Candel Therapeutics Reports Both Prolonged Median Overall Survival and Long Tail of Survival in Phase 2a Clinical Trial of CAN-2409 in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Non-Responsive to Immune Checkpo

Candel Therapeutics Reports Both Prolonged Median Overall Survival and Long Tail of Survival in Phase 2a

Clinical Trial of CAN-2409 in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Non-Responsive to Immune Checkpoint Inhibitor

NEEDHAM, Mass., March 26, 2025 (GLOBE NEWSWIRE) Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical

stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, today announced final survival data from a phase 2a clinical trial of CAN-2409 in

patients with stage III/IV NSCLC, inadequately responding to ICI treatment. mOS was 24.5 months in 46 evaluable patients receiving 2 courses of CAN-2409 (per protocol population; cohort 1 and 2) and 21.5

months in evaluable patients from cohort 2 (n=41) that presented with progressive disease at baseline, despite ICI treatment. mOS in patients with progressive disease despite ICI treatment, was 9.8-11.8 months in other studies, including those with

standard of care of docetaxel chemotherapy, which has a very poor prognosis, did not exceed 12 months in other published studies. (1, 2) This final analysis included extended follow-up data (1 year after the previous data cut) with a median follow up time for the per protocol population of 32.4 months. Data showed a sizeable percentage of patients with survival exceeding 24 months,

evidence of a long tail of survival, with 37% of patients with progressive disease despite treatment with ICI alive 2 years after CAN-2409 administration.

Biomarker research showed an enhanced immunological and clinical response after CAN-2409 administration in patients

with non-squamous histology compared to squamous histology, and improved mOS was in this population (25.4 months in patients with progressive disease despite ICI treatment and

non-squamous NSCLC, n=33).

Treatment options are quite limited for patients with unresectable NSCLC who

progress on anti-PD-1 therapy, said Charu Aggarwal, MD, MPH, Leslye Heisler Professor for Lung Cancer Excellence at the University of Pennsylvania s Perelman

School of Medicine and Principal Investigator of the study. The survival benefit seen in this study is striking, especially when compared to both the current standard of care treatment of docetaxel chemotherapy and other therapies under

investigation for this patient group, she added.

Pre-treatment and mid-treatment dropout rates were comparable to those reported

in other clinical trials in similar populations of patients with advanced NSCLC.(1, 3) Three patients were enrolled, but did not receive treatment, 22 patients received only one injection of CAN-2409, 51 patients received at least 2 injections of CAN-2409, but 5 patients did not complete treatment. 46 patients received complete treatment (2 courses of CAN-2409 plus prodrug) and were included in the evaluable, per protocol population. The per protocol population was representative of the overall enrolled population in terms of baseline demographics and prognostic

These updated survival data confirm and

strengthen our previously reported findings, demonstrating that CAN-2409 has the potential to extend survival for patients with advanced NSCLC, who have limited treatment options after failing to respond to,

or progressing, despite immune checkpoint inhibitor therapy, said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. CAN-2409 may represent an entirely new approach

to solid tumor treatment, with its unique mechanism of action and favorable safety profile to date, enabling potentially meaningful improvements in outcomes beyond current standard of care. These compelling results mark a potentially transformative

advance in our fight against this aggressive disease.

The extension of survival in patients with

non-squamous disease is notable even when compared to data that have been reported for other investigational products, such as antibody-drug conjugates, for this patient population, said W. Garrett

Nichols, MD, CMO of Candel. CAN-2409, in addition to continued ICI treatment, may prolong survival beyond that offered by docetaxel chemotherapy, and has the potential to be better tolerated.

Based on these positive findings, the Company will advance its development program for CAN-2409 in NSCLC, including

preparation and enabling work for a future, potentially registrational, clinical trial in patients with NSCLC with non-squamous histology. The U.S. Food and Drug Administration (FDA) previously granted Fast

Track Designation for CAN-2409 plus valacyclovir in combination with ICI treatment for the treatment of stage III/IV NSCLC in patients who are resistant to first line

PD-(L)1 inhibitor therapy and who do not have activating molecular driver mutations or have progressed on directed molecular therapy.

