The purpose of this clinical trial is to evaluate the effects of adding CAN-2409 + prodrug for stage III/IV NSCLC patients who are on standard of care first line immune checkpoint inhibitor (ICI) treatment with evidence that the clinical response is inadequate. CAN-2409 is a viral immunotherapy approach that induces tumor-infiltrating T-cells and a consequent PD-L1 up-regulation. A combination of CAN-2409 added to standard of care (SOC) checkpoint inhibitors may lead to improved long-term outcomes for patients with NSCLC who have suboptimal response to ICI therapy.

Start Date13 Oct 2020

Sponsor / Collaborator

Candel Therapeutics, Inc.

[+1]

NCT03603405 / RecruitingPhase 1/2IIT

Phase I-II Study Evaluating HSV-tK + VALACYCLOVIR GENE THERAPY Combination With Radiotherapy and Chemotherapy for Newly Diagnosed Anaplastic Astrocytoma and Glioblastoma Multiforme.

Study to assess the safety and efficacy of HSV-tk (gene therapy), valacyclovir, radiotherapy and chemotherapy in newly diagnosed glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA).

Start Date28 Feb 2018

Sponsor / Collaborator

THE METHODIST HOSP RESEARCH INSTITUTE

100 Clinical Results associated with Aglatimagene besadenovec

100 Translational Medicine associated with Aglatimagene besadenovec

100 Patents (Medical) associated with Aglatimagene besadenovec

172

Literatures (Medical) associated with Aglatimagene besadenovec

01 Oct 2023·Molecular therapy : the journal of the American Society of Gene Therapy

Combined cytotoxic and immune-stimulatory gene therapy using Ad-TK and Ad-Flt3L: Translational developments from rodents to glioma patients

Review

Author: Castro, Maria G ; Lowenstein, Pedro R ; Faisal, Syed M

Gliomas are the most prevalent and devastating primary malignant brain tumors in adults. Despite substantial advances in understanding glioma biology, there have been no regulatory drug approvals in the US since bevacizumab in 2009 and tumor treating fields in 2011. Recent phase III clinical trials have failed to meet their prespecified therapeutic primary endpoints, highlighting the need for novel therapies. The poor prognosis of glioma patients, resistance to chemo-radiotherapy, and the immunosuppressive tumor microenvironment underscore the need for the development of novel therapies. Gene therapy-based immunotherapeutic strategies that couple the ability of the host immune system to specifically kill glioma cells and develop immunological memory have shown remarkable progress. Two adenoviral vectors expressing Ad-HSV1-TK/GCV and Ad-Flt3L have shown promising preclinical data, leading to FDA approval of a non-randomized, phase I open-label, first in human trial to test safety, cytotoxicity, and immune-stimulatory efficiency in high-grade glioma patients (NCT01811992). This review provides a thorough overview of immune-stimulatory gene therapy highlighting recent advancements, potential drawbacks, future directions, and recommendations for future implementation of clinical trials.

01 Oct 2023·Human gene therapy

Clinical Efficacy and Safety of AdV-tk Gene Therapy for Patients with Cervical Squamous Intraepithelial Lesion: A Prospective Study.

Article

Author: Tang, Huadong ; Li, Yanmei ; Liu, Xin ; Liu, Qing ; Hou, Ying ; Zhou, Yuxiang ; Li, Ning ; Li, Xiulan ; Bian, Meina ; Wang, Nan ; Xu, Fuqiang

Cervical cancer is the fourth most common type of cancer for women in 2020, and many more women have cervical precancerous lesion-squamous intraepithelial lesion (SIL). Early treatment of cervical SIL to reverse or delay its progression is an important approach to reduce the incidence of cervical cancer. The efficacy and safety of adenovirus-based vectors expressing the thymidine kinase gene (AdV-tk) in the treatment of multiple types of cancers shows promise for its use in gynecology. We aim to provide relevant clinical efficacy and safety data after introducing AdV-tk for the treatment of cervical SIL for the first time through this prospective study. We conducted a maximum of 6 sessions to administer AdV-tk gene therapy to 23 patients (mean age: 35 years old) with cervical low-/high-grade SIL (LSIL/HSIL) who were enrolled from August 2015 to April 2018 and analyzed the clinical characteristics and follow-up outcomes (mean follow-up period: 7.3 months). The present study consisted of 17 patients (73.9%) with cervical HSIL and 6 patients with LSIL confirmed by colposcopy-directed biopsy. We observed an overall histological remission and regression rate of 87.0% (20/23, 95% confidence interval [95% CI]: 73.2-100, p < 0.001) after AdV-tk gene therapy. Eight patients (34.8%) were detected with human papillomavirus (HPV) 16/18 subtypes and 13 patients were found to be positive with at least one of the other 13 high-risk HPV (HR-HPV) subtypes, while 2 patients did not have any of the 15 HR-HPV subtypes. The overall clearance rate of HR-HPV was 76.2% (16/21, 95% CI: 58.0-94.4, p = 0.016) after AdV-tk gene therapy. For safety evaluation, no severe complications were reported in any of the 23 patients. The most commonly reported symptom was fever in 52.2% (12/23) of patients and all symptoms were fully resolved after symptomatic treatment. Our data indicate that AdV-tk gene therapy has high efficacy and safety in the treatment of cervical SIL among gynecological patients. Our findings provide clinical evidence on the potential promotion and application of AdV-tk in the treatment of cervical SIL, and potentially for cervical cancer, among gynecological patients.

