abiprubart (KPL-404) / Kiniksa - LARVOL DELTA

A Study to Evaluate the Efficacy and Safety of Abiprubart in Participants With Sjögren's Disease (clinicaltrials.gov) - P2 | N=200 | Active, not recruiting | Sponsor: Kiniksa Pharmaceuticals International, plc | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2027 ➔ May 2025 | Trial primary completion date: Dec 2026 ➔ Mar 2025

Enrollment closed • Trial completion date • Trial primary completion date • Sjogren's Syndrome

Corporate Update (GlobeNewswire) - "Kiniksa announced today that it is advancing KPL-1161 towards clinical development with a target profile of quarterly SC dosing...Kiniksa announced today that it plans to discontinue abiprubart development in Sjögren’s Disease. The company will explore strategic alternatives for the asset; Kiniksa announced today that it has exercised its right to terminate its exclusive license agreement for mavrilimumab with MedImmune."

Commercial • Pipeline update • Cardiovascular • Rheumatoid Arthritis • Sjogren's Syndrome

New Developments and Therapeutic Drug Monitoring Options in Costimulatory Blockade in Solid Organ Transplantation: A Systematic Critical Review. (PubMed, Ther Drug Monit) - "The routine use of costimulation blockade in SOT is hindered by problems in efficacy compared with the standard of care. Costimulatory inhibitors could be combined in a calcineurin inhibitor-free regimen. Future PK/pharmacodynamic studies in costimulatory agents and personalized medicine could warrant TDM of these agents."

Journal • Review • Hepatology • Solid Organ Transplantation • Transplantation • CD40LG • CD80 • TNFSF4

Efficacy, Safety, Pharmacokinetics of Anti-CD40 Antibody Abiprubart in Patients with Rheumatoid Arthritis: A Phase 2, Randomized, Placebo-Controlled 12-week-treatment Proof-of-Concept Study (ACR Convergence 2024) - "Abiprubart was well-tolerated in pts with b/tsDMARD-refractory RA, and reductions in DAS28-CRP at Wk 12 for all abiprubart groups were greater than PBO, with statistical significance in the 5mg/kg SC qwk dose group and pooled analysis. Abiprubart may provide benefit in autoimmune diseases involving CD40/CD154 costimulation. A phase 2B study [Fig 3] in Sjögren's Disease is planned."

Clinical • IO biomarker • P2 data • PK/PD data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CD40 • CD40LG • CRP

A Study to Evaluate the Efficacy and Safety of Abiprubart in Participants With Sjögren's Disease (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Kiniksa Pharmaceuticals, GmbH

New P2 trial

Kiniksa Pharmaceuticals Commences Enrollment in Abiprubart Phase 2b Clinical Trial in Sjögren’s Disease (Kiniksa Press Release) - "Kiniksa Pharmaceuticals International, plc...today announced that it has commenced enrollment of the Phase 2b clinical trial of abiprubart in Sjögren’s Disease. Abiprubart is an investigational humanized anti-CD40 monoclonal antibody designed to inhibit CD40-CD154 (CD40 ligand) interaction....The randomized, double-blind, placebo-controlled Phase 2b clinical trial is designed to evaluate the treatment response of chronic subcutaneous (SC) administration of abiprubart in patients with Sjögren’s Disease....The primary endpoint is change from baseline in EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) versus placebo at Week 24. Subsequently, patients will enter a long-term extension in which active treatment will be given in all study arms for an additional 24 weeks."

