Lilotomab pre-dosing of NHL patients before Betalutin® therapy lowers haematological toxicity

Oslo, Norway, 5 September 2016

Nordic Nanovector ASA (OSE: NANO) announces that two papers recently published in The Journal of Nuclear Medicine have shown that pre-dosing with the anti-CD37 antibody lilotomab (previously referred to as HH1), prior to injection with Betalutin® (177Lu-lilotomab) reduces haematological toxicity without adversely impacting the amount of radiation absorbed by the tumour. Betalutin® is a novel anti-CD37 antibody-radionuclide-conjugate (ARC) currently in Phase 1/2a. Two pre-dosing regimens have been investigated, one with 40 mg unlabeled lilotomab antibody (Arm 1) and one without (Arm 2). Data from eight patients were included in both papers.

The first paper 1) looked at the risk that pre-dosing with lilotomab could block the CD37 antigen on tumour tissues adversely impacting the amount of radiation absorbed by the tumour. The research shows that there was no difference in the tumour absorbed dose for patients in Arm 1 and Arm 2. The reduced distribution volume and clearance in Arm 1 might explain this finding as it implies that the concentration of Betalutin® in the blood was higher for Arm 1 patients than for Arm 2 patients, therefore increasing concentration counteracts any eventual blocking of CD37 on tumour tissue.

The second paper 2) looked at the radiation exposure of the red bone marrow (RM) which is often the primary organ at risk in radioimmunotherapy. Irradiation of the marrow may induce short and long-term haematological toxicity.

Researchers found that the RM radiation doses were significantly higher in the patients who did not receive pre-dosing. This difference indicates that pre-dosing with lilotomab has a protective effect for RM, most likely thanks to the unlabeled antibody, which blocks the binding to CD37 in the RM.

Jostein Dahle, Nordic Nanovector CSO, commented -The results outlined in these two publications further support our hypothesis that pre-dosing with lilotomab provides a protective effect on healthy tissues when used prior to Betalutin® treatment and importantly that pre-dosing does not adversely impact the radiation absorbed by the tumor. These findings also support our development strategy for Betalutin®, where we are looking at different pre-dosing regimens in order to identify the optimal dose regimen of this novel antibody-radionuclide-conjugate to take into later stage clinical trials.

The Lymrit 37-01 study is a Phase 1/2 open label, single injection ascending dose study investigating three dose levels of Betalutin® and different pre-dosing regimens in patients with relapsed NHL with the aim of identifying an optimal dose regimen to take into the Phase 2 PARADIGME study, which is expected to start in 2H 2017.

1) J Nucl Med Published August 4, 2016 as doi:10.2967/jnumed.116.173922
2) J Nucl Med Published September 1, 2016 as doi:10.2967/jnumed.116.180471

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