01 Jan 2023·Frontiers in medicine

Uncovering transcriptomic landscape alterations of CAN-2409 in in vitro and in vivo glioma models.

Article

Author: Zdioruk, Mykola ; Hoetker, Michael S ; Nowicki, Michal O ; Tabatabai, Ghazaleh ; Barone, Francesca ; Lawler, Sean E ; Koch, Marilin S ; Tak, Paul P ; Herbert, Zachary T ; Chiocca, E Antonio

Rationale:

CAN-2409 is a locally delivered oncolytic therapy, which results in vaccination against the injected tumor. CAN-2409 consists of a non-replicating adenovirus armed with the Herpes virus thymidine kinase, which metabolizes ganciclovir into a phosphorylated nucleotide that is incorporated into the tumor cell's genome, thereby inflicting immunogenic cancer cell death. While CAN-2409's immunological impact has been well characterized, its effects on the tumor cells transcriptome remains unknown. We compared the transcriptomic landscape after treatment of glioblastoma models with CAN-2409 in vitro and in vivo to assess how the interplay with the tumor microenvironment influences CAN-2409-mediated transcriptome alterations.

Methods:

We performed RNA-Seq with CAN-2409 treated patient-derived glioma stem-like cells and tumors of C57/BL6 mice and compared KEGG pathway usage and differential gene expression focusing on immune cell and cytokine profiles. T-cell -killing assays were performed to assess candidate effectors.

Results:

PCA analysis showed distinct clustering of control and CAN-2409 samples under both conditions. KEGG pathway analysis revealed significant enrichment for p53 signaling and cell cycle pathway, with similar dynamics for key regulators of both pathways in vitro and in vivo, including MYC, CCNB1, PLK1 and CDC20. Selected alterations (PLK1 and CCNB1) were validated at the protein level. Cytokine expression analysis revealed upregulation of pro-inflammatory IL12a under both conditions; immune cell gene profiling showed reduction of myeloid associated genes. T-cell-killing assays showed increased killing in the presence of IL-12.

Conclusion:

CAN-2409 significantly alters the transcriptome both in vitro and in vivo. Comparison of pathway enrichment revealed mutual and differential utilization of pathways under both conditions, suggesting a modulating influence on the cell cycle in tumor cells, and of the tumor microenvironment on the transcriptome in vivo. IL-12 synthesis likely depends on interactions with the tumor microenvironment, and it facilitates CAN-2409 cell killing. This dataset provides potential to understand resistance mechanisms and identify potential biomarkers for future studies.

