false 0001841387 0001841387 2022-12-06 2022-12-06












Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): December 6, 2022




(Exact name of Registrant as Specified in Its Charter)




Delaware   001-40629   52-2214851

(State or Other Jurisdiction

of Incorporation)



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117 Kendrick St., Suite 450

Needham, MA

(Address of Principal Executive Offices)     (Zip Code)

Registrant’s Telephone Number, Including Area Code: (617) 916-5445

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)



Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:


Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)


Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)


Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))


Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:


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Common Stock, $0.01 par value per share   CADL   The Nasdaq Global Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company  

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  




Item 7.01

Regulation FD Disclosure.

On December 6, 2022, Candel Therapeutics, Inc. (the “Company”), will host a virtual Research and Development (R&D) Day from 11:00 am – 1:30 pm ET. The event will provide an extensive overview of the Company’s viral immunotherapy approach and oncology-focused pipeline, with new data being presented from its phase 2 clinical trial of CAN-2409 in combination with anti-PD-1 agents in patients with stage III/IV non-small cell lung cancer, as well as an update on its phase 3 clinical trial of CAN-2409 in high-grade glioma.

A copy of the full corporate presentation is filed as Exhibit 99.1 to this Current Report on Form 8-K and incorporated by reference herein.

The information in this Current Report on Form 8-K (including the exhibit) is furnished pursuant to Item 7.01 and shall not be deemed to be “filed” for the purpose of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section. This Current Report on Form 8-K will not be deemed an admission as to the materiality of any information in the Report that is required to be disclosed solely by Regulation FD.


Item 9.01

Financial Statements and Exhibits.

(d) Exhibits






99.1    R&D Day Corporate Presentation dated December 6, 2022
104    Cover Page Interactive Data File (embedded within the Inline XBRL document)


Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.


    Candel Therapeutics, Inc.
Date: December 6, 2022     By:  

/s/ Paul Peter Tak

      Paul Peter Tak, M.D., Ph.D., FMedSci
      President and Chief Executive Officer

Exhibit 99.1 Research & Development Day Virtual | December 6, 2022 NASDAQ: CADL

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, projected costs, prospects, plans, objectives of management and expected market size, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “expect,” “intend,” “plan,” “anticipate,” “believe,” “estimate,” “target,” “seek,” “predict,” “potential,” “continue” or the negative of these terms or other comparable terminology. Although we believe that the expectations reflected in these forward-looking statements are reasonable, these statements relate to our strategy, future operations, future financial position, future revenue, projected costs, prospects, plans, objectives of management and expected market size, and involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by these forward-looking statements. Forward-looking statements in this Presentation include, but are not limited to, statements about: the initiation, timing, progress, results, and cost of our research and development programs and our current and future preclinical and clinical studies, including statements regarding the timing of initiation and completion of studies or trials and related preparatory work, the period during which the results of the trials will become available, and our research and development programs; our ability to efficiently discover and develop product candidates; our ability to initiate, recruit and enroll patients in and conduct our clinical trials at the pace that we project; our ability to obtain and maintain regulatory approval of our product candidates; our ability to compete with companies currently marketing or engaged in the development of treatments that our product candidates are designed to target; our reliance on third parties to conduct our clinical trials and to manufacture drug substance for use in our clinical trials; the size and growth potential of the markets for our product candidates and our ability to serve those markets; the ability and willingness of our third-party strategic collaborators to continue research and development activities relating to our development candidates and product candidates; our ability to obtain and maintain adequate intellectual property rights; our estimates of our future expenses, revenue, capital requirements or our need for or ability to obtain additional financing; the potential benefits of strategic collaboration agreements, our ability to enter into additional strategic collaborations or arrangements, and our ability to attract collaborators with development, regulatory and commercialization expertise; our financial performance; developments and projections relating to our competitors or our industry; the effect of the COVID-19 pandemic, including mitigation efforts and economic effects, on any of the foregoing or other aspects of our business operations, including but not limited to, our preclinical studies or current and future clinical trials. We caution the recipient not to place considerable reliance on the forward-looking statements contained in this Presentation. The forward-looking statements in this Presentation speak only as of the date of this document, and we undertake no obligation to update or revise any of these statements. Our business is subject to substantial risks and uncertainties, including those referenced above. Certain information contained in this Presentation relates to or is based on estimates, projections and other information concerning the Company’s industry, its business and the markets for its programs and product candidates and studies, publications, surveys and other data obtained from third-party sources and the Company's own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this Presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this Presentation involves a number of assumptions; there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source. These forward-looking statements are based on the beliefs of our management as well as assumptions made by and information currently available to us. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. If such assumptions do not fully materialize or prove incorrect, the events or circumstances referred to in the forward-looking statements may not occur. We undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation to conform these statements to actual results or to changes in our expectations, except as required by law. Accordingly, readers are cautioned not to place undue reliance on these forward- looking statements. Additional risks and uncertainties that could affect our business are included under the caption “Risk Factors” in our most recent report filed with the Securities and Exchange Commission. 2

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-2409 in NSCLC Phase 1 clinical trial of CAN-2409 in combination with nivolumab and standard of care in 12:00 – 12:10 pm newly diagnosed high-grade glioma 12:10 – 12:25 pm Phase 1 clinical trial of CAN-3110 in recurrent high-grade glioma 12:25 – 12:40 pm The enLIGHTEN™ Discovery Platform Penn – Candel discovery partnership: Combination therapy to overcome 12:40 – 12:55 pm CAR-T resistance in solid tumors 12:55 – 1:30 pm Closing and Q&A 3

