Candel Therapeutics, Inc. · NASDAQ:CADL
Candel Therapeutics — Breakfast Event during ASCO 2022 Annual Meeting
46 slides from Candel Therapeutics's conference presentation, Jun 6, 2022
Slide 1: Breakfast Event during ASCO 2022 Annual Meeting
Exhibit 99.1 Breakfast Event during ASCO 2022 Annual Meeting (NASDAQ: CADL)
Slide 2: Tipping the balance in favor of the immune system to fight cancer
Tipping the balance in favor of the immune system to fight cancer Paul Peter Tak, MD, PhD, FMedSci President and Chief Executive Officer Candel Therapeutics, Needham, MA 1
Slide 3: Forward-Looking Statements
Forward-Looking Statements This Presentation contains forward-looking statements and information. All statements other than statements of historical facts contained in this Presentation, including express or implied statements regarding our strategy, future financial condition, future operations, pr
Slide 4: Candel overview: Oncolytic viral immunotherapies
Candel overview: Oncolytic viral immunotherapies Two clinical stage investigational medicines and an innovative discovery platform • CAN-3110 o Engineered, replication-competent herpes simplex virus with tumor-specificity o Ongoing phase 1 clinical trial in recurrent HGG o Potential for expansion of
Slide 5: CAN-3110: HSV Nestin 34.5 construct
CAN-3110: HSV “Nestin 34.5” construct Nestin expression in tumor cells Nestin induces ICP34.5 expression, Promoter resulting in tumor-specific replication ICP34.5 CAN-3110 Virus expands in Nestin expressing tumor cells, causing oncolytic activity 4
Slide 6: Oncolytic HSV infection and CD8+ T cell infiltration after CAN-3110 treatment
Oncolytic HSV infection and CD8+ T cell infiltration after CAN-3110 treatment in patients with recurrent high-grade glioma 6 HSV1 antigen 6 weeks after injection of 1x10 pfu Infiltration by CD8+ cytotoxic T cells 6 1.79 x 10 copies of viral DNA/mg (tumor infiltrating lymphocytes) 5 2.97 x 10 copies
Slide 7: Survival in ongoing phase 1b trial of CAN-3110 in recurrent HGG
Survival in ongoing phase 1b clinical trial after single dose of CAN-3110 in recurrent high-grade glioma 100 N = 30 Median ove Me rall ds ia un r v O iv Sa : l:1 1 11.7 .7 m mo on nth thss Cutoff date: 21 April 2021 Expected median overall survival: <6-9 months 50 0 0 6 12 18 24 30 36 Months 6 Proba
Slide 8: Single agent activity of CAN-3110 in recurrent HGG with abscopal effect
Single agent activity of CAN-3110 in recurrent HGG patient with abscopal effect Secondary lesion Injected lesion Baseline Day 168 Day 0 Day 56 Day 111 Day 280 Black hole within tumor Reduction in contrast area Patient back to work image is injection site with no additional 6 10 PFU dose treatment Cl
Slide 9: CAN-2409: Induction of CD8+ TILs in prostate and pancreatic cancer
CAN-2409 treatment: Induction of CD8+ tumor-infiltrating lymphocytes in prostate cancer and pancreatic cancer PROSTATE CANCER PH 1/2 STUDY PANCREATIC CANCER PH 1/2 STUDY Post-treatment with CAN-2409 Tumor infiltrating Pre-treatment lymphocytes in tissue and prodrug 140 120 Loss of glandular architec
Slide 10: Completed phase 2 trial of CAN-2409 in localized prostate cancer
Completed phase 2 trial of CAN-2409 shows consistently improved freedom from failure rates in newly diagnosed, localized prostate cancer n= 64 99 203 31 92 127 255 102 21 177 184 103 10 • Pathological complete response (pCR) observed in 93% of the biopsies available at 2yrs (37%-73% in control popul
Slide 11: Significant survival benefit after CAN-2409 treatment in HGG
Significant survival benefit after CAN-2409 treatment in HGG Compared to contemporary controls fulfilling the same inclusion and exclusion criteria All patients: Prespecified subgroup: All high-grade glioma, glioblastoma with gross total resection All resection extent Median overall survival Median
Slide 12: Key achievements and future milestones
