Slide 1: Safety and survival outcomes in recurrent high-grade glioma patients treated with CAN-3110
Safety and survival outcomes in recurrent high-grade glioma patients treated with CAN-3110, a first-in-class ICP34.5 expressing oncolytic HSV1 Francesca Barone, MD, PhD Chief Scientific Officer, Candel Therapeutics, Inc. CONFIDENTIAL
Slide 2: CAN-3110 a novel oncolytic virus engineered for enhanced activity and safety
CAN-3110 a novel oncolytic virus engineered for enhanced activity and safety HSV-1 engineered for immunogenic potency and specificity ⎼ ICP34.5-null viruses have shown safety, but replicate poorly ⎼ CAN-3110: ICP34.5 expression under control of Nestin promoter ⎼ Nestin overexpressed in gliomas (and
Slide 3: CAN-3110 induces tumor cell death and reprograms the immunosuppressive microenvironment of HGG
CAN-3110 induces tumor cell death and reprograms the highly immunosuppressive microenvironment of HGG Nestin ⎼ Tumor cell death Promoter ICP34.5 ⎼ Release of tumor antigens ⎼ Expansion of T cell repertoire ⎼ Activation of local microenvironment CAN-3110 3 Cold tumor Hot tumor Highly immunosuppressiv
Slide 4: Trial Design: Phase 1b Clinical Trial of CAN-3110 in Recurrent High-Grade Glioma
Trial Design: Phase 1b Clinical Trial of CAN-3110 in Recurrent High-Grade Glioma PI: Dr. E. Antonio Chiocca (Brigham & Women’s) Dose escalation (Cohort I-IX) Single stereotactic injection of CAN-3110 3+3 dose escalation Primary Endpoints Arm A 1 x 106 to 1 x 1010 PFU in half-log increments 30 patien
Slide 5: Patient demographics and baseline characteristics
Patient demographics and baseline characteristics Arm A (n=41*) Arm B (n=9) Total (n=50*) Age, Median (range) 54 years (27 - 74) 54 years (41 - 70) 55 years (27 - 74) Sex, n (%) Female 21 (51%) 3 (33%) 24 (48%) Male 20 (49%) 6 (67%) 26 (52%) Race, n (%) White 38 (93%) 8 (89%) 46 (92%) Black or Afric
Slide 6: CAN-3110 related SAEs in rHGG (arms A and B)
CAN-3110 related SAEs in rHGG (arms A and B) Number of Number of Number of Dose Level Time Cohort (arm) treated patients with patients with Case # (PFU) (days) patients DLT related SAE 1 (A) 3 1x106 0 0 NA NA 2 (A) 3 3x106 0 0 NA NA 3 (A) 3 1x107 0 0 NA NA 4 (A) 3 3x107 0 0 NA NA 5 (A), 1 (B) 6 1x10
Slide 7: Safety summary: related adverse events in rHGG
Safety summary: related adverse events* (AEs) in rHGG Arm A (n=41) n (%) Arm B (n=9) n (%) General disorders and administration site conditions Nervous system disorders Fever 3 (7%) Edema Cerebral 1 (11%) Musculoskeletal and connective tissue disorders Hemianopia 1 (11%) Muscle weakness 3 (7%) Hypoe
Slide 8: Safety summary: adverse events in rHGG
Safety summary: adverse events in rHGG Arm A (n=41*) Arm B (n=9) o No patients experienced a DLT in Cohorts I-X o All patients (n=9) experienced at least 1 AE o All patients (n=41) experienced at least 1 AE o 11% of patients (n=1) experienced at least 1 related AE • 001-060: Grade 2 – Edema cerebral
Slide 9: Encouraging overall survival in rHGG after single injection (arm A)
Encouraging overall survival in rHGG after single injection (arm A) N = 41 Median overall survival: 11.8 months Cutoff date: 20 Apr 2023 Expected median overall survival: <6-9 months • 41 unique patients were dosed; one patient was treated twice, in cohort IX and X • A total of 50 unique patients 9
Slide 10: Overall survival data rHGG arm B confirms data in arm A
Overall survival data rHGG arm B confirms data in arm A N = 9 patients pretreated with cyclophosphamide Median overall survival: 12 months Cutoff date 20 Apr 2023 Expected median overall survival: <6-9 months 10 CONFIDENTIAL
Slide 11: Monotherapy activity of CAN-3110 in rHGG (arm A)
