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By Jeremy Golden, Benzinga
Candel Therapeutics, Inc. (NASDAQ: CADL) is helping pioneer the next generation of viral immunotherapy by leveraging a data-driven approach to create new assets and further the development of existing drug candidates.
Candel Therapeutics’ enLIGHTEN Discovery Platform integrates artificial intelligence-selected, therapeutic payloads into programmable vectors for delivery into the tumor microenvironment
This tailored approach to discovery and development of new therapeutics has been designed to address the complexity of the tumor microenvironment and the diversity of the tumor response to existing treatments.
Using large patient datasets, the enLIGHTEN™ Discovery Platform identifies druggable properties that correlate with clinical outcomes and predicts optimal therapeutic payload combinations in silico. Real-world testing of these predicted payload combinations is used to rapidly evaluate their therapeutic effects. Next, validated multigene payloads are integrated into one of Candel’s programmable viral vectors that are engineered with tunable features to address a specific unmet need in cancer treatment.
The enLIGHTEN™ immunotherapy candidates represent a novel class of bespoke immunotherapies with each one tailored for a specific indication, disease stage, or rationally designed therapeutic combination therapy.
First Experimental Candidate
During the Society for Immunotherapy of Cancer (SITC) 2023 Annual Meeting and the International Oncolytic Virus Conference in November 2023, Candel presented the first experimental immunotherapy candidate from its discovery platform: Alpha 201-macro-1, an investigational,viral immunotherapy designed to activate innate immune surveillance. Preclinical data demonstrated that programmable, vector-mediated delivery of a novel gene payload designed to interfere with the CD47/SIRPα pathway significantly impede tumor growth when compared to systemic anti-CD47 antibody therapy in a mouse model of breast cancer.
Soon afterwards, at the American Association for Cancer Research (AACR) Annual Meeting in April 2024, the company presented late-breaking data from its second immunotherapy candidate based on this platform: a therapeutic able to induce organized lymphocyte aggregates that resemble tertiary lymphoid structures (TLS) within solid tumors. Formation of TLS in tumors correlates with a positive response to immune checkpoint inhibitors and better prognosis. To date, there has not been any drug able to induce therapeutic TLS formation in cancer.
The effects of Candel’s new immunotherapy candidate are based on two mechanisms. First, profiling of the biological response to the enLIGHTEN™ programmable vector demonstrated its potential to orchestrate changes in the tumor microenvironment, which bolster effective anti-tumor immune responses to immune checkpoint inhibitor treatment. Second, delivery of two unique payload combinations using this programmable vector resulted in TLS formation associated with monotherapy anti-tumor activity, and enhanced responses in combination with immune checkpoint inhibitor treatment in mouse models of solid tumors. Combining the immunological and oncolytic effects mediated by the viral vector with the biological activity of the transgene payloads results in a unique multimodal therapeutic able to induce the formation of TLS and inhibit the tumor.
“With the enLIGHTEN Discovery Platform, we are leveraging our internal expertise and capabilities to design a new class of multimodal therapeutics that can overcome mechanisms of resistance present in the tumor microenvironment and address critical unmet needs for patients with cancer,” said Francesca Barone, M.D. Ph.D., CSO at Candel Therapeutics. “This platform has been designed for collaborations focused on rational combination therapies to induce disease remission in cancer. ”
More exciting developments are on the horizon. Candel Therapeutics and the University of Pennsylvania are collaborating in a discovery partnership that will leverage enLIGHTEN™ programmable vectors with therapeutic payloads to potentially overcome barriers to Chimeric antigen receptor (CAR) T-cell therapies. Through the partnership, the University of Pennsylvania researchers – led by the Director of the T-Cell Engineering Lab within Penn’s Center for Cellular Immunotherapies, Neil C. Sheppard, Ph.D. – will explore the ability of Candel’s novel viral immunotherapies to enhance the effects of the university’s CAR T-cell therapies in solid tumor models.
Featured photo by National Cancer Institute on Unsplash
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 cancer (phase 2), and localized, non-metastatic prostate cancer (phase 2 and phase 3). CAN-3110 is the lead product candidate from the HSV platform and is currently in an ongoing investigator-sponsored phase 1 clinical trial in recurrent high-grade glioma (HGG). 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.
This article 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 the timing and availability of additional data, key data readout milestones, including CAN-3110 in HGG; expectations regarding the potential benefits conferred by Fast Track Designation; expectations regarding the therapeutic benefit of its programs, including the potential for its programs to extend patient survival; and expectations regarding cash runway and expenditures. 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 our 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, and strategic plans for the Company’s business and product candidates, and other risks identified in the Company’s SEC filings, 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.
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