Calidi Biotherapeutics presents a compelling opportunity as a clinical-stage biotech at the forefront of oncolytic virotherapy (OV), a promising multi-billion-dollar area in cancer treatment. Calidi is pioneering the development of both systemic and localized OVs, leveraging engineered viruses to target and destroy cancer cells while arming the immune system for a comprehensive attack on tumors. Calidi's cell-based technologies uniquely protect OVs from immune system elimination, ensuring higher efficacy and opening the tumor microenvironment to treatment. This approach has shown promising efficacy in initial studies, while the company’s breakthrough IV-based technology and direct tumor administration methods differentiate it within the oncology field.

Targeting metastatic melanoma, glioblastoma, triple-negative breast cancer, head & neck cancer, and lung cancer, Calidi addresses a substantial and growing market with an estimated $13 billion to $15 billion annual total addressable market in the US alone. The need for effective treatments in these areas remains high, providing a significant opportunity for growth and impact. Calidi’s current development pipeline includes:

• NeuroNova (CLD-101): This pioneering program targeting high-grade glioma (HGG), one of the most aggressive brain cancers. NeuroNova utilizes neuronal stem cells combined with an engineered adenovirus (CRAD-s-Pk7). Following strong safety and efficacy signals from an earlier Phase 1 study, the FDA cleared the IND for a Phase 1b/2 trial in newly diagnosed HGG, set to begin enrollment in Q1 2025 at Northwestern University. Ongoing trials for recurrent HGG at City of Hope (COH) continue to advance.
• SuperNova (CLD-201): Leveraging an engineered vaccinia virus (CAL1) delivered via allogeneic adipose-derived mesenchymal stem cells, SuperNova targets advanced solid tumors such as TNBC and soft tissue sarcomas. Early studies demonstrated strong safety and initial efficacy signals, and a Phase 1 study is set to launch in 2H24. This program exemplifies Calidi’s adaptability across cancer types, with applications for combination therapies involving checkpoint inhibitors.
• RTNova (CLD-400): A systemic breakthrough for metastatic and advanced cancers, RTNova employs extracellular enveloped vaccinia virus (envRT-01) technology. This platform is designed to evade immune system clearance, enabling intravenous administration and the targeting of multiple metastatic tumor sites. Preclinical data presented in 2024 at leading conferences demonstrated 87%-92% tumor growth inhibition in metastatic lung cancer and Head & Neck cancers. Clinical trials are targeted for initiation in Q2 2026. RTNova’s transformative potential was further validated by key collaborations and partnerships.

Recent collaborations, including with SIGA Technologies, underscore the company’s attractiveness to biopharma partners for co-development and commercialization opportunities, while Calidi’s innovative technology, robust development pipeline, and significant market potential lay the foundation for significant potential upside. Three analysts cover Calidi with buy ratings and average price target of $13.30 per share (split adjusted).