Monotherapy activity of CAN-3110 in rHGG (arm A) Clinical effect on injected tumor and uninjected tumor Baseline Day 0 Day 56 Day 111 Day 168 Day 280 Black hole within tumor Reduction in contrast area Patient back to work image is injection site with no additional treatment 106 PFU dose 56 YOM, IDH
Slide 12: Durable response for 2Yrs after CAN-3110 in rHGG (arm A)
Durable response for 2Yrs after CAN-3110 in rHGG (arm A) Initial lesion Day -262 Day -259 Day -47 Day -30 Day -14 Initial presentation Initial resection Tumor recurrence 2 nd subtotal resection Rapid progression Tumor bed injection site Needle visible on MRI Day 0 Day 91 Day 96 Day 630 CAN-3110 Inje
Slide 13: Continued improvement for >12Mos after CAN-3110 monotherapy (arm B)
Continued improvement for >12Mos after CAN-3110 monotherapy (arm B) CAN-3110 Injection cavity Initial lesion Cytoxan Increased enhancement Progressive reduction (day-2) in enhancement Pre-op Day -4 Day 0 Day 64 Day 106 CAN-3110 injection Reduction in enhancement with tumor involution Stable disease
Slide 14: Biomarker Analysis
Biomarker Analysis 14 CONFIDENTIAL
Slide 15: Persistent HSV antigen expression associated with CD8+ T cell infiltration
Persistent HSV antigen expression associated with CD8+ T cell infiltration after CAN-3110 treatment Preoperative Patient A (6 weeks post-HSV 10e6 PFUs) Intraoperative injection HSV1 Ag Patient B (9 mos post-HSV 10e9 PFUs) Recurrence Anti HSV Day 253 CD8+ 13/27 patients presented positive oHSV antige
Slide 16: Persistent HSV antigen expression in uninjected lesion 8 Mos after injection
Persistent HSV antigen expression in uninjected lesion 8 Mos after CAN-3110 injection in multifocal rHGG Uninjected lesion HSV-1 Pre-treatment Post-treatment* Uninjected Uninjected lesion lesion Injected *8 Mos lesion 16 CONFIDENTIAL
Slide 17: Increased infiltration by immune cells at the site of the tumor after CAN-3110
Increased infiltration by immune cells at the site of the tumor after CAN-3110 treatment in rHGG H&E CD20 CD4 CD8 Post-injection * * * * # necrotic tumor areas surrounded # # # by T cells # necrosis; * immune cell infiltrate 3 x107 PFU 3 x107 PFU 1 x108 PFU CD8+ T cells CD4+ T cells CD20+ B cells P<
Slide 18: Changes in tumor microenvironment after CAN-3110 are associated with improved survival
Changes in tumor microenvironment after CAN-3110 are associated with improved survival in rHGG 17 paired samples bioinformatic analyses by BostonGene, Inc. 18 CONFIDENTIAL
Slide 19: Changes in protein biomarkers in peripheral blood after CAN-3110 injection
Changes in protein biomarkers in peripheral blood after CAN-3110 injection in rHGG From 96 protein panel biomarkers, 53 showed statistically significant changes compared to baseline at the 1st or 2nd time points after treatment; those include IL-6, PTN, MMP12, CCL19, CD40L 19 CONFIDENTIAL
Slide 20: T cell receptor (TCR) analysis interpretation tool
T cell receptor (TCR) analysis interpretation tool Relationship between clonality and diversity/entropy 20 CONFIDENTIAL
Slide 21: Increases in T cell density, entropy, and clonality in long survivors
Increases in T cell density, entropy, and clonality are observed in long survivors after CAN-3110 injection Long survivors Short survivor CAN-3110 injection 21 CONFIDENTIAL
Slide 22: Conclusions
Conclusions o Treatment with CAN-3110 in rHGG is well tolerated with no dose-limiting toxicity observed o Persistence of HSV antigen expression associated with tumor necrosis and increased immune cell infiltration after CAN-3110 injection in both injected and uninjected lesions o Evidence of abscopa
Slide 23: Acknowledgements
Acknowledgements Alexander Ling Andrea Manzanera Isaac H. Solomon Maria Lucia Silva Polanco Ana Montalvo Landivar Garrett Nichols Hiroshi Nakashima Paul Peter Tak Andres Santos Nafisa Masud Patrick Wen Keith Leigon David Reardon Sengupta Soma E. A. Chiocca 23 CONFIDENTIAL