Candel Therapeutics, Inc. · NASDAQ:CADL
Candel Therapeutics — Investor Day (December 2022)
107 slides from Candel Therapeutics's investor day presentation, Dec 6, 2022
Slide 1: Research & Development Day
Exhibit 99.1 Research & Development Day Virtual | December 6, 2022 NASDAQ: CADL
Slide 2: 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 3: R&D Day 2022 Agenda
R&D Day 2022 December 6, 2022 (EST) 11:00 – 11:10 am Introduction to Candel Therapeutics Intratumor viral immunotherapy: a new approach to induce systemic anti-tumor 11:10 – 11:20 am immunity 11:20 – 11:30 am Clinical perspective on viral immunotherapy 11:30 – 12:00 pm Phase 2 clinical trial of CAN-
Slide 4: Speakers
Speakers Charu Aggarwal Daniel H. Sterman Roy Herbst Paul Peter Tak James P. Allison Padmanee MD, MPH MD MD, PhD MD, PhD, FMedSci PhD Sharma MD, PhD Perelman School of NYU Langone Health Yale Cancer Center Candel Therapeutics MD Anderson MD Anderson Medicine at UPenn Cancer Center & Cancer Center Pa
Slide 5: Candel Therapeutics
Candel Therapeutics Paul Peter Tak, MD, PhD, FMedSci 5
Slide 6: Paul Peter Tak, MD, PhD, FMedSci
Paul Peter Tak, MD, PhD, FMedSci Candel Therapeutics Dr. Paul Peter Tak is President, CEO, and Board Director of Candel Therapeutics. Dr. Tak received his medical degree from the Free University in Amsterdam and was trained as an internist and immunologist at Leiden University Medical Center, where
Slide 7: Candel overview
Candel overview o Two investigational medicines in the clinic and a discovery platform • CAN-2409 o Engineered, replication-defective adenoviral gene construct encoding herpes simplex virus (HSV)-thymidine kinase o Ongoing clinical trials in non-small cell lung cancer (NSCLC), pancreatic cancer, and
Slide 8: Leadership team with decades of experience in oncology, immunology, and drug development
Leadership team with decades of experience in oncology, immunology, and drug development Paul-Peter Tak, M.D., Ph.D., Jason Amello FMedSci Chief Financial Officer President & Chief Executive Officer Nathan Caffo Francesca Barone, M.D., Ph.D. Chief Business Officer Chief Scientific Officer Christophe
Slide 9: CAN-2409: Systemic immunotherapy delivered intratumorally
CAN-2409: Systemic immunotherapy delivered intratumorally 1. CAN-2409 locally administered combined with oral prodrug 3. CAN-2409 induces CD8+ cytotoxic T cells Tumor Inflammatory Dendritic cell B-cell Valacyclovir antigens mediators Macrophage Fibroblast CAN-2409 Cytotoxic metabolite Thymidine kina
Slide 10: Prostate cancer: Significant unmet need
Prostate cancer: Significant unmet need Incidence of localized prostate cancer o No new treatments approved for newly diagnosed, localized prostate cancer during in the US by risk level the last 10+ years o Currently available treatments are associated HIGH with significant side effects INTERMEDIATE
Slide 11: Phase 2 trial of CAN-2409 in prostate cancer (active surveillance)
Fully accrued phase 2 clinical trial of CAN-2409 in patients with prostate cancer (active surveillance) PI: Dr. S. Eggener (U of Chicago) Active Surveillance + CAN-2409 + Valacyclovir (2 injections) Primary Endpoints o Disease Free Survival N=187 Secondary Endpoints Fully enrolled 2:1 o Progression
Slide 12: Phase 3 trial of CAN-2409 in prostate cancer (intermediate/high risk)
Fully accrued phase 3 clinical trial of CAN-2409 in patients with prostate cancer (newly diagnosed, intermediate/high risk) PIs: Dr. T. DeWeese (JHU) and Dr. P. Scardino (MSKCC) CAN-2409 + Valacyclovir (3 injection courses + radiotherapy) Primary Endpoints o Disease free survival N=711 Fully enrolle
Slide 13: CAN-2409 well tolerated in phase 2b prostate cancer trial
CAN-2409 is generally well tolerated in ongoing phase 2b clinical trial in patients with prostate cancer (monotherapy; active surveillance population) CTC grade n=187 Most common PT (>=5%) 1 2 3 4 Total (%) Flu-like symptoms 40 (21) 20 (11) 1 (1) 61 (33) Chills 39 (21) 13 (7) 1 (1) 53 (28) Fever 39
Slide 14: Intra-prostate injection tolerated same or better than biopsy
Most patients tolerate intra-prostate injection same or better than prostate biopsy (ongoing phase 3 clinical trial; combined with radiotherapy +/- androgen deprivation therapy) In total > 2,000 intra-prostate injections (40% transperineal; 56% transrectal; 4% not reported) “How did you tolerate the