News (Medical) associated with Aglatimagene besadenovec

01 Jul 2024

·www.prnewswire.com

Oncolytic Viruses: Unlocking a New Era in Cancer Immunotherapy | DelveInsight

The potential of oncolytic viruses as a novel approach to cancer treatment is exciting and offers a targeted approach that holds promise for overcoming treatment resistance and achieving durable responses in a range of malignancies. LAS VEGAS, July 1, 2024 /PRNewswire/ -- Oncolytic viruses are either RNA or DNA viruses. RNA viruses such as reoviruses, paramyxoviruses, and picornaviruses, which encode only a few genes, often undergo rapid proliferation and lysis of tumor cells. On the other hand, oncolytic DNA viruses such as herpes viruses, adenoviruses, or poxviruses allow for the insertion of multiple foreign genes but are slower in replication and amplification. Among the selected cancers, bladder cancer accounted for the maximum cases as compared to other selected indications in 2023 among the 7MM. As per the DelveInsight assessment, in 2023, the total incident cases of melanoma, non-melanoma skin cancer, pancreatic cancer, renal cell carcinoma, prostate cancer, brain cancer, bladder cancer, and ovarian cancer combined in the United States were 1.1 million. Currently, only two oncolytic virus therapies are approved, namely, IMLYGIC (Talimogene laherparepvec/T-VEC; Amgen) and DELYTACT (teserpaturev/G47∆; Daiichi Sankyo). Learn more about the FDA-approved oncolytic viruses @ Oncolytic Viruses Cancer Treatment IMLYGIC (T-VEC), developed by Amgen, became the first oncolytic virus to receive approval from the FDA in 2015. It is indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with recurrent melanoma following initial surgery. Subsequently, in December 2015, the European Commission (EC) also approved for its use in treating adults with unresectable melanoma that has regionally or distantly metastasized (Stage IIIB, IIIC, and IVM1a), excluding bone, brain, lung, or other visceral diseases. This genetically modified herpes simplex virus type 1 is engineered to replicate within tumors and express an immune-stimulating protein known as granulocyte-macrophage colony-stimulating factor (GM-CSF). DELYTACT (G47Δ) is a modified form of herpes simplex virus type 1 (HSV-1) with three mutations, designed to selectively replicate within cancer cells. In 2021, it received provisional approval from the Japan Ministry of Health, Labour and Welfare (MHLW) for hospital-based commercialization, specifically for treating malignant glioma patients over 7 years. This approval followed a Phase II trial demonstrating improved one-year survival rates among patients with recurrent glioblastoma, previously treated with radiotherapy and temozolomide chemotherapy. DELYTACT marks the world's first oncolytic virus therapy for brain cancer and only the third globally available oncolytic virus treatment. To learn more about oncolytic viruses cancer treatment options, visit @ Oncolytic Virus Cancer Therapy The field of oncolytic virus therapy is still developing. Further research is needed to determine their long-term efficacy and potential challenges. Still, early results seem encouraging, suggesting that oncolytic viruses may become a powerful tool for the treatment of patients with cancer. Presently, oncolytic virus therapy is only approved for melanoma and malignant glioma (in Japan). However, the pipeline suggests its emergence as a potential treatment for various cancers, including ovarian cancer, non-small cell lung cancer, breast cancer, renal cell carcinoma, and others. The pipeline for oncolytic viruses is robust, with major pharmaceutical companies such as Replimune (RP1), Genelux (Olvi-Vec), Candel Therapeutics (CAN-2409), Imugene (CF33-HNIS), EpicentRx (AdAPT-001), and others actively engaged in research to enhance cancer treatment options. Discover which therapies are expected to grab major oncolytic virus therapy market share @ Oncolytic Virus Therapy Market Report Olvi-Vec is a proprietary oncolytic vaccinia virus engineered to enhance safety, tumor selectivity, and therapeutic potential. Originally a non-human pathogen used in the smallpox vaccine, the vaccinia virus induces immunogenic cell death and activates the immune system for long-term cancer immunotherapy. According to Genelux's recent corporate presentation, topline results for the Phase III OnPrime/GOG-3076 study are expected in the second half of 2025. In November 2023, Genelux announced that the US FDA granted Fast Track Designation for Olvi-Vec (olvimulogene nanivacirepvec) in treating patients with platinum-resistant/refractory ovarian cancer. The drug is currently in Phase III clinical development, with the study anticipated to be completed by 2026. RP1 is Replimune's leading product candidate, developed from a proprietary new strain of herpes simplex virus. It has been genetically modified and enhanced with a fusogenic protein (GALV-GP R-) and GM-CSF to enhance tumor-killing potency, improve the immunogenicity of tumor cell death, and stimulate a systemic anti-tumor immune response. In April 2024, Replimune presented interim results from ARTACUS, a Phase I/II clinical trial testing RP1 monotherapy for skin cancers in patients who have undergone solid organ or hematopoietic cell transplants. Currently, RP1 is in the Phase II IGNYTE study, a multi-cohort clinical trial combining RP1 with OPDIVO. AdAPT-001 is an experimental immunotherapy featuring a TGF-β receptor-immunoglobulin Fc fusion