Sellas Life Sciences Group, Inc. · NASDAQ:SLS
Sellas Life Sciences — Investor Day (November 2019)
83 slides from Sellas Life Sciences's investor day presentation, Nov 15, 2019
Slide 1: R&D Day 2019 Welcome and Introductions
R&D Day 2019 Welcome and Introductions Angelos M. Stergiou, MD, ScD h.c. New York City, NY 15 November 2019 NASDAQ: SLS
Slide 2: Forward Looking Statements
2 FORWARD LOOKING STATEMENTS Today’s presentations contain 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 i
Slide 3: Agenda
3 AGENDA Sellas Life Sciences KOL Breakfast Symposium Galinpepimut-S (GPS): The Next Generation of Cancer Immunotherapy 8:15 - 8:25 Welcome and Introduction Dr. Angelos Stergiou, President & CEO of SELLAS Life Sciences 8:25 - 8:45 Acute Myeloid Leukemia (AML) Landscape Dr. Hagop M. Kantarjian, Unive
Slide 4: Company Overview
COMPANY OVERVIEW ¢eLLAS (i Vike SCIENCES GROUP
Slide 5: Late-Stage Cancer Immunotherapy Company
LATE-STAGE CANCER IMMUNOTHERAPY COMPANY Pivotal Phase 3 • Galinpepimut-S (GPS) WT1 peptide immunotherapy • Acute myeloid leukemia (AML) in second complete remission (CR2) Development • Orphan drug designation (ODD) and fast track status Program • Trial to be initiated by end of 2019 Innovative • Inv
Slide 6: Experienced Management Team
EXPERIENCED MANAGEMENT TEAM NAME POSITION PRIOR EXPERIENCE / AFFILIATIONS President, Chief Angelos Stergiou, M.D., ScD h.c. Executive Officer Chief Medical Nicholas J. Sarlis, M.D., Ph.D., FACP Officer EVP, General Counsel & Barbara Wood, J.D. Corporate Secretary VP, Finance & John T. Burns, CPA Cor
Slide 7: GPS: Engineered & Differentiated Immunotherapy
GPS: ENGINEERED & DIFFERENTIATED IMMUNOTHERAPY WT1: #1 ranked immunotherapy target by Heteroclitic peptide increases the NCI; oncogene, which is immune response and mitigates highly tumor selective, tolerance, while maintaining found in cancer cells and antigenicity profile cancer stem cells GPS Pep
Slide 8: Clinical Data Overview
Clinical Data Overview Galinpepimut-S (GPS): WT1 peptide vaccine In settings of Minimal Residual Disease/ low disease burden → used as maintenance monotherapy • Acute myeloid leukemia (AML): In CR1 setting, Phase 2 study with older patients (≥60 years; historical controls: ~12 months) median overall
Slide 9: Development Pipeline: GPS
DEVELOPMENT PIPELINE: GPS PROGRAM PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Galinpepimut-S – Multiple Indications Acute Myeloid Leukemia (AML) Basket Study in combination w/pembrolizumab Malignant Pleural Mesothelioma (MPM) in combination with nivolumab Malignant Pleural Mesothelioma (MPM) Multiple Myelom
Slide 10: Anticipated GPS Near-Term Milestones
ANTICIPATED GPS NEAR-TERM MILESTONES Program Milestone Projected Date AML PH3 Start AML Phase 3 randomized trial Q4 2019 MPM Combo Start MPM Phase 1 trial in combination with nivolumab Q4 2019 First set of clinical data from Phase 1/2 combination trial with PD-1 Basket Study 2H 2020 inhibitor (pembr
Slide 11: Board of Directors
BOARD OF DIRECTORS NAME POSITION PRIOR EXPERIENCE / AFFILIATIONS Board Chair, Nominating and Jane Wasman Governance Committee Chair Angelos Stergiou, MD, ScD h.c. Chief Executive Officer John Varian Audit Committee Chair Compensation Robert Van Nostrand Committee Chair Science Committee Dr. David Sc