Enrollment open • Immunology • Sjogren's Syndrome

EFFICACY, SAFETY, AND PHARMACOKINETICS OF ANTI-CD40 ANTIBODY ABIPRUBART (KPL-404) IN PATIENTS WITH RHEUMATOID ARTHRITIS: A PHASE 2, RANDOMIZED, PLACEBO-CONTROLLED 12-WEEK-TREATMENT PROOF-OF-CONCEPT STUDY (EULAR 2024) - "Treatment with abiprubart, an anti-CD40 monoclonal antibody, resulted in a statistically significant reduction in DAS28-CRP at Week 12 in the 5mg/kg SC weekly dosing group, compared to placebo, in refractory RA pts. Sustained treatment with abiprubart was well tolerated, with a PK profile that supports practical chronic SC dosing. A fourth cohort, administering a 600mg loading dose followed by fixed doses of 400 mg SC q4wk or placebo for 12 weeks is ongoing."

Clinical • IO biomarker • P2 data • PK/PD data • Immunology • Inflammatory Arthritis • Otorhinolaryngology • Rheumatoid Arthritis • Rheumatology • CD40LG • CRP

Study to Assess the Safety, Pharmacokinetics, and Efficacy of KPL-404 in Participants With Rheumatoid Arthritis With Inadequate Response or Intolerance to at Least One Biologic Disease-modifying Anti-rheumatic Drug or a Janus Kinase Inhibitor (clinicaltrials.gov) - P2 | N=145 | Completed | Sponsor: Kiniksa Pharmaceuticals, Ltd. | Active, not recruiting ➔ Completed

Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Kiniksa Pharmaceuticals Announces Development Indication for Abiprubart (GlobeNewswire) - "Kiniksa is planning to initiate a randomized, double-blind, placebo-controlled Phase 2b trial designed to evaluate the treatment response of chronic subcutaneous (SC) administration of abiprubart in patients with Sjogren’s Disease....The trial is expected to initiate in the second half of 2024."

New P2b trial • Immunology • Sjogren's Syndrome

Kiniksa Pharmaceuticals Announces Development Indication for Abiprubart (GlobeNewswire) - P2 | N=145 | NCT05198310 | Sponsor: Kiniksa Pharmaceuticals, Ltd. | "The Phase 2 rheumatoid arthritis trial uses a randomized, double-blind, placebo-controlled design to evaluate pharmacokinetics (PK), safety, and efficacy of chronic SC administration of abiprubart and to provide optionality to evaluate abiprubart across a range of autoimmune diseases...In the Cohort 4 abiprubart 400 mg SC monthly dose group (n=31), the LS mean change [95% CI] from baseline in DAS28-CRP at Week 12 was -1.87 [-2.54, -1.21] points, compared to -1.30 [-1.98, -0.62] points in placebo recipients (n=20), (LS Mean Difference = -0.58, p=0.109)...Additionally, Kiniksa today announced a post-hoc analysis of data pooled from the Cohort 3 and Cohort 4 abiprubart and placebo groups."

P2 data • Rheumatoid Arthritis

Study to Assess the Safety, Pharmacokinetics, and Efficacy of KPL-404 in Participants With Rheumatoid Arthritis With Inadequate Response or Intolerance to at Least One Biologic Disease-modifying Anti-rheumatic Drug or a Janus Kinase Inhibitor (clinicaltrials.gov) - P2 | N=131 | Active, not recruiting | Sponsor: Kiniksa Pharmaceuticals, Ltd.

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Study to Assess the Safety, Pharmacokinetics, and Efficacy of KPL-404 in Participants With Rheumatoid Arthritis With Inadequate Response or Intolerance to at Least One Biologic Disease-modifying Anti-rheumatic Drug or a Janus Kinase Inhibitor (clinicaltrials.gov) - P2 | N=131 | Active, not recruiting | Sponsor: Kiniksa Pharmaceuticals, Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

First-in-Human Phase 1 Randomized Trial with the Anti-CD40 Monoclonal Antibody KPL-404: Safety, Tolerability, Receptor Occupancy, and Suppression of T-Cell-Dependent Antibody Response. (PubMed, J Pharmacol Exp Ther) - P1 | "The pharmacokinetic profile, duration of full CD40 receptor occupancy, and magnitude and duration of memory immune response suppression observed confirms pharmacodynamic activity regardless of administration route. These data provide evidence that chronic KPL- dosing regimens (intravenous or subcutaneous) could be practical."

