Sellas Life Sciences Group, Inc. · NASDAQ:SLS
Sellas Life Sciences — SELLAS Life Sciences Group Inc. Conference Call (October 2018)
25 slides from Sellas Life Sciences's conference presentation, Oct 22, 2018
Slide 1: Phase 2b Clinical Data of Nelipepimut-S Plus Trastuzumab in Breast Cancer
PHASE 2B CLINICAL DATA OF NELIPEPIMUT-S PLUS TRASTUZUMAB IN BREAST CANCER OCTOBER 22, 2018 8:00 A.M. EDT/ 2:00 P.M. CET
Slide 2: Forward Looking Statements
FORWARD LOOKING STATEMENTS This presentation contains forward-looking statements. You can identify such forward-looking statements by the use of the words “expect,” “believe,” “will,” “anticipate,” “estimate,” “plan,” “project” and other words of similar import. The forward-looking statements in thi
Slide 3: Nelipepimut-S (NPS): General Background
NELIPEPIMUT-S (NPS): GENERAL BACKGROUND Elizabeth A. Mittendorf, MD, PhD Rob and Karen Hale Distinguished Chair in Surgical Oncology Director of Research, Breast Surgical Oncology Brigham and Women’s Hospital Director, Breast Immuno-Oncology Program Dana-Farber/Brigham and Women’s Cancer Center Bost
Slide 4: Nelipepimut-S: Stimulates T-Cell Activity Against HER2-Expressing Cells
NELIPEPIMUT-S: STIMULATES T-CELL ACTIVITY AGAINST HER2-EXPRESSING CELLS • Nelipepimut-S (NPS) contains the immunodominant peptide derived from the extracellular domain (ECD) of the HER2 protein • NPS is a major histocompatibility complex (MHC) class I epitope which stimulates a CD8+ CTL response • T
Slide 5: Triple-Negative Breast Cancer Is an Unaddressed Disease
TRIPLE-NEGATIVE BREAST CANCER IS AN UNADDRESSED DISEASE • Triple-negative breast cancer applies to tumors that lack the expression of ER, PR and amplification of HER2, which are therefore non-amenable to therapy with agents targeting these molecular moieties (i.e., hormone receptor and HER2 signalin
Slide 6: HER2 Is a Challenging Target When Not Overexpressed
HER2 IS A CHALLENGING TARGET WHEN NOT “OVEREXPRESSED” HER2 Is Still Detectable in High-Frequency in BC but at Much Lower Abundance vs. “Classically” HER2-Positive (IHC 3+) Tumors HER2 EXPRESSION LEVELS BY FREQUENCY HER2 “low-expressor” BC • HER2 expression is not binary but a range and, as measured
Slide 7: HER2 Overexpression May Facilitate Immune Escape
HER2 OVEREXPRESSION MAY FACILITATE IMMUNE ESCAPE • There is a significant inverse correlation between the expression of HER2 and total MHC class I (HLA-A, -B, and -C) surface expression • It has been shown that HER2 over-expressing tumors (IHC 3+) are more prone to escape from HLA-A2 restricted CTLs
Slide 8: NPS Mechanism of Action: Active Specific Immunotherapy
NPS MECHANISM OF ACTION: ACTIVE SPECIFIC IMMUNOTHERAPY NPS induces de novo anti-HER2 immune response, which stimulates production of antigen-specific CD8+ cytotoxic T lymphocytes NPS (E75)-MHC Class I Peptide-TCR complex Induces proliferation of NPS (E75) NPS-specific T-cell +GM-CSF clones Millions
Slide 9: Molecular/Cellular Basis for Nelipepimut-S Plus Trastuzumab Synergistic Effect
MOLECULAR/CELLULAR BASIS FOR NELIPEPIMUT-S PLUS TRASTUZUMAB SYNERGISTIC EFFECT IN HER2 IHC1+/2+ BREAST CANCER • Trastuzumab (TZ) is able to bind HER2 in BC cells with levels of HER2 expression lower than IHC3+ • Synergy between NPS and TZ involves significantly enhanced internalization and processin
Slide 10: NPS + Trastuzumab (TZ) Randomized Phase 2b Trial
NPS + TRASTUZUMAB (TZ) RANDOMIZED PHASE 2B TRIAL George E. Peoples, MD, FACS Director, Cancer Vaccine Development Program, The Metis Foundation Professor, Surgery, Uniformed Services University Professor (adjunct), Surgical Oncology, MD Anderson Cancer Center San Antonio, TX, USA
Slide 11: Background
BACKGROUND • Patients with HER2 low-expressing breast cancer (IHC 1–2+) are not eligible for adjuvant trastuzumab, approximately 60-70% of patients • NSABP B-47 confirmed trastuzumab does not improve outcomes in HER2 low-expressing breast cancer1 1. Fehrenbacher L, et al. SABCS 2017. Abstract GS1-02
Slide 12: Study Design
STUDY DESIGN Primary Secondary endpoint: endpoint: DFS at DFS at 24 months 36 months Other secondary GM-CSF endpoints + Randomization TZ • Safety 1:1 • Cardiac toxicity (N = 275) NeuVax • Immunologic (NP-S + GM-CSF) response + TZ Standard TZ dosing Booster series Primary vaccine series • This trial
Slide 13: Key Inclusion Criteria Assessments