Slide 12: Scientific Advisory Board – World Renowned Experts in Immunotherapy and Oncology
SCIENTIFIC ADVISORY BOARD – WORLD RENOWNED EXPERTS IN IMMUNOTHERAPY AND ONCOLOGY NAME POSITION Deputy Director of the Perlmutter Cancer Center, Co-director of the Melanoma Research Jeffrey Weber, M.D., Ph.D. - Chair Program at the New York University (NYU)-Langone Cancer Center Chief, Melanoma & Imm
Slide 13: Agenda
3 Sellas Life Sciences KOL Breakfast Symposium Galinpepimut-S (GPS): The Next Generation of Cancer Immunotherapy AGENDA 8:15 - 8:25 Welcome and Introduction 8:15 - 8:25 Sellas Dr. LifeStergiou, Angelos Sciences KOL Breakfast President Welcome and Introduction Symposium & CEO of SELLAS Life Sciences
Slide 14: Acute Myeloid Leukemia (AML) Therapeutic Landscape
Acute Myeloid Leukemia (AML) Therapeutic Landscape Hagop M. Kantarjian, MD Professor and Chair of the Department of Leukemia Samsung Distinguished Leukemia Chair in Cancer Medicine The Univ. of Texas – M D Anderson Cancer Center Houston, Texas
Slide 15: Overview of AML Therapeutic Landscape: 1973 - 2017
Overview of AML Therapeutic Landscape: 1973 - 2017 Yates, Cancer Chemother Rep. 1973 First Line: Intensive Remission Induction ChemoRx followed by Allogeneic SCT Relapse Second Line: Salvage ChemoRx For Patients Unable to Undergo or Declining Intensive Remission Induction: Low-intensity Chemotherapy
Slide 16: Overview of AML Therapeutic Landscape: 2017 to Today
Overview of AML Therapeutic Landscape: 2017 to Today Major Changes Due to Introduction of Novel, More Effective and Generally Better Tolerated Molecularly Targeted Therapies Recognition of the Complexity of the Genomic Landscape (Molecular Heterogeneity) of AML 16 Papaemmanuil, N Engl J Med. 2016
Slide 17: AML Therapeutic Landscape (any line of Rx) - 2019
AML Therapeutic Landscape (any line of Rx) - 2019 Approved Agents & Corresponding Molecular Targets (excluding standard cytotoxic ChemoRx) Target Agent (Marketed products and Agents in Clinical Studies) Bcl2 Venetoclax CD123 Tagraxofusp-erzs^ (approval for BPCDN) CD33 Gemtuzumab ozogamicin; Actimab-
Slide 18: Focus on Relapsed/Refractory (R/R) AML
Focus on Relapsed/Refractory (R/R) AML Standard Definitions (ELN) • Primary refractory disease • No CR or CRi after 2 courses of intensive induction treatment; excluding patients with death in aplasia or death due to indeterminate cause • Relapse • Hematologic (morphological) relapse: bone marrow bl
Slide 19: Common salvage regimens in patients not responding to a 1st induction cycle
Common salvage regimens in patients not responding to a 1st induction cycle or with relapsed disease who are candidates for intensive therapy Döhner, Blood. 2017 19
Slide 20: CR Rates with Various Salvage Regimens in R/R AML
CR Rates with Various Salvage (2nd Line) Regimens using Conventional Chemotherapy in R/R AML Patients Complete Remission Rate (%) Megias-Vericat, Ann Hematol. 2018 20
Slide 21: Median Overall Survival with Various Salvage Regimens
Median Overall Survival (OS) with Various Salvage Regimens using Conventional Chemotherapy in R/R AML Patients Median Overall Survival (Months*) *From the time of relapse (not time of achievement of CR2) Megias-Vericat, Ann Hematol. 2018 21
Slide 22: Outcomes in R/R AML Patients: Persistence of Large Unmet Medical Need