trap. It is designed to neutralize isoforms 1 and 3 of the profibrotic, proangiogenic, prohypoxic, and immunosuppressive cytokine, TGF-β, and make resistant tumors more responsive to checkpoint blockade. In the ongoing Phase I/II BETA PRIME trial, AdAPT-001 is being administered alone and in combination with checkpoint inhibitors to patients with treatment-resistant tumors. Notably, AdAPT-001 combined with checkpoint inhibitors has shown improved toxicity and adverse event profiles compared to the typical results seen with checkpoint inhibitors alone. Discover more about oncolytic viruses in development @ Oncolytic Viruses Cancer Therapy Clinical Trials The anticipated launch of these emerging therapies are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the oncolytic virus cancer therapy market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for oncolytic virus therapy is expected to grow with a significant CAGR by 2034. As per DelveInsight, the United States accounts for the largest oncolytic virus market size accounting for more than 70% of the total market, in comparison to EU4 (Germany, Spain, Italy, France), the United Kingdom, and Japan. Among all the emerging oncolytic virus therapies, RP1 is the most promising therapy accounting for ~40% of the oncolytic virus market in the coming decade due to its high efficacy. DelveInsight's latest published market report titled as Oncolytic Virus Market Size, Target Population, Competitive Landscape & Market Forecast – 2034 will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the oncolytic virus country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The oncolytic virus market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Incident Cases of Selected Cancer Types Target Patient Pool of Oncolytic Virus Cancer Therapy by Cancer Types Total Treated Cases by Line of Therapies The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM oncolytic virus market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this oncolytic virus market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the oncolytic virus market. Also, stay abreast of the mitigating factors to improve your market position in the oncolytic virus therapeutic space. Related Reports Oncolytic Virus Competitive Landscape Oncolytic Virus Competitive Landscape – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key oncolytic virus companies, including Genelux Corporation, Candel Therapeutics, CG Oncology, DNAtrix, SillaJen Biotherapeutics, Oncolytics Biotech, Wuhan Binhui Biotechnology, Oryx GmbH, Jiangsu Sinorda Biomedicine Co., Ltd, Virogin Biotech, Replimune, Viralytics, Oncolys Biopharma, Istari Oncology, Immvira Pharma, Seneca Therapeutics, Treovir, LLC, Targovax, Lokon Pharma, ORCA Therapeutics, Beijing SyngenTech, ViruCure, Tasly Pharmaceuticals, Turnstone Biologics, BioInvent, Transgene, Elicera Therapeutics, Orgenesis, Virttu Biologics, Imugene, Astellas Pharma, Wuhan Binhui Biotechnology Co., Ltd., Mustang Bio, Virogin Biotech, Vaxiion Therapeutics, ImmVirX, Memgen, Replimune, Immvira Pharma, ViroCure, GeneMedicine, PsiOxus Therapeutics, VCN Biosciences, Candel therapeutics, Sorrento Therapeutics, Imugene Limited, Calidi Biotherapeutics, Replimune, TILT Biotherapeutics, Guangzhou Virotech Pharmaceutical, DNAtrix, Oncorus, BioEclipse Therapeutics, among others. Oncology Drugs Market Oncology Drugs Market Insight, Competitive Landscape, and Market Forecast – 2030 report delivers an in-depth understanding of market trends, market drivers, market barriers, and key oncology drugs companies, including GlaxoSmithKline, Eli Lilly & Company, F. Hoffmann-La Roche Ltd, AbbVie Inc., Amgen Inc, Sanofi, Merck & Co., Inc, Novartis AG, Pfizer Inc, AstraZeneca, Bristol Myers Squibb., Gilead Sciences, Inc., Janssen Global Services, LLC, BAYER AG., Celldex Therapeutics Inc., Alaunos Therapeutics, Inc., Astellas Pharma Inc., Genentech, Inc., Sandoz International GmbH, BeiGene, among others. Melanoma Market Melanoma Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key melanoma companies including IO Biotech, Merck Sharp & Dohme, Eisai, Regeneron Pharmaceuticals, Iovance Biotherapeutics, Highlight Therapeutics, Linnaeus Therapeutics, Spring Bank Pharmaceuticals, Taiga Biotechnologies, Inc., Aivita Biomedical, Inc., Genentech, Inc., Dana-Farber Cancer Institute, BioMed Valley Discoveries, Inc, Amgen, Checkmate Pharmaceuticals, Astellas Pharma Inc, Galectin Therapeutics Inc., Eucure (Beijing) Biopharma Co., Ltd, Mologen AG, Ultimovacs ASA, Seagen Inc., MedImmune LLC, OnKure, Inc., Syntrix Biosystems, Inc., Anaveon AG, iOx Therapeutics, Portage Biotech, ModernaTX, Inc., Nektar Therapeutics, BioNTech SE, Sapience Therapeutics, HUYABIO International, LLC., Provectus Biopharmaceuticals, Inc., Cantargia AB, Turnstone Biologics, Corp., Aura Biosciences, F-star Therapeutics, Inc., Day One Biopharmaceuticals, Inc., Kinnate Biopharma, Xencor, Inc., HiFiBiO Therapeutics, among others. Pancreatic Cancer Market Pancreatic Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key pancreatic cancer companies including FibroGen, OSE Immunotherapeutics, Lokon Pharma, Oncotelic Inc., Tesaro, Inc., Helix BioPharma Corporation, Theradex, Tvardi Therapeutics, Incorporated, AIM ImmunoTech Inc., BioNTech SE, Prestige Biopharma Limited, HCW Biologics, Cantex Pharmaceuticals, XBiotech, Inc., Lumicell, Inc., CARsgen Therapeutics Co., Ltd., Panbela Therapeutics, Inc. , among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP

