On October 14, 2019 Femtogenix Ltd, a UK biotechnology company developing the next generation of DNA-interactive Antibody Drug Conjugate (ADC) payloads, reported data verifying the favourable toxicity profile and potent efficacy of its Pyridinobenzodiazepine (PDD) ADC payload platform in tumour cell models (Press release, Femtogenix, OCT 14, 2019, View Source [SID1234540987]). The data was presented by Professor David Thurston, Chief Scientific Officer, Femtogenix, on 11 October at World ADC 2019 in San Diego, CA.
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ADCs are capable of delivering highly cytotoxic payloads directly at the tumour site. When attached to antibodies or other targeting moieties, Femtogenix’s novel PDD platform allows reversible/irreversible DNA minor groove binding, in a sequence-interactive manner, leading to highly targeted cytotoxicity towards tumour 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 tumour cells.
These new data describe details of Femtogenix’s latest payload molecules for ADC use, and demonstrate that high potency mono-alkylators derived through the PDD platform have a favourable toxicity profile in rats, coupled with potent in vivo efficacy (sub mg/kg doses) and excellent tolerability (i.e., MTDs > 10 mg/kg) when conjugated to antibodies1. Femtogenix also introduced a new class of DNA cross-linking ADC payloads at the World ADC conference, based on its proprietary PDD platform, with potent in vivo efficacy and substantially enhanced tolerability profiles compared to competing technologies.
Dr Christopher Keightley, Chief Executive Officer of Femtogenix, commented: "These data show that our PDD technology overcomes many of the limitations of existing approaches to ADC payloads. The toxicity profile and ease of conjugation of the PDD mono-alkylators, along with their novel mechanism of action and significant in vitro and in vivo efficacy, suggest they represent a promising new payload class. We are delighted with the progress as we conclude significant collaborations with pharma partners who will help us achieve the practical application of our innovative approach to a new generation of ADCs."
Femtogenix has generated extensive data on the specific interaction of these payload molecules with DNA using a variety of biophysical techniques, including DNA footprinting and FRET studies. The molecules have been designed through proprietary molecular modelling methodologies to maximise interaction within the DNA minor groove. The design methodology has led to the creation of molecules with a range of potencies and has also been used to generate novel DNA cross-linking payloads that form unique DNA adduct structures with differing modes of action. Payloads with differing potencies and modes of action may be suitable for particular uses or specific target situations.
1. Professor David Thurston, Scientific Co-Founder and Chief Scientific Officer, Femtogenix: ‘New Developments with the Pyridinobenzodiazepine (PDD) Payload Platform’, 8.40-9.10am, 11 October 2019, World ADC, as part of the talk ‘What Lies Ahead for ADCs’.