Key achievements and future milestones Phase 2 CAN-2409 with ICI st in NSCLC 1 patient dosed Phase 3 CAN-2409 in prostate cancer enrollment completed Phase 3 Phase 2 prostate cancer CAN-2409 blinded safety data prostate cancer Phase 2 CAN-2409 Phase 3 patient reported active surveillance intra-prost
Slide 13: Leadership team with decades of experience in oncology
Leadership team with decades of experience in oncology, immunology, and drug development Paul-Peter Tak, M.D., Ph.D., FMedSci President & Chief Executive Officer Francesca Barone, M.D., Ph.D. Chief Scientific Officer Nathan Caffo Chief Business Officer John Canepa Chief Financial Officer Christopher
Slide 14: Research Advisory Board of premier thought leaders
Research Advisory Board of premier thought leaders James Allison, Ph.D. Roy Herbst, M.D., Ph.D. Chair of the Department of Immunology Chief of Medical Oncology MD Anderson Cancer Center Yale Cancer Center Director of the Parker Institute for Cancer Research 2018 Nobel Recipient Edward Benz, M.D. Phi
Slide 15: Non-small cell lung cancer opportunity for CAN-2409
Non-small cell lung cancer opportunity for CAN-2409 o Patients treated with immune checkpoint Prevalence of NSCLC in the US* inhibitors often combined with chemotherapy st as 1 line treatment o Median overall survival 22 months rd nd 3 Line st 2 Line 1 Line o < 40% of patients survive > 30 months 21
Slide 16: First report from a phase 2 clinical trial of CAN-2409 in NSCLC
First report from a phase 2 clinical trial of CAN-2409 in inadequate responders to immune checkpoint inhibitors for stage III/IV NSCLC Daniel Sterman, MD Thomas and Suzanne Murphy Professor of Pulmonary and Critical Care Medicine, at the New York University Grossman School of Medicine, and Director
Slide 17: CAN-2409: Mechanism of action
CAN-2409: Mechanism of action 1. CAN-2409 locally 4. Local immunization yields administered and oral prodrug systemic anti-tumor response Inflammatory Tumor Dendritic cell B-cell Valacyclovir mediators antigens Macrophage Fibroblast CAN-2409 Cytotoxic metabolite Thymidine kinase enzyme Valacyclovir
Slide 18: CAN-2409 teaches the immune system to fight cancer in injected and uninjected tumors
CAN-2409 teaches the immune system how to fight cancer in injected tumor and uninjected metastases Decrease in uninjected lung metastases Uninjected lung metastases Virus injected flank tumor Mice receive one of four treatment regimens 1. PBS 2. Radiotherapy 3. CAN-2409 with prodrug 4. CAN-2409 with
Slide 19: Response to CAN-2409 is dependent on CD8+ T cells
Response to CAN-2409 is dependent on 3000 CD8+ T cells and transferable in mouse models of cancer 2500 140 Control vector 120 2000 + prodrug w/ CD8 mAb 100 1500 80 60 1000 Control vector CAN-2409 + prodrug 40 + prodrug 500 w/ CD8 mAb 20 CAN-2409 + prodrug prodrug 0 0 Control cells only Naïve CD8+ ce
Slide 20: Phase 1 mechanistic trial in resectable NSCLC
Phase 1 mechanistic trial in resectable NSCLC: Safety and feasibility of intratumoral administration of CAN-2409 Evidence of monotherapy activity both via biomarkers and clinical response CAN-2409 and valacyclovir Newly diagnosed Day 0 Day 1-15 Day 21 +6-8 weeks +6 months (one course) stage I-III St
Slide 21: CAN-2409 stimulates local and systemic CD8+ T-cell response in NSCLC
CAN-2409 stimulates local and systemic CD8+ T-cell response in patients with NSCLC Non-small cell lung cancer Ph 1 study (n=12) TISSUE PERIPHERAL BLOOD CD8 Ki67 CD8 Ki67 30 80 p<0.001 p=0.02 CD38 HLA-DR 60 CD38 HLA-DR 20 80 50 p=0.002 p=0.008 40 10 40 20 60 30 0 0 40 Pre Rx Post Rx Pre Rx Post Rx 20
Slide 22: Monotherapy activity of CAN-2409 in NSCLC
Monotherapy activity of CAN-2409 in NSCLC 70 yr old male with a 14.8 cm stage IIIA sarcomatoid carcinoma Day 22 Day 0 Tumor Dimensions: 100 x 34 x 75 mm Tumor Dimensions: 148 x 40 x 82 mm 12 10 vp dose Nearly 50% decrease in tumor volume* at 3 weeks after CAN-2409 monotherapy Predina JD et al. Mol T
