HL2351 / Handok, Genexine - LARVOL DELTA

Development of a Pharmacokinetic Model Describing FcRn-Mediated Recycling of HL2351, a Novel Hybrid Fc-Fused IL1Ra, to Optimize Dosage Regimen. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Optimized doses were considered based on average concentrations of IL1R bound to anakinra and HL2351. HL2351 at doses of 326 mg or 4.267, 4.982, 5.288, 5.458, or 5.748 mg/kg once weekly; or HL2351 at 1726 mg or 21.92, 26.86, 29.10, 30.36, or 32.53 mg/kg once biweekly would have similar therapeutic effects with anakinra at a dose of 100 mg, or 1, 2, 3, 4, or 8 mg/kg administered once daily, respectively."

Journal • PK/PD data • IL1R1

A Dose-Block Randomized, Placebo Controlled (Double-blind), Active Controlled(Open-label), Dose-escalation Study (clinicaltrials.gov) - P1; N=58; Recruiting; Sponsor: Handok Pharmaceuticals Co., Ltd.

New P1 trial • Biosimilar

Safety, tolerability and pharmacokinetics and pharmacodynamics of HL2351, a novel hybrid Fc-fused IL-1 receptor antagonist, in healthy subjects: a first-in-human study. (PubMed, Br J Clin Pharmacol) - "HL2351 was well tolerated and showed linear pharmacokinetic characteristics after a single SC administration at doses up to 12 mg/kg in healthy subjects. HL2351 remained in the body 7-11 times longer than anakinra. HL2351 can be developed as a potential therapeutic alternative to anakinra."

Clinical • Journal • P1 data • PK/PD data

Survivors of Murine Pneumosepsis Exhibit Long-Term Behavior Change and Primed Brain IL-1β Expression (ATS 2019) - "Methods : Male C57BL/6 mice, 8-10 weeks old, received Klebsiella pneumoniae (KPA, strain 43816, serotype 2) at 1x104 colony forming units (CFU) or saline intranasally (IN), followed by ceftriaxone (CTX) 7.5mg/kg IP for days 3-5. We have developed a clinically relevant, low-mortality model of KPA pneumosepsis. Acute infection is associated with weight loss, bacterial dissemination, and systemic inflammation, which improve with antibiotic treatment. Survival of sepsis is associated with increased sickness behavior in the presence of primed brain pro-inflammatory cytokine expression, including IL-1β, a primary mediator of sickness behavior."