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. Exhibit 99.1
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 tumors
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 Cold tumor Highly immunosuppressive TME Cancer cell proliferation Hot tumor Inflamed TME Cancer cell necrosis Tumor cell death Release of tumor antigens Expansion of T cell repertoire Activation of
Slide 4: Phase 1b clinical trial of CAN-3110 in recurrent high-grade glioma
Phase 1b clinical trial of CAN-3110 in recurrent high-grade glioma Primary Endpoints Safety Determine maximum tolerated dose Secondary Endpoints Immunological biomarkers MRI assessment of disease and progression free survival MRI alteration of permeability and flow at injection site Patients with re
Slide 5: Patient demographics and baseline characteristics
Patient demographics and baseline characteristics 41 unique patients were dosed; one patient was treated twice, in cohort IX and X A total of 50 unique patients * See below 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 (%)
Slide 6: CAN-3110 related SAEs in rHGG (arms A and B)
CAN-3110 related SAEs in rHGG (arms A and B) Cohort (arm) Number of treated patients Dose Level (PFU) Number of patients with DLT Number of patients with related SAE Case # Time (days) 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
Arm A (n=41) n (%) General disorders and administration site conditions Fever 3 (7%) Musculoskeletal and connective tissue disorders Muscle weakness 3 (7%) Nervous system disorders Seizure 3 (7%) Safety summary: related adverse events* (AEs) in rHGG Arm B (n=9) n (%) Nervous system disorders Edema C
Slide 8: No patients experienced a DLT in Cohorts I-X
No patients experienced a DLT in Cohorts I-X All patients (n=41) experienced at least 1 AE 27% of patients (n=11) experienced at least 1 related AE 59% of patients (n=24) experienced at least 1 serious AE Most Serious AEs: Edema Cerebral (n=8 [20%]) and Seizure (n=5 [12%]) 5% of patients (n=2) exper
Slide 9: Encouraging overall survival in rHGG after single injection (arm A)
Encouraging overall survival in rHGG after single injection (arm A) N = 30 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
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
Slide 11: Monotherapy activity of CAN-3110 in rHGG (arm A)
Day 56 Reduction in contrast area with no additional treatment Day 111 Patient back to work Baseline Clinical effect on injected tumor and uninjected tumor Day 168 Day 280 Day 0 Black hole within tumor image is injection site 106 PFU dose 56 YOM, IDH wild-type, MGMT partially methylated, right front
Slide 12: Durable response for 2Yrs after CAN-3110 in rHGG (arm A)
Durable response for 2Yrs after CAN-3110 in rHGG (arm A) Day -47 Tumor recurrence Day -30 2nd subtotal resection Day -262 Initial presentation Day -14 Rapid progression Day -259 Initial resection 61 YOF, IDH wild-type, MGMT methylated glioblastoma, right temporal lesion initially treated with surger
Slide 13: Continued improvement for >12Mos after CAN-3110 monotherapy (arm B)
Continued improvement for >12Mos after CAN-3110 monotherapy (arm B) Day 0 CAN-3110 injection Day 64 Day 106 Pre-op Day -4 52 YO RH WF, IDH mutant, MGMT methylated grade IV astrocytoma (left frontal, invading corpus callosum in a butterfly fashion and lobulating into lateral and third ventricle). Rec
Slide 14: Biomarker Analysis
Biomarker Analysis Tissue Pre-treatment Post-treatment PBMC/plasma Ss 1 2 7 28 56 112 168 224 280 336 tumor: fos 4 er umors Luminex multiplex “\( — cytokine analysis cog abot TISSUE BANK O | Plasma we —~ biopsy resection 1 PBMC | RBCs ee “ ” sequencing & ES bulk RNA-seq Qe an oe haters Sey histol ay
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 Patient A (6 weeks post-HSV 10e6 PFUs) HSV1 Ag Day 253 Preoperative Intraoperative injection Anti HSV CD8+ Recurrence Patient B (9 mos post-HSV 10e9 PFUs) 13/27 patients presented positive oHSV antige
Slide 16: Persistent HSV antigen expression in uninjected lesion 8 Mos after injection
Injected lesion Uninjected lesion Uninjected lesion Pre-treatment Post-treatment* *8 Mos Persistent HSV antigen expression in uninjected lesion 8 Mos after CAN-3110 injection in multifocal rHGG HSV-1 Uninjected lesion
Slide 17: Increased infiltration by immune cells at the tumor site after CAN-3110 treatment
P<0.0001 P<0.0001 P<0.0005 P<0.0001 21/29 tumors p =0.0016 24/29 tumors p <0.0001 14/29 tumors CD8 CD4 CD20 Increased infiltration by immune cells at the site of the tumor after CAN-3110 treatment in rHGG Post-injection necrotic tumor areas surrounded by T cells anti HSV H&E 3 x107 PFU d 24 1 x108 P
Slide 18: Changes in tumor microenvironment associated with improved survival in rHGG
Changes in tumor microenvironment after CAN-3110 are associated with improved survival in rHGG 17 paired samples bioinformatic analyses by BostonGene, Inc.
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
Slide 20: T cell receptor (TCR) analysis interpretation tool
T cell receptor (TCR) analysis interpretation tool Relationship between clonality and diversity/entropy
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 Short survivor CAN-3110 injection Long survivors
Slide 22: Conclusions
Conclusions Treatment with CAN-3110 in rHGG is well tolerated with no dose-limiting toxicity observed Persistence of HSV antigen expression associated with tumor necrosis and increased immune cell infiltration after CAN-3110 injection in both injected and uninjected lesions Evidence of abscopal effe
Slide 23: Acknowledgements
Acknowledgements Alexander Ling Isaac H. Solomon Ana Montalvo Landivar Hiroshi Nakashima Andres Santos Nafisa Masud Patrick Wen Keith Leigon David Reardon Sengupta Soma E. A. Chiocca Andrea Manzanera Maria Lucia Silva Polanco Garrett Nichols Paul Peter Tak