On April 28, 2025 Calidi Biotherapeutics Inc. (NYSE American: CLDI) ("Calidi"), a clinical-stage biotechnology company developing a new generation of targeted antitumor virotherapies, reported the selection of IL15 superagonist (Il15-IL15Ra) as the first payload to be delivered into tumors using its systemic antitumor virotherapy platform, RTNova (Press release, Calidi Biotherapeutics, APR 28, 2025, View Source [SID1234653211]). New preclinical data were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 27, 2025, in Chicago, IL.
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The first candidate developed using RTNova is a vaccinia virus (virotherapy) that is engineered to be tumor selective and produced in an enveloped form that allows the virus to survive bloodstream circulation and reach metastatic tumor sites where viral replication can destroy cancer cells while also activating an immune response. RTNova can be further engineered to deliver transgenes or gene medicines for expression in tumor cells. Data presented at AACR (Free AACR Whitepaper) demonstrates that the ability of the enveloped virotherapy to express IL15 superagonist specifically in the tumor microenvironment measurably increases the number of complete responses, or tumor eliminations, in preclinical models after a single systemic administration.
"IL15 superagonist is a potent cytokine capable of generating robust and durable immune responses against tumors but can induce severe toxicity when administered systemically" said Antonio F. Santidrian, PhD, Chief Scientific Officer at Calidi. "By using tumor-targeted virotherapies systemically delivered to express therapeutic proteins like IL-15 superagonist directly into the tumor microenvironment, we believe we can effectively boost immune response against the tumors precisely where it is needed while minimizing systemic toxicity".
"While intratumoral use of oncolytic viruses has shown positive clinical results, their applicability has been limited to injectable cancers," said Eric Poma, PhD, Chief Executive Officer at Calidi. "Our RTNova platform builds on the clinical success of current intratumoral oncolytic viruses but is designed for systemic administration, allowing us to target metastatic disease patients with high unmet need. RTNova also allows for the delivery of payloads like IL-15 superagonist to the tumor microenvironment, inducing a profound anti-tumor immune activation."
With the RTNova platform, Calidi Biotherapeutics is pioneering the systemic delivery of virotherapies, a major step forward in treating metastatic cancers. This adaptable platform can also deliver different therapeutic payloads, allowing a bespoke approach to candidate design determined by the intrinsic properties of different tumor types.
A copy of the poster presented at AACR (Free AACR Whitepaper) featuring data on delivering IL15 superagonist is available here.