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 Parker Institute for Cancer Research E. Antonio Chiocca Francesca Barone Carl H. June Neil C. Sheppard Patrick Y. Wen MD, PhD MD, PhD MD DPhil MD Brigham and Women’s Candel Therapeutics Center for Cellular Center for Cellular Dana-Farber Cancer Hospital & Harvard Immunotherapies at Immunotherapies Institute & Harvard Medical School Medical School UPenn & Parker Institute at UPenn for Cancer Research 4

Candel Therapeutics Paul Peter Tak, MD, PhD, FMedSci 5

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 he also received his PhD. He worked as a scientist at the University of California San Diego and next served as Professor of Medicine and Chair of the Department of Clinical Immunology and Rheumatology at Amsterdam University Medical Center. He has published extensively in peer-reviewed journals (> 590 publications, H-index 137, > 80,000 citations), received numerous awards, has been elected Fellow of the Academy of Medical Sciences, is an Honorary Senior Visiting Fellow at the University of Cambridge, and was recognized by PharmaVOICE100 in 2021. At GlaxoSmithKline, Dr. Tak served as Senior Vice President, Chief Immunology Officer, and Global Development Leader (2011-2018), and brought a large portfolio of investigational medicines to clinical development and approval. 6

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 prostate cancer o Pipeline in a product o Phase 2 clinical trial data update in NSCLC • CAN-3110 o Engineered, replication-competent HSV designed for tumor-specificity o Ongoing clinical trial in recurrent high-grade glioma (HGG) o Opportunity for creation of pipeline in a product by expansion of indications outside the brain o Phase 1b clinical trial data update in recurrent HGG • enLIGHTEN™ Discovery Platform based on Advanced Analytics and HSV technology o Company Update • Strong scientific support from high-profile Research Advisory Board • Significant unmet need and commercial opportunity for each selected indication • Cash and cash equivalents of $77.2M as of September 30, 2022; runway into Q1 2024 7

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 Christopher Matheny, Pharm.D., Garrett Nichols, M.D., M.S. Ph.D. Chief Medical Officer Vice President, Development Leader Seshu Tyagarajan, Ph.D., RAC Susan Stewart, J.D. Chief Technical and Development Officer Chief Regulatory Officer 8

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 kinase enzyme Valacyclovir CAN-2409 T-cell 2. Localized cytolytic mechanism combined with 4. Local immunization yields systemic CD8+ T cell proinflammatory viral particles mediated against injected tumor and uninjected metastases 9

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 LOW 30K 75K 45K o Significant opportunity for new treatment with favorable tolerability profile that will prevent disease progression Target label for CAN-2409: - Indicated in newly diagnosed localized prostate cancer in combination with radiotherapy +/- short-term ADT, in patients with intermediate- to high-risk disease - Indicated in newly diagnosed localized prostate cancer in patients with NCCN-defined low-risk disease, or patients with # intermediate-risk disease undergoing active surveillance # Market research combined with interviews with 22 KOLs (12 US; 10 EU) and 10 US payors. Dec 2020 10

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 to radical Patients chose Randomization treatment, pathological response/PSA kinetics active surveillance o Proactive Surveillance Score o Quality of life o Immunological biomarkers Active Surveillance + Placebo + Valacyclovir (2 injections) NCT02768363 11

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 enrolled Secondary Endpoints Newly diagnosed, 2:1 o PSA freedom from intermediate-high Randomization biochemical failure o Prostate cancer specific risk, localized survival prostate cancer o Overall survival o Quality of life o Immunological biomarkers Placebo + Valacyclovir (3 injection courses + radiotherapy) NCT01436968 Conducted under agreement with FDA under Special Protocol Assessment 12

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 (21) 9 (5) 1 (1) 49 (26) Fatigue 27 (14) 10 (5) 1 (1) 38 (20) Elevated AST/ALT 28 (15) 3 (2) 1 (1) 32 (17) Elevated Creatinine 23 (12) 5 (3) 1 (1) 2 (1) 31 (17) Study is still blinded Headache 20 (11) 5 (3) 25 (13) 187 patients treated Urinary tract infection 1 (1) 15 (8) 2 (1) 18 (10) 362 injections performed Nausea 12 (6) 4 (2) 16 (9) Low Hemoglobin 15 (8) 15 (8) Diarrhea 10 (5) 3 (2) 13 (7) Malaise 10 (5) 2 (1) 12 (6) Hematuria 12 (6) 12 (6) Urinary frequency 9 (5) 2 (1) 11 (6) Urinary tract pain 6 (3) 3 (2) 9 (5) Urinary urgency 7 (4) 2 (1) 9 (5) Elevated Alkaline Phosphatase 8 (4) 1 (1) 9 (5) Elevated Bilirubin 7 (4) 3 (2) 10 (5) ~ 33% patients experienced flu-like symptoms < 1% infections requiring hospitalization AdMeTech Foundation’s Fifth Global Summit on Precision Diagnosis and Treatment of Prostate Cancer, September 2021 13

