Slide 1: Preclinical Assessment of 212Pb-Radio-DARPin Therapeutic (RDT) Targeting DLL3 in SCLC
Preclinical Assessment of 212Pb- 212Pb Radio-DARPin Therapeutic (RDT) Targeting DLL3 in SCLC DLL3 Amelie Croset, PhD Senior Director - Head of Preclinical Platforms at Molecular Partners EANM - 22 October 2024
Slide 2: Disclosures
Disclosures • The presented research was funded by Molecular Partners and Orano Med • All authors are employees of Molecular Partners or Orano Med • Amelie Croset owns stocks in Molecular Partners 2
Slide 3: MP0712, the first 212Pb-DLL3 targeted radiotherapy under investigation
MP0712, the first 212Pb-DLL3 targeted radiotherapy under investigation Combining distinctive DARPin features with the power of 212Pb for efficacious cancer therapy 212Pb for Targeted Alpha Therapy DLL3 LINKER SCLC as indication • Aggressive cancer with high unmet medical need • Strong cytotoxicity (
Slide 4: MP0712 showed favorable biodistribution and tumor specificity
MP0712 showed favorable biodistribution and tumor specificity DLL3 expression & distribution by IHC ATH nude mice double xenografted s.c. NCI-H82 tumors hDLL3-MC38 tumors with hDLL3-MC38 + R2G2 mice xenografted s.c. with R2G2 mice xenografted i.v. with WT-MC38 NCI-H82 NCI-H82 Human SCLC tumors T:K a
Slide 5: A favorable safety profile
MP0712 showed a favorable safety profile Body weight (BW) change (%) Hematology 30 WBC LYMP treatment 15 15 treatment Body Weight Change (relative to initial) (%) 20 LYMP (109/L) 10 10 WBC (109/L) 10 5 5 Average ± SEM 0 0 10 20 30 40 0 0 -10 0 10 20 30 -10 0 10 20 30 Days since treatment Days since
Slide 6: Good efficacy & tumor stabilization
MP0712 showed good efficacy & tumor stabilization Median survival 2000 Buffer MP0712 MP0712 Rova Rova MP0712 (1x10µCi) Buffer 1x10Ci 4x10Ci 1x10Ci 4x10Ci MP0712 (4x10µCi) R2G2 mice xenografted s.c. with 212 Pb-Rova (1x10µCi) 4.7 wks 7.9 wks 15.7 wks 7.9 wks 8.9 wks NCI-H82 212 Pb-Rova (4x10µCi)
Slide 7: Good efficacy & tumor stabilization
MP0712 showed good efficacy & tumor stabilization Median survival 2000 Buffer MP0712 MP0712 Rova Rova MP0712 (1x10µCi) Buffer 1x10Ci 4x10Ci 1x10Ci 4x10Ci MP0712 (4x10µCi) R2G2 mice xenografted s.c. with 212 Pb-Rova (1x10µCi) 4.7 wks 7.9 wks 15.7 wks 7.9 wks 8.9 wks NCI-H82 212 Pb-Rova (4x10µCi)
Slide 8: Summary
Summary ✓ MP0712, the first 212Pb-DLL3 Targeted Radio-DARPin Therapy TARGET RESEARCH PRECLINICAL RIGHTS – High tumor uptake observed DLL3 MP0712 Target 2 – Reached T:K > 2 in mouse models expressing DLL3 Target A – Showed a favorable safety profile in vivo up to 30µCi Target B Target X – Induced goo
Slide 9: Acknowledgments
Acknowledgments The joint team at Orano Med & Molecular Partners Contributing authors of this presentation Amelie Croset1, Amal Saidi2, Francesca Malvezzi1, Tania Stallons2, Madlaina Mettier1, Amy Wong2, Jitka Rantanen1, Federico Rojas Quijano2 Stephan Wullschleger1, Yvonne Kaufmann1, Tamara Lekishv
Slide 10: Thank you for your interest!
212Pb DLL3 Thank you for your interest!