Gamida Cell — Technical Presentation (2022)
17 slides from Gamida Cell's technical presentation, Aug 14, 2022
Slide 1: HSCT with Omidubicel Associated with Enhanced Circulatory pDC, NK and CD4+ T Cells
HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) WITH OMIDUBICEL IS ASSOCIATED WITH ENHANCED CIRCULATORY PLASMACYTOID DENDRITIC CELLS (PDC), NK CELLS AND CD4+ T CELLS WITH LOWER RATES OF SEVERE INFECTION COMPARED TO STANDARD UMBILICAL CORD BLOOD TRANSPLANTATION PAUL SZABOLCS, MD1, XIAOHUA CHEN, MD, PH
Slide 2: Disclosures
DISCLOSURES ¡ Forge Therapeutics – Co-inventor/licensee ¡ Gamida Cell – Consulting, clinical trial participation ¡ Prevail Therapeutics – Consulting
Slide 3: Limitations of Cord Blood Transplantation
LIMITATIONS OF CORD BLOOD TRANSPLANTATION • Delayed hematopoietic recovery Potential solution: ex vivo manipulation • Delayed immune recovery • Increased transplant related mortality of cord blood stem cells (omidubicel) There is a delay in T cell recovery following cord A robust recovery of NK cell
Slide 4: Omidubicel Using Nicotinamide Technology Delivers CD34+ Progenitor and Immune Cells
OMIDUBICEL USING NICOTINAMIDE TECHNOLOGY DELIVERS A SPECTRUM OF CD34+ PROGENITOR CELLS AND IMMUNE CELLS ¡ Omidubicel is an advanced cell therapy for allogeneic HSCT that uses nicotinamide based proprietary technology to preserve multipotency of progenitor cells and increase cell quantity for transpl
Slide 5: Transplant with Omidubicel: Significantly Faster Time to Engraftment
TRANSPLANT WITH OMIDUBICEL: SIGNIFICANTLY FASTER TIME TO ENGRAFTMENT Median Time to Neutrophil Engraftment (1° endpoint) P<0.001 P<0.001 22 20 Number of Days 12 Omidubicel 10 UCB ITT (N=125) AT (n=108) AT, as-treated; ITT, intent-to-treat; UCB, umbilical cord blood. Horwitz ME, et al. Blood 2021;138
Slide 6: Transplant with Omidubicel: Reduced Risk of Bacterial, Fungal, and Viral Infections
TRANSPLANT WITH OMIDUBICEL: REDUCED RISK OF BACTERIAL, FUNGAL, AND VIRAL INFECTIONS First Grades 2/3 Bacterial or Invasive Fungal Infection* First Grade 3 Viral Infection* 1.0 Randomized treatment 1.0 Randomized treatment Cumulative Incidence Omidubicel Omidubicel Cumulative Incidence 0.8 UCB 0.8 UC
Slide 7: Immune Reconstitution Substudy Following Omidubicel Transplantation
IMMUNE RECONSTITUTION SUBSTUDY FOLLOWING OMIDUBICEL TRANSPLANTATION Research questions: 1. Is rapid neutrophil engraftment followed by rapid recovery of other cell lineages? 2. What is driving the reduced risk of infections? Methods: • Optional substudy – 14 clinical centers participating • 37 patie
Slide 8: Baseline Patient and Graft Characteristics
BASELINE PATIENT AND GRAFT CHARACTERISTICS Omidubicel (n=17) UCB (n=20) Median age (range), years 30 (13–62) 43 (19–55) Male, n (%) 10 (59) 12 (60) Primary diagnosis, n (%) Acute leukemia (ALL, AML) 14 (82) 18 (90) Other (CML, MDS, lymphoma) 3 (18) 2 (10) Disease risk, n (%) Medium – high/very high
Slide 9: Patient Outcomes