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 study procedure as compared to a prostate biopsy?” Patient questionnaire substudy in 32 patients Transperineal Transrectal Much harder to tolerate Much harder to tolerate 4 % 0% Little harder to tolerate Little harder to tolerate 30 % 11% Same or better tolerated Same or better tolerated 89 % 65 % 0 20 40 60 80 0 20 40 60 80 100 28th Annual Prostate Cancer Foundation Scientific Retreat, October 2021 14

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 well tolerated by patients: • Administration to prostate takes 15-20 min in outpatient setting, often tolerated the same or better than prostate biopsy, which is a routine procedure in urology • Administration to lung tumor takes 15-20 min in outpatient setting via bronchoscopy, which is a routine procedure in pulmonary medicine • For future indications, any location can be reached using image-guided injection, robotic delivery, etc. o Procedures with proven benefit/risk, patient tolerability, and cost-effectiveness will be implemented by clinicians • Stem cell transplantation, implant radiotherapy, interventional radiology, interventional cardiology 15

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 preliminary data – expected Q4 2023 ⎯ Phase 2 prostate cancer; localized, low- to intermediate-risk (active surveillance) – readout expected Q4 2023 ⎯ Phase 3 prostate cancer; localized, intermediate- to high-risk – readout expected Q4 2024 • CAN-3110: Replication-competent HSV with tumor-specificity ⎯ Phase 1b recurrent HGG; updated clinical and biomarkers - presented at SITC and today • enLIGHTEN Discovery Platform based on use of Advanced Analytics and HSV technology o Significant unmet need and commercial opportunity for each selected indication o Management team with proven success in immunology, oncology, and development o Cash and cash equivalents of $77.2M as of September 30, 2022 • Funds currently planned operations into Q1 2024 16

Intratumor viral immunotherapy James P. Allison, PhD 17

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 Immunotherapy Platform at MD Anderson Cancer Center. His well-known research is focused on the mechanisms of T cell development and activation, development of novel strategies for tumor immunotherapy, and he is recognized as one of the first to isolate the T-cell antigen receptor complex protein. In 2018, Dr. Allison received the Nobel Prize in Physiology or Medicine for the discovery of cancer therapy by inhibition of negative immune regulation. Since April 2021, Dr. Allison has been on the Research Advisory Board for Candel. 18

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 Chair for Cancer Research Distinguished Scholar, Cancer Prevention and Research Institute of Texas Candel R&D Day 2022 19

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

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 signaling – Resistance to apoptosis • Pathogenic types: replication, pathogenicity (in birds) and oncolytic proficiency is determined by the viral fusion protein: – Lentogenic (nonpathogenic) strains: limited replication and lysis – Mesogenic and velogenic (pathogenic) strains: best replication and lysis 21

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

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.↑Surface HSPs Danger signals and ecto-CRT 4.↑Type I IFN PAMPS PAMPS virus Zamarin D. and Wolchok J.D., Molecular Therapy-Oncolytics 1 (2014) 23

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+FoxP3- CD4+FoxP3+ Cells /g tumor

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, Allison JP. Sci. Transl. Med. 2014 5:226ra 3 Tumor size (mm ) 3 Tumor size (mm ) Percent survival

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 1000 500 Immune checkpoint 0 blockade 26 p-value (-Log10) MFI

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 80 100 Days Days post challenge 27 Zamarin D, Wolchok JD, Allison JP. Sci. Transl. Med. 2014 5:226ra Percent survival Percent survival

Combination therapy with NDV and CTLA-4 blockade induces inflammatory changes in distant tumors 28

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

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. 2014 5:226ra Percent survival

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

Clinical perspectives on viral immunotherapy Padmanee Sharma, MD, PhD 32

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 Professor in the departments of Genitourinary Medical Oncology and Immunology, Associate VP of Immunobiology and the T.C. and Jeanette D. Hsu Endowed Chair in Cell Biology at MD Anderson Cancer Center. She is also the inaugural Scientific Director for the Immunotherapy Platform and the Director of Scientific Programs for the James P. Allison Institute at MD Anderson Cancer Center. She’s written and conducted multiple innovative immunotherapy clinical trials, with emphasis on obtaining patients’ tumor samples for in-depth laboratory studies, including the first neoadjuvant trial with immune checkpoint therapy and first clinical trial with immune checkpoint therapy for patients with bladder cancer. Her studies have identified novel resistance mechanisms to immune + checkpoint therapy, including loss of interferon (IFN) signaling, VISTA immunosuppressive cells, + increased EZH2 expression in T cells, TGF-b signaling in bone metastases, and CD73 myeloid cells in GBM. These data have led to initiation of new research studies focused on developing rational combination immunotherapy strategies for the treatment of cancer patients. As a result of her outstanding contributions to the field of cancer immunotherapy, Dr. Sharma was selected as a member of the American Society for Clinical Investigation (ASCI) as well as awarded the Emil Frei III Award for Excellence in Translational Research in 2016, the Coley Award for Distinguished Research for Tumor Immunology in 2018, the Women in Science with Excellence (WISE) award in 2020, the Heath Memorial Award in 2021 and the Randall Prize for Excellence in Cancer Research in 2021. 33

Clinical perspectives on viral immunotherapy Padmanee Sharma, MD, PhD 34

CAN-2409 in non-small cell lung cancer Charu Aggarwal, MD, MPH Daniel H. Sterman, MD Roy Herbst, MD, PhD 35

