Positive early Phase 1 clinical data in healthy volunteers support Kangpu Biopharmaceuticals’ plan to advance KPG-818 into clinical trials in patients with systemic lupus erythematosus (SLE) or blood cancers.
KPG-818 is a small molecule designed to inhibit the activity of the CRL4-CRBN protein complex. CRBN, or cereblon, is a protein with a key role in ubiquitination of other proteins, which means tagging with a marker for degradation called ubiquitin. Through this suppression, KPG-218 — Kangpu’s lead product — is intended to modulate the activity of immune cells involved in autoimmune diseases and hematological malignancies.
Preclinical studies have indicated that KPG-818 can effectively block pro-inflammatory signals and prevent the proliferation of immune cells. Studies in animal models have also suggested that this investigational therapy could represent an alternative strategy to tackle myeloma and lymphoma malignant cells.
A recently completed Phase 1 trial explored the safety, tolerability, and pharmacokinetics of KPG-818 in healthy volunteers. Pharmacokinetics refers to a compound’s absorption, distribution, metabolism, and excretion in the body.
Conducted in the United States, the double-blind trial (NCT03949426) enrolled 40 women and men ages 18–55 who were randomly assigned to take one of five doses of KPG-818 — 2, 5, 10, 20, or 30 mg — or a dose-matching placebo given as oral capsules. Each dose group included eight participants, six taking KPG-818 and two taking the placebo.
All participants underwent physical evaluations, which included assessment of vital signs and heart function. Potential adverse reactions were monitored within the following 72 hours and in a follow-up visit 10 days after taking the capsules. Blood and urine samples were also collected 72 hours after taking KPG-818 or the placebo for additional laboratory analysis.
Results showed that KPG-818 was generally safe and well-tolerated, with no safety issues reported. No serious adverse reactions or toxicity events were described for any KPG-818 dose tested, according to the company.
KPG-818 also showed a favorable pharmacological profile that supports once-daily oral dosing. The positive Phase 1 data also revealed no difference in exposure to the experimental therapy when dosing under fed versus fasting conditions.
Kangpu will use the collected data to identify the most suitable doses of its treatment candidate to be tested in clinical trials in people with SLE or blood cancer.