Outcomes in R/R AML Patients Treated in Rand. Clinical Trials: Persistence of Large Unmet Medical Need Trends in CR rates (%) over time Experimental Treatments Standard Treatments “No … improvement in disease outcomes, including OS, in RR AML patients treated within randomized clinical trials over T
Slide 23: AML Outcomes by Age: ECOG Data
AML Outcomes by Age: ECOG Data Relapse 5-Yr OS Rates Pts N CR1, % rates, % From Relapse, % Age ≤ 55 yrs 1,699 68 35 11 Age > 55 yrs 742 49 65 6 Rowe, ASH Abst. 546, Blood. 2005; Ganzel, Am J Hematol. 2018 23
Slide 24: Survival for Pts With Relapsed AML
Survival for Pts With Relapsed AML Effect of Duration of Historical CR1 1.0 Probability of Survival 0.8 0.6 0.4 0.2 0 0 26 52 78 104 130 156 182 208 234 260 Wks Wks Pts Censored of CR1 Pts Deaths at > 1, 2 Yrs CR1 <12 mo 0-26 436 413 0, 0 mOS ~ 5-6 mo (78% of pts) 27-52 175 162 2, 0 53-78 98 86 6, 3
Slide 25: Most AML Patients Die Within 1 Year After R/R Disease Diagnosis
Most AML Patients Die Within 1 Year After R/R Disease Diagnosis No. ORR, % mOS* Therapy Data Source Pts (CR + CRi) (mo) IDAC VALOR (phase III study)[1] 355 19 6.1 Intensive salvage^ Phase II study[2] 44 41 6.3 Investigator’s choice† CLAVELA (phase III study)[3] 190 21 3.3 Hypomethylating Multicenter
Slide 26: The Advent of FLT3 Inhibitors: ADMIRAL Study Design
The Advent of FLT3 Inhibitors ADMIRAL Study Design N = 371 2:1 Abbreviations: FLAG-IDA, fludarabine, cytarabine, and granulocyte- • Median age: 60 years colony stimulating factor with idarubicin; HSCT, hematopoietic stem cell transplant; LoDAC, low dose cytarabine; MEC, mitoxantrone, • Relapsed AML
Slide 27: ADMIRAL Study Primary Endpoint: Overall Survival
ADMIRAL Study Primary Endpoint: Overall Survival (Interim Analysis) Gilteritinib: median OS 9.3 mo (95% CI: 7.7, 10.7) vs. 5.6 mo with salvage chemotherapy (95% CI: 4.7, 7.3) HR = 0.64 (95% CI: 0.49, 0.83); P=0.0004 Gilteritinib Gilteritinib Perl, AACR Abst. CT184, Cancer Res. 2019 27
Slide 28: ADMIRAL Study CRc Rates and Duration
ADMIRAL Study CRc Rates and Duration (Final Analysis) Gilteritinib Salvage Chemotherapy Characteristics N=247 N=124 CRc Rate (%) Median 54.3% (47.8-60.6) 21.8% (14.9-30.1) Duration of CRc (95% CI), weeks Median 4.6 (3.7-7.7) Not estimable (NE) (1.8-NE) Perl, AACR Abst. CT184, Cancer Res. 2019; Xospa
Slide 29: The Advent of IDH Inhibitors: Enasidenib in R/R AML
The Advent of Isocitrate Dehydrogenase (IDH) Inhibitors: Pro-differentiating Effect in AML in Pts with IDH mutations IDH2 Inhibitor Enasidenib (AG-221) in R/R AML Pts with IDH2 mutations Response Enasidenib Pts With IDH2 Mutations (%) and mOS (N = 239) (mo) in R/R 100 mg QD All Doses* AML Pts (n = 1
Slide 30: Ivosidenib in R/R AML Pts with IDH1 mutations
Ivosidenib in R/R AML Pts with IDH1 mutations Efficacy Results in Patients Receiving Ivosidenib 500 mg QD (N = 125) CR+CRh 30.4% CR 21.6% Median duration of CR+CRh 8.2 mo Median duration of CR 9.3 mo Overall response rate (CR+CRi/CRp+PR+MLFS) 41.6% • Toxicities: • Most common AEs (n=258): Diarrhea (
Slide 31: Treatment Algorithm for Relapsed/Refractory AML
Treatment Algorithm for Relapsed/ Refractory AML Modified from Thol, Blood. 2015 31
Slide 32: Wilms Tumor (WT1) Protein: A Top-Priority Target for Immunotherapy in AML