KEY INCLUSION CRITERIA ASSESSMENTS • Women ≥18 years • Local and systemic toxicity • High-risk invasive breast cancer with • Cardiac toxicity HER2 expression of 1–2+ by IHC • Node Positive (+/-HR) • Immunologic in vivo response OR • Disease-free survival • Node Negative (-HR, thus TNBC) • Clinically
Slide 14: Demographics and Disease Characteristics – Active vs. Control
DEMOGRAPHICS AND DISEASE CHARACTERISTICS – ACTIVE VS. CONTROL Patient Tz (+ GM- Tz (+ GM- Demographics and NPS + Tz P- Pt Demographics & NPS + Tz CSF) P- CSF) BL Diz Baseline Disease (n = 136) (n = 139) Value (n = 136) (n = Value Characteristics Characteristics 139) Age, years 52.2 50.5 .38 ER statu
Slide 15: Timing of Analyses / Parameters Presented
TIMING OF ANALYSES PARAMETERS PRESENTED • Pre-specified interim analysis (IA) 6 months • Safety after the last patient was enrolled • Treatment-Emergent Adverse Events (TEAE) • Database Lock: early MAR. 2018 • Treatment-Related Adverse even (TRAE) • Median follow up: 18.8 months • Efficacy MARCH 28,
Slide 16: TNBC Cohort Patient Demographics & Disease Characteristics
TNBC COHORT PT DEMOGRAPHICS & DISEASE CHARACTERISTICS (FOR COMPARABILITY) Randomization Arm Randomization Arm NPS + GM-CSF + Tz Tz + GM-CSF NPS + GM-CSF + Tz Tz + GM-CSF N=53 N=45 N=53 N=45 N %age N %age P-value N %age N %age P-value Age median 52.9 55.1 AJCC7 I 10 18.9% 10 22.2% 29.4- .469 Stage ra
Slide 17: Safety: Treatment-Related Adverse Events – Final Analysis
SAFETY: TREATMENT-RELATED ADVERSE EVENTS – FINAL ANALYSIS ➢ Treatment-Emergent Adverse Events Maximum Related Graded Toxicity Per Patient 100% (TEAE) 90% • Majority were mild or moderate 80% (G1/2) 70% • Local: 98%; systemic: 93% Patients, % 60% • Majority of G3 systemic TEAEs were 50% unrelated to
Slide 18: Safety – Cardiac Ejection Fraction – Final Analysis
SAFETY – CARDIAC EJECTION FRACTION – FINAL ANALYSIS 63 • No difference between 62 treatment arms in cardiac 62 61 ejection fraction over time (P 61 = .558) and at each time point LVEF (%) 60 60 59 • The addition of NeuVax to TZ 59 did not result in any additional 58 cardiotoxicity compared with 58 N
Slide 19: ITT Population - Disease Free Survival – Final Analysis
ITT POPULATION - DISEASE FREE SURVIVAL (DFS) – FINAL ANALYSIS ITT POPULATION P = .175 HR = 0.62 (across the duration of the study) Event Probability (Ratio) 37.0% reduction in risk of recurrence or death at 24 mo. Control N = 139 Interim Analysis: Median F/U = 25.7 mo. P = .257 24-mo DFS = 83.8% HR
Slide 20: TNBC Cohort - Disease Free Survival – Final Analysis
TNBC COHORT - 97 PATIENTS (36% OF ITT) - DISEASE FREE SURVIVAL – FINAL ANALYSIS TNBC COHORT (36% of ITT) P = .013 HR = 0.260 75.2% reduction in risk of recurrence or Event Probability (Ratio) death at 24 mo. Control N=44 Interim Analysis: Median F/U = 26.1 mo. P = .023 24 mo. DFS = 70.2% HR = 0.26 M
Slide 21: No Hormone Treatment Cohort - Disease Free Survival Final Analysis
NO HORMONE TREATMENT COHORT – 110 PATIENTS (40% OF ITT) - DISEASE FREE SURVIVAL FINAL ANALYSIS NO HORMONE TREATMENT COHORT P = .008 HR = 0.246 75.9% reduction in risk of recurrence Event Probability (Ratio) or death at 24 mo. Control N=50 Interim Analysis: Median F/U = 25.6 months P = .009 24-mo DFS
Slide 22: Forest Plot for Various Cohorts – TNBC Cohort – Interim Analysis
FOREST PLOT FOR VARIOUS COHORTS BASED ON DICHOTOMOUS DATA CUTS FOR EACH VARIABLE TESTED (LOG HR SCALE) – TNBC COHORT – INTERIM ANALYSIS Relative decrease in the risk of progression or death over the study time period of 71% TNBC cohort: difference between the active and control arm persists across a
Slide 23: In Vivo Immune Response by Delayed Type Hypersensitivity
IN VIVO IMMUNE RESPONSE (IR) BY DELAYED TYPE HYPERSENSITIVITY (DTH) • There was a statistically DELAYED TYPE HYPERSENSITIVITY significant difference between 12 IR (by DTH) between the Control and Active (NPS) arms 10 Orthogonal Mean • Over time across all time 8 points: P = .002 6 • Within the Contr
Slide 24: Conclusions
CONCLUSIONS • Treatment-emergent AE’s were of mild or moderate severity − No enhanced cardiac toxicity with the combination vs. TZ alone • NPS + TZ may provide clinically meaningful benefit to patients with HER2 low‐expressing breast cancers • The NPS + TZ combination in the adjuvant setting demonst
Slide 25: Thank You!
THANK YOU!
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