Phase 2Phase 3Clinical ResultImmunotherapyFast Track

18 Jun 2024

·www.globenewswire.com

Candel Therapeutics to Participate in the H.C. Wainwright 2nd Annual Immune Cell Engager Virtual Conference

NEEDHAM, Mass., June 18, 2024 (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 that Paul Peter Tak, MD, PhD, FMedSci, Candel’s President and Chief Executive Officer, will participate in a fireside chat at the H.C. Wainwright 2nd Annual Immune Cell Engager Virtual Conference on Tuesday, June 25, 2024 at 3:00 p.m. ET. A live webcast of the fireside chat will be available by selecting Events and Presentations under the News & Events tab in the Investors section on candeltx.com. A replay of the webcast will be archived for up to 90 days following the session date. About Candel Therapeutics Candel is a 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. Candel has established two clinical stage multimodal biological immunotherapy platforms based on novel, genetically, modified adenovirus and herpes simplex virus (HSV) gene constructs, respectively. CAN-2409 is the lead product candidate from the adenovirus platform and is currently in ongoing clinical trials in non-small cell lung cancer (NSCLC) (phase 2), borderline resectable pancreatic ductal adenocarcinoma (phase 2), and localized, non-metastatic prostate cancer (phase 2 and phase 3). The Company recently announced encouraging overall survival data for CAN-2409 in both pancreatic cancer and NSCLC. CAN-2409 received Fast Track Designation from the FDA for prostate cancer, pancreatic cancer, and NSCLC as well as Orphan Drug Designation in pancreatic cancer. Topline data are expected for both the phase 2b (active surveillance population) and the phase 3 (intermediate-to-high-risk prostate cancer) randomized, placebo-controlled clinical trials in localized prostate cancer in Q4 2024. 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 (rHGG). Clinical activity and biomarker data were published in Nature in October 2023. CAN-3110 received Fast Track Designation as well as Orphan Drug Designation from the FDA for recurrent high-grade glioma. The Company expects sharing further clinical updates in the second half of 2024. Finally, Candel’s enLIGHTEN™ Discovery Platform is a systematic, HSV-based discovery platform leveraging human biology and advanced analytics to create new viral immunotherapies for solid tumors. During the Society for Immunotherapy of Cancer (SITC) 2023 Annual Meeting, the Company presented encouraging data on the first immunotherapy candidate from this platform, Alpha 201-macro-1, which was designed to interfere with the CD47/SIRP1α pathway, in mouse models of breast cancer and lung cancer. During the American Association for Cancer Research (AACR) Annual Meeting in April 2024, the Company presented preclinical data on its immunotherapy candidate for induction of tertiary lymphoid structures (TLS), being developed as a novel therapeutic strategy for solid tumors, its second candidate from the enLIGHTEN™ Discovery Platform. For more information about Candel, visit: 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 development programs, including expectations regarding the therapeutic benefit of the Company’s programs, the ability of the Company’s programs to extend patient survival; and expectations regarding the potential benefits conferred by the Company’s inclusion in the broad-market Russell 3000 Index. 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; the Company’s ability to continue as a going concern; expectations regarding the therapeutics 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 Quarterly Report on Form 10-Q filed with the SEC, and 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. Investor Contact:Theodore JenkinsVP, Investor Relations and Business DevelopmentCandel Therapeutics, Inc.tjenkins@candeltx.com Media Contact:Kyle EvansICR WestwickeCandelPR@westwicke.com

Fast TrackImmunotherapyPhase 2Phase 1Orphan Drug

12 Jun 2024

·www.prnewswire.com

Pancreatic Cancer on the Rise: How Biotech Firms are Developing Groundbreaking Treatments