Slide 15: Systemic immunotherapy delivered intratumorally
Systemic immunotherapy delivered intratumorally o Intra-tissue injection is a proven strategy for in situ vaccination o Delivery designed to minimize systemic toxicity o Systemic immune response: not all metastases need to be injected o Durable responses after only 2-3 administrations o Procedure is
Slide 16: Candel overview: near- and mid-term inflection points
Candel overview o Promising assets with near- and mid-term inflection points • CAN-2409: Systemic immunotherapy delivered intratumorally ⎯ Phase 2 NSCLC; updated clinical data – to be presented today o Additional data expected in Q3 2023 ⎯ Phase 3 HGG; ready to commence ⎯ Phase 2 pancreas preliminar
Slide 17: Intratumor viral immunotherapy
Intratumor viral immunotherapy James P. Allison, PhD 17
Slide 18: James P. Allison, PhD
James P. Allison, PhD MD Anderson Cancer Center Dr. James Allison is the Regental Professor and Chair of the Department of Immunology, the Olga Keith Wiess Distinguished University Chair for Cancer Research, Director of the Parker Institute for Cancer Research, and the Executive Director of the Immu
Slide 19: Intratumor viral immunotherapy: A new approach to induce systemic anti-tumor immunity
Intratumor viral immunotherapy: A new approach to induce systemic anti-tumor immunity Jim Allison, PhD Regental Professor and Chair, Immunology Vice-President, Immunobiology Director, James Patrick Allison Institute Executive Director, Immunotherapy Platform Olga Keith Weiss Distinguished University
Slide 20: How oncolytic viruses are thought to work
How oncolytic viruses are thought to work Primary infection Virus amplification and tumor cell lysis Secondary infection, Virus amplification, tumor cell lysis and virus spread Inflammatory response 20
Slide 21: Example of viral immunotherapy: Newcastle Disease Virus
An example of viral immunotherapy: Newcastle Disease Virus (NDV) F • Family: Paramyxoviridae: negative-strand RNA virus (same as HN mumps, HPIV, measles) M • Natural host: birds • Cell surface receptor: sialic acid N • Determinants of cancer cell-specificity: L P – Deficiency in innate immune signal
Slide 22: Efficacy of oncolytic viruses depends on adaptive immune response
Therapeutic efficacy of oncolytic viruses is dependent on the adaptive immune response rather than virus replication Implant Inject PBS/NDV -luciferase flank tumors IT into right tumor Day 0 7 9 11 Days after Tumor Challenge 7 9 11 13 17 21 PBS NDV NDV + aCD4 NDV + aCD8 22
Slide 23: Oncolytic viruses make cancer cells more immunogenic
Oncolytic viruses don’t just lyse cancer cells, they make them more immunogenic Activation and recruitment of HSPs Ecto-CRT innate and adaptive immune effectors B7-1,2 1. DC maturation 2. ↑MHC 1.↑MHC, 3. ↑Costimulatory ligands 2.↑Cos mulatory 4. ↑Cytokines, chemokines ligands MHC Tumor antigens 3.↑S
Slide 24: Systemic immune effects of intratumoral NDV treatment
Systemic immune effects of intratumoral NDV treatment Day 7 0 4 10 13 Virus-treated tumor Distant tumor 24h 48h 72h 96h mock NDV 6 6×10 ns ** * **** 6 5×10 6 mock 4×10 NDV 6 3×10 6 2×10 6 1×10 mock NDV NDV mock 0 Zamarin D, Wolchok JD, Allison JP. Sci. Transl. Med. 2014 5:226ra 24 CD3+ C 8+ D CD4+Fo
Slide 25: Intratumoral NDV controls injected and distant tumors
Intratumoral NDV controls virus-injected and distant tumors Day 7 0 4 10 13 100 Injected tumors Distant tumors 200 500 80 400 150 PBS 60 300 100 PBS NDV NDV 40 200 NDV ** *** PBS 50 20 100 ** 0 0 0 0 10 20 30 40 50 0 5 10 15 20 3 6 7 11 13 15 18 Days Days post challenge Days 25 Zamarin D, Wolchok JD
Slide 26: NDV upregulates immune negative feedback pathways
NDV upregulates a range of immune negative feedback pathways in tumors 8 PD-L1 6 PD-L2 Anti-PD-1 BTLA CSF1 TIM3 TIGIT 4 LAG3 CD47 IL-10 PD-1 T cell IDO1 CSF1R Anti- TGFB1 2 PD-L1 TGFB3 TGFB2 0 Anti- -0.5 0.0 0.5 1.0 1.5 2.0 2.5 CTLA-4 Fold Change (Log2) CD8 CTLA-4 MFI * 2500 PBS APC NDV 2000 1500 10
Slide 27: NDV with checkpoint blockade leads to tumor rejection
Intratumoral NDV with systemic immune checkpoint blockade leads to rejection of the treated and distant tumors Day 4 7 10 0 13 B16-F10 100 MB49 100 80 80 p=0.0047 PBS 60 60 NDV+isotype *** p=0.0002 PBS+anti-CTLA-4 PBS 40 40 * NDV+anti-CTLA-4 NDV 20 aCTLA-4 20 NDV+aCTLA-4 0 0 0 20 40 60 80 0 20 40 60
