Sellas Life Sciences Group, Inc. · NASDAQ:SLS
Sellas Life Sciences — 44th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) 20 (March 2018)
23 slides from Sellas Life Sciences's conference presentation, Mar 19, 2018
Slide 1: Clinical benefit after galinpepimut-S (GPS) correlates with antigen-specific immune responses in high-risk multiple myeloma
Clinical benefit after galinpepimut-S (GPS), a Wilms’ tumor 1 (WT1) immunotherapeutic, correlates with antigen-specific immune responses in high-risk multiple myeloma: Complete analysis of the Phase 2 GPS maintenance study G. Koehne, MD, PhD1,2, S. Devlin, PhD2, N. Korde, MD3, S. Mailankody, MBBS3,
Slide 2: Disclosures
Disclosures • G. Koehne is a consultant to Sellas Life Sciences Group, Inc. • Support for this study was provided by Leo A. Guthart and Kathryn Medina Research Fund in Multiple Myeloma, and Sellas Life Sciences Group, Inc. Koehne G, et al. EBMT 2018. 2
Slide 3: WT1 gene product in MM
WT1 gene product in MM • The WT1 protein is a zinc finger transcription factor – A true oncogene, with roles in cell proliferation, differentiation, apoptosis, and organ development – National Cancer Institute top-ranked antigen for anticancer immunotherapy1 • WT1 overexpression in MM cells by IHC,
Slide 4: IHC with WT1 monoclonal antibody 6F-H2 in MM
IHC with WT1 monoclonal antibody 6F-H2 in MM WT1 (red) staining of kidney biopsy CD138 (brown) staining of BM biopsy WT1 (red)/CD138 (brown) co-staining of BM biopsy BM, bone marrow; CD, cluster of differentiation; IHC, immunohistochemistry; MM, multiple myeloma; WT1, Wilms’ tumor 1. Tyler EM, et al
Slide 5: WT1 peptides are presented efficiently via an MHC/antigen complex to the TCR
WT1 peptides are presented efficiently via an MHC/antigen complex to the TCR Demonstrated by successful targeting of WT1 by TCR-like mAbs (ESK1) WT1 peptide TCR TCR-like anti-WT1 mAb Cytotoxic (ESK1) CD8+ T cell Malignant plasma cell MHC class I (HLA-A, -B, -C) CD, cluster of differentiation; HLA, h
Slide 6: Binding of anti-WT1 monoclonal antibody ESK1 to PBMCs from healthy donors
Binding of anti-WT1 monoclonal antibody ESK1 to PBMCs from healthy donors HLA-A02+ HLA-A02– 100 100 80 80 CD33 60 60 40 40 20 20 0 0 • Gated cells are listed on the 100 1 10 100 1000 10000 100 1 10 100 1000 10000 y-axis (single representative 80 80 Normal of 16 samples) CD19 60 60 40 40 20 20 0 0 1
Slide 7: ESK1 staining of MM BMMCs of a patient with plasma cell leukemia
ESK1 staining of MM BMMCs of a patient with plasma cell leukemia 3.14 95.8 0.0382 0.573 105 105 104 104 ESK1 hIgG APC- A APC- A 103 103 102 102 0 0 0.966 0.0805 3.7 95.7 0 102 103 104 105 0 102 103 104 105 FITC- A FITC-A CD38 CD38 100 100 Percentage of max Percentage of max 80 80 • BB7: mouse Ab 60
Slide 8: Heteroclitic technology-based cancer immunogens/vaccines
Heteroclitic technology-based cancer immunogens/ vaccines Heteroclitic peptide • GPS is a mixture of 2 native and 2 GPS administration (WT1 fragment) synthetic WT1 peptide sequences: Naive CD8+ the heteroclitic peptides – bearing cell point mutations (*) – were created to stimulate both CD4+ and CD8
Slide 9: GPS: Differentiated WT1 vaccine immunotherapeutic
GPS: Differentiated WT1 vaccine immunotherapeutic1–6 Multivalent immunogen – Heteroclitic peptide increases 4 peptide chains: immune response and mitigates Two of the 4 peptides are tolerance, while maintaining Peptide sequences (position) heteroclitic – bearing point antigenicity profile mutations
Slide 10: Phase 2 study of GPS in MM: Key features and GPS administration schedule
Phase 2 study of GPS in MM: Key features and GPS administration schedule N = 19 (evaluable) • GPS biweekly s.c. administration (dose • GPS monthly s.c. administration (dose Study number: • 15/19 pts HR CG*,1 of 200 μg for each of the 4 peptides) of 200 μg for each of the 4 peptides) NCT01827137 at b
Slide 11: Efficacy endpoints: Updated results
Efficacy endpoints: Updated results OS and PFS Therapeutic response*,1 over time No. of evaluable patients N = 19** N = 19** N = 16# N = 15† N = 11‡ CR and VGPR PR and SD PD Response category (%) Event probability OS, N = 19 PFS, N = 19 Median OS has not been reached to date Current median PFS: 23.6
