PII-079 - PHARMACOKINETIC/PHARMACODYNAMIC MODELING SUPPORTS POTENTIAL QUARTERLY SUBCUTANEOUS DOSING OF TOUR006, A FULLY HUMAN, HIGH-AFFINITY, ANTI-IL-6 MONOCLONAL ANTIBODY FOR ATHEROSCLEROTIC CARDIOVASCULAR DISEASE TREATMENT.

E. deGoma¹, Y. Chyung¹, S. Mehr², S. Debroy², K. Erickson¹, J. Walsh¹, C. Comisar²; ¹Tourmaline Bio, Inc., New York, NY, United States, ²Certara, Radnor, PA, United States.

Background: Extending the dosing interval of preventive therapies remains a key priority of innovation in order to maximize adherence and real-world effectiveness. TOUR006 is a long-acting, fully human, high-affinity mAb against IL-6. In prior Phase 1/2 studies, TOUR006 administered to patients with high-grade inflammatory autoimmune diseases achieved durable reductions in C-reactive protein (CRP), a pharmacodynamic biomarker of IL-6 activity, as assessed by the high-sensitivity (hs) assay. As such, a pharmacokinetic/pharmacodynamic (PK/PD) model was developed to evaluate extended dosing intervals of TOUR006 once every 90 days.

Methods: A PK/PD model was developed from 5 studies of TOUR006 in healthy volunteers (n=46) and patients with rheumatoid arthritis (n=31), Crohn’s disease (n=178), and systemic lupus erythematosus (138) (Li, 2019). Simulations were performed using multiple dosing regimens and by sampling participants from a population with baseline hs-CRP levels of >2 mg/L, a threshold consistent with residual systemic inflammatory risk, and ≤10 mg/L. Sensitivity analyses were performed using sampling populations with higher baseline hs-CRP levels and bodyweight.

Results: At baseline, mean age in the primary sampling population was 53 years, median hsCRP was 4.1 mg/L, and bodyweight was 59 kg. Simulations were performed for TOUR006 SC 50 mg quarterly, 25 mg quarterly, and 15 mg monthly, and the percentage of virtual patients achieving hs-CRP < 2 mg/L at Day 90 was >90%, >85%, and >90%, respectively (Table). Sensitivity analyses of sampling populations with higher baseline median hs-CRP (6.3 mg/L) and bodyweight (102 kg) showed comparable results to the primary analysis.

Conclusion: PK/PD modeling supports the potential for quarterly SC dosing of TOUR006 in patients with systemic inflammation characteristic of ASCVD. The ongoing TRANQUILITY Phase 2 study (NCT06362759) is evaluating quarterly and monthly dosing of TOUR006 in patients with chronic kidney disease and elevated hs-CRP.