CD38 Antibody Recruiting Molecule (ARM)+Allogeneic NK Cell Combination Therapy
Kleo’s first clinical candidate targets CD38, a validated approach in multiple myeloma (MM). Kleo is initiating a clinical trial in newly diagnosed, minimum residual disease positive (MRD+), post-autologous stem cell transplant patients with a CD38-targeting ARM (KP1237) as a combination product with autologous NK cells and low-dose IL-2. The trial is supported by compelling preclinical data showing that KP1237 synergistically enhances the anti-tumor efficacy of autologous NK cells. Dosing of the first patient is expected in 3Q2020.
Kleo has also initiated two research collaborations, with South Korea-based GC LabCell and US-based Celularity Inc. to investigate using our ARM+NK cell combination therapy approach to combat multiple myeloma (MM). We have demonstrated a synergistic effect of using our ARM to enhance the anti-tumor efficacy of autologous NK cells.
Systemic Administration of CD38 Antibody Recruiting Molecule (ARM)
Unlike the NK cell combination therapy, systemic delivery of CD38-targeting ARMs will redirect a patients’ own antibodies to fight the cancerous cells. CD38-targeting ARMs have multiple mechanisms of action. Unlike monoclonal therapeutic antibodies in this indication, Kleo’s ARM’s are expected to provide both short-term tumor clearance and a longer-term vaccination effect.
- Enlisting immune cells. ARMs can, upon binding CD38 on multiple myeloma/plasma cells, recruit the body’s immune cells to attack the tumor. ARMs recruit these cells (macrophages, NK cells) by linking CD38 to FcγRIIIII receptors.
- Activating longer-term immunity. Through a similar process, ARMs can recruit dendritic cells to encourage the immune system to adapt to the CD38 proteins. The immune memory cells (e.g., T-cells) then instill longer-term immunity.