CLD-201 Viral Therapy Receives FDA Fast Track Designation for Soft Tissue Sarcoma

The FDA has granted fast track designation to CLD-201 (SuperNova), a first-in-class, allogeneic stem cell–loaded oncolytic virus, for the treatment of patients with soft tissue sarcoma.¹

A first-in-human, open-label, multicenter phase 1 trial is planned to investigate the safety, tolerability, and efficacy of CLD-201 in patients with sarcoma, head and neck squamous cell carcinoma, and triple-negative breast cancer (TNBC). Calidi Biotherapeutics, Inc, the regimen’s developer, anticipates the first patient to be dosed in this trial during the third quarter of 2025.²

“FDA investigational new drug clearance and fast track designation represents an important milestone in the development of CLD-201,” Guy Travis Clifton, MD, chief medical officer of Calidi stated in a news release.¹ “This designation underscores the unmet medical need in sarcoma and provides scientific and regulatory validation of CLD-201. We believe CLD-201 has the potential to provide durable and transformational treatment to patients with sarcoma, as well as patients with other advanced tumor types. We want to thank the FDA for its support and partnership and look forward to continued collaboration with the agency.”

CLD-201 is composed of adipose-derived mesenchymal stem cells that are loaded with an oncolytic vaccinia virus. One of the previously described challenges associated with oncolytic virotherapy is the rapid elimination of oncolytic viruses by the immune system.³ Stem cell loading of oncolytic viruses provides protection for the virus from the body’s immune system and allows the virus to grow within the stem cell.¹ In preclinical animal models, this treatment method has been associated with increased drug potency, immune activation, and efficacy.

Notably, CLD-201 is specifically designed for intratumoral administration, decreasing some of the cost, scalability, and reproducibility barriers associated with autologous stem cells loaded with the vaccinia virus CAL1, which has been shown to be effective in multiple tumor types, particularly when combined with checkpoint inhibition.³

A selection of preclinical studies, data from which were presented at the 2024 ASCO Annual Meeting, investigated the efficacy and tumor selectivity of CLD-201 in immune-compromised and immunocompetent mouse models with melanoma, TNBC, and squamous cell carcinoma. Results demonstrated that the CAL1 virus had preferential amplification in tumor cells and that CLD-201 showed improved resistance to immune system inactivation compared with the unprotected CAL1 virus. Additionally, CLD-201 significantly inhibited tumor growth even when administered at a low dose of 1.5 x 10³ cells that contained 1.6 x 10⁴ viral PFUs. Furthermore, infiltrations of CD4 and CD8 T cells were observed across both treated and untreated tumors.

Regarding safety, animals treated with the maximum tolerated dose of the agent displayed no signs of adverse toxicity. In addition, a disease-free model showed no toxicity findings associated with CLD-201. Moreover, in animal models, virus detection in the lungs was cleared within 2 weeks after CLD-201 treatment.

The phase 1 study will consist of 3 parts. Part 1 will have a classical 3+3 design and will test 3 to 6 patients each at 3 dose levels; patients will be enrolled to each dose level depending on the dose-limiting toxicities observed. The CLD-201 expansion dose will be identified in part 1. In part 2, 10 patients from each of the trial’s 3 indications in the part 1 population who experienced the most favorable biological activity will be selected to receive the CLD-201 dose chosen in part 1. In part 3, which is the phase 2 portion of the trial, 30 to 50 patients with the best responses in part 2 will receive the expansion dose of CLD-201.

References

1. Calidi Biotherapeutics receives FDA fast track designation for CLD-201 (SuperNova), a first-in-class stem-cell loaded viral therapy for the treatment of patients with soft tissue sarcoma. News release. Calidi Biotherapeutics, Inc. July 29, 2025. Accessed July 31, 2025. https://www.calidibio.com/calidi-biotherapeutics-receives-fda-fast-track-designation-for-cld-201-supernova-a-first-in-class-stem-cell-loaded-viral-therapy-for-the-treatment-of-patients-with-soft-tissue-sarcoma/
2. Calidi Biotherapeutics reports fourth quarter and full-year 2024 financial results and recent operational highlights. News release. Calidi Biotherapeutics, Inc. March 31, 2025. Accessed July 31, 2025. https://www.globenewswire.com/news-release/2025/03/31/3052779/0/en/Calidi-Biotherapeutics-Reports-Fourth-Quarter-and-Full-Year-2024-Financial-Results-and-Recent-Operational-Highlights.html
3. Nguyen D, Minev I, Songco S, et al. Non-clinical evidence supporting the upcoming CLD-201 clinical trial: cell-based oncolytic virotherapy for multiple solid tumors. J Clin Oncol. 2024;42(suppl 16):2553. doi:10.1200/JCO.2024.42.16_suppl.2553