In our first trial, Calidi Biotherapeutics used fresh stem cells derived from each patient’s fat tissue (SVF) to protect oncolytic vaccinia virus (VV) in autologous settings. This Phase I clinical study was designed to establish the safety and tolerability of SVF/VV and assess initial efficacy signals in relationship to SVF/VV. The aggregate safety, tolerability, and PK results indicated that SVF/VV was well tolerated in this study of 25 patients with advanced tumors (Stage III or IV). Note: the Maximum Tolerated Dose (MTD) was not reached. Based on these results, we are currently working with the Food and Drug Administration (FDA) on an Investigational New Drug (IND) application to commence a Phase 1b/2a clinical trial for our leading product candidate.
In this study we documented the following important findings:
- The results of the plasma cytokine assays suggested mild inflammatory reaction starting approximately one week after treatment, not associated with any clinical symptoms or side effects.
- All patients experienced virus-related & inflammation-related symptoms at the tumor sites approximately two weeks after treatment, suggesting efficient delivery of the oncolytic virus
- The results of the flow cytometry assays show induction of immune response with memory T cells approximately one month after treatment
- Fourteen out of 25 patients (56%) survived six months post-treatment; 11 out of 25 patients (44%) survived 12 months post-treatment
- Most surviving patients are clinically stable, some with significant tumor size reduction
- These promising initial clinical results merit further investigation of therapeutic utility
After the success of our initial study, Calidi Biotherapeutics has proceeded to develop cell-based delivery systems that can be used in a majority of cancer patients. To achieve this goal, we focused on the development of a universal and potent allogeneic cell-based delivery vehicle for oncolytic viruses. Our new allogeneic stem cell platform can be used in a wider group of patients and is also effective in amplifying and protecting the oncolytic viruses better than the SVF delivery platform.