Slide 28: NDV and CTLA-4 blockade induces inflammatory changes in distant tumors
Combination therapy with NDV and CTLA-4 blockade induces inflammatory changes in distant tumors 28
Slide 29: NDV combination activity depends on CD8 cells, NK cells, IFN
Anti-tumor activity of NDV combination therapy is dependent on CD8 cells, NK cells, IFN , and type I IFN Depletion of specific immune cell subtypes 29 Zamarin D, Wolchok JD, Allison JP. Sci. Transl. Med. 2014 5:226ra
Slide 30: Virus delivery to the tumor is essential for abscopal response
Virus delivery to the tumor is essential for the abscopal response B16-MC38 B16-no right tumor B16-B16 No right tumor Right MC38 tumor 100 PBS NDV+anti-CTLA-4 NDV+anti-CTLA-4 (no right tumor) 80 60 40 **** 20 0 0 20 40 60 Days after challenge 30 Zamarin D, Wolchok JD, Allison JP. Sci. Transl. Med. 2
Slide 31: Infection of tumor sharing antigens required for T cell priming
Infection of a tumor sharing antigens with distant tumors is required for priming of T cells specific for distant tumors B16-B16 MC38-B16 Trp1 Trp1 31
Slide 32: Clinical perspectives on viral immunotherapy
Clinical perspectives on viral immunotherapy Padmanee Sharma, MD, PhD 32
Slide 33: Padmanee Sharma, MD, PhD
Padmanee Sharma, MD, PhD MD Anderson Cancer Center Dr. Padmanee Sharma is an immunologist and oncologist whose research work is focused on investigating mechanisms and pathways within the immune system that facilitate tumor rejection or elicit resistance to immune checkpoint therapy. She is a Profes
Slide 34: Clinical perspectives on viral immunotherapy
Clinical perspectives on viral immunotherapy Padmanee Sharma, MD, PhD 34
Slide 35: CAN-2409 in non-small cell lung cancer
CAN-2409 in non-small cell lung cancer Charu Aggarwal, MD, MPH Daniel H. Sterman, MD Roy Herbst, MD, PhD 35
Slide 36: Charu Aggarwal, Daniel Sterman, Roy Herbst
Charu Aggarwal, MD, MPH Perelman School of Medicine at UPenn Dr. Charu Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania’s Perelman School of Medicine. She is also an active member of the Abramson Cancer Center where
Slide 37: ICIs have transformed NSCLC treatment, but most patients still progress
ICIs have transformed treatment of advanced NSCLC, but most patients still progress and long-term survival is low • After progression, 2L SoC is chemotherapy, associated with poor prognosis and significant toxicity • Recent Ph2 and Ph3 trials have explored alternative approaches post ICI progression
Slide 38: Phase 2 trial of CAN-2409 in advanced NSCLC (LuTK02)
Phase 2 clinical trial of CAN-2409 in advanced NSCLC (LuTK02) Enrolls spectrum of disease to support signal generation and refinement of the patient population Cohort 1 Primary Endpoints Stable Disease o Response by RECIST (>18 wks ICI) CAN-2409 and criteria o Safety Stage III/IV valacyclovir non- (
Slide 39: LuTK02 Consort diagram
LuTK02 Consort diagram Enrolled (n=55) Ineligible (n=3) 1 Safety population (n=52) Cohort 3 Cohort 1 Cohort 2 (n=6) (n=5) (n=41) 2 2 2 Evaluable Treatment Evaluable Evaluable In treatment In treatment Treatment 3 3 (n=2) dropouts (n=4) (n=26) (n=4) window (n=1) window (n=3) dropouts (n=12) Progressi
Slide 40: Patient demographics and characteristics
Patient demographics and characteristics 52 patients who received at least 1 dose of CAN-2409 comprise the safety population Age Years Baseline ECOG n (%) 0 or 1 21 (40); 31 (60) Median (Range) 68.5 (43-88) Sex n (%) Smoking History n (%) Female 21 (40) Former or current 41 (79); 7 (13) Male 31 (60)
Slide 41: CAN-2409 treatment is generally well tolerated
CAN-2409 treatment is generally well tolerated Treatment-related adverse events reported in ≥5% of recipients Grade 1 Grade 2 Grade 3 Grade 4 Total SOC/Adverse Event ( ≥5%) • Majority of treatment-related n (%) n (%) n (%) n (%) (n=52) AEs (TRAEs) were mild Gastrointestinal disorders Constipation 2
Slide 42: Durable disease stabilization: swimmer plot
CAN-2409 is associated with durable disease stabilization Swimmer plot of evaluable patients in Cohorts 1 and 2 (n=30) Time on ICI Subject ID PD-L1 ICI Regimen* (mo)** Pembro/pemetrex PA-003 < 1% 15.5 PA-007 < 1% Pembro/pemetrex 5.0 UH-001 < 1% Pembro 6.7 VB-007 < 1% Pembro 7.8 MU-002 N/A Pembro 16.
