Development of an immunotherapeutic agent for treatment of osteomyelitis

The National Institute of Allergy and Infectious Diseases awarded $320,863 to Celdara Medical, LLC on August 21, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop CM-HZ01, a high-avidity interleukin-2 super agonist for treatment of osteomyelitis.

Celdara will streamline production of CM-HZ01, demonstrate its ability to expand cytotoxic CD8 and natural killer cells under bacterial challenge, and evaluate the agent in a rodent osteomyelitis model while assessing its effects on bone growth. The therapeutic targets Staphylococcus aureus osteomyelitis by preferentially activating immunostimulatory lymphocytes rather than immunosuppressive regulatory T-cells, addressing the toxicity profile that has limited clinical use of interleukin-2 despite its four-decade track record in clinical settings.

Performance of the Phase I work takes place in Lebanon, New Hampshire, with a period of performance ending July 31, 2027. Celdara is a self-certified small disadvantaged business developing cell-based and protein-engineering therapeutics for cancer immunotherapy, neurological disorders, viral diseases, and metabolic conditions. The award is a Project Grant, classified as assistance funding.

Abstract

Osteomyelitis is an inflammation of bone tissue, often caused by an infection with staphylococcus aureus (S. Aureus). This condition can arise after trauma, during bacteremia, or following surgery, making IT a potential risk for anyone. Diabetics are especially prone vulnerable, due to the high occurrence of infected foot ulcers. S. Aureus infection depletes and exhausts cytotoxic CD8 T-cells, creating an immunosuppressive environment that allows bacteria to thrive. The immune system is closely connected to the skeletal system, with cytokines, growth factors, and immune cells playing essential roles in bone development, remodeling, and repair. Interleukin-2 (IL- 2) is a crucial cytokine used in clinical settings for over 40 years, but its widespread therapeutic use is limited due to significant toxicity. IL-2 modulates the immune response by selectively activating both immune-stimulating cytotoxic CD8 T-cells and NK cells, as well as immunosuppressive regulatory T-cells, through different receptor binding affinities. This dual affinity is the main cause of its toxicity. Attempts to engineer IL-2 to favor the activation of immunostimulatory cells have faced challenges due to weak receptor binding. We are developing CM-HZ01, a high-avidity IL-2 super agonist designed to preferentially promote the expansion of cytotoxic CD8 and NK cells. In this phase I application, we aim to streamline CM-HZ01 production, demonstrate its ability to expand cytotoxic lymphocytes under bacterial challenge, and treat osteomyelitis in a rodent model while promoting healthy bone growth.