ImmunityBio Submits Biologics License Application for N-803 Plus BCG for Patients with BCG-Unresponsive Non-Muscle Invasive Bladder Cancer Carcinoma in Situ - Seite 2

The BLA submission for BCG-unresponsive NMIBC is based on data from 171 subjects from Phase I and 2 trials in bladder cancer and on 84 subjects treated in ImmunityBio’s Pivotal Phase 2/3 QUILT 3032 study of the combination of N-803 and BCG. The combination had a well-tolerated profile and the full results of this study will be presented at an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual meeting to be held June 3-7 in Chicago.

ImmunityBio’s IL-15 superagonist N-803 (Anktiva)

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of the natural killer (NK) and T cells. N-803 is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. Its mechanism of action is direct specific stimulation of CD8+ T cells and NK cells through beta gamma T-cell receptor binding (not alpha) while avoiding T-reg stimulation. N-803 has improved pharmacokinetic properties, longer persistence in lymphoid tissues and enhanced anti-tumor activity compared to native, non-complexed IL-15 in vivo.

N-803 is currently being evaluated for adult patients in two clinical NMIBC trials. QUILT 2005 is investigating use of N-803 in combination with BCG for patients with BCG-naïve NMIBC; QUILT 3032 is studying N-803 in combination with BCG in patients with BCG-unresponsive NMIBC CIS and Papillary Disease.

Mechanism of Action & Contribution of N-803 and BCG for Bladder Cancer

Trained immunity is a recently discovered immune system response triggered by BCG. Natural Killer (NK) and T cells are activated by BCG resulting in bladder cancer cell death. When an appropriate secondary stimulus is administered along with BCG, that trained immune response is enhanced to induce immune memory resulting in a prolonged duration of immunological response. N-803, an IL-15 superagonist which proliferates NK and T cells, serves as this enhancing secondary boost and augments the immunological response when given in combination with BCG. ImmunityBio believes this mechanism of action of inducing trained innate immune memory, through the combination of N-803 and BCG, contributes to the high complete response rate and prolonged 24-month durable complete response reported in this trial.