Slide 43: Durable disease stabilization: spider plot
CAN-2409 is associated with durable disease stabilization Spider plot of evaluable patients in Cohorts 1 and 2 (n=30) Cohort 1 Cohort 2 As of cutoff date 21 Oct 2022 43
Slide 44: CAN-2409 favorably changes trajectory of tumor growth
CAN-2409 favorably changes the trajectory of tumor growth Tumor trajectories pre-study and Monthly tumor growth rate following CAN-2409 administration * months • Serial scans available for up to one year prior to treatment with CAN-2409 in 9 patients • Monthly tumor growth rate calculated pre-study
Slide 45: Evidence that CAN-2409 improves disease control
Evidence that CAN-2409 improves disease control Most patients entering trial with progressive disease achieved disease control Waterfall plot Summary of efficacy Cohort/ DoR for PR SD duration Pre-trial N PR SD PD ORR or DCR (mo) (mo) status * 1 ORR 25% SD at 4 1 3 0 4.1+ 1.4+ to 6.2 study DCR N/A e
Slide 46: Slowing tumor growth may translate into PFS benefit
Slowing tumor growth may translate into PFS benefit Cohort 1 N=4 mPFS 11.0 Cohort 2 N=26 mPFS 8.1 • Progression free survival (PFS) in evaluable patients receiving both courses of CAN-2409 + prodrug and completed 12-wk treatment window based on progression per Investigator assessment • Median follow
Slide 47: Local injection induces systemic anti-tumor activity
Local injection induces systemic anti-tumor activity Regression of uninjected lesions NY-007 (Cohort 2) • 74M, Stage IV Nonsq • PD-L1 <1% • Diagnosed Feb‘19 • Platinum-based chemo Feb– Jul’19 • Nivolumab monotherapy abscopal response Sep‘19 through trial lack of abscopal response • PR by local and c
Slide 48: Partial response in extended lung mass
Partial response in extended lung mass with durable post-treatment tumor regression (> 1 yr) PA-003 (Cohort 1) • 73 yo M, Stage III Nonsq • PD-L1<1% • Diagnosed Jan’20 • Started pembro + carbo + pemetrexed Feb’20 • Pembro + pemetrexed Jun’20 through trial Baseline Week 28 st 1 injection (baseline) R
Slide 49: CAN-2409 induces expansion of CD8+ granzyme B+ T cells
CAN-2409 induces expansion of CD8+ granzyme B+ T cells in the tumor microenvironment Pre CAN-2409 Post CAN-2409 PA006 Cytokeratin CD8 Granzyme B Double positive granzyme B+ CD8T cells Cytokeratin Cytokeratin CD8 CD8 Granzyme B Granzyme B Double positive granzyme B+ CD8 T cells Double positive granzy
Slide 50: CAN-2409 increases circulating cytotoxic T cells and soluble granzymes
CAN-2409 significantly increases frequency of circulating cytotoxic T cells and levels of soluble granzymes Circulating T-cells (mean, n=23) CD8+Ki67+GZMB+ T cells Soluble granzymes (mean, n=14) CD8+Ki67+IFNg+ T cells CD4+Ki67+T cells CD8 CM* T cells CD4+Ki67+IFNg+ Regulatory T cells T cells *CM= ce
Slide 51: Bronchoscopic delivery of CAN-2409 is well tolerated
Bronchoscopic delivery of CAN-2409 is a simple extension of existing care for NSCLC patients and is well tolerated Therapeutic delivery tool based on extensive experience with bronchoscopic biopsy, a routine outpatient procedure (15 min, outpatient setting) Transbronchial needle injection (TBNI) pre
Slide 52: Promising picture of safety, clinical activity and immune changes
Promising picture of safety, clinical activity and immune changes Favorable safety/tolerability profile in comparison to SoC 2L options • Only two administrations with relatively simple procedure; most TRAEs were Gr1/2 Consistent induction of local and systemic cytotoxic T cell response • Increased
Slide 53: CAN-2409 + nivolumab in high-grade glioma
CAN-2409 + nivolumab in high-grade glioma Patrick Y. Wen, MD 53
Slide 54: Patrick Y. Wen, MD
Patrick Y. Wen, MD Dana-Farber Cancer Institute & Harvard Medical School Dr. Patrick Y. Wen is a Professor of Neurology at Harvard Medical School, and Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute in Boston, MA. Dr. Wen’s research focuses on development of new novel thera
Slide 55: Phase 1 trial of CAN-2409 with nivolumab in newly diagnosed high-grade glioma