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 she serves as Physician Leader for the clinical research program for Airways Malignancies. Dr. Aggarwal specializes in the management of patients with lung and head and neck cancer, with a specific and clinical research focus on the development of novel immunotherapeutic approaches, and the discovery and application of biomarkers to guide therapy and monitor treatment. She is a co-principal investigator for Candel’s phase 2 clinical trial of CAN-2409 followed by valacyclovir in combination with standard of care immune checkpoint inhibitors in patients living with late-stage NSCLC. Daniel H. Sterman, MD NYU Langone Health Dr. Daniel Sterman is the Thomas and Suzanne Murphy Professor of Pulmonary and Critical Care Medicine in the Departments of Medicine and Cardiothoracic Surgery at the New York University Grossman School of Medicine, Director of the Division of Pulmonary, Critical Care, and Sleep Medicine, and Director of the Multidisciplinary Pulmonary Oncology Program at NYU Langone Health in New York City. For more than two decades, Dr. Sterman has focused on the translation of laboratory discoveries from the bench to the bedside: conducting multiple human clinical trials of gene therapy and vaccine therapy for lung cancer, mesothelioma, and other pleural malignancies. Dr. Sterman obtained his MD from Weill Cornell Medical College of Cornell University. He is a co-principal investigator for Candel’s phase 2 clinical trial of CAN-2409 followed by valacyclovir in combination with standard of care immune checkpoint inhibitors in patients living with late-stage NSCLC. Roy Herbst, MD, PhD Yale Cancer Center Dr. Roy Herbst is the Ensign Professor of Medicine (Medical Oncology) and Professor of Pharmacology; Director, Center for Thoracic Cancers; Deputy Director, Clinical Affairs; Assistant Dean for Translational Research, Office of the Dean, School of Medicine; Chief of Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital; and Associate Cancer Center Director, Translational Science. Dr. Herbst is best known for his work in developmental therapeutics and the personalized therapy of non-small cell lung cancer, in particular the process of linking genetic abnormalities of cancer cells to novel therapies. His work has led to the approval of several therapies such as gefitinib, cetuximab, bevacizumab, and axitinib. Dr. Herbst authored a high-profile review of the 20-year progress in lung cancer as well as authored or co-authored more than 350 publications including peer-reviewed journal articles, abstract, and book chapters. Since April 2021, he has been on Candel’s Research Advisory Board. 36

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 Ph2 ramucirumab + pembrolizumab (RP) Ph3 evaluating treatment beyond vs chemotherapy (SoC) progression with atezolizumab Lung-MAP substudy OAK study 168 (of 332) patients treated with atezolizumab were treated beyond progression (TBP) mPFS mOS TRAE ≥ Gr3 mOS 12.7 mo; ORR 7% RP 4.5 mo 14.5 mo 42% SoC 5.2 mo 11.6 mo 60% Reckamp K. et al. J Clin Onc 2022;40:2295-2306 Gandara D. et al. J Thorac Onc 2018;13:1906-1918 37 ICI: immune checkpoint inhibitor, mPFS: median PFS, mOS: median overall survival; ORR: overall response rate, TRAE: treatment-related adverse event, SoC: standard of care

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- (2 courses) Secondary Endpoints resectable Cohort 2 o Overall survival NSCLC with with Progressive Disease o Progression free survival suboptimal standard of care (>18 wks ICI) o Quality of life response to anti-PD-1/PD-L1 o Immunological first-line ICI +/- biomarkers o Response by iRECIST chemotherapy Cohort 3* and itRECIST Refractory Disease (Exploratory) (>9 wks ICI) *Cohort 3 closed as of Jun 2022 NCT04495153 38

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) Progressive disease 1 (n=4) Safety population: Received at least 1 injection of CAN-2409 Progressive disease (n=7) 2 Evaluable: Received both injections of CAN-2409 + prodrug and completed 12- Patient withdrawal (n=2) 4 week treatment course Adverse events (n=3) 3 In treatment window: Post-enrollment but not yet reached 12-week assessment 4 Adverse events: Empyema grade 3 possibly related to study drug, pneumonia grade 3 and bullous dermatitis grade 3 unrelated to study drug Cohort 3 closed as of Jun 2022 As of cutoff date 21 Oct 2022 39

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) Tumor Stage n (%) Race n (%) Stage III 8 (15) Black/African American 7 (13) Stage IV 44 (85) Asian 1 (2) Histology n (%) White 41 (79) Non-Squamous 37 (71) Unknown 3 (6) Squamous 15 (29) Ethnicity n (%) ICI at study entry n (%) Not Hispanic or Latino 48 (92) Durvalumab 2 (4) Not Reported 4 (8) Nivolumab 5 (10) PD-L1 Expression n (%) Nivolumab/Ipilimumab 1 (2) 22 (42) <1% Pembrolizumab 44 (85) 1-49% 15 (29) Chemotherapy at study entry n (%) ≥50% 10 (19) Pemetrexed 17 (33) Unknown 5 (10) None 35 (67) As of cutoff date 21 Oct 2022 40

