Kira Pharmaceuticals Presents Positive Results of KP104 Phase 2 Study in Complement-Naïve Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) at the 2023 ASH Annual Meeting

• An Interim analysis of 18 patients, completing 24/25 weeks of treatment in a phase 2 study in complement-naïve PNH patients demonstrates that KP104 is safe, well-tolerated, and has successfully met all primary and secondary endpoints.
• KP104 effectively managed both intravascular and extravascular hemolysis, with all 18 patients achieving a 2g/dL increase of hemoglobin from baseline in the absence of RBC transfusions and the majority of patients achieving normalization range of hemoglobin and LDH levels.
• The interim results support the advancement of KP104 to Phase 3 studies as an optimal and safe treatment for PNH patients to address currently unmet medical needs.

CAMBRIDGE, Mass., Dec. 14, 2023 /PRNewswire/ -- Kira Pharmaceuticals, a global biotechnology company pioneering transformational complement therapies to treat immune-mediated diseases, presented the interim safety and efficacy results from its Phase 2 study of KP104 in complement inhibitor-naïve patients with PNH at the 2023 American Society of Hematology (ASH) Annual Meeting held in San Diego, on December 10^th in an oral presentation. The presentation has also been selected to be featured in the 2024 Highlights of ASH. KP104 is a first-in-class bifunctional biologic engineered to inhibit both alternative and terminal complement pathways.

This open-label Phase 2 clinical trial (NCT05476887) aims to assess the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of KP104 in patients diagnosed with PNH who have not received prior complement inhibitors. The primary objectives of the study are to evaluate key clinical markers including lactate dehydrogenase (LDH) and hemoglobin (Hgb) levels, transfusion requirements, and FACIT-fatigue scores. The interim analysis of the Phase 2 study for KP104 demonstrated positive outcomes from 18 patients who have completed 24/25 weeks of treatment across three escalating doses:

• Patients showed rapid and sustained improvements in hemoglobin levels (Figures 1 and 2). At Week 24/25: 
  • 100% (18/18) achieved a ≥2g/dL increase from baseline;
  • 56% (10/18) attained hemoglobin normalization (≥12g/dL) in the absence of RBC transfusions, with the remaining patients approaching near-normal level;
  • Average Hgb levels for Cohort 1, 2 and 3 are 11.7 g/dL (SD 1.0), 14.2 g/dL (SD 1.9) and 12.5 g/dL (SD 1.9), respectively. 
• Patients demonstrated rapid reduction and sustained control of LDH levels (Figure 3). At Week 24/25:
  • 83% (15/18) sustained levels below 1.5x ULN;
  • 72% (13/18) sustained levels below 1x ULN 
• All patients remained free from RBC transfusion between Day 1 and Week 24/25 of KP104 treatment.
  
  
• Rapid and clinically significant improvements in absolute reticulocyte counts, bilirubin levels, and FACIT-fatigue scores were consistently observed in all three cohorts through Week 24/25.
  
  
• KP104 was safe and well-tolerated without treatment-emergent adverse events (TEAEs) at or above Grade 3. Common AEs included transient injection site induration, headache, and COVID19 infection, all of which were promptly or duly resolved.
  
  
• Convenient dosing regimen with SC administration every 2 weeks.

Kira Pharmaceuticals is committed to advancing KP104 as an innovative therapy for patients with PNH and other complement-mediated diseases. The interim results of the Phase 2 study in complement-naïve PNH patients study represent a significant step forward in developing KP104 as an optimal and safe treatment for PNH patients to address currently unmet medical needs. These data also provide a proof-of concept and strong foundation for future clinical trials in other complement-mediated diseases, such as IgA nephropathy (IgAN), complement 3 glomerulopathy (C3G), and thrombotic microangiopathies secondary to systemic lupus erythematosus (SLE-TMA).

Title: KP104, a bifunctional C5 antibody/factor H fusion protein, effectively controls both intravascular and extravascular hemolysis: interim results from a phase 2 study in complement inhibitor-naïve PNH patients
Authors: Fengkui Zhang, Bing Han, Li Zhang, Chen Yang, Chunrong Wang, Changhe Yue, Hui Yan, Jay Ma, Helen Fu, Chaomei He, Ping Tsui, Jingtao Wu, Richard Lee, Wenru Song
Session: 508. Bone Marrow Failure: Unraveling the Future of PNH Therapy from Clinical Trials

Oral Presentation Time: December 10th, 2023, 4:45pm PT

About KP104
KP104 is a first-in-class bifunctional biologic designed to simultaneously 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 enhanced 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. 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 Paroxysmal Nocturnal Hemoglobinuria
Paroxysmal Nocturnal Hemoglobinuria is a rare, life-threatening blood disease that is characterized by the destruction of red blood cells, formation of blood clots, and impairment of bone marrow function. PNH affects between 1 and 5 people per million and is almost always caused by genetic mutations that result in production of aberrant hematopoietic stem cells. These stem cells produce irregular red blood cells that are highly susceptible to destruction via complement activation. Current therapies include C5 inhibitors, which do not address extravascular hemolysis (EVH) related to the alternative pathway or a C3 inhibitor, which may address EVH but may not adequately block C5 downstream, leading to life-threatening breakthrough hemolysis (Breakthrough Hemolysis in PNH with Proximal or Terminal Complement Inhibition, N Engl J Med, July 14, 2022).

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.

Contact: [email protected]

SOURCE Kira Pharmaceuticals