Slide 1: GEN-009 Ph1/2a Part B Discussion of Initial Clinical Data
GEN-009 Ph1/2a Part B Discussion of Initial Clinical Data July 30, 2020
Slide 2: Disclaimer
This presentation contains “forward-looking” statements that are within the meaning of federal securities laws and are based on our management’s beliefs and assumptions and on information currently available to management. Forward-looking statements include information concerning our possible or ass
Slide 3: Agenda
Agenda • ATLAS overview – Jessica Flechtner, Ph.D., Chief Scientific Officer, Genocea • GEN-009 introduction – Tom Davis, M.D., Chief Medical Officer, Genocea • GEN-009 initial Part B data review – Maura Gillison, M.D, Ph.D., Professor, Dept. of Thoracic/Head and Neck Medical Oncology, MD Anderson C
Slide 4: Genocea at a glance
Genocea at a glance Revolutionary antigen discovery platform TARGETS MATTER GEN-009 GEN-011 Two differentiated, clinical stage programs Neoantigen Neoantigen vaccine cell therapy IND filed in Q2 2020 Q3 2020 Significant near-term, Mid-2021 initial clinical data value-creating milestones initial clin
Slide 5: Why do targets matter?
Why do targets matter? Lesson from infectious Lesson from cancer Targeting the right disease vaccines immunotherapy neoantigens delivers clinical responses Wrong antigens no protection Responses to neoantigens Challenge: identifying drive checkpoint inhibitor surface-presented and (CPI), TIL thera
Slide 6: The ATLAS antigen selection difference
The ATLAS™ antigen selection difference output All surface-presented True peptides eliciting anti- antigens tumor T cell responses T cell Are peptides surface- ATLAS identifies antigens TCR presented? of pre-existing responses Peptide Limit of Not MHC 1st-gen Are peptides recognized necessarily Our
Slide 7: ATLAS: high throughput platform harnessing the immune system for antigen selection
ATLAS: high throughput platform harnessing the immune system for antigen selection Tumor NGS biopsy analysis Unique Bacterial plasmids for vectors Autologous every expressing each dendritic cell candidate candidate neoantigen Autologous T cell Blood sample 7
Slide 8: Inhibigen identification and exclusion is critical to ensure efficacy
Inhibigen identification and exclusion is critical to ensure efficacy 1,600 Adjuvant only 1,000 ) 1,400 Protective vaccine Adjuvant only 3 ) 3 1,200 Protective vaccine + Inhibigen 800 Inhibigens + Adjuvant 1,000 600 800 400 600 400 200 (mm volume Tumor 200 Tumor volume (mm volume Tumor 0 0 0 6 8 10
Slide 9: ATLAS selects the right neoantigens that can drive anti-tumor responses
ATLAS selects the right neoantigens - the neoantigens that can drive anti-tumor responses Therapeutically Relevant Neoantigens Only Included: Antigens relevant both to tumor and patient immune system (surface-presented and immunogenic) Excluded: Inhibigens, uniquely identified by ATLAS Comprehensive
Slide 10: GEN-009 Neoantigen Vaccine: Unprecedented immune responses; Emerging clinical efficacy
GEN-009 Unprecedented immune responses; Neoantigen Vaccine Emerging clinical efficacy 10
Slide 11: Simple, scalable production and delivery
Simple, scalable production and delivery 11
Slide 12: GEN-009 phase 1/2a trial design Part A
GEN-009 phase 1/2a trial design Part A • Vaccine monotherapy in patients with no evidence of disease • Multiple tumor types with CPI approval • Objectives: safety, immunogenicity • Status: all patients in long-term follow-up
Slide 13: Unparalleled immune responses in Part A
Unparalleled immune responses in Part A Frequency Effector Central Memory % neoantigens with Function Response immune responses (ex vivo assay) (IVS assay) CD4+ CD8+ CD4+ CD8+ Best peer results3 60% 99% 51% GEN-0092 87% 41% 57% 57% 23% Best peer results1 GEN-0092 Achieved in combination Monotherapy
Slide 14: No disease progression in almost all Part A patients
No disease progression in almost all Part A patients Patient Tumor Type Recurrence-free Survival of Part A Patients Median follow up of 14 months A NSCLC Compares favorably with expected relapse rates in these malignancies B Urothelial C Melanoma Patient H had low ex vivo immune responses compared t
Slide 15: GEN-009 phase 1/2a trial design Part B
GEN-009 phase 1/2a trial design Part B • Combination of GEN-009 and standard-of-care PD-1-based regimens in patients with advanced disease • Tumor types: Melanoma, NSCLC, SCCHN, Urothelial, RCC • Objectives: safety, immunogenicity, efficacy • Vaccination contribution to be determined after CPI respo
Slide 16: GEN-009 studied in checkpoint-responsive and checkpoint-refractory groups