USA News Group Commentary Issued on behalf of Oncolytics Biotech Inc. VANCOUVER, BC, June 12, 2024 /PRNewswire/ -- After looking at public health records for 3.8 million patients with invasive spreading cancer, researchers recently discovered that Generation X may be experiencing larger per-capita increases in the incidence of leading cancers, including the very deadly pancreatic cancer, compared to previous generations. The startling revelations come from a study conducted by experts at the National Cancer Institute's Division of Epidemiology and Genetics and was published in JAMA Network Open. Compared with baby boomers, Gen X women had projected increases in pancreatic, thyroid, kidney, rectal, uterine, colon, and ovarian cancers, as well as non-Hodgkin's lymphoma and leukemia. Among those, pancreatic cancer is generally considered the deadliest, with its very low five-year survival rate, typically late diagnosis, and aggressive nature. In order to significantly enhance patient health outcomes, several biotech developers are actively working on innovative solutions, including recent developments coming from O ncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), Verastem, Inc. (NASDAQ: VSTM), Candel Therapeutics, Inc. (NASDAQ: CADL), FibroGen, Inc. (NASDAQ: FGEN), and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN). Presented recently at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) presented two abstracts related to their novel immunotherapy, pelareorep, an intravenously delivered immunotherapeutic agent. One of the abstracts presented was a trial-in-progress for cohort 5 of the GOBLET study. This cohort will examine the effectiveness of combining pelareorep and modified FOLFIRINOX (mFOLFIRINOX) with and without atezolizumab —made by Roche Holding AG (OTCQX: RHHBY)— in newly diagnosed patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The cohort is funded by a US$5 million Therapeutic Accelerator Award grant from the Pancreatic Cancer Action Network (PanCAN). Oncolytics Biotech expects to begin enrollment for this cohort this quarter, having received regulatory clearance to begin the enrollment process in May. "The first abstract outlines the design of a new GOBLET PDAC cohort that could significantly expand the potential of the company's pancreatic cancer program," said Dr. Matt Coffey, President and CEO of Oncolytics. "The chemotherapy regimens of mFOLFIRINOX and gemcitabine/nab-paclitaxel are the two most common standards of care in metastatic pancreatic cancer. We previously reported that the combination of pelareorep, gemcitabine, nab-paclitaxel, and atezolizumab yielded tumor response rates nearly triple historical results. Should the combination of pelareorep and mFOLFIRINOX produce a similarly positive outcome, an even broader range of metastatic PDAC patients may benefit from pelareorep-based therapy." The GOBLET cohort 5 abstract and poster outline a study evaluating new treatments for patients with newly diagnosed metastatic PDAC using a Simon two-stage design. This design helps determine if a treatment is promising enough to continue testing. In the first stage, 15 patients in each treatment arm will be randomly assigned to receive either pelareorep with mFOLFIRINOX or pelareorep with mFOLFIRINOX and atezolizumab. The main goals are to measure how well the treatments work and their safety. Additionally, the study will look at progression-free survival (how long patients live without the cancer getting worse), overall survival (how long patients live overall), and biomarkers (indicators of how the body responds to the treatment). If the first stage is successful, one or both groups may proceed to Stage 2, which will include 17 more patients per treatment arm. Blood and tumor samples will be collected for further analysis throughout the study. Also presented at ASCO's meeting were positive initial interim safety and efficacy results from Verastem, Inc. (NASDAQ: VSTM) in an ongoing Phase 1/2 trial evaluating its avutometinib plus defactinib in combination with gemcitabine and Nab-paclitaxel for first-line treatment in patients with metastatic pancreatic cancer. Like Oncolytics' pelareorep, Verastem's avutometinib received funding from PanCAN through its Therapeutic Accelerator Award. " Verastem was the inaugural recipient of the PanCAN Therapeutic Accelerator Award, which has been an important part of PanCAN's approach to advancing innovative treatments for pancreatic cancer," said Anna Berkenblit, M.D., MMSc, Chief Scientific and Medical Officer at PanCAN. "There is a critical need for new treatment options in this disease, and we hope that the results from this study lead to improved outcomes for patients with pancreatic cancer." As of May 14, 2024, Verastem reported that patients receiving the combination therapy achieved a confirmed overall response rate (ORR) of 83%, with 5 out of 6 patients responding positively. The release of these results led to a positive market reaction, boosting Verastem's shares in pre-market trading in the process. Notably, there was one case of dose-limiting toxicity (febrile neutropenia) in the dose level 1 cohort. However, this dose level was cleared after enrolling additional patients in three other cohorts of the study. "The initial interim results from the RAMP 205 trial evaluating avutometinib and defactinib in combination with standard of care first-line chemotherapy are encouraging and demonstrate the importance of targeting the RAS/MAPK pathway, as more than 90% of pancreatic tumors have a KRAS mutation," said John Hayslip, M.D., Chief Medical Officer of Verastem Oncology. "We continue to progress the study evaluating other dose and schedule regimens to determine the