Clinical • Journal • P1 data • Immunology • Transplant Rejection • CD40LG

Immune Monitoring of The First Cardiac Xenotransplant From Genetically engineered pig to a Human (IPITA-IXA-CTRMS 2023) - "Induction included ATG (after xTX), Rituxan (one dose only), C1 esterase, and costimulation blockade with humanized anti-CD40 (KPL404) antibody. Our study demonstrates that immune monitoring accurately reflects the immune response status of the recipient after cardiac xTX and continuous monitoring will aid in the early detection of rejection even and allow effective intervention."

Hematological Disorders • Transplantation • CD8 • IFNG • IL17A • TNFA

Study to Assess the Safety, Pharmacokinetics, and Efficacy of KPL-404 in Participants With Rheumatoid Arthritis With Inadequate Response or Intolerance to at Least One Biologic Disease-modifying Anti-rheumatic Drug or a Janus Kinase Inhibitor (clinicaltrials.gov) - P2 | N=131 | Recruiting | Sponsor: Kiniksa Pharmaceuticals, Ltd. | N=91 ➔ 131 | Trial completion date: Mar 2024 ➔ Jun 2024 | Trial primary completion date: Dec 2023 ➔ Mar 2024

Enrollment change • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Kiniksa Pharmaceuticals Reports Second Quarter 2023 Financial Results and Recent Portfolio Execution (GlobeNewswire) - "Kiniksa Pharmaceuticals, Ltd...today reported second quarter 2023 financial results and recent portfolio execution...ARCALYST net product revenue was $54.5 million for the second quarter of 2023...Kiniksa is enrolling patients in the Phase 2 clinical trial of KPL-404 in rheumatoid arthritis. The company expects data from the trial in the first half of 2024...Vixarelimab...In the second quarter of 2023, Kiniksa recognized a $15.0 million development milestone related to a new indication under its global license agreement with Genentech, a member of the Roche Group (Genentech)...Total revenue for the second quarter of 2023 was $71.5 million, compared to $27.0 million for the second quarter of 2022...As of June 30, 2023, Kiniksa had $185.0 million of cash, cash equivalents, and short-term investments and no debt."

Commercial • P2 data • Sales • Cardiovascular • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Inflammatory Arthritis • Pulmonary Disease • Rheumatoid Arthritis

Kiniksa Pharmaceuticals Reports First Quarter 2023 Financial Results and Recent Portfolio Execution (GlobeNewswire) - "ARCALYST net product revenue was $42.7 million for the first quarter of 2023. Since launch, more than 1,000 prescribers have written ARCALYST prescriptions for recurrent pericarditis....Kiniksa is enrolling the final cohort of the Phase 2 clinical trial of KPL-404 in rheumatoid arthritis. The company expects data from the trial in the first half of 2024."

Commercial • Enrollment status • P2 data • Sales • Cardiovascular • Immunology • Rheumatoid Arthritis

Dose-dependent Suppression of T Cell-Dependent Antibody Response in Healthy Volunteers by KPL-404, an Anti-CD40 Monoclonal Antibody, Supports Phase 2 Study in Patients with Rheumatoid Arthritis (ACR Convergence 2022) - "Inhibition of the CD40-CD154 co-stimulatory interaction holds promise for the management of a spectrum of autoimmune diseases. KPL-404 demonstrated prolonged absorption/excretion capable of suppressing TDAR for extended periods allowing for use of extended dosing intervals irrespective of IV or SC dosing. These analyses supported the design of the ongoing Phase 2 study assessing the efficacy and safety KPL-404 in RA.Figure 1."

