Allogene Therapeutics, Inc. · NASDAQ:ALLO
Allogene Therapeutics — Technical Presentation (December 2018)
15 slides from Allogene Therapeutics's technical presentation, December 2018
Slide 1: Preliminary Data on Safety, Cellular Kinetics and Anti Leukemic Activity of UCART19
Preliminary Data on Safety, Cellular Kinetics and Anti Leukemic Activity of UCART19, an Allogeneic Anti-CD19 CAR T-cell Therapy in Adult and Pediatric Patients with CD19+ Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia – A Pooled Analysis of the CALM and PALL Phase 1 Trials Reuben BENJAMIN,
Slide 2: R/R B-cell ALL in Children and Adults
R/R B-cell ALL in Children and Adults • Prognosis of R/R ALL is very poor (<10% overall survival) • Standard therapy involves combination of chemotherapy ± allogeneic SCT • New treatments include BiTEs, ADCs and autologous CAR T-cell therapies • Still unmet medical need in advanced R/R ALL • The “of
Slide 3: UCART19: the First Off the Shelf Anti-CD19 Allogeneic CAR T-cell Therapy
UCART19: the First “Off the Shelf” Anti-CD19 Allogeneic CAR T-cell Therapy Transgene expression using lentiviral transduction • CAR: anti-CD19 scFv and CD3ζ + 4-1BB • RQR8 (= CD20 mimotope): safety switch Gene knock-out using TALEN® technology • TRAC KO: to prevent TCR mediated recognition of patien
Slide 4: PALL / CALM – Study Main Objectives
PALL / CALM – Study Main Objectives Objectives PALL (pediatric study) CALM (adult study) Primary • Safety and tolerability of • Safety and tolerability of UCART19 UCART19 • Determine maximum tolerated dose (MTD) and lymphodepleting (LD) regimen Secondary • Remission rate at D28 Exploratory • Anti-le
Slide 5: PALL / CALM Study Schema
PALL / CALM Study Schema Single Response and End of UCART19 Safety/DLT Study infusion assessments Response assessment Response assessments Patient Inclusion consent Optional redosing with UCART19 Lympho- Screening Treatment period Follow-up period LTFU study depletion D-21 D-7 D0 D28 M3 M12 Safety a
Slide 6: PALL / CALM Key Eligibility Criteria
PALL / CALM Key Eligibility Criteria Inclusion Criteria • Age: PALL from 6 months to <18 yrs; CALM from 16 yrs to <70 yrs • Patients with CD19+ relapsed or refractory (R/R) B-ALL ü R/R defined as ≥ 2nd BM relapse or any BM relapse after allo-HSCT or chemorefractory ü morphologically confirmed (≥ 5%
Slide 7: High-Risk, Heavily Pretreated Patients
High-Risk, Heavily Pretreated Patients Baseline Characteristics PALL (N =7) CALM (N =14) POOLED (N =21) Median age (range) - years 2.7 (0.8-16.4) 29.5 (18-62) 22 (0.8-62) Number of previous lines of therapy 1 to 3 3 4 7 ≥4 4 10 14 Median (range) 4 (2-6) 4 (1-5) 4 (1-6) High cytogenetic risk * 3 6 9
Slide 8: PALL / CALM - Patients Status
PALL / CALM - Patients Status Cut-off date: 23 Oct 2018 Screened (N= 31) 10 screen failures (7 CALM, 3 PALL) * 1 additional death was reported post cut-off date 8
Slide 9: UCART19 Shows an Acceptable Safety Profile
UCART19 Shows an Acceptable Safety Profile G1 G2 G3 G4 G5 All grades N=21 n (%) n (%) n (%) n (%) n (%) n (%) AEs related to UCART19 Cytokine release syndrome 4 (19.0) 12 (57.1) 2 (9.5) 1* (4.8) - 19 (90.5) Neurotoxicity events 7 (33.3) 1 (4.8) - - - 8 (38.1) Acute skin graft-versus-host disease **
Slide 10: 82% Achieved CR/CRi in FCA-treated Population
82% Achieved CR/CRi in FCA-treated Population - CR/CRi: 14/17 pts in FCA-treated pts - MRD-: 10/14 pts (71%) * - Allo-SCT: 11/14 pts (78%) - Overall CR/CRi: 14/21 pts (67%) ** UCART19 infusion * This patient died post cut-off date Patient in MRD- status after 2 dose, underwent allo-SCT (data reporte
Slide 11: UCART19 Kinetics Measured by qPCR and Flow
UCART19 Kinetics Measured by qPCR and Flow UCART19 by qPCR UCART19 by flow PALL (n=6) CALM (n=14) + PALL (n=1) • UCART19 expansion observed in 15/17 pts with FCA • UCART19 expansion observed in 0/4 pts with FC • 3 pts had UCART19 persistence beyond D42 and upto D120 in 1 pt • Response is linked to e
Slide 12: Trend for a Deeper and More Sustained Host T-cell Depletion with FCA
Trend for a Deeper and More Sustained Host T-cell Depletion with FCA Maximum value of the cell range is plotted from the CALM study 12
Slide 13: Redosing Allowed Further UCART19 Expansion
Redosing Allowed Further UCART19 Expansion and 2 out of 3 pts Achieved MRD- 200 First infusion (FCA) Second infusion (FC) UCART19 count (cell/µl) ü Patient 1 150 • MRD- at D28 100 • Relapse and 2nd infusion 3 months after 1st dose 50 • MRD- at D28 after redosing 0 0 3 7 10 14 17 21 24 28 day 200 Fir
Slide 14: Key Messages
Key Messages • 82% (14/17) CR/CRi rate in FCA-treated pts – 71% (10/14) achieved MRD- status – 67% (14/21) CR/CRi rate in overall population – No UCART19 expansion and no response in 4/4 FC-treated pts • UCART19 has shown an acceptable safety profile: – no moderate/severe acute GvHD, no severe neuro
Slide 15: Acknowledgements
Acknowledgements § Patients participating in CALM & PALL trials and their families § Teams involved in UCART19 studies at study centres, Servier and Allogene teams PALL trial active centers - Great Ormond Street Hospital, London, UK - W. Qasim - Hospital Robert Debré, Paris, France - A. Baruchel CAL
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