Wilms Tumor 1 (WT1) Protein: A Top-Priority Target for Immunotherapy in AML • WT1 is broadly detectable in hematological malignancies, including AML (where it is densely and almost universally expressed)1 as well as assorted solid tumors; not found appreciably in adult tissues, which lowers potentia
Slide 33: Galinpepimut-S: Peptide Vaccine with Uniquely Differentiated Properties
Galinpepimut-S (GPS): Peptide Vaccine with Uniquely Differentiated Properties as an IO Agent in AML Pinilla-Ibarz, Leukemia. 2006; Gomez-Nunez, Leuk Res. 2006; May, Clin Cancer Res. 2007; Maslak, Blood. 2010; Krug, Cancer Immunol Immunother. 2010 IO: immuno-oncology 33
Slide 34: GPS: Clinical and Immune Response Data as post-CR Maintenance in AML
GPS: Impressive Clinical and Immune Response Data when Administered as post-CR Maintenance in AML CR1 Setting CR2 Setting OVERALL SURVIVAL (ALL AGES) OVERALL SURVIVAL (MEDIAN AGE = 74) mOS = NR (>67.6 mo) mOS = 16.3 mo ---- Control ---- GPS Controls: mOS= 5.4 mo N = 10 N = 15 Time since achievement
Slide 35: Previously Reported Outcomes in Matching Control Populations
Previously Reported Outcomes in Matching Control Populations CR1 Setting; Patients Older than 65 yrs Smith, Blood Rev. 2011; Lowenberg, N Engl J Med. 2009; Pollyea, Haematologica. 2013; Kantarjian, Blood. 2010; Freeman, J Clin Oncol. 2013; Maslak, Blood Adv. 2018; SELLAS, data on file. N.B.: All med
Slide 36: Galinpepimut-S WT1 Vaccine: Randomized Pivotal Phase 3 Study in AML
Galinpepimut-S WT1 Vaccine: Randomized Pivotal Phase 3 Study in AML Patients for Maintenance Therapy After CR2/CR2p • Primary Endpoint: Median Overall Survival (mOS) • Secondary Endpoints • Toxicity • Efficacy (LFS; MRD) CR: complete remission; GM-CSF: granulocyte-macrophage colony • Exploratory End
Slide 37: AML Competitive Landscape For Agents Given After Second Line Rx
AML Competitive Landscape For Agents to Be Given After Second Line Rx With or After Allo-SCT Phase 3 or 4 Studies Phase 2 Studies FLT3- or IDH-targeting With or After Allo-SCT • Plerixafor (Mozobil) • Azacitidine (+ DLI) • ALT-803 (haplo NK cells) • MG4101 (NK cells) Other Agents (non-IO), but with
Slide 38: Patient Flow Towards Post-CR2 Maintenance in AML
Patient “Flow” Towards Post-CR2 Maintenance in AML → Candidate Position of GPS: A Potential New Treatment Paradigm 38
Slide 39: Evolving Treatment Landscape for Patients Achieving CR2: Key Take-away Points
Evolving Treatment Landscape for Patients Achieving CR2 after Salvage Therapy for R/R AML Conclusions and Key Take-away Points ➢ R/R AML remains a huge unmet clinical need ➢ Newly introduced 2nd line therapies have led to modest improvements in molecularly predefined populations (FLT3, IDH mut), wit
Slide 40: Cancer Vaccines
Cancer Vaccines Javier Pinilla-Ibarz, MD, PhD Senior Member & Director of Immunotherapy Department of Malignant Hematology Moffitt Cancer Center Tampa, Florida
Slide 41: General Mechanism of Action of Therapeutic Cancer Vaccines
General Mechanism of Action of Therapeutic Cancer Vaccines Cancer cells express some antigens recognized by the host immune system, and present the peptide derived from this antigen/HLA class I complex on the cell surface. Antigen-specific cytotoxic lymphocytes that are elicited by peptide-based can
Slide 42: Wilms Tumor (WT1) Protein: A Top-Priority Target for Immunotherapy
