Femtogenix presents efficacy and toxicity data on their ADC platform

Studies demonstrate superior efficacy and cytotoxicity of Femtogenix’s sequence-selective DNA-interactive payload molecules

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HARPENDEN, UK—Femtogenix Ltd. announced today data verifying the favorable toxicity profile and potent efficacy of the company’s Pyridinobenzodiazepine (PDD) ADC payload platform in tumor cell models. The data was presented by Professor David Thurston, scientific co-founder and chief scientific officer of Femtogenix, on October 11 at World ADC 2019 in San Diego, CA.
ADCs are capable of delivering highly cytotoxic payloads directly at the tumor 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 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 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 favorable 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 antibodies.
“These data show that our PDD technology overcomes many of the limitations of existing approaches to ADC payloads,” said Dr. Christopher Keightley, chief executive officer of Femtogenix. “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 also introduced at the World ADC conference a new class of DNA cross-linking ADC payloads based on the company’s proprietary PDD platform, with potent in vivo efficacy and substantially enhanced tolerability profiles compared to competing technologies.
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 modeling methodologies to maximize 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. Femtogenix believes that payloads with differing potencies and modes of action may be suitable for particular uses or specific target situations. 

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