Slide 23: Ongoing phase 2 trial of CAN-2409 with ICI in stage III/IV NSCLC
Current, ongoing phase 2 clinical trial of CAN-2409 in combination with ICI in stage III/IV NSCLC Cohort 1 Stable Disease (>18 wks ICI) Stage III/IV Primary Endpoints CAN-2409 and o Response by RECIST Criteria Non-resectable valacyclovir o Safety NSCLC with (2 courses) inadequate Cohort 2 Secondary
Slide 24: Demographics
Demographics 35 patients enrolled between October 2020 and April 2022 Data cutoff was April 20, 2022 23
Slide 25: Most frequent treatment-related adverse events
Most frequent treatment-related adverse events Generally, CAN-2409 was shown to be well tolerated with no Grade 4 and few Grade 3 events 24
Slide 26: Swimmer plot for all evaluable patients
Swimmer plot for all evaluable patients 20 patients received 2 courses of CAN-2409 with valacyclovir and were evaluable at 12 weeks * Stage: at time of enrollment to study ‡ SOC ICI: at enrollment to study. + Chemotherapy = pemetrexed ǁ Time on SOC ICI prior to Study Enrollment: Initiation of ICI to
Slide 27: Radiographic best responses for all evaluable patients
Radiographic best responses for all evaluable patients Majority of patients experienced reduction in tumor burden ! #$%&# ' ()*+),* '$)-. &-# 40 PD * 0 -20 PR ** Cohort 1 -40 Cohort 2 Cohort 3 -60 *PD by local read **PR by local read -80 PR= partial response; PD= progressive disease 26 NY-004 NY-008
Slide 28: Encouraging clinical responses
Encouraging clinical responses Disease control rate in cohort 2 of 87.5% in patients who were progressing at trial entry Completed DoR for PR DoR for SD Cohort 12-week PR SD PD DCR (w) (w) treatment 1 2 1** 1 0 50% 24.1+ 26.9 5.4+ - 2 16 2 12 2 87.5% 26.7-37.9+ 50.4+ 3 2 0 0 2* 0% n/a n/a PR= partia
Slide 29: Spider plot of cohort 2 suggests durable and stable response
Spider plot of cohort 2 suggests durable and stable response CAN-2409 led to disease stabilization in most patients who were progressing at entry Cohort 2 Baseline Progressing * * New lesion 28
Slide 30: Limited patient numbers in cohorts 1 and 3
Limited patient numbers in cohorts 1 and 3 Cohort 1: challenging recruitment because stable disease in NSCLC was considered acceptable by treating physician nd Cohort 3: patients were often too ill to get to the 2 CAN-2409 administration Cohort 1 Cohort 3 Baseline Stable Baseline Refractory 100 PA-0
Slide 31: Patient with partial response in extended lung lesion
Patient with partial response defined by local read in extended lung lesion and consolidation PA-003 (Cohort 1) 73M, Stage III Non-SQ PD-L1<1% PR by local read Diagnosed Jan’20 Started pembro + carbo + pemetrexed Feb’20, pembro + pemetrexed cont. Schematics to show general lesion injection orientati
Slide 32: Patient with partial response and evidence of abscopal effect NY-007
Patient with partial response and evidence of abscopal effect NY-007 (Cohort 2) 74M, Stage IV Non-SQ PD-L1 <1% Diagnosed Feb’19 PR by local and central read cisplatin/etoposide Feb’19 to Jul’19, nivolumab monotherapy from Sep’19 Schematics to show general lesion injection orientation; not to scale t
Slide 33: Patient with partial response and evidence of abscopal effect MU-002
Patient with partial response and evidence of abscopal effect MU-002 (Cohort 2) 69F, Stage III 2013, Stage IV 2019; Non- PR by local and central read SQ; PD-L1 unknown; Started pembro monotherapy Jan’20 through trial Schematics to show general lesion injection orientation; not to scale LN = lymph no
Slide 34: CAN-2409 increases immune cell infiltration in post-treatment tumor biopsies
CAN-2409 increases immune cell infiltration in post-treatment tumor biopsies Patient: VC-001 Patient: PA-007 Tumor (CK) CD3 CD4 CD8 Tumor (CK) CD8 Granzyme B Tumor (CK) CD8 PD-L1 CD68 200um 200um 500um 200um 200um 100um 33 Post treatment Pre treatment