Wilms Tumor 1 (WT1) Protein: A Top-Priority Target for Immunotherapy • WT1 is broadly detectable in hematological malignancies, including AML (where it is densely and almost universally expressed)1 as well as assorted solid tumors; not found appreciably in adult tissues, which lowers potential off-t
Slide 43: GPS: Novel Peptide Mixture Engineered for Differentiated Immunotherapy
GPS: Novel Peptide Mixture Engineered for Differentiated Immunotherapy Pinilla-Ibarz, Leukemia. 2006; Gomez-Nunez, Leuk Res. 2006; May, Clin Cancer Res. 2007; Maslak, Blood. 2010; Krug, Cancer Immunol Immunother. 2010 43
Slide 44: GPS Has Shown Activity Across Multiple HLA Types
GPS has Shown Activity Across Multiple HLA types, Potentially Allowing for Treatment of Global Pt populations Composition and Immunobiological Features of GPS Galinpepimut-S addresses 25 WT1 epitopes predicted to be reactive with 10 HLA-A and HLA-B Alleles (MHC-type I) and numerous HLA-DRB1-XX Molec
Slide 45: GPS: Heteroclitic Technology-Based, First-in-Class Peptide Vaccine
GPS: Heteroclitic Technology-Based, First-in-Class Peptide Vaccine with Direct Anti-Cancer Immunizing Properties • GPS is a mixture of 2 native and 2 synthetic (heteroclitic) WT1 peptide sequences • Heteroclitic peptides: A. have higher affinity for HLA B. are prone to break tolerance and C. generat
Slide 46: GPS Immunization is Associated with Epitope Spreading
GPS Immunization is Associated with Epitope Spreading 1,2: A Key Element for a Clinically Successful Cancer Immunotherapy • Reactivity of lymphocytes from pts treated with GPS tested against a collection of overlapping peptide GPS-specific T-Tells recognize and epitopes of the entire WT1 protein (~2
Slide 47: Comparison Among WT1-Targeting Vaccines
Comparison Among WT1-Targeting Vaccines DSP-7888 (nelatimotide/ OCV-501 GPS (Galinpepimut-S) Parameters of Interest adegramotide) Otsuka SELLAS Dainippon Number of Peptides 2 1 4 126-134^, 427-445, 331-352, WT1 Amino Acids 235-243, 126-133 335-350 122-140^ Heteroclitic Yes No Yes HLA-A-201, A301, A2
Slide 48: Ph1 (Pilot) and Ph2 Study Design in AML Patients: GPS Maintenance in CR1
Ph1 (Pilot)1 and Ph22 Study Design in AML pts GPS Maintenance Rx in CR1 Duration of therapy: Up to 15 mo ➢ Treatment: ➢ Eligibility: • Age > 18 y • GPS (s.c. administration): • AML in first complete response (CR1) - Four WT1 peptides (200 mg each; total amount of GPS mixture per • Completion of indu
Slide 49: Positive Ph2 Clinical Results in AML (in CR1)
Positive Ph 2 Clinical Results in AML (in CR1)1 • Primary endpoint of 3-year OS > 34% was met → 47.4% • Prolonged median overall survival: 67.6 months (all ages) (vs current SOC of 17.5 - 25 mo) • Aggregate population of patients > 60 years (Phase 3 population): median overall survival (mOS) = 35.3
Slide 50: GPS: Phase 2 Study Overall Survival Results in AML (CR1)
GPS: Phase 2 Study- Overall Survival Results in AML (in CR1)1,2 Source for hist controls (blue curve): Source for hist controls (yellow curve): • Pts in the Freeman cohort comparable Walter RB, et al. J Clin Oncol. 2010; 28:1766-71. Freeman SD, et al. J Clin Oncol. 2013; 31:4123-31 to the GPS study
Slide 51: GPS Pilot Study (Moffitt CC) – Efficacy Results
GPS Pilot Study (Mof fitt CC) – Ef ficacy Results 1 Maintenance in Adult CR2 AML Patients with W T1(+) Disease (After Completion of salvage therapy with adequate reconstitution of blood counts) OVERALL SURVIVAL RELAPSE-FREE SURVIVAL ---- Control ---- Control ---- Galinpepimut-S Patients ---- Galinpe
