CTATTM is an innovative enzymatic linker technology for conjugating different payloads with antibodies, without affecting their specificity, binding properties or stability. In the presented xenograft trial, the tested CTAT-ADC showed superior efficacy versus a commercially available ADC.
An anti-Her2 antibody conjugated to the maytansinoid DM1 using the novel CTATTM-linker technology (“CTAT-ADC”) was tested in nude mice with SKOV-3 cancer cell xenografts for maximum tolerated dose (“MTD”) and efficacy. Three different dosages of the CTAT-ADC were compared to a commercially available Trastuzumab-DM1-ADC (“T-DM1-ADC”, Kadcyla),to naked antibody and to the delivery vehicle.
In the MTD part the CTAT-ADC was well tolerated by the animals in a dosage of up to 70 mg/kg body weight. No animals were lost, and only in the highest dosage group a slight and temporary loss of body weight was observed.
In the xenograft trial, tumor volume kinetics was monitored after two applications of the CTAT-ADC and the control substances. The first dose was applied at study start and a second dose after recurrence of substantial tumor growth in the individual study groups.During a period of 29 days, the CTAT-ADC at 35mg/kg dosage was the best performing regimen and the only group which showed sustained tumor reduction.
This group of test animals also showed very homogeneous results compared to the Group treated with T-DM1-ADC (see Figures 2 + 3). The commercial T-DM1-ADC at 10mg/kg and the CTAT-ADC at 70 mg/kg dosage showed good suppression of tumor growth during the initial phase of the treatment but towards the end of the 29 days tumor growth was observed again. The third CTAT-ADC dosage group (10 mg/kg) achieved an initial Tumor growth inhibition comparable to T-DM1-ADC, but also in this group the tumor resumed growth closer to the end of the observation period.
In-vitro data of the CTAT-technology were presented earlier. The CTAT-ADC used in the presented xenograft trial, and additional ADCs based on different antibodies and on a Fabfragment showed efficacy against a variety of cancer cell lines. All of these constructs were generated using the CTATTM linker technology for conjugation. Plasma stability and a welldefined drug-antibody-ratio (“DAR”) of 1 and 2 have been proven.
About CTATTM-Technology
The CTATTM linker technology enables directed conjugation of antibodies with a broad spectrum of different payload molecules, mainly for oncology indications. It offers the benefits of efficient C-terminal, site-directed conjugation without affecting the specificity and binding properties or the stability of the antibody. The CTATTM enzyme recognizes a defined, three-amino acid sequence motif added to the C-terminus of the antibody, cleaves this sequence and attaches the payload by forming a new peptide bond in a nucleophilic Addition reaction (transamidation). This allows a controlled drug antibody ratio (DAR). The CTATTM-substrate peptides are minimally immunogenic, and the CTATTM-technology can also be used for bispecific antibodies.
About Eucodis Bioscience
EUCODIS Bioscience is an Austrian, Vienna based, biotechnology company with core competence in Enzyme Engineering, offering over 50 enzymes for applications in the pharmaceutical, fine chemicals and cosmetics industry. The CTATTM-technology is the latest development.
Licensing Opportunity
The CTATTM-technology is available for licensing on a target basis or as a whole. If you are interested or want further information please contact Dr. Karl Hübler, CEO.
Tel: +43 1 8900804-0
Email: huebler@eucodis.com
September 2015
EUCODIS Bioscience GmbH
Campus Vienna Biocenter 2
Viehmarktgasse 2a, 1030 Wien, Austria
Tel: +43 1 8900804-10 Fax: +43 1 8900804-11
www.eucodis.com
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