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 (4) 1 (2) 3 (6) • No DLTs or treatment-related Nausea 7 (13) 7 (13) AEs ≥Gr4 reported Vomiting 3 (6) 3 (6) General disorders and administration site conditions • Only five Gr3 TRAEs were Chills 3 (6) 3 (6) reported: single occurrences Fatigue 11 (21) 3 (6) 14 (27) of pyrexia, empyema, Pyrexia 7 (13) 1 (2) 8 (15) lymphocyte count decreased, Investigations platelet count decreased, and Alanine aminotransferase increased 3 (6) 3 (6) pneumonitis Aspartate aminotransferase increased 3 (6) 3 (6) Blood creatinine increased 5 (12) 1 (2) 6 (12) • No serious injection-related Musculoskeletal and connective tissue disorders complications Muscular weakness 2 (4) 1 (2) 3 (6) Respiratory, thoracic and mediastinal disorders Cough 2 (4) 1 (2) 3 (6) Dyspnea 2 (4) 3 (6) 5 (10) As of cutoff date 21 Oct 2022 41

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 16.6 MU-004 < 1% Pembro 5.2 NY-001 1-49% Pembro 7.0 NY-003 1-49% Nivo 12.1 NY-004 ≥ 50% Pembro 11.7 NY-007 < 1% Nivo 16.2 NY-008 1-49% Pembro 10.3 Durva NY-013 1-49% 13.3 Pembro NY-015 6.3 ≥ 50% Pembro/pemetrex PA-005 < 1% 19.1 Pembro/pemetrex PA-006 < 1% 8.2 Pembro PA-008 < 1% 11.1 Pembro/pemetrex PA-010 < 1% 11.8 PA-011 ≥50% Pembro 13.2 PA-013 1-49% Pembro/pemetrex 45.2 RV-001 1-49% Nivo 38.4 UC-001 1-49% Pembro 13.0 UC-002 1-49% Pembro 16.6 VB-003 1-49% Pembro 10.8 VB-005 1-49% Pembro/pemetrex 12.1 VB-009 < 1% Durva 12.1 VC-001 < 1% Pembro/pemetrex 5.4 VC-004 1-49% Pembro/pemetrex 5.4 As of cutoff date VC-006 ≥50% Pembro 15.1 VC-007 1-49% Pembro/pemetrex 5.7 21 Oct 2022 VC-008 <1% Pembro/pemetrex 6.4 * ICI Regimen: At enrollment to study ** Time on ICI: Initiation of ICI before enrollment to first CAN-2409 injection 42 § Irradiation included target lesion, no longer RECIST evaluable

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

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 (during prior therapy of ICI +/- *patient in Cohort chemo) and on-study, based on total sum of diameters assuming linear growth rate 3 (discontinued As of cutoff date arm) 21 Oct 2022 44

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 entry 2 ORR 12% Cohort 1 PD at 26 3 17 6 2.8 to 14.2+ 1.4+ to 11.6 Cohort 2 study DCR 77% entry Data shown based on blinded independent central review (BICR) of radiographic data per RECIST 1.1 in evaluable patients Evaluable patients are those receiving 2 courses of CAN-2409 + prodrug and completed 12-wk treatment window *new lesion + indicates response is ongoing ORR: overall response rate, DCR: disease control rate, DoR: duration of response, PR: partial response, SD: stable disease, PD: progressive disease As of cutoff date 21 Oct 2022 45

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 up 11.2 mo for Cohort 2 • 47% (14/30) patients censored (ongoing SD, PR) As of cutoff date 21 Oct 2022 46

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 central read • Abscopal response in 14/21 patients (67%) presenting with multiple lesions* Site of injection • Abscopal response was observed in patients injected in either lymph nodes and/or lung lesions * Decrease of at least 5% observed in at least one noninjected lesion 47 # of patients

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) Right middle lobe Right middle lobe nodule nodule LA: 118.6 mm LA: 85.8 mm Target lesion nd 2 Target lesion Site of both injections injection (week 6) Legend LN: lymph node, LA: long axis, SA: short axis RECIST target lesions (red) 48

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 granzyme B+ CD8T cells Cytokeratin CD8 Granzyme B 49 Double positive granzyme B+ CD8T cells

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= central memory CAN-2409 injections B W2 W6 W8 W12 F/U As of cutoff date 21 Oct 2022 B baseline CAN-2409 injections F/U follow-up 50 -3 -6 p-values range from 25x10 to 626 x 10 Log 2 change from baseline Log2 change from baseline

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) presents similar complication rate as biopsy (extremely rare) Latest generation of TBNI includes ultrasound-guided transbronchial injection of lymph nodes and robotic bronchoscopy (already in use in LuTK02) Majority of lung and thoracic lymph node lesions are accessible for outpatient bronchoscopic injection DeMaio A, Sterman D. Eur Respir Rev 2020; 29: 200028 51

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 infiltration of CD8+ T cells in the tumor microenvironment, systemic expansion of effector T cells and increase in soluble granzyme B in peripheral blood Robust evidence of local and systemic anti-tumor activity • CAN-2409 favorably changed the trajectory of tumor progression • Decrease in tumor size of RECIST target lesions in most patients • Reduction in uninjected tumor lesions: 14/21 patients (67%) • ORR of 13% (4/30) across cohorts 1 and 2 • DCR of 77% (20/26) in patients entering trial with progressing disease (cohort 2) • Sustained and ongoing clinical responses of longer than 1 year • Durable disease stabilization translating into promising preliminary PFS 52