Slide 52: GPS Pilot Study (Moffitt CC): Other Key Results
GPS Pilot Study (Moffitt CC) Maintenance in Adult CR2 AML Patients: Other Key Results1 Drug-Related Adverse Events (N=16)* Evaluable N=10 • Median age: 74 yrs • All pts had documented MRD (+) status at time of study entry • Mean interval between achievement of CR2 status and first GPS administration
Slide 53: GPS Pilot Study: Vaccine Induces Antigen-Specific IFNg Production
GPS Pilot Study (Moffitt CC): Vaccine Induces Antigen- Specific IFNg Production by Patients’ T-Cells1 CC: Cancer Center; ELISPOT: enzyme-linked immune absorbent spot 1. Brayer, ASCO Abst. 3089, J Clin Oncol. 2014 (assay); IFNg: interferon-gamma 53
Slide 54: GPS Pilot Study: Patients Maintained Molecular Remission
GPS Pilot Study: Patients who Continued on Per-Protocol Vaccinations were Able to Maintain Molecular Remission (MRD measured by WT1 PCR) 1. Brayer, ASCO Abst. 3089, J Clin Oncol. 2014 MRD: minimal residual disease; GPS: galinpepimut-S qRT-PCR: quantitative real-time polymerase chain reaction 54
Slide 55: Competitive Immunotherapy Landscape in AML
Competitive Immunotherapy Landscape in AML Name of Agents/Product with Manufacturer Class Immunologically-mediated MOA* Anti-CD45-RAI conjugate - Myeloablative agent -- prior to Actinium Pharmaceuticals Iomab-B CD45 Allo-SCT Amgen AMG 330 & AMG 673 anti-CD33/CD3 BiTE antibodies AMG 427 FLT3/CD3 BiTE
Slide 56: Key Take-Away Points
Key Take-Away Points ✓ GPS is a Sophisticated First-in-Class Heteroclitic, non-HLA-Restricted Peptide Vaccine, Specifically Designed to Induce both CD8+ and CD4+ Immunoresponses ✓ GPS has Multiple Innovative Properties Optimal for both the Current and Future Immuno- Oncology Landscape in AML and oth
Slide 57: Phase 3 Trial of GPS in AML (CR2 Setting) Clinical Overview
Phase 3 trial of GPS in AML (CR2 Setting) Clinical Overview Nicholas J. Sarlis, MD, PhD Chief Medical Officer New York City, NY - 15 November 2019
Slide 58: Clinical Study Introduction
Clinical Study Introduction A Randomized, Open-Label Study of the Efficacy and Safety of Galinpepimut-S (GPS) Maintenance Monotherapy Compared to Investigator's Choice of Best Available Therapy in Subjects with Acute Myeloid Leukemia Who Have Achieved Complete Remission After Second-Line Salvage The
Slide 59: Study Objectives
Study Objectives Primary Endpoint - Comparison of the efficacy (median Overall Survival; mOS) of GPS monotherapy (active arm) vs. Investigator's choice of Best Available Therapy (BAT - control arm) in the maintenance setting post-CR2/CR2p Secondary Endpoints - Toxicity: ➢ Safety & tolerability of GP
Slide 60: Trial Schema and Design: N=116
Trial Schema and Design: N=116 • Galinpepimut-S (200 µg of each peptide x 4; total 800 µg) • Montanide (500 µl/ dose) • AML in CR2 post-2nd line Rx in patients ≥ 18 • GM-CSF (sargramostim; Leukine® ; yrs (incl. CR2p, but with adequate WBC 70 µg/dose; d-2 & d0) counts) • Ineligible/unable to undergo
Slide 61: Study Treatments
Study Treatments Active Arm: GPS Administration Schedule Control Arm (Physician Choice): All drugs are administered per label/ NCCN/ ASCO/ ASH/ EHA guidelines, per standard of care ➢Stratum 1: Observation1 ➢Stratum 2: Low-dose Cytarabine (Ara-C) (LDAC)2 ➢Stratum 3: Hypomethylating Agent ✓ Decitabine
