Calidi Biotherapeutics Announces IL15 Superagonist as First Payload to be Delivered by Systemic Antitumor Virotherapy Platform at AACR Annual Meeting

SAN DIEGO, April 28, 2025 (GLOBE NEWSWIRE) -- Calidi Biotherapeutics Inc. (NYSE:CLDI) ("Calidi"), a clinical-stage biotechnology company developing a new generation of targeted antitumor virotherapies, today announced the selection of IL15 superagonist (Il15-IL15Ra) as the first payload to be delivered into tumors using its systemic antitumor virotherapy platform, RTNova. New preclinical data were presented at the American Association for Cancer Research (AACR) Annual Meeting on April 27, 2025, in Chicago, IL.

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 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 featuring data on delivering IL15 superagonist is available here.

About Calidi Biotherapeutics

Calidi Biotherapeutics (NYSE:CLDI) is a clinical-stage immuno-oncology company with proprietary technology designed to arm the immune system to fight cancer. Calidi's novel stem cell-based platforms are utilizing potent allogeneic stem cells capable of carrying payloads of oncolytic viruses for use in multiple oncology indications, including high-grade gliomas and solid tumors. Calidi's clinical stage off-the-shelf, universal cell-based delivery platforms are designed to protect, amplify, and potentiate oncolytic viruses leading to enhanced efficacy and improved patient safety. Calidi's preclinical off-the-shelf enveloped virotherapies, are designed to target disseminated solid tumors. This dual approach can potentially treat, or even prevent, metastatic disease. Calidi Biotherapeutics is headquartered in San Diego, California. For more information, please visit www.calidibio.com.

Forward-Looking Statements

This press release may contain forward-looking statements for purposes of the "safe harbor" provisions under the United States Private Securities Litigation Reform Act of 1995. Terms such as "anticipates," "believe," "continue," "could," "estimate," "expect," "intends," "may," "might," "plan," "possible," "potential," "predicts," "project," "should," "towards," "would" as well as similar terms, are forward-looking in nature, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements include, but are not limited to, statements concerning upcoming key milestones (including the reporting of interim clinical results and the dosing of patients), planned clinical trials, and statements relating to the safety and efficacy of Calidi's therapeutic candidates in development. Any forward-looking statements contained in this discussion are based on Calidi's current expectations and beliefs concerning future developments and their potential effects and are subject to multiple risks and uncertainties that could cause actual results to differ materially and adversely from those set forth or implied in such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that Calidi is not able to raise sufficient capital to support its current and anticipated clinical trials, the risk that early results of clinical trials do not necessarily predict final results and that one or more of the clinical outcomes may materially change following more comprehensive review of the data, and as more patient data becomes available, the risk that Calidi may not receive FDA approval for some or all of its therapeutic candidates. Other risks and uncertainties are set forth in the section entitled "Risk Factors" and "Cautionary Note Regarding Forward-Looking Statements" in the Company's Registration Statements filed with the SEC on (i) Form S-4 filed on August 2, 2023 and the corresponding prospectus filed on August 4, 2023, and (ii) on Form S-1 filed on April 15, 2024, and the Company's periodic reports filed with the SEC on Form 10-K filed on March 31, 2025. These reports may be amended or supplemented by other reports we file with the SEC from time to time.

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