PATIENT OUTCOMES Omidubicel UCB P-value (n=17) (n=20) Median time to neutrophil engraftment (range), days 10 (6–28) 18.5 (14–40) <0.001 Patients with >95% chimerism, n (%) Day 21/28 17 (100) 20 (100) ‒ Day 100 16 (100)* 18 (100)† ‒ Grade 2/3 infections over 365 days, n (%) Bacterial infections 7 (41
Slide 10: Robust Early Recovery of T Cell, B Cell, NK Cell, and Dendritic Cell Subsets
ROBUST EARLY RECOVERY OBSERVED FOR T CELL, B CELL, NK CELL, AND DENDRITIC CELL SUBSETS (DAY 0 TO DAY 28) CD4+ cells B cells NK cells Day 7 Day 14 Day 21 Day 28 Day 7 Day 14 Day 21 Day 28 Day 7 Day 14 Day 21 Day 28 200 400 10 50 P=0.022 10 700 180 350 9 45 9 600 8 P=0.013 160 P=0.003 8 40 P=0.026 300
Slide 11: Despite Lower T Cell Input, CD4+ Subsets at Weeks Are Higher with Omidubicel
DESPITE A LOWER T CELL INPUT, CD4+ SUBSETS AT 2 WEEKS ARE HIGHER IN PATIENTS WHO RECEIVED OMIDUBICEL Th1 CD4+ Th2 CD4+ HLA- DR+ Treg CD4+ Naïve CD4 CM CD4+ EM Day 14 Day 14 Day 14 Day 14 Day 14 Day 14 Day 14 P=0.004 70 60 P=0.001 103 cells/mL 50 40 P=0.013 P=0.005 P=0.025 30 P=0.002 P=0.002 20 10 0
Slide 12: Proportional Recovery of Different CD4+ Subsets Is Comparable
THE PROPORTIONAL RECOVERY OF DIFFERENT CD4+ SUBSETS IS COMPARABLE CD4+ Subgroups Day 14 – OMIDUBICEL CD4+ Subgroups Day 14 – UCB Th1 Th2 CD4+ HLA- DR+ Treg CD4+ Naïve CD4+ CM CD4+ EM CM, central memory cells; EM, effector memory cells; HLA, human leukocyte antigen; Th, T helper cells; Treg, T regula
Slide 13: Durability of Recovery Up to 1 Year Post-Transplant
DURABILITY OF RECOVERY OBSERVED FOR UP TO 1 YEAR POST-TRANSPLANT (DAY 100 TO DAY 365) CD4+ cells B cells NK cells Day 100 Day 180 Day 365 Day 100 Day 180 Day 365 Day 100 Day 180 Day 365 3000 6000 1000 P=0.028 P=0.001 P=0.017 900 2500 5000 800 700 2000 4000 600 1500 3000 500 400 1000 2000 300 1000 20
Slide 14: Omidubicel Supports Comparable TCR Repertoire Diversity and Thymic T Cell Output
OMIDUBICEL SUPPORTS A COMPARABLE TCR REPERTOIRE DIVERSITY AND THYMIC T CELL OUTPUT POST-TRANSPLANTATION Omidubicel UCB Clones Shannon diversity Clonality Omidubicel UCB Omidubicel UCB Omidubicel UCB Day 365 Day 180 Visit Day Day 100 Screening 10,000 20,000 30,000 10,000 20,000 30,000 6 8 10 12 6 8 1
Slide 15: CD4+ Recent Thymic Emigrants Demonstrate Recovery by One Year
CD4+ RECENT THYMIC EMIGRANTS (RTE) DEMONSTRATE RECOVERY BY ONE YEAR CD4+ RTE Day 100 CD4+ RTE Day 180 CD4+ RTE Day 365 100 100 100 90 90 90 80 80 80 70 70 70 103 cells/mL 60 60 60 50 50 50 40 40 40 30 30 30 20 20 20 10 10 10 0 0 0 Omidubicel UCB CD4+ subset / CD4+, CD31, CD45RA subset. RTE, recent t
Slide 16: Conclusions
CONCLUSIONS HSCT with omidubicel results in rapid hematopoietic recovery, reduced rates of infections, and no increase in GvHD rates compared with standard UCB In the omidubicel group, enhanced recovery of circulatory mDC, pDC, NK cell, and CD4+ T cells within the first 28 days and sustained B-cell
Slide 17: Acknowledgments
ACKNOWLEDGMENTS ¡ Patients and families who participated in this research ¡ Co-investigators and centers who participated in the substudy − Isabel Badell, Hospital Sant Pau, Spain − Claudio Brunstein, University of Minnesota, MN, USA − Olga Frankfurt, Northwestern University Hospital, IL, USA − Nels