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Novel Data on Reduced Potency Payload Antibody-drug Conjugates

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Femtogenix, a UK biotechnology company developing DNA-interactive Antibody Drug Conjugate (ADC) payloads, has announced data demonstrating the potent efficacy and favorable toxicity profile of a reduced potency analogue from its Pyridinobenzodiazepine (PDD) ADC payload platform in solid tumor models. The data is being presented at AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Boston, USA.

Within its PDD platform, Femtogenix has developed a lower potency DNA mono-alkylator, illustrating a promising new approach in the development of ADCs for difficult-to-treat tumors. When attached to antibodies or other targeting moieties, Femtogenix’s novel PDD payload platform allows reversible/irreversible DNA minor groove binding, in a sequence-interactive manner, leading to highly targeted cytoxicity towards tumor cells. The payloads are designed to have a novel mechanism of action and IP space compared to existing DNA-interactive payloads, to have minimal hydrophobicity and to be resistant to P-Glycoprotein pumps in tumor cells.

These new data demonstrate that Femtogenix’s reduced potency payload has a favorable toxicity profile in rats, potent in vivo efficacy (MED < 1 mg/kg), and improved tolerability (i.e., MTD of 40 mg/kg) in solid tumor models when conjugated to antibodies.1 Its toxicity profile and wide therapeutic window is coupled with the ability to increase drug-antibody ratio (DAR) beyond the traditional limit of two, for increased conjugation to antibodies.

Professor David Thurston, Chief Scientific Officer, commented: “The favorable hydrophobicity profile of the low potency mono-alkylator and its ease of conjugation, along with the significant in vivo efficacy and tolerability of the ADCs produced, suggest that this payload represents a promising new approach in ADC development, specifically for the treatment of solid tumor malignancies.”   

Femtogenix has generated data on mechanism of action (MOA) of the ADC payload, illustrating a primary MOA of DNA alkylation, coupled with an ability to inhibit transcription factors. The molecules have been designed through proprietary molecular modeling methodologies to maximize interaction within the DNA minor groove. Payloads with differing potencies and modes of action may be suitable for particular uses or specific target situations.