 |
Biomarker data demonstrates proof-of-concept for KP104's dual-targeting mechanism via dose-dependent inhibition of alternative and terminal pathways and supports intravenous and subcutaneous administration of KP104 in phase 2 studies
CAMBRIDGE, Mass. and SUZHOU, JIANGSU, China, Nov. 3, 2022 /PRNewswire/ -- Kira Pharmaceuticals, a global biotechnology company pioneering transformational complement therapies to treat immune-mediated diseases, today presented complete first-in-human data from its SYNERGY-1 trial of KP104 at the American Society of Nephrology (ASN) Kidney Week 2022 in Orlando, FL. KP104 is a first-in-class bifunctional biologic engineered to selectively target the alternative and terminal complement pathways.
"The data indicate that we can effectively regulate complement activity in healthy volunteers via simultaneous upstream and downstream inhibition at two key intervention points in the alternative and terminal pathways with our bifunctional asset KP104," said Frederick Beddingfield, MD, PhD, CEO of Kira Pharmaceuticals. "Given the presence of complement in both healthy individuals and those living with chronic disease, we're confident in the clinical translation of these results to patients and look forward to initiating Phase 2 evaluation of KP104 in a range of immunologic conditions with limited treatment options."
Key biomarker data demonstrate dose-dependent inhibition by KP104 of the alternative pathway (AP) and terminal pathway (TP) of complement activation, as assessed by a C3b deposition assay and a free C5 assay, respectively. Biomarker assay also included a rabbit red blood cell (RBC) hemolysis assay which measures the combined inhibitory effect of KP104 on AP and TP. Following a single 1200 mg dose administered intravenously, a 99.9% decrease in free C5 and a 98.6% decrease in C3b deposition were observed. At the same dose, 99.4% inhibition of rabbit RBC hemolysis was observed, making KP104 the only biologic in clinical development that can achieve effective alternative and terminal pathway inhibition after a single treatment. Overall, inhibition of rabbit RBC lysis, C3b deposition, and free C5 reached 80-100% from baseline at administered drug concentrations greater than 150 mg/mL.
Pharmacokinetic (PK) and pharmacodynamic (PD) results from the multiple ascending dose (MAD) cohort demonstrate sustained levels of KP104 in the blood during the dosing period and suggest subcutaneous (SC) dosing is clinically effective following an initial single intravenous (IV) loading dose. The bioavailability of 4 weekly SC doses was approximately 67%, and this dosing regimen achieved sustained reduction in free C5 and C3b deposition as well as inhibition of rabbit RBC hemolysis observed over the course of the treatment period. Data from the Synergy-1 trial also indicate that KP104 is safe and well tolerated in healthy volunteers with no deaths, serious treatment emergent adverse effects (TEAEs), or discontinuations due to related TEAEs reported.
The data support future clinical trials in complement-mediated kidney diseases, including IgA nephropathy (IgAN) and complement 3 glomerulopathy (C3G), in addition to other immunologic conditions. Kira plans to initiate Phase 2 studies of KP104 in three trials that span several indications later this year: a renal basket study including IgAN and C3G, thrombotic microangiopathies secondary to systemic lupus erythematosus (SLE-TMA), and paroxysmal nocturnal hemoglobinuria (PNH).
The presentation will be available via the online meeting platform for in-person and virtual participants through Wednesday, December 21, 2022. The poster can also be viewed on Kira's website starting on November 5, 2022.
Presentation details are as follows:
Title: SYNERGY-1: A Phase 1, first-in-human, safety, tolerability, immunogenicity, PK and PD study of KP104 in escalating single and multiple doses
Authors: Paul Wabinitz1, Xiang Gao2, Jay Ma2, Ping Tsui2, Martin Rabe2, Helen Fu2, Chaomei He2, Jingtao Wu2, Brian York2, Qing Yu Christina Weng2,3, Jon Rankin4, Frederick Beddingfield2,5, Wenru Song2, Nicholas Farinola1, Richard Lee2
Abstract Number: 3761666
Session Title: Glomerular Diseases: IgA and Complement-Mediated GN [PO1302-3]
Session Date and Time: November 5, 2022, from 10:00 AM to 12:00 PM
1Cancer Research Institute, University of South Australia, 2Kira Pharmaceuticals, 3Massachusetts General Hospital – Harvard Medical School, 4Syneos Health, and 5David Geffen School of Medicine – UCLA
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 www.kirapharma.com and on LinkedIn.