Product Candidate for Metastatic Melanoma

The incidence of metastatic melanoma is steadily on the rise and is now a major cause of cancer death in the US and in Europe. Metastatic melanoma is usually lethal within 1 to 2 years, with a 5-year survival rate of <15%. The current standard of care of surgical resection, radiotherapy and chemotherapy are associated with trauma and/or toxicity, and do not address cancer recurrence, which make up more than two-thirds of all reported local or regional melanoma diagnoses (~20,000 patients). Hence, there is a critical unmet need for a nontoxic, effective, consolidation therapy for these patients.

Antigen-specific immunotherapy is emerging as a new treatment modality, and dendritic cells are recognized as the most efficient antigen presenting cells, with their high ability for molecular identification and transmission. The best source of antigens may come from a patient’s own (autologous) self-renewing, cancer-initiating cells. Caladrius has the unique ability to isolate these cancer-initiating cells and proliferate them in culture. Thus, Caladrius’ immuno-oncology technology (CLBS20, also NBS20) consists of autologous dendritic cells loaded with irradiated autologous cancer-initiating cells which proliferate in cell culture. The potential of CLBS20 for antigen-specific immunotherapy differentiates itself from available therapeutics through:

  1. Presenting the entire spectrum of antigens from the patient’s own tumor rather than targeting an insufficient number of specific antigens
  2. Isolating and re-administering specific cells from the patient’s tumor that are self-renewing, that is, those that can regenerate the cancer and cause metastatic spread against which an immune response is most needed.
  3. The non-toxic nature compared to other approved therapies.
  4. Excellent long-term survival rates, even in patients who have had Stage IV disease.
  5. Survival rates comparable to most active agents even in patients with measurable metastatic disease.
  6. The therapy’s focus on increasing recognition of tumor associated antigens rather than optimizing existing immune response (by enhancing e.g. IL2, or reducing suppression, e.g. Anti-CTLA4 or anti-PD1 or PDL1).
  7. Induction and enhancement of long-term anti-tumor immunity that is potentially synergistic with other approved therapies.

CLBS20: Uniquely targets cancer-initiating cells (CICs)

Phase 2: Two Trials; Consistent, Compelling Data

A Phase 2 randomized clinical trial was conducted comparing subcutaneous injections of CLBS20 versus injections of autologous tumor cells in patients with advanced melanoma (recurrent Stage III or Stage IV) (N=42). The trial demonstrated superior survival outcomes at two years—survival was increased to 72% compared to 31% for control patients treated with only their own tumor cells suspended in granulocyte macrophage colony stimulating factor (GM-CSF) (p=0.007). The two-year survival rate of 72% confirmed previous trial’s findings in which dendritic cells loaded with antigens from autologous tumor cells demonstrated a 72% 2-year survival (N=54), with a median survival of five years. The toxicity profile was favorable with no grade IV and only one grade III (allergic reaction to the FDA approved immune stimulant GM-CSF) event. There were no significant toxicities or adverse effects on hematopoietic cells or renal function, liver function, or patient performance status.