Pharma Update

赞茶医药 Roche ZN-1041 in HER2+ BC with brain metastases Building on HER2+ breast cancer franchise, exploring novel combinations Potential best-in-class HER2 TKI Encouraging preliminary activity and safety Zion Pharma Ph Ic combination results with trastuzumab and capecitabine results¹ Overall tumor size changed from baseline CNS tumor size changed from baseline TKI AUC br.u/AUC plu Efflux transporter (P-gp/BCRP) substrate? Tucatinib 0.004 Yes Lapatinib 0.010 Yes Neratinib 0.013 Yes Pyrotinib 0.024 Yes Epertinib 0.080 Yes ZN-1041 0.470-0.770 No • Differentiated by high blood-brain-barrier permeability and CNS retention • ZN-1041 is not effluxed by P-gp and BCRP transporters, resulting in better CNS retention (>100-fold vs. tucatinib)1 • Best change (%) 0 -10- -20- -30- -40- -50- -60- -70- -80- -90- -100- Patients Best change (%) 0 -10 -20 -30 -40 -50 -60 -70- -80- -90 -100 Patients Well tolerated and promising Gl safety profile observed compared to other HER2 TKIS • • May be combined with other established anti-HER2 backbones (e.g., Phesgo, Kadcyla, Enhertu) to improve efficacy outcomes, for both prevention and treatment of brain metastases Ph I trial in patients with HER2+ breast cancer ongoing 1 Ma F, et al., ASCO 2023; BC=breast cancer; TKI-tyrosine kinase inhibitor; CNS-central nervous system; AUC-area under the curve; BCRP-breast cancer resistance protein; P-gp-P-glycoprotein; Gl=gastrointestinal; HER2-Human Epidermal growth factor Receptor 2 2023 ASCO ANNUAL MEETING 77

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