GEN-009 is being studied in two distinct patient groups: checkpoint-responsive and checkpoint-refractory Checkpoint-Responsive / Controlled GEN-009 Dosing +/- prior therapy SOC and GEN-009 Manufacture Biopsy Enroll Progression and GEN-009 Dosing Salvage Treatment Checkpoint-Refractory SOC Therapy Me
Slide 17: Part B patients
Part B patients Subject ID Data Available* Histology Ranking by predicted ORR to 1st line CPI SOC Checkpoint-Responsive / Controlled 058 ✓ NSCLC, adeno PD-L1: 60% 057 ✓ RCC Intermediate risk 105 ✓ SCCHN PD-L1: 20% 001 ✓ UC PD-L1: 20% 031 NSCLC, adeno PD-L1: 95% 030 NSCLC, squamous PD-L1 positive 078
Slide 18: Safety profile for GEN-009 dosing
Safety profile for GEN-009 dosing GEN-009 is very well tolerated without additive toxicity Related Serious Events Related to GEN-009 Events 8 / 8 patients Part A Grade 1 and Grade 2 injection site reactions, 0 Grade 2 fever 6 / 11 patients Part B 0 Grade 1 injection site reactions Data Cutoff Date:
Slide 19: Maura L. Gillison, MD, PhD
Maura L. Gillison, MD, PhD Professor of Medicine, Department of Thoracic/Head and Neck Medical Oncology MD Anderson Cancer Center Member, National Academy of Medicine
Slide 20: Broad and potent immunogenicity demonstrated in all five patients
Broad and potent immunogenicity demonstrated in all five patients Antigen-specific CD4+ and CD8+ T cell responses detected in 100% of patients (N=5) • Every patient is responding to multiple antigens • Generated both ex vivo and after in vitro stimulation • Strong magnitude of response Amplification
Slide 21: Sample CPI spider plot: Decreasing change in expected outcome over time
Sample CPI spider plot: Decreasing change in expected outcome over time Topalian et al., NEJM 366: 2443-54, 2012 21
Slide 22: Trial design enables assessment of vaccine specific contribution
Trial design enables assessment of vaccine specific contribution to clinical responses Each patient can serve as own control Pre-Vaccination Post-Vaccine Dose 1 20 PD (+20%) Scan 0 Baseline -20 PR (-30%) -40 -60 Effect attributable % Change in Target Lesion Sum Target in Change% to vaccine -80 Vacci
Slide 23: Patient case: RCC
Patient 057 Ex Vivo Immunogenicity 40 Scan 500 Pool 4 20 PD (+20%) 400 Pool 3 PBMC 6 300 Pool 2 0 Baseline Pool 1 200 -20 100 SFC per 1x10 PR (-30%) 0 -40 Baseline Post-Checkpoint Post-Vaccine -60 • 68 yo female with stage 3 RCC diagnosed at % Change in Target Lesion Sum Target in Change% resection
Slide 24: Patient case: oropharyngeal cancer
Patient 105 Ex Vivo 20 PD (+20%) Immunogenicity Scan 1000 Pool 4 0 Baseline 750 Pool 3 PBMC 6 Pool 2 Sum −20 500 Pool 1 Lesion PR (-30%) 250 −40 SFC per 1x10 Target 0 Baseline Post-Checkpoint Post-Vaccine −60 % % Change in • 66 yo male diagnosed with stage 1 oropharyngeal −80 cancer Nov ‘18 • Receiv
Slide 25: Patient case: lung adenocarcinoma
Patient 058 20 PD (+20%) IVS Immunogenicity Scan 2000 500 cells cells + 0 Baseline + 400 1500 CD8 CD4 4 4 300 1000 200 Sum −20 500 100 PR (-30%) SFC per 2 x 10 0 SFC per 2 x 10 0 Lesion −40 Baseline Post-Vaccine Baseline Post-Vaccine Target • 68 yo female diagnosed with stage 4 adeno of lung Oct −60
Slide 26: Patient case: bladder carcinoma
Patient 001 20 PD (+20%) Ex Vivo Immunogenicity Scan 125 0 Baseline Pool 4 100 Pool 3 PBMC 6 Sum 75 Pool 2 −20 Pool 1 50 Lesion PR (-30%) 25 −40 Target SFC per 1x10 0 Baseline Post-Checkpoint Post-Vaccine −60 % % Change in • 68 yo male diagnosed with bladder carcinoma June ‘19 −80 GEN-009 Dose 1 • P
Slide 27: Patient case: oropharyngeal carcinoma
Patient 106 40 Ex Vivo Immunogenicity 400 Pool 4 20 PD (+20%) 300 Pool 3 PBMC 6 Pool 2 0 Baseline Sum 200 Pool 1 100 Lesion −20 PR (-30%) SFC per 1x10 N.T. 0 Target −40 Scan Baseline Post-Checkpoint Post-Vaccine • 62 yo male with stage 4, P16+ oropharyngeal carcinoma −60 Jul ’19 % % Change in GEN-00
Slide 28: Tumor reduction trend in 1st evaluable Part B patients suggests unique GEN-009 effect
Tumor reduction trend in 1st 5 evaluable Part B patients suggests unique GEN-009 effect 20 PD (+20%) 20 PD (+20%) 20 PD (+20%) 105 (SCCHN) 058 (NSCLC) 001 (UC) 0 Baseline 0 Baseline 0 Baseline Sum Sum Sum −20 −20 −20 Lesion Lesion Lesion PR (-30%) PR (-30%) PR (-30%) −40 −40 −40 GEN-009 Target Targe
Slide 29: GEN-009: Delivering on the promise of neoantigen therapies
GEN-009: Delivering on the promise of neoantigen therapies Compelling early signal Clear anti-tumor activity and immunogenicity; More data to come “Targets matter” Highly differentiated results Powerful readthrough to GEN-011 ATLAS enables unique breadth and specificity 29
Slide 30: Q&A
A genocea Q&