Calidi to advance IL-15-armed onco virus into first-in-human in Australia

Calidi Biotherapeutics, based in San Diego, has engaged Avance Clinical, a full-service contract research organization (CRO), to facilitate Australian regulatory approval and initiate a first-in-human trial for CLD-401, the company’s lead oncolytic virotherapy candidate. CLD-401 is a genetically modified vaccinia virus designed for intravenous delivery to patients with advanced solid tumors. Calidi (NYSE American: CLDI) stated it will also pursue an IND filing with the US FDA in 2026.

CLD-401 is the first candidate derived from Calidi’s RedTail platform, which the company also refers to as featuring engineered enveloped oncolytic virus technology. The platform uses an envelope designed to shield the virus from immune clearance in the bloodstream, enabling systemic intravenous delivery rather than direct intratumoral injection. CLD-401 is a vaccinia virus engineered to replicate selectively in tumor cells and express an IL-15 superagonist, an activator of innate and adaptive immune responses, within the tumor microenvironment.

The planned Phase I trial will evaluate safety, pharmacodynamics, and efficacy of CLD-401 as monotherapy in patients with solid tumors who have exhausted other therapeutic options. Preclinical data on CLD-401 have been published evaluating tumor targeting, efficacy, and safety in animal models.

Competitive context

Calidi has indicated that initial target indications for CLD-401 include non-small cell lung cancer, head and neck cancer, and other advanced solid tumors. The company is also expanding the RedTail platform to incorporate T-cell engager approaches for solid tumors, although no additional candidates have been publicly disclosed.

The oncolytic virus field includes several companies pursuing systemic intravenous delivery, an approach for which no products are currently approved. Programs exploring this strategy include:

• Olvi-Vec (GL-ONC1) — Genelux — Phase II — intravenously delivered engineered vaccinia virus • Pelareorep — Oncolytics Biotech — late-stage/registration-directed development — intravenously delivered reovirus • CF33/VAXINIA — Imugene — Phase I — intravenously delivered chimeric poxvirus • TG6002 — Transgene — early-stage clinical development — vaccinia virus evaluated with intravenous administration

Approved oncolytic virus therapies, such as Talimogene laherparepvec for melanoma, rely on local administration rather than systemic delivery. Other advanced candidates, including Cretostimogene grenadenorepvec, remain investigational and are also delivered locally.

Calidi’s approach — using an engineered viral construct designed to enhance systemic circulation and reduce immune clearance — aims to address a longstanding limitation in the field, although these features are supported by preclinical data and have not yet been validated in human studies.

The decision to initiate clinical work in Australia rather than the United States reflects a regulatory pathway that can offer faster trial activation timelines. Calidi stated it will pursue the Australian regulatory process in parallel with its US FDA IND submission.