On May 3, 2022 Nordic Nanovector ASA (OSE: NANOV), a clinical-stage biotech company focused on CD37-targeted therapies for haematological cancers and immune diseases, reported the publication of two new research papers highlighting approaches to improve the potential therapeutic effect of its novel CD37-targeting radioimmunoconjugate Humalutin (177Lu-DOTA-NNV003) in B-cell malignancies, such as Non-Hodgkin Lymphoma (NHL) (Press release, Nordic Nanovector, MAY 3, 2022, View Source [SID1234613451]).

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The first publication by the Company’s scientists and its collaborators, published in PLOS One (Ref. 1), reports on the combined effect of Humalutin with olaparib, a member of the class of anticancer therapies known as PARP inhibitors, on NHL cell lines.

In the studies, the combination of Humalutin and olaparib was found to be synergistic or conditionally synergistic leading to cell death in 6 of 7 NHL cell lines (diffuse large B cell lymphoma and mantle cell lymphoma). Where the combination was conditionally synergistic (i.e. both synergistic and antagonistic), the effect was dependent on the concentration of each drug, showing the importance of optimising the parameters for further studies.

Humalutin acts by inducing potentially cytotoxic DNA breaks in the NHL cells, sensitising these cells to olaparib, which prevents the repair of DNA breaks by blocking the activity of DNA repair enzymes poly (ADP ribose) polymerase 1 and 2 (PARP1 and PARP2). Olaparib is approved in the US and most markets globally for BRCA mutated ovarian and breast cancer.

The authors concluded that further in vivo studies evaluating the anti-tumour effect of the combination of radioimmunotherapies, including Humalutin, and PARP inhibition are warranted.

Separately, Nordic Nanovector reports the publication of a paper in the high-impact open access journal Scientific Reports (Ref. 2) on the potential of a non-invasive diagnostic imaging approach to select NHL patients who are more likely to respond to or are at risk for developing CD37-induced haematological toxicities from CD37-targeted radioimmunotherapy.

The imaging approach used a radioimmunoconjugate ([89Zr]Zr-N-sucDf-NNV003) comprising the Company’s proprietary anti-CD37 antibody NNV003 (a component of Humalutin), and zirconium-89, a radioisotope that is well-suited to commonly used positron emission tomography (PET) imaging, to assess CD37-expression, biodistribution and tumour-uptake levels in mice bearing human B cell lymphomas and to predict the possible therapeutic effects of Humalutin in NHL patients.

A good manufacturing practice (GMP)-compliant production process has also been established to enable administration to patients in future studies.

Jostein Dahle, Nordic Nanovector’s Chief Scientific Officer, said: "These two publications add to the growing scientific evidence supporting CD37 as a valuable tumour target both for therapeutic and diagnostic applications in NHL. This evidence provides important validation of our pipeline approach, building on the significant data we have collected from our preclinical and clinical studies with Betalutin and now expanding to our next-generation CD37-targeting radioimmunoconjugate Humalutin. We look forward to continuing to grow our understanding around CD37 and the potential of our emerging pipeline."

References

1. Malenge, M.M. et al. Anti-CD37 radioimmunotherapy with 177Lu-NNV003 synergizes with the PARP inhibitor olaparib in treatment of non-Hodgkin’s lymphoma in vitro. PLOS One (2022): 17(4): e0267543

2. Giesen, D. et al. 89Zr-PET imaging to predict tumor uptake of 177Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma. Sci Rep 12, 6286 (2022). View Source