Slide 62: Statistical Considerations (Top-Line)
Statistical Considerations (Top-Line) • Planned number of deaths is 105 (out of a total N of 116) at the time of Final Analysis (FA) • At least 90% power under an assumed hazard ratio (HR) of 0.52, based on a mOS of 5.4 mo (BAT) vs. 10.4 mo (GPS) (92.6% relative difference) • Overall 1-sided signifi
Slide 63: Current Operational Status
Current Operational Status • Study design and statistics discussed and precleared with FDA • Global full-service CRO contracted and fully engaged • Worldwide Clinical Trials; www.worldwide.com • Reach out process initiated in multiple sites in all selected countries (US, Germany, Belgium, Netherland
Slide 64: Thank you
Thank you ¢eLLAS (i Vike SCIENCES GROUP
Slide 65: PD-1 Blockade Alone and in Combination with Vaccines: Rationale for Combination with GPS
PD-1 blockade alone, in combination with vaccines, and the rationale for its combination with Galinpepimut-S: Results to-date and ongoing clinical studies Jeffrey S. Weber, MD, PhD Deputy Director, Laura & Isaac Perlmutter Cancer Center Co-Director, Melanoma Program & Head of Experimental Therapeuti
Slide 66: The End of the Beginning…
PD-1/PDL1 Blockade is an Established Therapeutic in Oncology with Registrations in Multiple Cancers: The End of the Beginning… … • It is now being applied in earlier stages of disease: Metastatic Refractory Disease → Metastatic/Advanced Disease 1st Line → Adjuvant Therapy in Low Tumor Burden/NED Set
Slide 67: PD-1/PDL1 Blockade: Continued Challenges, Immune-related Adverse Events
The bad news: PD-1/PDL1 Blockade: Continued Challenges Immune-related Adverse Events (irAEs) Champiat, Ann Oncol. 2016 67
Slide 68: PD-1/PDL1 Blockade: Resistance to CPI Effect
The bad news: PD-1/PDL1 Blockade: Continued Challenges Resistance to CPI Effect → Key Mechanism Underlying the Lack of Universal Clinical Efficacy of CPIs Across Indications/Tumor Types Where oncologic vaccines may help Modified from Jenkins, Br J Cancer. 2018 68
Slide 69: Molecular Locus of Action of Various IO Therapies
Molecular Locus of Action of Various IO Therapies The Basis for Synergy Between CPIs and Cancer Vaccines Antigen-Specific Peptide Vaccine The T-cell receptor (TCR) binds to an antigen found on the MHC on the surface of the cancer cell (1) Stimulatory response activates T cells to remove cancer cells
Slide 70: Paradigms For Clinical Uses of Cancer Vaccines
Paradigms For Clinical Uses of Cancer Vaccines • AS MONOTHERAPY OR IN COMBINATION WITH APPROVED ADJUVANT IMMUNOTHERAPIES IN THE MAINTENANCE/ ADJUVANT SETTING SURGERY, OR UPFRONT Lack of demonstrable ADMINISTRATION OF TUMOR DEBULKING tumor burden: OPTIMIZED VACCINE • Complete Remission • Surgery; or:
Slide 71: PD-1 Blockade with Neoantigen Peptide Vaccine
PD-1 blockade with Neoantigen Peptide Vaccine Ott, Nature. 2017 71
Slide 72: Peptide T-cell Responses After PD-1 Blockade
Peptide T-cell Responses After PD-1 Blockade 72 Ott, Nature. 2017
Slide 73: Ph1 Study of Peptide Vaccine Plus Nivolumab in Melanoma and NSCLC
Ph1 Study of Peptide Vaccine (from NEON) Plus Nivolumab in Melanoma and NSCLC - Does Vaccine Increase PD-1’s Clinical Benefit? Ott. Abst. P437, SITC 2019 73
Slide 74: HPV Long Peptide Vaccine + PD-1 Blockade in Oropharyngeal Cancer