CAN-2409 + nivolumab in high-grade glioma Patrick Y. Wen, MD 53

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 therapies for brain tumors, especially targeted molecular agents. His other clinical interests include neurologic complications of cancer. Dr. Wen graduated from the Medical College of St. Bartholomew’s Hospital, University of London, completed his internal medicine training at the University of London postgraduate hospitals and his neurology residency in the Harvard-Longwood Neurology Training Program. Dr. Wen is a principal investigator on Candel’s open label phase 1 clinical trial of CAN-2409 plus valacyclovir in combination with nivolumab and standard of care in newly diagnosed high-grade glioma. 54

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

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 survival < 15 months Radiation and temozolomide induce lymphopenia Corticosteroids may impact immune response Negative prognostic factors influencing survival: High grade glioma Age, sex, MGMT* methylation status, IDH**, extent of tumor resection Weller M et al. Nat Rev Neurol 2017; 13:363-374 *O6-methylguanine-DNA methyl-transferase (MGMT) gene promoter Grossman SA et al. Clin CA Res 2011; 17:5473-5480 **Isocitrate dehydrogenase Chongsathidkiet P et al Nat Med 2018; 24:1459-1468 56

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 40 aPD1 20 5 20 * Mock 0 0 0 Ganciclovir - + - + - + - + D2 D3 D4 0 20 40 60 80 100 CAN-2409 2 2 10 10 50 50 (vp/ml) CAN-2409 Day(s) Model: Intracranial injection of Model: In vitro experiments with murine CT-2A-Luc HGG cells murine CT-2A-Luc HGG cells in mice ***p ≤ 0.001, ****p ≤ 0.0001 N=26; ***p≤ 0.001, **p ≤ 0.01, *p≤ 0.05 Speranza MC et al. Neuro Oncol 2018; 20:225-235 57 Cell survival PD-L1 (% of alive cells) Mock Percent survival

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 Primary Endpoint Newly o Safety Surgery + diagnosed high- CAN-2409 + grade glioma Secondary Endpoints valacyclovir o Overall survival intended for chemoradiation + o Progression free survival gross total nivolumab o Radiologic changes resection o Immunological biomarkers Unmethylated MGMT promoter (~66%) Continue RT + nivolumab NCT03576612 Methodology for primary endpoint: Evaluate safety of the combination of CAN-2409 +VCV + nivolumab +/- temozolomide (TMZ) Enrolment in sets of 9 patients (~3 methylated and 6 unmethylated) If DLT rate ≤33%, proceed with next set of 9 patients Target ~12 methylated and ~24 unmethylated evaluable patients 58

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) Unmethylated 25(61) Black/African American 3(7) American Indian or IDH* * 1(2) Alaska Native Wild type 39(95) Asian 1(2) Mutant 2(5) Not reported 2(5) Histopathologic diagnosis Ethnicity Glioblastoma 40(98) Not Hispanic or Latino 38(93) Diffuse astrocytoma 1(2) Hispanic or Latino 1(2) Unknown 1(2) Type of resection Gross total resection 30(73) Not reported 1(2) Subtotal resection 11(27) *Karnofsky Performance Scale **IDH Isocitrate dehydrogenase As of cutoff date 59 30 Sep 2022

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 the acute monitoring period (2 weeks after the 4th dose of nivolumab). Safety population: Any patient who received investigational agent. 60

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 GTR WT GTR WT GTR WT GTR Day 15: Initiate TMZ & nivolumab As of cutoff date Day 8: Begin radiation therapy (RT) 61 30 Sep 2022 CAN-2409 Injection & valacyclovir

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 period (0-71 days) are shown below Most common adverse events Additional grade 3-4 adverse events occurring in >10% of patients occurring in >1 patient CTC grade Total=41 Adverse Event CTC grade Total=41 1 2 3 4 N (%) Event 3 4 N (%) Fatigue 11 (27) 4 (10) 1 (2) 0 16 (39) Neutrophil count decreased 1 (2) 1 (2) 2 (5) Nausea 9 (22) 1 (2) 2 (5) 0 12 (29) Acute kidney injury 2 (5) 0 2 (5) ALT increased 9 (22) 0 1 (2) 0 10 (24) Headache 6 (15) 0 2 (5) 0 8 (20) Hypertension 2 (5) 0 2 (5) Anemia 3 (7) 3 (7) 1 (2) 0 7 (17) Fever 5 (12) 2 (5) 0 0 7 (17) 9 discontinuations due to adverse events: AST increased 7 (17) 0 0 0 7 (17) • 3 expected temozolomide toxicity (myelosuppression) Hyponatremia 4 (10) 2 (5) 1 (2) 0 7 (17) • 3 expected nivolumab toxicity (1 aseptic meningitis, 2 Vomiting 4 (10) 1 (2) 1 (2) 0 7 (17) AST/ALT increase) Platelet count decreased 4 (10) 0 0 2 (5) 6 (15) • 2 due to underlying disease symptoms 4 (10) 1 (2) 0 0 5 (12) Blood bilirubin increased • 1 unrelated medical event (prostate cancer) As of cutoff date 30 Sep 2022 62

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 resection As of cutoff date STR – subtotal resection 30 Sep 2022 OS – overall survival 63