CAN-2409, Candel s most advanced multimodal biological immunotherapy candidate, is an investigational, off-the-shelf,

replication-defective adenovirus engineered to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient s specific tumor and induce an individualized, systemic immune response against the tumor. HSV-tk is an enzyme that

locally converts orally administered valacyclovir into a toxic nucleotide analogue that kills nearby cancer cells. Together, this regimen is designed

to induce an individualized and specific CD8+ T cell-mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity, based on in-situ vaccination against a variety of tumor antigens. Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Encouraging monotherapy

activity, as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors, have previously been shown in several preclinical and clinical settings. More than 1,000 patients have been dosed

with CAN-2409 with a favorable tolerability profile to date, supporting the potential for combination with other therapeutic strategies.

Candel s clinical development program for CAN-2409 includes completed phase 2a clinical trials in both non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC), as well as a positive pivotal randomized, placebo-controlled phase 3 clinical trial of CAN-2409

in localized, non-metastatic prostate cancer. In December 2024, Candel announced that CAN-2409 achieved its primary endpoint in a phase 3 clinical trial in men with intermediate-to-high-risk, localized prostate cancer, demonstrating statistically significant and clinically meaningful improvement in disease-free survival when added to SoC

radiation therapy +/- androgen deprivation therapy. In the Company s randomized controlled phase 2a clinical trial of CAN-2409 in borderline resectable PDAC, positive survival data showed notable

improvement in estimated median overall survival of 31.4 months after experimental treatment with CAN-2409 plus standard of care versus 12.5 months in the control group in patients with PDAC, who received only

standard of care. Median survival post-progression was 21.2 months in patients who received CAN-2409 compared to 6.4 months in the control arm. CAN-2409 plus prodrug has

been granted Fast Track Designation by the FDA for the treatment of PDAC, stage III/IV NSCLC in patients who are resistant to first line PD-(L)1 inhibitor therapy and who do not have activating molecular

driver mutations or have progressed on directed molecular therapy, and localized primary prostate cancer. The FDA has also granted Orphan Drug Designation to CAN-2409 for the treatment of PDAC. Candel s

pivotal phase 3 clinical trial in newly diagnosed, localized prostate cancer was conducted under a Special Protocol Assessment (SPA) agreed with the FDA.

About Candel Therapeutics

Candel is a BLA ready clinical stage biopharmaceutical company focused on developing

off-the-shelf multimodal biological immunotherapies that elicit an individualized, systemic anti-tumor immune response to help patients fight cancer. CAN-2409 is the lead product candidate from the adenovirus platform. CAN-3110 is the lead product candidate from the HSV platform and is currently in an ongoing phase 1b

clinical trial in recurrent high-grade glioma. In October 2023, the Company announced that Nature published initial results from this ongoing clinical trial: CAN-3110 was well tolerated and the

investigators observed nearly two-fold increase in median overall survival compared to historical controls after a single CAN-3110 injection in this therapy-resistant

condition.4 Finally, Candel s enLIGHTEN Discovery Platform is a systematic, iterative

HSV-based discovery platform leveraging human biology and advanced analytics to create new viral immunotherapies for solid tumors.

For more information about Candel, visit: www.candeltx.com

Forward-Looking Statements

This press release includes

certain disclosures that contain forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, express or implied statements regarding the timing and

advancement of current and future development programs; including the timing and availability of additional data and key data readout milestones and presentations; expectations regarding early biological readouts as predictor of clinical response;

and expectations regarding the therapeutic benefit of the Company s programs, including the ability of CAN-2409 to treat a broad range of solid tumors and improve disease-free survival, overall survival,

and post-progression survival. The words may, will, could, would, should, expect, plan, anticipate, intend, believe,

estimate, predict, project, potential, continue, target and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements

contain these identifying words. Any forward-looking statements in this press release are based on management s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual

events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties related to the timing and advancement of

development programs; expectations regarding the therapeutic benefit of the Company s programs; that final data from the Company s pre-clinical studies and completed clinical trials may differ

materially from reported interim data from ongoing studies and trials; the

Company s ability to efficiently discover and develop product candidates; the Company s ability to obtain and maintain regulatory approval of product candidates; the Company s

ability to maintain its intellectual property; the implementation of the Company s business model, including strategic plans for the Company s business and product candidates; and other risks identified in the Company s filings with

the U.S. Securities and Exchange Commission (SEC) including the Company s most recent Annual Report on Form 10-K filed with the SEC and any subsequent filings with the SEC. The Company cautions you not to

place undue reliance on any forward-looking statements, which speak only as of the date they are made. The Company disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events,

conditions, or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press

release represent the Company s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date.

VP, Investor Relations and Business Development