Q3 2020 Sales Performance slide image

Q3 2020 Sales Performance

Tumor volume (mm³) Zejula A unique PK profile may explain the benefit in HR-proficient patients 1200- 1000- BRCAmut TNBC model MDA-MB-436 (BRCA1mut) • Vehicle (n=6) • Niraparib (75 mg/kg qd n=6) Olaparib (75/67 mg/kg bid n=6) 800- 600- 400- 200- 0 0 5 10 15 20 25 30 Time (days) Tumor volume (mm³) gsk BRCAwt ovarian model A2780 (BRCAwt) 3000- Vehicle (n=15) 2500- Niraparib (62.5 mg/kg qd n=6) Olaparib (100 mg/kg qd n=6) 2000- P=0.005** 1500- 1000- 500- 0 ° 2 10 Time (days) www.oncotarget.com Oncotarget, 2018, Vol. 9, (No. 98), pp: 37080-37096 Research Paper A comparative pharmacokinetic study of PARP inhibitors demonstrates favorable properties for niraparib efficacy in preclinical tumor models Kaiming Sun, Keith Mikule', Zebin Wang, Grace Poon', Aparajitha Vaidyanathan², Gillian Smith', Zhi-Yi Zhang', Jeffrey Hanke, Sridhar Ramaswamy' and Jing Wang "Our results show that at steady state, tumor exposure to niraparib is 3.3 times greater than plasma exposure in tumor xenograft mouse models. In comparison, the tumor exposure to olaparib is less than observed in plasma. In addition, niraparib crosses the blood-brain barrier and shows good sustainability in the brain, whereas sustained brain exposure to olaparib is not observed in the same models. Consistent with its favourable tumor and brain distribution, niraparib achieves more potent tumor growth inhibition than olaparib in BRCAwt models and an intracranial tumor model at maximum tolerated doses." Sun et al 50 50
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