Platforms

Candel has established two off-the-shelf clinical stage investigational viral immunotherapies designed to produce an individualized cancer response. They are 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 CAN-3110 is the lead product candidate from the HSV platform. 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.

Our Approach

Immunotherapy has transformed the way cancer is treated.

However, typically only 15-40% of patients respond to immune checkpoint inhibitor (ICI) treatment.

Poor response to ICI treatment is believed to be explained by the ability of the tumor to disguise antigen presentation and to generate an immunosuppressive microenvironment. In addition, most conventional immunotherapies are not designed to educate the patient’s immune system how to recognize the patient’s variety of tumor antigens and neoantigens.

At Candel, we have devised a multifactorial approach, leveraging the ability of viral gene constructs to activate cancer-killing mechanisms, exposing multiple tumor antigens and inhibiting the immunosuppressive tumor microenviroment. Together, this has been shown to produce an individualized immune response, specific to the patient and their cancer based on the effects of in situ vaccination.

Our viral immunotherapy approach utilizes intratumoral administration of genetically engineered viruses to selectively induce tumor cell death and elicit both an innate and an adaptive systemic immune response against the injected tumor and uninjected distant metastases. Local delivery enables us to achieve these effects while aiming to minimize systemic toxicity.

The specific immune cells induced by our viral immunotherapies are believed to target patients’ own specific tumor antigens, as evidenced by the observed abscopal effects in animal models as well as in patients.

CAN-2409

Off-the-shelf therapy, individualized cancer response

CAN-2409 (aglatimagene besadenovec) is an adenoviral replication-defective engineered gene construct encoding the thymidine kinase gene derived from herpes simplex virus (HSV). CAN-2409 is injected directly into the tumor or target tissue. Our method of localized injection into tissue is akin to the standard approach for vaccination. Localized injection is believed to minimize the chance of development of anti-drug antibodies and systemic toxicities associated with systemic administration. The adenoviral construct serves as a vector to transport the HSV-thymidine kinase gene into tumor cells at the site of injection. These tumor cells can then express HSV-thymidine kinase, which converts generic, FDA-approved anti-herpes drugs, such as ganciclovir, acyclovir and valacyclovir (used as prodrugs which are widely available, inexpensive and generally well-tolerated) into a toxic nucleotide analogue, which blocks DNA synthesis in dividing cells. Cells exposed to the toxic nucleotide analogue in the tumor microenvironment have been observed to undergo immunogenic cell death. At the same time, the adenoviral serotype 5 capsid protein elicits a strong pro-inflammatory signal in the tumor microenvironment. This creates the optimal conditions to induce a specific CD8+ T cell mediated response against the injected tumor and uninjected distant metastases for broad and systemic anti-tumor activity.

Because of its versatility, CAN-2409 has the potential to treat a wide range of solid tumors. Monotherapy activity as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, androgen deprivation therapy, and immune checkpoint inhibitors have previously been shown in several preclinical and clinical settings, supporting the potential for combination with other therapeutic strategies. Furthermore, CAN-2409 has demonstrated a favorable tolerability profile; more than 950 patients have been dosed to date in a range of solid tumor indications. Currently, Candel is evaluating the effects of treatment with CAN-2409 in patients with non-small cell lung cancer, pancreatic cancer, and localized, non-metastatic prostate cancer in ongoing clinical trials. For more information on our clinical trials, please visit our Clinical Trials page.

CLINICAL TRIALS

Learn how CAN-2409 works

Mechanism of Action by Visual Science, 2023

CAN-3110

Oncolytic virus with tumor-specificity

CAN-3110 is a replication-competent herpes simplex virus (HSV) engineered to enhance selective killing of cancer cells while sparing healthy neighboring cells. CAN-3110 is engineered for selective replication by placing ICP34.5, the gene controlling HSV replication, under the control of the Nestin promoter. Nestin has been shown to be highly expressed in high-grade glioma cells, but is absent in healthy adult brain cells, which may explain why dose-limiting toxicity was not observed in a study of a single injection of CAN-3110 into the brain tumor in patients with recurrent high-grade glioma. Nestin expression has also been detected in aggressive tumors other than high-grade glioma, which broadens the possibility of expanding the use of CAN-3110 into other indications, also outside the brain, and creating a future pipeline-in-a-product. The ICP34.5 gene is typically deleted in other oncolytic viruses, which may result in poor replication ability and a limited ability to generate an effective anti-tumor immune response.

Currently, the effects of multiple doses of CAN-3110 are being evaluated in patients with recurrent high-grade glioma in an ongoing investigator-sponsored phase 1 clinical trial.

For more information on this clinical study, please visit our Clinical Trials page.

Learn how CAN-3110 works

Mechanism of Action by Visual Science, 2023

The enLIGHTEN™ Discovery Platform

The complexity of the tumor microenvironment and the diversity of the tumor response to existing treatments requires a multimodal and tailored approach to the discovery and development of new therapeutics. Candel Therapeutics’ enLIGHTEN™ Discovery Platform is a systematic, data-driven platform based on human biology and advanced analytics to create new herpes simplex virus (HSV)-based gene constructs to modulate the tumor microenvironment in specific solid tumors by design. Built on our suite of proprietary HSV vectors and a bespoke data-driven approach for the selection of multi-gene viral payloads, the enLIGHTEN™ Discovery Platform is uniquely positioned to combine, in a single therapeutic, the tunable features of viral immunotherapies with personalized modulation of tumor biological properties.

The enLIGHTEN™ Discovery Platform deconvolutes the complexity of the tumor microenvironment to identify druggable properties that correlate with clinical outcomes. These discoveries are translated into optimized multi-gene payloads of tumor modulators with the aim of creating a novel class of viral immunotherapy candidates that are tailored for specific indications, disease stage, and rationally designed therapeutic combinations. Candel Therapeutics and the University of Pennsylvania are collaborating in a discovery partnership that will leverage Candel’s new engineered viruses to potentially overcome barriers to CAR-T therapies.