recommended Phase 2 dose in the trial." In another recent update, Candel Therapeutics, Inc. (NASDAQ: CADL) reported "very encouraging results" from its phase 2 clinical trial of CAN-2409, which targets borderline resectable pancreatic cancer. The data showed that patients treated with CAN-2409 had an estimated median overall survival of 28.8 months, compared to just 12.5 months for the control group. Furthermore, at 24 months, the survival rate was 71.4% for those treated with CAN-2409, whereas the control group had a survival rate of only 16.7% following chemoradiation. "Given the frequent recurrence and short survival with SoC chemotherapy for non-metastatic PDAC, effective new treatment options are urgently needed," said Garrett Nichols, MD, MS, Chief Medical Officer of Candel. "We are very encouraged by the improved survival associated with CAN-2409, which has been shown to be durable after prolonged follow-up based on the updated data in this randomized clinical trial. CAN-2409 was generally well tolerated without significant additional local or systemic toxicity when added to SoC chemoradiation." Because pancreatic cancer is considered a solid tumor, news of a joint effort between FibroGen, Inc. (NASDAQ: FGEN) and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announcing a supply agreement to evaluate FG-3165 as a monotherapy and in combination with LIBTAYO in patients with select solid tumors is relevant. Under the clinical study collaboration and supply agreement, Regeneron will provide drug supply to FibroGen, who will be the sponsor of each Phase 1 monotherapy and combination trial. Each company retains all rights to their respective compounds, including as a monotherapy or as combination therapies. "We are very excited to collaborate with Regeneron Pharmaceuticals to evaluate two separate novel combination approaches to treat patients with select solid tumors," said Deyaa Adib, M.D., Chief Medical Officer of FibroGen. "We believe that the mechanisms of action for both FG-3165 (anti-Gal9) and FG-3175 (anti-CCR8) have the potential to be synergistic with cemiplimab, providing the possibility for an improvement in clinical outcomes for patients. We look forward to building a collaborative relationship with Regeneron, who is a leader in oncology therapeutic products development and commercialization." In their Q1 2024 financial results, FibroGen announced several upcoming milestones. The company expects to release topline data from the PanCAN Precision Promise Phase 2/3 study of pamrevlumab in metastatic pancreatic cancer by mid-2024. Additionally, they anticipate delivering topline data from the LAPIS Phase 3 study of pamrevlumab in locally advanced unresectable pancreatic cancer (LAPC) in Q3 2024. "Looking ahead, we expect to report topline data from our two late-stage clinical trials of pamrevlumab in pancreatic cancer in the coming months," said Thane Wettig, CEO of FibroGen. Article Source: USA NEWS GROUP [email protected] (604) 265-2873 DISCLAIMER: Nothing in this publication should be considered as personalized financial advice. We are not licensed under securities laws to address your particular financial situation. No communication by our employees to you should be deemed as personalized financial advice. Please consult a licensed financial advisor before making any investment decision. This is a paid advertisement and is neither an offer nor recommendation to buy or sell any security. We hold no investment licenses and are thus neither licensed nor qualified to provide investment advice. The content in this report or email is not provided to any individual with a view toward their individual circumstances. USA News Group is a wholly-owned subsidiary of Market IQ Media Group, Inc. ("MIQ"). MIQ has been paid a fee for Oncolytics Biotech Inc. advertising and digital media from the company directly. There may be 3rd parties who may have shares of Oncolytics Biotech Inc., and may liquidate their shares which could have a negative effect on the price of the stock. This compensation constitutes a conflict of interest as to our ability to remain objective in our communication regarding the profiled company. Because of this conflict, individuals are strongly encouraged to not use this publication as the basis for any investment decision. The owner/operator of MIQ own shares of Oncolytics Biotech Inc. which were purchased in the open market, and reserve the right to buy and sell, and will buy and sell shares of Oncolytics Biotech Inc. at any time without any further notice commencing immediately and ongoing. We also expect further compensation as an ongoing digital media effort to increase visibility for the company, no further notice will be given, but let this disclaimer serve as notice that all material, including this article, which is disseminated by MIQ has been approved by Oncolytics Biotech Inc.; this is a paid advertisement, we currently own shares of Oncolytics Biotech Inc. and will buy and sell shares of the company in the open market, or through private placements, and/or other investment vehicles. While all information is believed to be reliable, it is not guaranteed by us to be accurate. Individuals should assume that all information contained in our newsletter is not trustworthy unless verified by their own independent research. Also, because events and circumstances frequently do not occur as expected, there will likely be differences between the any predictions and actual results. Always consult a licensed investment professional before making any investment decision. Be extremely careful, investing in securities carries a high degree of risk; you may likely lose some or all of the investment. SOURCE USA News Group

