(14.10) Phase 1 Healthy Volunteer Data Supports Phase 2 Study of LASN01 in Thyroid Eye Disease (TED) – Actively Enrolling

Interleukin-11 (IL-11) is a key effector of fibro-inflammatory disease processes in multiple organs.  IL-11 is elevated in both orbital fibroblasts and serum of thyroid eye disease (TED) patients and stimulates hyaluronic acid (HA) production from TED patient-derived orbital fibroblasts (OF). LASN01 inhibits a number of signals which are known to be associated with TED including hyaluronic acid elevation and procollagen. In patient-derived orbital fibroblasts IGF-1 and IL-11 induced HA release, as well as TGFβ stimulated procollagen production were inhibited by LASN01.

Methods: LASN01 is a highly specific, fully human monoclonal antibody that binds to IL-11R with high affinity and inhibits IL-11 signaling. A randomized, placebo controlled (3:1) Phase 1 trial was conducted in healthy volunteers to assess safety, pharmacokinetics (PK) and target engagement with single and multiple ascending doses (SAD and MAD) of intravenous LASN01 in healthy volunteers.

Results:

Fifty-eight volunteers were dosed in 5 single dose cohorts (25-1200 mg) and 2 multiple dose cohorts (600-1200 mg). Sixty-one treatment emergent adverse events (TEAEs) were reported by 35 subjects, which included no serious or severe adverse events. The most common AEs were headaches (13) and light headedness/dizziness (5). Data from healthy volunteers in the Phase 1 SAD/MAD Phase 1 trial show favorable safety and predictable and linear PK and dose-dependent target engagement.  The half-life in the 1200 mg cohort was approximately 11 days.  This data supports monthly dosing in the Phase 2 study.

Discussion/Conclusion: A proof-of-concept, global, randomized, double-masked Phase 2 trial is actively enrolling.  Patients with diagnosed Graves’ disease and active, moderate to severe thyroid eye disease (TED), within 12 months of start of symptoms and with a Clinical Activity Score (CAS) ≥ 3, will be randomized to 3 treatment arms (high and low dose LASN01 and placebo) and will be treated Q4 weeks for 12 weeks with a follow-up period of 12 weeks. The primary endpoint is the percentage of patients with response in proptosis (≥2mm) on active treatments vs. placebo.  Secondary endpoints include degree of proptosis reduction, assessment of diplopia, lid retraction, and extraocular movements.  Orbital MRIs will be collected to assess proptosis and extraocular muscles.
LASN01 is the only agent being developed for TED which offers the possibility of addressing the fibro-inflammatory pathology of TED.