Iksuda Therapeutics, formerly known as Glythera, confirmed that it has signed a licensing agreement with Femtogenix. The agreement gives Iksuda access to Femtogenix’s therapeutic, sequence-selective DNA-interactive, payloads to advance it’s lead antibody-drug conjugates for difficult-to-treat solid tumors.

Using Femtogenix’s highly potent and broad-acting DNA mono-alkylating payloads in combination with Iksuda’s proprietary PermaLink® conjugation platform, the company aims to significantly improve the therapeutic index of its ADCs and further advance the current standard of care for solid tumor types, which can be resistant to treatment.

Gaining ground
Antibody-drug conjugates are rapidly gaining ground. Enabling selective delivery of a potent cytotoxic payload to target cancer cells, this important tool in the fight against cancer results in improved efficacy, reduced systemic toxicity, and preferable pharmacokinetics (PK)/pharmacodynamics (PD) and biodistribution compared to traditional chemotherapy, killing cancer cells but limiting damage to healthy tissues.

Boosted by the successes of U.S. Food and drug Administartion (FDA-) approved antibody drug conjugates, including brentuximab vedotin (Adcetris®; Seattle Genetics/Takeda) and ado-trastuzumab emtansine (Kadcyla®, Genentech/Roche), this drug class has been rapidly growing along with more than 100 antibody-drug conjugates currently in clinical trials.

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However, clinical utility of antibody-drug conjugates depends on the stability of the conjugation chemistry and the current industry-standard maleimide approach is prone to the premature release of toxic payloads which limits the dose that can be administered safely to patients and, subsequently, reduces the drug’s therapeutic index.

Iksuda’s PermaLink® is an alternative conjugation chemistry platform which may offer greater stability and delivery metrics.

The foundation of Iksuda’s antibody-drug conjugate development program is its proprietary conjugation chemistry PermaLink®, which is associated with industry-leading conjugation stability. The conjugation platform is a cysteine-specific, vinyl pyridine-based chemistry that demonstrates inherent conjugation stability and, unlike many other approaches to conjugation, this chemistry is not susceptible to drug de-conjugation. As a result, the technology enables the safer use of ultra-potent toxins which, when conjugated to antibodies that are directed to well-selected targets, results in more efficacious ADCs.

“Our conjugation technology provides a highly selective and safe alternative to the current maleimide chemistries, whilst reducing the significant risk associated with de-drugging of potent toxins and adverse events in the clinic,” noted Robert Lutz, Ph.D, Iksuda’s Chief Scientific Officer who spent 23 years with Immunogen (*), culminating in his role as Vice President of Translation Research and Development.

The agreement marks another key step in the build-out of Iksuda’s antibody-drug conjugate technology-suite and drug pipeline, from which it aims to progress multiple candidates towards first clinical studies in 2020.

“This agreement is an exciting progression of our ADC pipeline as it maximizes potential for the greatest anti-cancer impact and enhanced therapeutic index, further underpinning our ambition to advance multiple ADCs to the clinic and treat the broadest patient population possible,” noted David Simpson, Ph.D, Iksuda Therapeutics’ Chief Executive Officer.

“We are pleased to be working with Iksuda to further validate the clinical potential of our payloads, which should provide improved efficacy and safety in comparison to those currently in the clinic,” said Chris Keightley, Ph.D, Femtogenix, Chief Executive Officer.

“We have developed a wide range of easily conjugated payloads with novel mechanisms of action and potency levels, and these are available for licensing. In particular, we are developing payloads that can recognise and bind to transcription factor recognition site profiles within the genome. Such profiles are characteristic of specific tumour types, and this allows Femtogenix to develop payloads with reduced toxicity and enhanced target specificity,” Keightley concluded.

Note: (*) Immunogen played a key role in the generation and early development of ado-trastuzumab emtansine, the first antibody-drug conjugate approved for the treatment of HER2-positive breast cancer.

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