Slide 1: BCMA-Targeted CART (HBI0101), a Safe and Efficacious Novel Modality for AL Patients
BCMA-Targeted CART (HBI0101), a Safe and Efficacious Novel Modality of Treatment for Light Chain Amyloidosis (AL) Patients Nathalie Asherie, PhD Department of Bone Marrow Transplantation and Cancer Immunotherapy ASGCT, Los Angeles, CA - May 2023-
Slide 2: Disclosures
Disclosures Dr Nathalie Asherie is employed by the Hadassah Medical Center. The CART technology is protected by a worldwide patent application. Immix Biopharma (Nasdaq: IMMX) has licensed HBI0101 CART technology (NXC-201).
Slide 3: AL Amyloidosis - Introduction
AL Amyloidosis - Introduction Multiple Myeloma AL amyloidosis https://www.healthinsight.ca/advocacy/making-myeloma-matter/ https://doi.org/10.1016/j.conctc.2017.08.012.
Slide 4: Therapeutic Strategies for the treatment of AL Amyloidosis
Therapeutic Strategies for the treatment of AL Amyloidosis Antibodies Proteasome Inhibitors Chemotherapy and Steroids Immune Modulators Others (IMiDs) Venetoclax https://doi.org/10.1016/j.jaccao.2021.09.003
Slide 5: Organ response is the ultimate goal in the treatment of AL amyloidosis
Organ response is the ultimate goal in the treatment of AL amyloidosis https://doi.org/10.1016/j.blre.2012.03.0
Slide 6: Anti-BCMA CART therapy has proven safe and efficient for multiple myeloma
Anti-BCMA CART therapy has proven safe and efficient for the treatment of multiple myeloma https://www.aacr.org/blog/2023/03/22/from-bench-to-bedside- new-frontiers-in-multiple-myeloma/ Journal of Hematology & Oncology.13:125. 2020.
Slide 7: Limitations of CART therapy approach in AL patients
Limitations of CART therapy approach in AL patients Oliver-Caldes et al. J Immunother Cancer. 2021 Oliver-Caldes et al. J Immunother Cancer. 2021
Slide 8: HBI0101, self-developed anti-BCMA CAR
HBI0101, self-developed anti-BCMA CAR
Slide 9: HBI0101 preclinical and clinical evaluation
HBI0101 preclinical and clinical evaluation HBI0101 CAR 100 86% 87% PR [MRD+] 82% PR [MRD-] 14 VGPR [MRD+] VGPR [MRD-] 14 sCR/CR [MRD+] ORR (%) 40 49 sCR/CR [MRD-] 50% 50 29 17 12 8 800x106 dose: 16 16 ORR- 87% 33 29 6 3 8 sCR/CR- 57% 6 0 2 3 MRD negativity- 73% ) ) 7) 0) =6 =7 =3 =5 N N N (N t( t(
Slide 10: BCMA targeting in the context of AL amyloidosis
BCMA targeting in the context of AL amyloidosis 150 ✱ 15 BCMA EXPRESSION (MFI) ns % BCMA+ 100 10 50 5 0 0 ) ) ) ) 9 8 9 8 =3 =1 =3 =1 (N (N (N (N M L M L A A M M Kfir-Erenfeld, S. et al. Clin. Cancer Res. 2022.
Slide 11: Anti-amyloidosis function of HBI0101
Anti-amyloidosis function of HBI0101 NT HBI0101 CD138 ✱ 2.5×10 4 800 40 ✱ ✱✱ 2×10 4 600 TNF-α (pg/mL) CD38 IFN-γ (pg/mL) 30 Pre-enrichment CD138 enrichment 1.5×10 4 % 4-1BB+ 400 20 MFI=1,006.1 1×10 4 MFI=492.2 200 Count (% of Max) 10 5×10 3 MFI=408.4 MFI=405.1 0 0 0 T 1 T 1 T 1 10 N 10 N 10 N I0 I0
Slide 12: Clinical Study of HBI0101 in myeloma AND AL amyloidosis patients
Clinical Study of HBI0101 in myeloma AND AL amyloidosis patients • A Phase Ia/Ib Dose Escalation and Safety Study of HBI0101 BCMA.CART in Relapsed Refractory Multiple Myeloma and AL amyloidosis Patients (NCT04720313). • The Phase Ia was designed as a dose-escalation 3+3 protocol (20 patients). • The
Slide 13: Patients’ baseline characteristics
Patients’ baseline characteristics *Concomitant MM ** Compassionate
Slide 14: Patients’ baseline characteristics