Phase 1 clinical trial of CAN-2409 in combination with nivolumab and standard of care in newly diagnosed high-grade glioma R&D Day December 6, 2022 Data cutoff as of September 30, 2022 55
Slide 56: Immunosuppressive microenvironment determines poor prognosis in high-grade glioma
Immunosuppressive tumor microenvironment and negative prognostic factors determine poor prognosis in high-grade glioma patients High-grade glioma tumor microenvironment is characterized by poor T cell infiltrate, enrichment in M2 suppressive macrophages and suppressive microglia Median overall survi
Slide 57: Opportunity for combination with checkpoint inhibitor in mouse glioma model
Potential opportunity for combination therapy with immune checkpoint inhibitor: improved effect in mouse model of high- grade glioma Induction of cell death Induction of PD-L1 expression Improved survival *** *** *** 100 25 100 CAN-2409 **** + aPD1 **** *** 80 20 80 **** CAN-2409 60 15 60 ** 40 10 4
Slide 58: Phase 1 trial of CAN-2409 plus valacyclovir with nivolumab in HGG
Phase 1 clinical trial of CAN-2409 plus valacyclovir combined with nivolumab in high-grade glioma A protocol of the Adult Brain Tumor Consortium (ABTC) in collaboration with Bristol-Myers Squibb (BMS) and Candel Therapeutics, Inc. Methylated MGMT promoter (~33%) Continue RT+ temozolomide+ nivolumab
Slide 59: Patient demographics safety population
Patient demographics safety population (41 patients) Characteristic N (%) Characteristic N (%) KPS* (Baseline) Age Median KPS 90 Median age (years) 62 Range 80-100 Range 28-81 Sex KPS (Day 15) Median KPS 80 Female 14(34) Range 20-100 Male 27(66) MGMT Race White/Caucasian 34(83) Methylated 16(39) Unm
Slide 60: CONSORT diagram
CONSORT diagram Enrollment February 2019 to March 2021 9 patients alive (30 Sep 2022 data cut off) **Received 26 nivolumab infusions *Received less than 80% of any planned dose of treatment regimen for reasons unrelated to study treatment Evaluable : Patients who completed >80% of treatment during t
Slide 61: Evaluable subject progress
Evaluable subject progress (35 patients) Type of IDH resection Status MUTANT STR WT STR WT STR WT STR WT GTR WT GTR WT GTR WT GTR WT GTR WT GTR WT GTR WT GTR WT GTR WT GTR WT GTR MUTANT GTR WT GTR WT GTR WT GTR WT STR WT GTR WT STR WT GTR WT STR WT GTR WT STR WT STR WT GTR WT GTR WT GTR WT GTR WT GT
Slide 62: Safety profile of CAN-2409, valacyclovir and nivolumab combination
Safety profile of the combination of CAN-2409 plus valacyclovir and nivolumab in patients receiving surgery, radiation and TMZ • No unexpected serious adverse events were observed • Adverse events considered at least possibly related to CAN-2409, valacyclovir or nivolumab during acute monitoring per
Slide 63: Evaluable population survival curves
Evaluable population survival curves: MGMT methylation status and extent of resection Methylated GTR Median OS: 30.6 m (n=10) Methylated STR Median OS: 12.6 m (n=5) Unmethylated GTR Median OS: 13.2 m (n=16) Unmethylated STR Median OS: 15.9 m (n=4) Median OS for all: 15.1 m (n=35) GTR – gross total r
Slide 64: Immune profiling in collaboration with CIMAC-CIDC
Immune profiling in collaboration with CIMAC-CIDC Longitudinal analysis in both tumor and peripheral blood: PBMCs Tumor tissue CYTOF Glioblastoma WES RNAseq TCR sequencing mRNA Seq OLINK proteomics Tim-3 MIBI on brain samples week 5 week 11 Progression week 3 64
Slide 65: Single administration elicits strong systemic immune response
Single administration of CAN-2409 to the resection bed after removal of the tumor elicits strong systemic immune response CyTOF data on longitudinal samples Key effector cells in OLINK data on longitudinal samples antitumoral response Week 3 Baseline LogFC>1, FDR<0.05 Kohli K et al. Cancer Gene Ther
Slide 66: Expansion of activated CD4 and CD8 T cells and decreased exhaustion
Combination of CAN-2409 and nivolumab shows expansion of activated CD4 and CD8 T cells and decreased exhaustion CyTOF data on longitudinal samples Increased T cell activation Decreased exhaustion B 3 5 11 P B 3 5 11 P B 3 5 11 P B 3 5 11 P Time post treatment (weeks) FDR adjusted p. value range (0.0
Slide 67: Expansion of TCR clone density, diversity and clonality
