Kira Pharmaceuticals says the US Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for KP104, a first-in-class bifunctional biologic that selectively and synergistically targets the alternative and terminal complement pathways. \n\n\n\nA phase 2 trial will evaluate the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of KP104 in participants with systemic lupus erythematosus associated thrombotic microangiopathy (SLE-TMA) in the U.S., China, and Australia. \n\n\n\nThe IND was supported by phase 1 data (SYNERGY-1 study), which demonstrated proof-of-mechanism for KP104 on both the terminal and alternative complement pathways and showed an encouraging profile for the phase 2 study in SLE-TMA.\n\n\n\n"We believe KP104, which uniquely modulates two targets, one in the proximal or alternative pathway and one in terminal pathway, offers immense potential to address complement-mediated diseases for which there are no currently approved treatments, such as SLE-TMA," said Frederick Beddingfield, CEO of Kira Pharmaceuticals. \n\n\n\n"This IND clearance is further testament to the dedication of the Kira team to advance KP104 and bring this next-generation therapeutic one step closer to patients awaiting improved treatment options."\n\n\n\nIncreased demand\n\n\n\nThe complement system is a key component of innate immunity that operates via several activation pathways comprising more than 30 proteins. Dysregulation within this system can be a critical driver of numerous immunologic conditions including SLE-TMA. \n\n\n\nThe complexity of the complement system has made development of selective and effective treatments a challenge, increasing the demand for next-generation complement-based therapeutics.\n\n\n\nTMA is a serious complication that can occur in patients with SLE for which there are no currently approved treatments. Kira Pharmaceuticals is pursuing several assets to address the unmet need for effective complement-targeted therapeutics, including treatments for SLE-TMA, with lead candidate KP104 showing significant promise in early clinical studies.\n\n\n\nAbout SLE-TMA\n\n\n\nThrombotic microangiopathies (TMA) are associated with a number of diseases and are characterized by destruction of red blood cells, low platelet counts, and organ damage. TMA can occur as a severe symptom of systemic lupus erythematosus (SLE), leading to poorer patient outcomes as compared to patients living with SLE or lupus nephritis (LN) alone. Complications resulting from TMA in SLE are a cause of significant morbidity and mortality. There are currently no approved therapies for SLE-TMA and the current standard of care treatments provide poor long-term benefits.\n\n\n\nAbout Kira Pharmaceuticals' KP104\n\n\n\nKP104 is a first-in-class bifunctional biologic designed to simultaneously and selectively block both the alternative and terminal complement pathways, providing a method of targeting validated drivers of complement-mediated disease. This dual-target mechanism of action uniquely positions KP104 to address complement-mediated diseases and potentially provide greater benefits than single-target complement agents. \n\n\n\nEngineered to have an extended half-life and potency, KP104 has a formulation suitable for both intravenous and subcutaneous administrations. KP104 is entering phase 2 POC trials across multiple renal disease and hematologic indications and has been granted orphan drug designation by the FDA for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). \n\n\n\nPhase 2 trials will be conducted globally, including in the U.S., China, Australia, and South Korea. KP104 is an investigational agent not yet approved for any indication by any health authority.