Patients’ baseline characteristics Pt 1* Pt 2 Pt 3 Pt 4** Pt 5 * Pt 6 Pt 7** Pt 8* Prior lines of 8 6 6 10 and 3 4 4 7 therapy MDS Best response/ VGPR/ VGPR/ CR/ CR/ VGPR/ VGPR/ VGPR/ VGPR/ which line 3rd 2nd 1st 1st + 4th 2nd 2nd 3rd 1st + 2nd Previous ASCT Yes Yes No Yes (as No No No Yes salvage)
Slide 15: Safety Results
Safety Results Pt 1 Pt 2 Pt 3 Pt 4 Pt 5 Pt 6 Pt 7 Pt 8 CAR+ cells infused 150 450 800 450 800 800 800 800 (x106) Adverse events of interest CRS No Yes Yes Yes Yes No Yes Yes CRS grade 2 3 3 1 1 2 Time to onset (days) 2 3 1 2 2 2 CRS duration (days) 2 4 1 1 1 1 Tocilizumab doses 0 1 3 1 1 0 0 1 Stero
Slide 16: Safety Results
Safety Results Pt 1 Pt 2 Pt 3 Pt 4 Pt 5 Pt 6 Pt 7 Pt 8 CAR+ cells infused (x106) 150 450 800 450 800 800 800 800 Hematologic AEs (grades) Neutropenia 1 3 3 4 3 0 2 4 Anemia 0 1 2 3 1 0 0 0 Thrombocytopenia 0 2 1 4* 1 0 0 0 Duration of Hematologic 4 3 5 Ongoing 2 0 2 6 AE** (days) >31 AL Organ deteri
Slide 17: HBI0101 induces fast, deep and durable responses
HBI0101 induces fast, deep and durable responses Pt 1 Pt 2 Pt 3 Pt 4 Pt 5 Pt 6 Pt 7 Pt 8 CAR+ cells infused 150 450 800 450 800 800 800 800 (x106) Best hematologic CR CR CR CR CR VGPR PR VGPR response iFLC at best 0.6 0.9 1 7 0.4 0 56 36 response (mg/L) dFLC at best 0 0 0 1.4 0.2 20 50 30 response (
Slide 18: HBI0101 induces organ responses
HBI0101 induces organ responses Pt 1 Pt 2 Pt 3 Pt 4 Pt 5 Pt 6 Pt 7 Pt 8 CAR+ cells infused 150 450 800 450 800 800 800 800 (x106) Best hematologic CR CR CR CR CR VGPR PR VGPR response Organ response Yes Yes Yes Yes No No Yes Yes complete Delta proBNP -4800 -1295 NA -1872 0 -4700 -3800 NA response (%
Slide 19: Patients’ responses over time
Patients’ responses over time P8 sCR/CR [MRD-] sCR/CR [MRD+] P7 VGPR [MRD+] VGPR [MRD-] P6 800x10^6 CAR+ PR [MRD-] PR [MRD+] P5 PD/SD Death P4 450x10^6 CAR+ P3 800x10^6 CAR+ P2 450x10^6 CAR+ P1 150x10^6 CAR+ 0 50 100 150 200 250 300 350 400 450 500 550
Slide 20: Efficacy Results: Pharmacokinetics
Efficacy Results: Pharmacokinetics 2.5×10 5 600 Patient 1 HBI0101 cell/mL Blood 5 HBI0101/mL Blood 2×10dFLC (mg/L) 500 1.5×10 5 Patient 2 2×10 5 600 HBI0101 cell/mL Blood 1×10 5 Patient 3 dFLC (mg/L) 400 5×10 4 Patient 4 dFLC (mg/L) 1.5×10 5 Patient 5 300 4×10 4 400 Patient 6 1×10 5 200 Patient 7 2×
Slide 21: Efficacy Results
Efficacy Results Bone Marrow plasma cells elimination FDG-PET avidity Patient 4 30 Before Patient 1 After 20 HBI0101 Before 10 %CD38+CD138+ CD38+CD138+ 1.0 0.8 CD138 Day +33 post HBI0101 0.6 0.4 0.2 Before After 0.0 Before After CD38 Kfir-Erenfeld, S. et al. Clin. Cancer Res. 2022.
Slide 22: Anti-BCMA CART is a clinically tested novel modality for relapsed and refractory AL patients
Anti-BCMA CART is a clinically tested novel modality of treatment for relapsed and refractory AL patients • BCMA expression on AL amyloidosis plasma cell is sufficient for in-vitro and clinical targeting by CART. • Largest cohort of AL amyloidosis patients (8 pts) treated with BCMA CART therapy desc
Slide 23: Evolution of Treatment in AL Amyloidosis
Evolution of Treatment in AL Amyloidosis 2021 Anti-BCMA CART Adapted from Bianchi, G. et al. JACC: CardioOncology. 2021.
Slide 24: Expanding access to HBI0101 therapy
Expanding access to HBI0101 therapy
Slide 25: Acknowledgements
Acknowledgements Hadassah Hebrew Prof. Polina Stepensky, MD University Medical R&D lab: Center Directors and Shlomit Kfir-Erenfeld, PhD Prof. Moshe Gatt, MD Management board Clinicians: Miri Assayag, PhD Prof. Dina Ben-Yehuda, MD Taly Sharon, PhD Sigal Grisariu, MD Nomi Bessig, PhD Batia Avni, MD Ve