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

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 2020; 29: 10–21 65

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 (0.04 - 0.00095) B= baseline P= progression/off study 66

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 Progression Progression Progression Recurrence Recurrence Recurrence Baseline Re-section Baseline Re-section Re-section Baseline Time Point Time Point Time Point *29 baseline tumors , 2 recurrences, 1 re-resection 67 PBMCs Tumor samples*

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 outcome analysis • Extensive longitudinal biomarker analysis supports CAN-2409 ability to activate systemic immune response, even after single administration • Combination of CAN-2409 and nivolumab shows expansion of activated circulating CD4 and CD8 T cells and decreased exhaustion • Preliminary analysis suggests ability of CAN-2409 and nivolumab to expand T cell repertoire density, diversity and clonality in the tumor tissue and in the peripheral blood 68

CAN-3110 in recurrent high-grade glioma E. Antonio Chiocca, MD, PhD 69

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 mutations replicate selectively in tumors with a specific defect in a tumor suppressor pathway. Before joining BWH, Dr. Chiocca was Chairman of the Department of Neurosurgery at the Ohio State University Medical Center. He has more than 300 peer-reviewed publications. Currently, Dr. Chiocca serves as the lead investigator to Candel’s phase 1 clinical trial studying the effects of CAN-3110 in recurrent malignant glioma. 70

Phase 1 clinical trial of CAN-3110 in recurrent high-grade glioma December 6, 2022 71

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 the brain) ⎼ Improves replication Nestin Promoter ⎼ Provides tumor-specific oncolytic activity ICP34.5 CAN-3110 Designed for safety o Disruption of ICP6 limits virus replication to dividing cells or cells with 3 p16 tumor suppressor pathway defects o Remains sensitive to anti-herpetic drugs o Nestin provides tumor specificity 72

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 immunosuppressive TME Inflamed TME Cancer cell proliferation Cancer cell necrosis 73

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 patients dosed o Determine maximum tolerated dose Dose expansion (Cohort X) Patients with 9 1 x 10 PFU recurrent Secondary Endpoints 12 patients high-grade glioma o Immunological biomarkers o MRI assessment of Lesions ≥ 1.0 cm Pre-administration of Cytoxan disease and progression 8 free survival +1 x 10 PFU 3 patients dosed o MRI alteration of 9 + 1 x 10 PFU permeability and flow at injection site 6 patients dosed Repeat dosing (up to 6) 8 +1 x 10 PFU x 6 doses 9 + 1 x 10 PFU x 6 doses NCT03152318 74 *Break Through Cancer initiative Arm A Arm B Arm C*

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 0 NA NA 8 6 (A) 3 3x10 0 0 NA NA 7 (A), 9 21 1x10 0 1 046(IDHmut) 2 10 (A), 2 (B) 9 8 (A) 3 3x10 0 1 033(IDHmut) 16 10 9 (A) 6 1x10 0 0 NA NA Time range TOTAL 50 0 2 2 to 16 (days)à As of cutoff date 75 28 Jul 2022 DLT: dose limiting toxicity, SAE: serious adverse event

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 survival: 11.6 months Data mature as of Oct 2022 0 0 6 12 18 24 30 36 Months EA Chiocca et al. Oral presentation. ASCO June 2021 A Ling et al. Oral presentation. SNO November 2022 76 (%) Probability of Survival

Complete response in injected and uninjected tumor without additional therapy following CAN-3110 CAN-3110 injection 77

Biomarker strategy 78

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

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 oHSV antigen in post-injection samples collected in a range of 24 to 801 days post treatment 80

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

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 =0.0016 p <0.0001 CD8+ P<0.0001 P<0.0001 Perivascular tumor areas surrounded anti HSV by T cells CD8+ 21/29 tumors 24/29 tumors 14/29 tumors 82

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 between the two groups using the log-rank test. 83

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 treatment samples with evidence for increased immune signatures and VDJ diversity in longer survivors after CAN-3110 o We are now evaluating whether multiple injections of CAN-3110 can fundamentally transform the treatment of high-grade glioma 84

enLIGHTEN™ Discovery Platform Francesca Barone, MD, PhD 85

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 previously served as Vice President and Head of Experimental Medicine at Flagship Pioneering’s Kintai Therapeutics, now Senda Biosciences. She has extensive experience in designing experimental medicine clinical trials to support rigorous decision-making across various programs and indications. Prior to joining the industry, Dr. Barone held the academic position of Reader in Translational Rheumatology and Academic Director of Business Engagement for the College of Medical and Dental Sciences at the University of Birmingham. During her tenure, she was also the Director of the laboratories for immuno-phenotyping in the Institute of Translational Medicine. 86

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 approach: viral immunotherapies designed to target the heterogeneous mechanisms in the TME and overcome immunotherapy resistance 87

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 systematic, iterative HSV-based discovery platform leveraging human biology and advanced analytics to create new viral immunotherapies for solid tumors 88

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

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

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

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

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 modulator expression (proinflammatory cytokine) (TNF family member) IFNg ELISA 3000 MOI 3 Alpha-201-GFP MOI 10 2000 Alpha-201-TNF family member MOI 3 1000 Alpha-201-TNF family member MOI 10 100 80 60 40 20 0 Payload production interval (day) MOI multiplicity of infection 93 pg/ml 0-2 2-4 4-6 0-2 2-4 4-6