Combination of CAN-2409 and nivolumab results in expansion of TCR clone density, diversity and clonality Density Diversity Clonality Suggested Baseline Week 3 Week 5 Week 11 Progression Suggested Baseline Week 3 Week 5 Week 11 Progression Baseline Week 3 Week 5 Week 11 Progression Suggested Progress
Slide 68: Conclusions
Conclusions • Combination of nivolumab and intratumoral CAN-2409 is well tolerated with no DLT observed and no added toxicity to standard of care • Median overall survival appears comparable to historical standard of care outcomes; small patient number in different subgroups hampers conclusive outco
Slide 69: CAN-3110 in recurrent high-grade glioma
CAN-3110 in recurrent high-grade glioma E. Antonio Chiocca, MD, PhD 69
Slide 70: E. Antonio Chiocca, MD, PhD
E. Antonio Chiocca, MD, PhD Brigham and Women’s Hospital & Harvard Medical School Dr. E. Antonio Chiocca is the Chair of the BWH Department of Neurosurgery and is the Harvey Cushing Professor of Neurosurgery at Harvard Medical School. His research has focused on how viruses with specific gene mutati
Slide 71: Phase 1 trial of CAN-3110 in recurrent high-grade glioma
Phase 1 clinical trial of CAN-3110 in recurrent high-grade glioma December 6, 2022 71
Slide 72: CAN-3110: conditional replication-competent oncolytic HSV-1
CAN-3110: a conditional replication-competent oncolytic virus HSV-1 engineered for immunogenic potency and specificity o ICP34.5-null viruses have shown safety but replicate poorly o CAN-3110: ICP34.5 expression under control of Nestin promoter ⎼ Nestin overexpressed in gliomas (and tumors outside t
Slide 73: CAN-3110 reprograms the immunosuppressive microenvironment
CAN-3110 induces tumor cell death and reprograms the highly immunosuppressive microenvironment in high-grade glioma Nestin Promoter Tumor cell death ICP34.5 Release of tumor antigens Expansion of T cell repertoire Activation of tumor microenvironment (TME) CAN-3110 Cold tumor Hot tumor Highly immuno
Slide 74: Phase 1 trial design of CAN-3110
Phase 1 clinical trial of CAN-3110 in recurrent high-grade glioma Sponsor/PI: Dr. E. Antonio Chiocca (Brigham & Women’s Hospital) Dose escalation (Cohort I-IX) Single stereotactic injection of CAN-3110 Primary Endpoints 3+3 dose escalation 6 10 o Safety 1 x 10 to 1 x 10 PFU in half-log increments 30
Slide 75: CAN-3110 related SAEs
CAN-3110 related SAEs (arm 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 6 1 (A) 3 1x10 0 0 NA NA 6 2 (A) 3 3x10 0 0 NA NA 7 3 (A) 3 1x10 0 0 NA NA 7 4 (A) 3 3x10 0 0 NA NA 8 5 (A), 1 (B) 6 1x10 0
Slide 76: Survival after single dose of CAN-3110
Survival in ongoing phase 1b clinical trial after single dose of CAN-3110 in recurrent high-grade glioma 100 N = 30 Median overall survival: 11.7 months Median OS : 11.7 months Cutoff date: 21 Apr 2021 Expected median overall survival: <6-9 months 50 Update from SNO 2022 N = 41 Median overall surviv
Slide 77: Complete response in injected and uninjected tumor
Complete response in injected and uninjected tumor without additional therapy following CAN-3110 CAN-3110 injection 77
Slide 78: Biomarker strategy
Biomarker strategy Tissue TISSUE BANK PeMciplasma 6S 1 (2 7 28 = “t —_ a ‘Luminex multiplex : \( * @ = ‘eytokine analysis | pa sony an lee |] Recs TCR alpha/beta targeting Sequencing EF BuiKRNA Soa histology Bioinformatic Analysis itumine Nos Data process Bioinformatc Longitudinal (Gipeines) wordow
Slide 79: Scientific questions asked in this clinical trial
Scientific questions asked in this clinical trial 1. Is there post-injection evidence of CAN-3110 persistence and replication? 2. Is there post-injection evidence of increased CD8+, CD4+ T cells and B cells in glioblastoma multiforme (GBM)? Cold tumor Hot tumor CAN-3110 79
Slide 80: Persistent HSV antigen associated with T-cell infiltration
Persistent HSV antigen associated with T-cell infiltration in post-injection samples after CAN-3110 treatment Preoperative Patient A (6 weeks post-HSV 10e6 pfus) Intraoperative injection HSV1 Ag Patient B (9 mo post-HSV 10e9 pfus) Recurrence Anti HSV CD8+ Day 253 12/29 patients presented positive oH
