C5 x CFH

CAMBRIDGE, Mass., Dec. 20, 2022 /PRNewswire/ -- Kira Pharmaceuticals, a global biotechnology company pioneering transformational complement therapies to treat immune-mediated diseases, announced today that the Chinese National Medical Products Administration (NMPA) and the Australian Therapeutic Goods Administration (TGA) have approved initiation of Phase 2 studies for evaluation of KP104, a first-in-class bifunctional biologic that selectively targets the alternative and terminal complement pathways, in a renal basket study including IgA nephropathy (IgAN) and complement 3 glomerulopathy (C3G). "These clearances add to the multiple INDs Kira has secured this year for KP104 and mark our first in IgAN and C3G, serious immune-mediated conditions that cause kidney damage and often result in kidney failure," said Frederick Beddingfield, M.D., Ph.D., CEO of Kira. "We believe that KP104's ability to simultaneously and synergistically block two key complement targets makes it a unique therapeutic option with the potential to make a profound impact on the lives of patients living with these kidney diseases around the world." IgAN is an autoimmune disease that damages the kidneys, impacting organ function and often resulting in end-stage kidney disease. Though the exact pathogenesis of IgAN remains unknown, immune complex deposition in the kidneys is characteristic of the disease, causing inflammation and glomerular damage. Recent studies have implicated complement activation across multiple complement pathways as a major contributor to kidney injury and disease progression in IgAN. Drugs that selectively inhibit either the alternative or terminal pathway have shown partial efficacy in recent human studies. KP104 is a potent inhibitor of both the alternative and terminal complement pathways. Thus KP104 may have the unique potential to address IgAN more effectively, where multiple pathways are involved. In C3G, a hyperactivated alternative complement pathway causes excessive cleavage and activation of complement protein 3 (C3) and complement protein 5 (C5), resulting in harmful C3 fragments getting lodged in the kidney and C5 split products contributing to further glomerular inflammation and damage. There are currently no approved therapies for the condition, making KP104 a novel therapeutic option with the potential for transformative patient impact. The Phase 2 studies will evaluate the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of KP104 in participants with IgAN and C3G in China and Australia. Phase 1 data from the SYNERGY-1 first-in-human (FIH) study of KP104 demonstrated clinical proof-of-mechanism (PoM) for the biologic, which received Orphan Drug Designation for treatment of paroxysmal nocturnal hemoglobinuria (PNH) from the US Food and Drug Administration (FDA) earlier this year. KP104 is currently undergoing Phase 2 evaluation in PNH and will additionally be evaluated in other hematology and nephrology indications in upcoming clinical trials. About IgA Nephropathy IgA Nephropathy (IgAN) is an autoimmune disease that damages the kidneys, impacting organ function and often resulting in end-stage kidney disease. IgAN is the most common form of glomerulonephritis, with a global population incidence of roughly 2.5 per 100,000 per year, though the exact pathogenesis of the disease remains unknown. In IgAN, the body produces abnormal immunoglobulin A (IgA) antibodies that stimulate an immune response and result in formation of immune complexes that become trapped in the kidney. The immune complexes in the kidney cause inflammation and tissue damage, potentially leading to renal failure. There remains significant unmet need for therapeutics that effectively address IgAN, with current treatment approaches for serious cases largely reliant on corticosteroids to manage inflammation. Recent studies have implicated aberrant complement activity as a major contributor to glomerular inflammation and disease progression of IgAN. KP104 is a potent inhibitor of the alternative and terminal complement pathways that offers unique potential to address IgAN through selective modulation of complement activity. About Complement 3 Glomerulopathy Complement 3 Glomerulopathy (C3G) encompasses dense deposit disease (DDD) and C3 glomerulonephritis (C3GN), two conditions that result in inflammation and damage of the glomeruli in the kidney. In C3G, abnormal complement system activation results in breakdown of C3, a complement protein. The products of this breakdown become lodged in the kidney, triggering inflammation and immune activity that injure the glomeruli. C3 breakdown also leads to C5 and terminal complement activation, causing further glomerular inflammation and damage. C3G has a global prevalence of 2-3 people out of every million, and roughly half of those living with C3G develop end-stage renal disease within 10 years of diagnosis. There are currently no approved therapies for the condition, making KP104 a novel therapeutic option with potential for transformative patient impact. About KP104 KP104 is a first-in-class bifunctional biologic designed to simultaneously and selectively block both the alternative and terminal complement pathways, providing a powerful and synergistic 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. Engineered 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). Phase 2 trials will be conducted globally, including in the U.S., China, and Australia. KP104 is an investigational agent not yet approved for any indication by any health authority. About Kira Pharmaceuticals Kira Pharmaceuticals is a clinical-stage biotechnology company pioneering complement-targeted therapies to treat immune-mediated diseases. Enabled by its LOGIC platform, the company has developed a robust pipeline of novel assets against validated complement targets. Headquartered in Cambridge, Massachusetts and with facilities in China and Australia, Kira Pharmaceuticals has established a global team committed to advancing life-changing therapies to patients around the world. More information on Kira can be found at and on LinkedIn. SOURCE Kira Pharmaceuticals

Phase 1 supporting data indicated an encouraging profile and confirmed the dual mechanism of action achieved through targeting both the alternative and terminal complement pathways CAMBRIDGE, Mass., Oct. 3, 2022 /PRNewswire/ -- Kira Pharmaceuticals, a global biotechnology company pioneering transformational complement therapies to treat immune-mediated diseases, announced today that 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. The 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 US, China, and Australia. The 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. "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, MD, PhD, CEO of Kira Pharmaceuticals. "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." The 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. The complexity of the complement system has made development of selective and effective treatments a challenge, amplifying the demand for next-generation complement-based therapeutics. TMA is a serious complication that can occur in patients with SLE for which there are no currently approved treatments. Kira is pursuing several assets to address the unmet need for highly effective complement-targeted therapeutics, including treatments for SLE-TMA, with lead candidate KP104 showing significant promise in early clinical studies. Kira has completed a Phase 1 first-in-human (FIH) study of KP104 demonstrating clinical proof-of-mechanism (POM) for the first-in-class bifunctional biologic. Furthermore, data in relevant animal models indicate a pharmacological profile optimal for continued development of KP104 for both intravenous and subcutaneous administration. The company will present safety, tolerability, PK, and PD data from the Phase 1 study at a medical conference later this year. About SLE-TMA Thrombotic 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. About KP104 KP104 is a first-in-class bifunctional biologic designed to simultaneously and selectively block both the alternative and terminal complement pathways, providing a powerful and synergistic 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. Engineered 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). Phase 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. About Kira Pharmaceuticals Kira Pharmaceuticals is a clinical-stage biotechnology company pioneering complement-targeted therapies to treat immune-mediated diseases. Enabled by its LOGIC platform, the company has developed a robust pipeline of novel assets against validated complement targets. Headquartered in Cambridge, Massachusetts and with facilities in China and Australia, Kira Pharmaceuticals has established a global team committed to advancing life-changing therapies to patients around the world. More information on Kira can be found at and on LinkedIn. SOURCE Kira Pharmaceuticals