Slide 12: PFS of MM patients with high-risk cytogenetics
PFS of MM patients with high-risk cytogenetics GPS + Len vs. Thal +/- Vel maintenance 1.0 PETHEMA 2005–001110–41 Thal +/- Vel maintenance 0.9 0.8 PFS = 12.6 months (estimated from time of ASCT) 0.7 PFS = 18.1 months Event probability 0.6 (from initiation of induction Rx) N = 19 0.5 GPS + Len GPS MSK
Slide 13: WT1-specific T-cell IRs over time: Methodology
WT1-specific T-cell IRs over time: Methodology Q1 Q2 0 0 FSC-A • Fix cells CD3+ • Permeabilize Q4 44.6 Q3 • Stain 52.0 48.0 CD3 APC PBMC WT1 peptides + Q9 35.2 Q10 0.048 sample brefeldin A FACS with gating to CD8+ and CD4+ T cells CD4PerCP Plotting against post-incubation production of IFNγ Q12 Q11
Slide 14: Induction of antigen-specific IRs (CD8/CD4) by GPS: T-cell frequencies over time
Induction of antigen-specific IRs (CD8/CD4) by GPS: T-cell frequencies over time (complete study database) Median values frequencies (cells/mL) – log scale 106 Absolute T-lymphocyte 105 3Q submedian 104 values (upper boundary of 3Q of the IQR) 103 102 1Q submedian- to-median 10 intervals* 0 At basel
Slide 15: Absolute number and percentage of patients with IR positivity (CD8/CD4) over time
Absolute number and percentage of patients with IR positivity (CD8/CD4) over time Against any of the WT1 antigenic variants of GPS Against “all-pool” WT1 fragments (cross-epitope reactivity) Timepoint Baseline Post-GPS × 6 Post-GPS × Baseline Post-GPS × 12 (pre-ASCT; N = 15) (N = 15) 12 (pre-ASCT; N
Slide 16: Rates of antigen-specific IR positivity (CD8/CD4) at the time of completion of GPS therapy
Rates of antigen-specific IR positivity (CD8/CD4) at the time of completion of GPS therapy 100 • IR+ rates for: Patients with antigen-specific IR positivity (%) – The 4 peptides in GPS 80 ▪ CD4 OR CD8: 72%–91% – The “all-pool” peptides ▪ CD4 OR CD8: 75% 60 • Up to 64% of patients 40 demonstrated IR
Slide 17: Exploratory correlations between IR positivity and clinical response
Exploratory correlations between IR positivity and clinical response (achievement of CR/VGPR) at the time of completion of GPS therapy • Rate of IR positivity in patients who achieved CR/VGPR – 81.8% demonstrated prior CD8 IR+ (N = 9) – 100% demonstrated prior CD4 IR+ (N = 11) • Rate of achievement
Slide 18: MM patients maintaining multivalent IRs were more prone to achieve clinical response
MM patients maintaining multivalent IRs (CD8/CD4) were more prone to achieve clinical response (CR/VGPR) at the time of completion of GPS therapy N=3 100 100 (patients in each individual subgroup, %) Rate of achievement of CR/VGPR 80 80 N=3 60 60 40 N=4 N=4 40 N=5 20 20 N=0 N=1 N=0 0 0 No. of native
Slide 19: Conclusions (1)
Conclusions (1) • Administration of the WT1 heteroclitic peptide mixture immunizer GPS in a Phase 2 study of 19 high-risk patients with MM has shown an excellent safety profile and a promising median PFS of 23.6 months (post-ASCT in first line) in a particularly challenging setting • Impressive, tim
Slide 20: Conclusions (2)
Conclusions (2) • Multifunctional cross-epitope T-cell reactivity was observed in 75% of patients to antigenic epitopes against which hosts were not specifically immunized, in a pattern akin to antigen cross-reactivity • A strong and bidirectional association was observed between achievement of CR/V
Slide 21: Questions?
Questions? GuentherK@baptisthealth.net Koehne G, et al. EBMT 2018. 21
Slide 22: GPS: Mechanism of action
GPS: Mechanism of action CD4 tc-PS T cell B cell MHC II i-PS CD8 Tumor cell MHC I T cell WT1 protein CD8 and CD4 Tumor cell APC T cells * * WT1 peptides in the GPS mixture (administered s.c.) Immunologically-mediated cell killing and antitumor effect *Mutated (heteroclitic) peptides. APC, antigen-pr
Slide 23: Clinical response category is associated with CD4 IR potency
Clinical response category (CR/VGPR vs. less) at the time of completion of GPS therapy is associated with CD4 IR potency (high vs. low) PR and SD CR and VGPR Rate of achievement of a specific clinical 100 80 * response category (patients, %) 70 * * 60 50 40 30 20 10 0 L H L H L H L H L H L H Aggrega