Slide 81: Scientific questions asked in this clinical trial
Scientific questions asked in this clinical trial 1. Is there post-injection evidence of CAN-3110 persistence and replication? 2. Is there post-injection evidence of increased CD8+, CD4+ T cells and B cells GBM? Cold tumor Hot tumor CAN-3110 81
Slide 82: Increased T and B cell GBM infiltrates after CAN-3110
Evidence of increased T and B cell GBM infiltrates after CAN-3110 H&E CD20 CD4 CD8 Post-injection * * * necrotic tumor * # areas surrounded # by T cells # # As of cutoff date # necrosis; * immune cell infiltrate 28 Jul 2022 7 7 8 3 x10 pfu 3 x10 pfu 1 x10 pfu d 24 d 140 d 91 P<0.0005 P<0.0001 p =0.0
Slide 83: CAN-3110 induces effector T cell infiltration and TCR repertoire changes
CAN-3110 induces infiltration by effector T cells and changes to the T cell receptor repertoire associated with improved clinical survival As of cutoff date Subjects were divided into two groups by median immune signature score for each signature. 28 Jul 2022 Statistical significance was calculated
Slide 84: Conclusions
Conclusions o Treatment with CAN-3110 is well tolerated, with no dose limiting toxicity observed o Detection of HSV1 antigen and evidence of HSV1 replication in almost half of post treatment samples o Significant increases in CD4+ and CD8+ T cells after CAN-3110 in the majority of post- CAN-3110 tre
Slide 85: enLIGHTEN Discovery Platform
enLIGHTEN™ Discovery Platform Francesca Barone, MD, PhD 85
Slide 86: Francesca Barone, MD, PhD
Francesca Barone, MD, PhD Candel Therapeutics Dr. Francesca Barone is the Chief Scientific Officer of Candel Therapeutics. At Candel, she leads scientific discovery, the development of their novel viral immunotherapies and biomarker strategy across their broad clinical portfolio. Dr. Barone previous
Slide 87: Breaking down the barriers to cancer immunotherapy
Breaking down the barriers to cancer immunotherapy Immunotherapy treatment failure arises from heterogeneous mechanisms present in diverse tumor microenvironments (TME) that are inadequately addressed by single-target therapies Carter E. et al. Trends in Cancer 2021; 11:1033-1046 Candel’s multimodal
Slide 88: The enLIGHTEN Discovery Platform
The enLIGHTEN Discovery Platform In silico selection and Deconvolution of human prioritization of multimodal tumor microenvironment payloads properties enLIGHTEN Advanced Analytics Design of experimental Integration into proprietary medicine clinical trials suite of HSV-1 vectors The first systemati
Slide 89: enLIGHTEN is centered on human data for discovery
enLIGHTEN is centered on human data for discovery enLIGHTEN datasets are based on Candel’s proprietary biomarker data and external datasets: • Collaborations • Publicly available datasets Opens the possibility to explore multiple indications and design tailored combination therapy 89
Slide 90: Overview of enLIGHTEN Advanced Analytics
Overview of enLIGHTEN Advanced Analytics Integrated computational approaches to design multimodal viral immunotherapies Selection of optimal modulator combination Enables deconvolution of tumor properties and selection of property modulator combination 90
Slide 91: Advanced Analytics applied to the Pan-Cancer Atlas
Application of enLIGHTEN Advanced Analytics to the Pan-Cancer Atlas Survival curves for BRCA* property NK-T cells * BRCA: invasive breast cancer TME properties 91 Tumor type
Slide 92: Property modulators selected in silico to design payloads
Property modulators are selected in silico to design indication-specific payloads Selection of optimal modulator combination TNF family member TNF family member 2 Macrophage function modulator Anti inflammatory cytokine In silico payload design TME properties 92 Property modulators
Slide 93: Establishment of single-gene mini-vector library
Establishment of single-gene mini-vector library In silico selected modulators are encoded into mini vectors Top modulator combination Modulator encoding vectors o 20+ mini-vectors encoded to date o Expression of both secreted and cell surface molecules Secreted modulator expression Cell-surface mod