HPV Long Peptide Vaccine + PD-1 blockade in Oropharyngeal Cancer (OPC)1 • 33% ORR is better than expected • 14-18% ORR with PD-1 alone2,3 1. Massarelli, JAMA Oncol. 2018; 2. Seiwert, Lancet Oncol. 2016 (Keynote-012 Study); 3. Cohen, Lancet. 2019 (Keynote-040 results) 74
Slide 75: Galinpepimut S (GPS) + Nivolumab Pilot Study in Ovarian Cancer
Galinpepimut S (GPS) + Nivolumab Pilot Study in Ovarian Cancer Patients with WT1(+) Recurrent Ovarian Cancer in 2nd or Greater Remission Study Schema (Open Label) Start of All eligible patients start GPS/Nivo within 4 months of completion of last chemotherapy Study (while in clinical remission/ no e
Slide 76: GPS + Nivolumab Pilot Study in Ovarian Cancer: Clinical Results
GPS + Nivolumab Pilot Study in Ovarian Cancer: 2nd/3rd Line Therapy, Clinical Results1 • Patient Characteristics: • N = 11 PFS (n=10) 1-Yr • 7 pts were in second remission and 4 pts were in third remission • Clinical activity • Landmark 1-year PFS rate = 70% in pts who received >1 dose of GPS + nivo
Slide 77: GPS + Nivolumab Pilot Study in Ovarian Cancer: Immunologic Results
GPS + Nivolumab Pilot Study in Ovarian Cancer: Immunologic Results • Immune responses WT1-specific IgG titers over time • WT1-specific IgG observed in 86% of pts (wks 6 – 27) • CD4 and CD8 T-cell responses also observed (wks 6 – 15) • IgG reactivity was seen both against all 4 individual peptides wi
Slide 78: GPS + Nivolumab Pilot Study: Peripheral Blood Lymphocyte Dynamics
GPS + Nivolumab Pilot Study in Ovarian Cancer: Peripheral Blood Lymphocyte Subpopulation Dynamics & T-cell Surface Activation Marker Distribution (non-antigen-specific) GPS + Nivolumab administration was associated with time-dependent: • Decrease in the expression of PD-1 in both CD4 and CD8 T-cells
Slide 79: GPS + Nivolumab Pilot Study in Malignant Pleural Mesothelioma
GPS + Nivolumab Pilot Study in Malignant Pleural Mesothelioma (MPM) Study Schema Single-arm Pilot study in relapsed (2nd line) or refractory MPM (Study # MSK17-654; NCT04040231) Key Study Features • Principal Investigator: Marjorie Zauderer, MD (MSKCC) • Independent-Sponsored Trial (IST); supported
Slide 80: Merck Combo Study: Pembrolizumab + Galinpepimut-S in 5 Tumor Types
Merck Combo Study Pembrolizumab + Galinpepimut-S in 5 tumor types: SLSG17-201 / MRK KN 770 (NCT03761914) - ‘Basket’ type, U.S. only study Initiated and Currently On-going Schema Currently prioritized indications (arms) Safety ORR (RECIST) (solid tumors) Morphologic CR (incl. CRi/CRp) (AML) 80 N.B.:
Slide 81: Merck Combination Study: Investigational Therapy Schedule
Merck Combination Study: Investigational Therapy Schedule • Up to 20 pts – for each of the Priority arms (OvC and CRC) • Up to 90 pts – for all 5 arms Co-Principal Investigators Roisin O’Cearbhaill, MD Richard Maziarz, MD Research Director Medical Director Gynecologic Medical Adult BMT & Cellular On
Slide 82: GPS + Checkpoint Inhibitors: Conclusions and Key Take-away Points
GPS + Checkpoint Inhibitors Potential for Synergistic Effective Immunotherapy Across Multiple Tumor Types Conclusions and Key Take-away Points • PD-1 antibodies have clinical activity across multiple histologies, inducing responses with long duration • Multiple lines of evidence, now clinical, sugge
Slide 83: SELLAS Life Sciences Group
¢eLLAS (i Vike SCIENCES GROUP
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