NNV024, a novel humanized anti-CD37 antibody with enhanced ADCC and prolonged plasma half-life in human FcRn transgenic mice for treatment of NHL

Generaloc, R.; Fiorito, E.; Foss, S.; Pascal, V.; Heyerdahl, H.; Repetto, A.; Andersen, J. T.; Tjonnfjord, G.; Skanland, S. S.; Dahle, J.

doi:10.1101/2023.07.12.548667

bioRxiv · 10.1101/2023.07.12.548667

NNV024, a novel humanized anti-CD37 antibody with enhanced ADCC and prolonged plasma half-life in human FcRn transgenic mice for treatment of NHL

Generaloc, R.·Fiorito, E.·Foss, S.·Pascal, V.·Heyerdahl, H.·Repetto, A.·Andersen, J. T.·Tjonnfjord, G.·Skanland, S. S.·Dahle, J.

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Abstract

There is an unmet medical need for new therapeutic approaches and targets for patients with non- Hodgkin lymphoma (NHL) who relapse or are refractory to anti-CD20 immunotherapy. Therefore, we developed a humanized IgG1 antibody targeting CD37, which was tailored to be afucosylated for enhanced antibody-dependent cellular cytotoxicity (ADCC) (NNV024). In line with this, NNV024 induced three-fold more potent ADCC activity against patient-derived chronic lymphocytic leukemia (CLL) cells compared with anti-CD20 obinutuzumab. Moreover, NNV024 showed 2-fold higher ADCC activity than anti-CD20 rituximab and a recombinant version of DuoHexaBody-CD37 against both NHL and CLL cells. Survival was significantly longer after NNV024 treatment than with obinutuzumab in a mouse model. In addition, NNV024 showed a favourable plasma half-life in human FcRn transgenic mice of about 9-days, which was 2-fold longer than that of obinutuzumab and DuoHexaBody-CD37. These results warrant the further development of NNV024 as a treatment for NHL.

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Generaloc, R., Fiorito, E., Foss, S., Pascal, V., Heyerdahl, H., Repetto, A., Andersen, J. T., Tjonnfjord, G., Skanland, S. S., Dahle, J.. 2023-07-12. NNV024, a novel humanized anti-CD37 antibody with enhanced ADCC and prolonged plasma half-life in human FcRn transgenic mice for treatment of NHL. https://doi.org/10.1101/2023.07.12.548667

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