Slide 94: Robust pipeline of assays to test payload combinations
Robust pipeline of assays to test payload combinations Multicellular tumor killing assays Mini-vector library In silico predictions Supervised multiplex Phagocytosis assay Macrophage Alpha 201 macro1 SIRPa CD47 Alpha -201 macro1 Development candidate : HSV-1 vector encoding Cancer cell nominated mul
Slide 95: HSV platform provides flexible delivery system for tumor-specific modulators
HSV platform provides a flexible delivery system for tumor-specific modulators Tunable viral vector features CAN-2409 high Payload Viral Insert TAA* expression replication Oncolysis capacity presentation CAN-3110 low high high low *TAA: tumor-associated antigens The suite of proprietary, engineered
Slide 96: Candel Alpha series: engineered for delayed oncolysis
Candel Alpha series: Engineered for delayed oncolysis to support sustained payload expression Expansion of APCs Alpha 201 Regulation of MHC-I expression Uninfected Replication defective HSV Alpha-201-GFP Alpha-201: first vector selected for enhanced immunostimulatory activity coupled with sustained
Slide 97: enLIGHTEN platform partnership with UPenn
enLIGHTEN platform partnership with UPenn: Example of enLIGHTEN discovery platform application Evaluation of a potential combination immunotherapy using tailored HSV-1 based viruses to deliver payloads that could enhance the activity of CAR-T cells Features of Successful Drug Challenge for CAR-T Cel
Slide 98: enLIGHTEN: Viral immunotherapy by design
enLIGHTEN: Viral immunotherapy by design o Strong focus on human biology to increase probability of success o Data-driven approach using advanced analytics to de-risk multimodal payload design enLIGHTEN o Suite of proprietary, engineered HSV-1 Advanced vectors to enable fast translation to clinic An
Slide 99: Candel Therapeutics
Candel Therapeutics Paul Peter Tak, MD, PhD, FMedSci 99
Slide 100: Clinical pipeline focused on value creation
Clinical pipeline focused on value creation PROGRAM INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Adenovirus Platform Localized, Intermediate/High Risk, under SPA CAN-2409 Prostate Cancer Active Surveillance CAN-2409 NSCLC + PD-1/PD-L1 Lung Cancer CAN-2409 Advanced Non-Metastatic Pancreatic Cancer
Slide 101: Clinical pipeline focused on value creation
Clinical pipeline focused on value creation PROGRAM INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Adenovirus Platform Localized, Intermediate/High Risk, under SPA CAN-2409 Prostate Cancer Active Surveillance CAN-2409 NSCLC + PD-1/PD-L1 Lung Cancer CAN-2409 Advanced Non-Metastatic Pancreatic Cancer
Slide 102: Key achievements and future milestones
Key achievements and future milestones st 1 patient dosed, NSCLC phase 2, CAN-2409 + ICI Full enrollment, prostate cancer phase 3, CAN-2409 Blinded safety data prostate cancer Read-out, phase 2, CAN-2409 prostate cancer phase 3, CAN-2409 Patient reported tolerability, prostate cancer Read-out, activ
Slide 103: R&D Day Highlights I
R&D Day Highlights I o CAN-2409 NSCLC phase 2 data • Favorable safety/tolerability profile in comparison to SoC 2L options • Consistent induction of local and systemic cytotoxic T cell response • Robust evidence of local and systemic anti-tumor activity • Additional data in Q3 2023 o CAN-2409 HGG in
Slide 104: R&D Day Highlights II
R&D Day Highlights II o CAN-3110 recurrent HGG phase 1 • Treatment with CAN-3110 is well tolerated, with no dose limiting toxicity observed • mOS of 11.6 months with a single dose of CAN-3110 • Persistent HSV-1 antigen and HSV-1 replication consistent with mechanism of action • Robust evidence of im
Slide 105: Q&A
Q&A CANDEL 105
Slide 106: Thank You
Thank You Candel's Virtual R&D Day | December 6, 2022 NASDAQ: CADL 106
Slide 107: List of abbreviations
List of abbreviations 2L Second line HNSCC Head and neck squamous cell carcinoma SA Short axis HPIV Human parainfluenza virus ADT Androgen deprivation therapy SD Stable disease HPV Human papillomavirus AE Adverse event SoC Standard of care HSV Herpes simplex virus BRCA Breast cancer gene SPA Special