADC assets, our programs are designed to deliver the best ADC for any given target. All our ADCs incorporate tumor-selective payload activation for enhanced efficacy and safety. This principle is now clinically validated though our own IKS014 (HER2-directed ADC) program, which has been shown to deliver potent anti-cancer activity with a much differentiated and improved tolerability profile for its class.
IKS014 delivers MMAF for cell killing – this being an appropriate mechanism for targeted tumors, especially for breast cancer. The glucuronide linker and trigger used in IKS014 considerably reduces the frequency and severity of ocular toxicity, known for this payload class, whist delivering high potency. The choice of MMAF also overcomes HER2-directed-ADC sequencing challenges.
This clinical validation of glucuronide linker formats enables the incorporation of novel platforms and novel targets in Iksuda’s onward ADC design. We are now building a pipeline of ProAlk-ADCs, whilst continuing to explore several other novel payload mechanisms.
Iksuda has its own proprietary bioconjugation platform, PermaLink, which has been designed to deliver 100% stability and is suitable for wild-type and engineered binders. Iksuda uses PermaLink in all its early-stage, ProAlk-ADC programs. We also have access to LCB’s ConjuAll platform, which is used in IKS03, IKS04 and IKS014.
Iksuda’s development choices are based on robust differentiation criteria in early preclinical testing. Our ADCs must demonstrate clinically meaningful differentiation vs in-clinic or on-market comparators/standard of care in both efficacy and safety. Simply, they are designed to deliver market leading therapeutic index (TI), through improvements in efficacy AND toxicity threshold.
02 Differentiated technology model
Iksuda has built an extensive portfolio of ADC assets through in-house research and strategic collaborations to help direct our choices, including stable, scalable bioconjugation chemistries, advanced tumor-selective linkers and multiple, novel payload choices with different mechanisms.
Our ADC design capability therefore enables us to overcome therapeutic index limitations, bioconjugation stability issues, payload resistance challenges and preclinical calibration guesswork.
Our highly advanced tumor-selective cleavable linkers and triggers help to eliminate on-site toxicity and heightened efficacy.. A major area of innovation for Iksuda, we continue to build on past formats to drive increased utility and expanded application.
Our three later-stage programs, IKS014, IKS03 and IKS04, validate the design principles of glucuronide linker/ triggers, with associated delivery of the most relevant payload MOA for the targeted tumors. IKS03 and IKS04 deliver potent DNA cross-linkers for B-cell cancers and those of the GI tract respectively. Our ProAlk-ADCs incorporate PermaLink alongside Iksuda’s tailored glucuronide linker formats.
Iksuda continues to build an extensive payload portfolio, with research programs on CDK11 pro-apoptotic kinases for selected tumors, topoisomerase II inhibitors and DNA modifiers, including monoalkylators.
Iksuda has its own proprietary ultra-stable bioconjugation chemistry, PermaLink, for proven ADC stability, whist we also have access to LCBs ConjuAll platform where engineered binders and homogeneous DAR make sense. We are also developing PermaLink variants and approaches for higher drug loading where this is appropriate.
Iksuda’s binders are selected for optimal ADC characteristics and are generally sourced through research collaborations with leading research institutions.
Binders |
Fit for purpose, with optimal ADC characteristics Sourced through proprietary discovery, engineering enhancement or in-license |
Bioconjugation |
Stable conjugation for wild type or site-specific antibodies LCB's 'ConjuAll' used in Iksuda's clinical-stage programs and IKS04 Iksuda's proprietary PermaLink, used in all other in-house ADC programs |
Linkers |
Highly advanced tumor-selective cleavable linker formats A major area of innovation within Iksuda, building on past formats to drive increased utility and expanded application Initial focus is on glucuronide-based formats, with research into next-generation variants and 'beyond glucuronide' approaches The 'Glu-linker format' is now clinically validated through our IKS014 program |
Payloads |
Expanding portfolio of advanced novel ADC payloads *Iksuda has access to LCB's PBD prodrug tech ology for selected targets |
03 World class ADC R&D Team
Building a successful ADC pipeline requires experience-based integration of multiple components. ADC expertise, coupled with an ability to learn from past experiences, is required to understand the nuances of the modality for maximal probability of success.
Iksuda’s strategy has been to build an R&D team with a world-class level of expertise and experience to move differentiated programs forward with high likelihood of progression through clinic. We have assembled a team of top ADC innovators and drug developers to successfully execute our ADC programs.
Our CEO, Dave Simpson, co-founded Iksuda Therapeutics in 2012 and over25 years of experience in building companies, driving business development and manufacturing/ developing biologic therapies.
Our R&D activities are overseen by Bob Lutz who has more than 30 years of ADC experience, including his role as VP Translational R&D at Immunogen.
Iksuda’s commercial elements are led by Ian Evetts who has over25 years of experience in the industry, including management and oversight of drug development, sales & marketing, deal making, business development and investment strategy creation for major pharmaceutical and biotech companies.
Iksuda is guided by an impressive advisory team of industry experts, previously representing companies such as Immunogen, Seattle Genetics, Takeda, Immunomedics, Igenica and Alexion.
04 Expanding therapeutics pipeline
Iksuda is building a pipeline of next-generation, class leading ADCs for cancers of high unmet need.
Our later stage ADCs target antigens with clinical validation in ADC formats, enabling clinical validation of the glucuronide-driven tumor-selective payload activation and release approach which is fundamental to all our ADC programs. These programs also benefit from the calibration of therapeutic efficacy and therapeutic margin through analysis of prior clinical experience and incorporation of these learnings into IKSUDA’s next generation ADCs.
Our early-wave ADC programs build on this clinical validation to permit the incorporation of novel platforms and novel targets. All our early-wave programs contain our novel ProAlk payload. Since ProAlk has wide utility across a range of tumors, all potential targets are triaged for ProAlk sensitivity and pre-clinical toxicology before fine tuning ahead of lead candidate nomination.
Our pipeline includes:
IKS014, a-HER2-targeting ADC which is in clinical trials for HER2+ solid tumors
IKS03, a CD19-directed ADC, currently in Phase 1 trials for B cell cancers
IKS04, a CA242-directed ADC in IND-enabling studies for GI tumors
IKS073, a B7H3-directed ProAlk-driven ADC which is currently in IND enabling studies lung and ovarian cancers and TNBC
Iksuda is building an extensive early-stage pipeline of ProAlk ADCs for prioritized tumors including those of the lung, colon, esophagus, head & neck, ovarian and kidney, and multiple myeloma.
05 Partner of choice for ADC development programs
Iksuda welcomes collaborations with partners for the development of class-leading ADCs. We offer our expertise and assets to design optimized ADCs against targets of each partner’s choice. For us, it is important to deliver the best ADC possible for each target and we therefore advise and guide through all steps of ADC design and preclinical validation.
Iksuda believes that flexibility is key for successful partnerships. We are happy to consider a variety of partnering structures depending on the strengths and capabilities of each Party.
All our ADC programs are available for license at any development stage, including under exclusive option should this be preferable to secure earlier-stage assets. Iksuda’s ADC platforms are also available for license against selected targets of interest.
We are constantly reviewing the ADC landscape and are always keen to talk with research groups that are developing ADC-relevant assets. Iksuda is flexible in its approach to collaborative development with its partners to accelerate ADC research and development.
If you are interested in talking with us about licensing or research collaboration, please contact us.
When I talk to the Iksuda team, I know that I can be completely open and honest as if I'm speaking with old friends. With Iksuda's expertise and a shared passion for innovation, I am confident that we are creating the best novel ADC drugs together.