Slide 35: Frequency analysis demonstrates enrichment in cytotoxic T cells
Frequency analysis demonstrates enrichment in cytotoxic T cells Patient: NY-004 Cell frequency proportion Cytox T cells Tumor cells RV-001 PA-008 PA-004 VC-004 NY-004 UC-001 log2 NY-001 PA-007 VC-001 Cytotoxic cells Pre Post Pre Post Tumor cells Vorenoi diagram illustrating frequency Heat map summar
Slide 36: Increased aggregation of cytotoxic T cells in post treatment biopsies
Increased aggregation of cytotoxic T cells in post treatment biopsies Proximity analysis was applied to immunofluorescence (IF) stained samples to evaluate number of CD8+ cytotoxic cells within a distance of 100um radius from tumor cells. Significant difference was observed in post treatment samples
Slide 37: CAN-2409 increases circulating cytotoxic T cells and decreases T regulatory cells
CAN-2409 increases circulating cytotoxic T cells and decreases circulating T regulatory cells Patient: NY-007 Bs Bs CD8+Ki67 +granzyme B + T cells CD8+Ki67 +IFNg +T cells NKT Wk12 W12 cells T regulatory cells Gamma delta NK cells + T cells Bs W2 W6 W8 W12 F/U t-SNE plot representing patient MU-002 a
Slide 38: Increase in circulating CD8+Ki67+granzyme B+ T cells and soluble granzymes
CAN-2409 induces an increase in circulating CD8+Ki67+granzyme B+ T cells associated with elevated soluble granzyme A, B, and H levels Soluble granzyme A, B Increase in granzyme B+Ki67+CD8 T cells and H increase over time Post treatment reduction in T-reg Post treatment increase in NK- T cells 37
Slide 39: Systemic increase in proliferating CD8+ and CD4+ IFNg producing effector cells
CAN-2409 induces a systemic increase in proliferating CD8+ and CD4+ IFNɣ producing effector cells Patient: PA-003 Gated on CD8+ W9 B W3 W6 Gated on CD4+ B W3 W9 W6 38
Slide 40: Biomarker analysis summary
Biomarker analysis summary Biomarker data consistent with hypothesized mechanism of action o Post treatment tumor biopsies: • Increased infiltration of cytotoxic T cells • Increased T cell aggregation in proximity to tumor cells o Post treatment peripheral blood samples: • Increased actively prolife
Slide 41: Summary of data from ongoing phase 2 clinical trial
Summary of data from ongoing phase 2 clinical trial: o Experimental treatment with CAN-2409 plus valacyclovir in patients with advanced NSCLC and an inadequate response to first-line ICI (±chemo) who continued ICI treatment appears to be generally well tolerated o Encouraging preliminary activity in
Slide 42: Perspective on clinical trial of CAN-2409 and anti-PD-1 in NSCLC
Perspective on clinical trial of CAN-2409 and anti-PD-1 in patients with NSCLC and inadequate response to anti-PD-1 agents Roy Herbst, MD, PhD Ensign Professor of Medicine (Medical Oncology) and Professor of Pharmacology at Yale School of Medicine Chief of Medical Oncology at the Yale Cancer Center
Slide 43: Key Findings
Key Findings o Experimental treatment with CAN-2409 plus valacyclovir in patients with advanced NSCLC and an inadequate response to first-line ICI (±chemo) who continued ICI treatment appears to be well tolerated o Encouraging preliminary activity in the first 20 evaluable patients at 12 weeks post-
Slide 44: NSCLC landscape
NSCLC landscape Current treatment paradigm Experience in treating NSCLC Role of Checkpoint targeted agents therapy Novel immuno-oncology combinations 43
Slide 45: Q&A
Q&A 44
Slide 46: Q&A
Q&A o How important is achieving stable disease in NSCLC patients? o What has been the response rate in PD-1 progressing patients treated beyond progression with anti-PD-1 or other agents? o What is your view of the monotherapy data for CAN-2409? o How quickly did patients experience tumor shrinkage
Candel Therapeutics — Breakfast Event during ASCO 2022 Annual Meeting on 6ix