Clinical • IO biomarker • P2 data • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CD40LG • CRP

DOSE-DEPENDENT SUPPRESSION OF T CELL-DEPENDENT ANTIBODY RESPONSE IN HEALTHY VOLUNTEERS BY KPL-404, AN ANTI-CD40 MONOCLONAL ANTIBODY, SUPPORTS CHRONIC DOSING STUDY IN PATIENTS WITH RHEUMATOID ARTHRITIS (EULAR 2022) - "Inhibition of the CD40-CD154 co-stimulatory interaction holds promise for the management of a spectrum of autoimmune diseases. KPL-404 demonstrated prolonged absorption/excretion capable of suppressing TDAR for extended periods allowing for use of extended dosing intervals irrespective of IV or SC dosing. These analyses supported the design of the ongoing Phase 2 study assessing the efficacy and safety KPL-404 in RA."

Clinical • IO biomarker • Cardiovascular • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CD40LG • CRP

SAFETY, TOLERABILITY, PHARMACOKINETICS, RECEPTOR OCCUPANCY, AND SUPPRESSION OF T-CELL-DEPENDENT ANTIBODY RESPONSE IN A PHASE 1 STUDY WITH KPL-404, AN ANTI-CD40 MONOCLONAL ANTIBODY (EULAR 2022) - "The safety and tolerability data and the PK/PD profile of KPL-404 support further investigation of KPL-404 in a broad range of autoimmune diseases, including rheumatoid arthritis. These data support the optionality for studying chronic KPL-404 dosing in patients with subcutaneous and/or intravenous administration."

Clinical • P1 data • PK/PD data • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Musculoskeletal Diseases • Orthopedics • Rheumatoid Arthritis • Rheumatology • CD40LG

Preclinical immunopharmacologic assessment of KPL-404, a novel, humanized, non-depleting antagonistic anti-CD40 monoclonal antibody. (PubMed, J Pharmacol Exp Ther) - "In vitro and in vivo findings characterize KPL-404 as a blocking anti-CD40 antibody that potently inhibits primary and secondary antibody responses at pharmacologically relevant concentrations with a favorable pharmacokinetic profile and did not deplete B-cells by antibody dependent cellular cytotoxicity or apoptosis ("non-depleting"). These findings support clinical development of KPL-404 as a potential therapeutic in autoimmune diseases."

Journal • Preclinical • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Sjogren's Syndrome • CD40LG

Study to Assess the Safety, Pharmacokinetics, and Efficacy of KPL-404 in Participants With Rheumatoid Arthritis With Inadequate Response or Intolerance to at Least One Biologic Disease-modifying Anti-rheumatic Drug or a Janus Kinase Inhibitor (clinicaltrials.gov) - P2; N=84; Recruiting; Sponsor: Kiniksa Pharmaceuticals, Ltd.

Clinical • New P2 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

[VIRTUAL] Safety, Tolerability, Pharmacokinetics, Receptor Occupancy, and Suppression of T-cell-Dependent Antibody Response in a Phase 1 Study with KPL-404, an anti-CD40 Monoclonal Antibody (ACR-CONVERGENCE 2021) - "The safety and tolerability data and the PK/PD profile of KPL-404 support further investigation of KPL-404 in a broad range of autoimmune diseases, including rheumatoid arthritis. These data support the optionality for studying chronic KPL-404 dosing in patients with subcutaneous and/or intravenous administration."

Clinical • P1 data • PK/PD data • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Musculoskeletal Diseases • Orthopedics • Rheumatoid Arthritis • Rheumatology • CD40LG

Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of KPL-404 in Healthy Subjects (clinicaltrials.gov) - P1; N=52; Completed; Sponsor: Kiniksa Pharmaceuticals, Ltd.; Active, not recruiting ➔ Completed

Clinical • Trial completion

Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of KPL-404 in Healthy Subjects (clinicaltrials.gov) - P1; N=52; Active, not recruiting; Sponsor: Kiniksa Pharmaceuticals, Ltd.; Recruiting ➔ Active, not recruiting; Trial completion date: Dec 2020 ➔ Mar 2021; Trial primary completion date: Dec 2020 ➔ Mar 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date