Kiniksa Announces Preliminary Data from Phase 1 Trial of KPL-404

- Receptor occupancy and TDAR suppression shown through Day 29 at 3 mg/kg intravenous

- Data to-date support subsequent study in patients, including potential intravenous or subcutaneous monthly administration -

- Final data and safety follow-up from all cohorts expected in 1H 2021 -

HAMILTON, Bermuda I November 30, 2020 I Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (“Kiniksa”), a biopharmaceutical company with a pipeline of assets designed to modulate immunological pathways across a spectrum of diseases, today announced preliminary data from the Phase 1 clinical trial of KPL-404 in healthy volunteers. KPL-404 is a monoclonal antibody inhibitor of the CD40-CD40 ligand (CD40L) interaction, a central control node of T-cell dependent, B-cell mediated humoral adaptive immunity.

“The preliminary data from the single-ascending-dose Phase 1 study of KPL-404 are encouraging,” said Sanj K. Patel, Chief Executive Officer and Chairman of the Board of Kiniksa. “We believe the data generated to-date suggest that KPL-404 has the potential to address a broad range of autoimmune diseases. We expect final data and safety follow-up from all cohorts of the Phase 1 study in the first half of 2021.”

The Phase 1 trial of KPL-404 is a randomized, double-blind, placebo-controlled, single-ascending-dose, first-in-human study that is divided into two parts: a single dose of KPL-404 0.03 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg intravenously (IV) and a single dose of KPL-404 1 mg/kg or 5 mg/kg subcutaneously (SC). The primary objective is to assess the safety and tolerability of KPL-404. Secondary endpoints include pharmacokinetics, CD40 receptor occupancy (RO), the immune response to the novel test antigen keyhole limpet hemocyanin (KLH) in clinically relevant dose cohorts, and the anti-drug antibody response.

All dose escalations occurred as per protocol with no dose limiting safety findings. All 6 subjects dosed with KPL-404 3 mg/kg IV showed full receptor occupancy through Day 29, which corresponded with complete suppression of the T-cell Dependent Antibody Response (TDAR) to KLH through Day 29. Consistent dose relatedness was shown in the lower dose level cohorts, including 0.03 mg/kg, 0.3 mg/kg, 1 mg/kg IV and 1 mg/kg SC. Data collection for the higher dose level cohorts, 10 mg/kg IV and 5 mg/kg SC, is ongoing.

The data to-date support subsequent study in patients, including potential IV or SC monthly administration. Kiniksa expects final data and safety follow-up from all cohorts in the first half of 2021.

The CD40-CD40L interaction has been implicated in diseases such as rheumatoid arthritis, Sjogren’s syndrome, Graves’ disease, and systemic lupus erythematosus and in prevention of solid organ transplant graft rejection, where external proof-of-concept has been previously shown.

“KPL-404 is designed to inhibit CD40-CD40L interaction, a key T-cell co-stimulatory signal pathway critical for B-cell maturation and immunoglobulin class switching. Additionally, dysregulation of the CD40-CD40L pathway has been implicated in multiple autoimmune disease pathologies and has broad reaching implications beyond humoral immunity, with its impact on dendritic cells and macrophage activity,” said John F. Paolini, MD, PhD, Chief Medical Officer of Kiniksa. “The preliminary Phase 1 data replicate and underscore the preclinical data from this program, which showed favorable pharmacokinetic and pharmacodynamic profiles, including suppression of TDAR. The data to-date support continued clinical development, and we look forward to further analyzing the totality of the dataset.”

About KPL-404
KPL-404 is an investigational humanized monoclonal antibody that is designed to inhibit CD40-CD40L interaction, a key T-cell co-stimulatory signal critical for B-cell maturation and immunoglobulin class switching and Type 1 immune responses. Kiniksa believes disrupting the CD40-CD40L interaction is an attractive approach for multiple autoimmune disease pathologies such as rheumatoid arthritis, Sjogren’s syndrome, Graves’ disease, systemic lupus erythematosus and solid organ transplant. Kiniksa owns or controls the intellectual property related to KPL-404.

About Kiniksa
Kiniksa is a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksa’s clinical-stage product candidates, rilonacept, mavrilimumab, vixarelimab and KPL-404, are based on strong biologic rationale or validated mechanisms, target underserved conditions and offer the potential for differentiation. These pipeline assets are designed to modulate immunological pathways across a spectrum of diseases. For more information, please visit www.kiniksa.com.

SOURCE: Kiniksa Pharmaceuticals

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