Clinical ResultPhase 1Phase 2ASCOImmunotherapy

100 Deals associated with Aglatimagene besadenovec

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KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Localized Prostate Carcinoma	Phase 3	US	Candel Therapeutics, Inc.	01 Sep 2011
Localized Prostate Carcinoma	Phase 3	PR	Candel Therapeutics, Inc.	01 Sep 2011
Non-Small Cell Lung Cancer	Phase 2	US	Candel Therapeutics, Inc.	13 Oct 2020
Prostatic Cancer	Phase 2	MX	Candel Therapeutics, Inc.	01 May 2016
Pancreatic adenocarcinoma	Phase 2	US	Candel Therapeutics, Inc.	01 Oct 2015
Pancreatic adenocarcinoma	Phase 2	MX	Candel Therapeutics, Inc.	01 Oct 2015
Glioblastoma Multiforme	Phase 2	US	Candel Therapeutics, Inc.	01 Mar 2007
Malignant glioma of brain	Phase 2	US	Candel Therapeutics, Inc.	01 Mar 2007
Breast Cancer	Phase 1	US	Candel Therapeutics, Inc.	01 Oct 2013
Malignant Pleural Effusion	Phase 1	US	Candel Therapeutics, Inc.	01 Oct 2013

Clinical Result

Indication

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04495153 (ASCO2024) Manual	Phase 2	Non-Small Cell Lung Cancer	73	CAN-2409 + valacyclovir	qrdjjibxlp(atlsqutuoo) = vlvrfsiskf flplbbvkmo (malkkuwkut, 14.3-NA) View more	Positive	24 May 2024
				CAN-2409 + valacyclovir (C1, stable disease)	qrdjjibxlp(atlsqutuoo) = vrvctmtjry flplbbvkmo (malkkuwkut )
NCT02446093 (PaTK02, Biospace) Manual	Phase 2	Pancreatic Cancer	13	CAN-2409+valacylovir or acyclovir+chemoradiation or SBRT	xcjfxxrecw(kcqhgvdfyi) = none lrtygbhcvf (khpyynlrje )	Positive	04 Apr 2024
				chemoradiation or SBRT
NCT00589875 (CTgov)	Phase 2	Glioblastoma Multiforme \| Malignant glioma of brain	52	Radiation therapy+Temozolomide+Valacyclovir+CAN-2409	vlzxixsimh(yhydiwlgmr) = nemgbstoti elzddnkydk (fowaixormu, zoldzduzxp - ivvdoarpas) View more	-	03 Apr 2024
NCT04495153 (Corporate Publications) Manual	Phase 2	Non-Small Cell Lung Cancer Second line	40	CAN-2409+valacyclovir+immune checkpoint inhibitor	faieoasgqy(vimphwqhty) = kdfqbiphmw smlzgytolv (jxuufxsrbh ) View more	Positive	26 Sep 2023
NCT03576612 (SITC2022) Manual	Phase 1	High grade glioma First line	41	valacyclovir+CAN-2409+nivolumab (patients with methylated MGMT promoter undergoing gross total resection (GTR))	yqttyptojl(rigqoddhnx) = nphkhsqked ynwtwxfzol (bmvmgukyeb )	Positive	01 Nov 2022
				valacyclovir+CAN-2409+nivolumab (patients with methylated MGMT promoter undergoing sub-total resection (STR))	yqttyptojl(rigqoddhnx) = lzziyvjrku ynwtwxfzol (bmvmgukyeb )
NCT04495153 (ASCO2022) Manual	Phase 2	Non-Small Cell Lung Cancer	28	ICI+Aglatimagene besadenovec (stable disease)	iijakfzwiz(ocxsizedrv) = Of the 14 RECIST evaluable patients who received 2 doses of CAN-2409, clinical response was seen in 4 patients rtsumvclet (qtoaglfaqc ) View more	Positive	02 Jun 2022
				ICI+Aglatimagene besadenovec (progressive disease after ≥18 weeks)
NCT03004183 (ASCO2021) Manual	Phase 2	metastatic non-small cell lung cancer	35	ADV/HSV-tk+pembrolizumab or nivolumab (ICI-naïve)	uoaqdngayi(escabxbjcy) = bdgtupozwu vfwtvsxgkr (demqsnmclw ) View more	Positive	20 May 2021
				ADV/HSV-tk+pembrolizumab or nivolumab (Previous ICI)	uoaqdngayi(escabxbjcy) = snbzeonkdw vfwtvsxgkr (demqsnmclw ) View more
NCT03131037 (ASCO2020) Manual	Phase 1	Non-Small Cell Lung Cancer Neoadjuvant	12	Valacyclovir+aglatimagene besadenovec	oeilzaakax(cpowpkwqdv) = CTC grade 1 fever (n = 1), flu-like symptoms (n = 1) and nausea/vomiting/diarrhea (n = 1). The only > grade 2 lab abnormality was transient grade 3 lymphopenia (n = 2) unlivwzftl (mxyunpwnoe )	Positive	29 May 2020
NCT00634231 (Pubmed \| Neuro Oncol) Manual	Phase 1	Ependymoma \| Malignant glioma of brain	8	valacyclovir+chemotherapy+AdV-tk	nvhzyyfjwh(tchjwhtksw) = uazsbldshy czoxifwgyw (mawimwcqpj )	Positive	18 Mar 2019
NCT00870181 (Pubmed)	Phase 2	Recurrent Malignant Glioma	53	Adenovirus-mediated delivery of herpes simplex virus thymidine kinase (ADV-TK)	eiaajcwwol(zwexejgdhh) = dbwvhtjzfu rjqrnvcgdv (ngxolqyjod ) View more	Positive	26 Jan 2016

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