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 multimodal payload 94 Don’t eat me % of dead cells

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 enLIGHTEN HSV-1 vectors allows for the delivery of multiple investigational immune-modulating gene products to tumors leveraging the immunogenic properties of a viral infection 95 Payload expression

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 payload expression and regulated oncolysis MHC-I 96 Experiments performed in PBMCs: cancer cells cocultures count CD11c+MHC-II+ cells

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 Cells in Solution via HSV-1-Based OV Development* Solid Tumors Features of the vector itself plus encoded Exposure at the Site of Action Insufficient CAR-T ingress factors turn cold tumors hot Expose TAAs* via oncolysis Target binding / engagement Antigenic heterogeneity Encode factors to engage CAR-T cells Encode cytokines to stimulate and activate CAR-T cells Expression of pharmacological activity Suppressive TME Encode inhibitors of key suppressive factors TAAs: tumor associated antigens OV: oncolytic virus 97 *Morgan P. et al. Drug Discovery Today 2012;17: 419- 424

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 Analytics o Rapid and iterative approach o Flexibility to design assets for monotherapy or combination therapy o Opportunity to create value through partnerships 98

Candel Therapeutics Paul Peter Tak, MD, PhD, FMedSci 99

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 Pancreatic Adenocarcinoma 1L High-Grade Glioma CAN-2409 Brain Cancer 1L High-Grade Glioma + Opdivo® HSV Platform CAN-3110 Recurrent High-Grade Glioma Brain Cancer enLIGHTEN™ Discovery Solid Tumors Programs SPA – special protocol assessment 100

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 Pancreatic Adenocarcinoma HSV Platform CAN-3110 Recurrent High-Grade Glioma Brain Cancer enLIGHTEN™ Discovery Solid Tumors Programs SPA – special protocol assessment 101

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, active phase 3, CAN-2409 surveillance prostate cancer phase 2, CAN-2409 Clinical data, pancreatic cancer phase 2, CAN-2409 2023+ Clinical data, NSCLC phase 2, CAN-2409 + ICI Clinical data, NSCLC 2022 phase 2, CAN-2409 + ICI Clinical data, HGG phase 1, CAN-3110 Clinical data, HGG phase 1, CAN-2409 + Opdivo Upcoming clinical data 102

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 combination with nivolumab phase 1 • Combination is well tolerated with no DLT observed and no added toxicity to standard of care • mOS appears comparable to historical standard of care outcomes • Biomarker analysis demonstrates induction of systemic immune response after single administration o CAN-2409 pancreas • Ongoing phase 2 clinical trial, preliminary data Q4 2023 o CAN-2409 prostate • Phase 3 in localized intermediate/high-risk prostate cancer expected to read out in Q4 2024 • Phase 2 in active surveillance, localized prostate cancer expected to read out in Q4 2023 103

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 immune activation • Evaluation of repeat dosing of CAN-3110 initiated o enLIGHTEN • Established discovery engine to generate novel viral immunotherapies targeting the TME o Company o Significant unmet need and commercial opportunity for each selected indication o In HGG, portfolio decision to prioritize CAN-3110 and not pursue phase 3 clinical trial of CAN-2409 o Strong scientific support from high-profile Research Advisory Board o Cash and cash equivalents of $77.2M as of September 30, 2022, with runway into Q1 2024 104

Q&A 105

Thank You Candel's Virtual R&D Day | December 6, 2022 NASDAQ: CADL 106

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 protocol assessment ICI Immune checkpoint inhibitor BTC Break Through Cancer STR Subtotal resection IFN Interferon CAIX Hypoxia-regulated carbonic anhydrase IX TAAs Tumor associated antigens JHU Johns Hopkins University CAR-T Chimeric antigen receptor TCR T-cell receptor KPS Karnofsky Performance Scale CEA Carcinoembryonic antigen TIL Tumor-infiltrating lymphocyte LA Long axis TME Tumor microenvironment CIMAC-CIDC Cancer Immune Monitoring and Analysis Centers TMZ Temozolomide LN Lymph node CLDN18.2 Claudin18.2 TNF Tumor necrosis factor CTC Common Terminology Criteria MGMT O6-methylguanine-DNA methyl-transferase TRAE Treatment-related adverse event CTLA-4 Cytotoxic T-lymphocyte–associated antigen 4 mOS Median overall survival VDJ Variability, diversity, and joining DCR Disease control rate mPFS Median progression free survival WT Wild type DLT Dose-limiting toxicity MSKCC Memorial Sloan Kettering MSLN Mesothelin DoR Duration of response NCCN National Comprehensive Cancer Network ECOG Eastern Cooperative Oncology Group NDV Newcastle Disease Virus EGFR Epidermal growth factor NK cell Natural killer cell EGJC Esophagogastric Junction Cancer F/U Follow up NSCLC Non-small cell lung cancer ORR Overall response rate FDA U.S. Food and Drug Administration OS Overall survival GBM Glioblastoma multiforme GD2 Disialoganglioside OV Oncolytic virus PD1 Progressive disease GFP Green fluorescent protein PD1 Programmed cell death protein 1 Gr3 CTC Grade 3 GTR Gross total resection PFS Progression free survival HER2 Human epidermal growth factor receptor 2 PR Partial response RNA Ribonucleic acid HGG High-grade glioma