Sling’s Linsitinib Maintains Proptosis Response Through Week 72 in LIDS Trial

Sling Therapeutics presented efficacy, safety and durability findings from its Phase 2b/3 LIDS trial of oral linsitinib in adults with moderate to severe active thyroid eye disease (TED) at the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) 57th Annual Fall Scientific Symposium on October 9, 2026.

LIDS Trial Design and Week 24 Efficacy Results

The randomized, double-masked, placebo-controlled trial (NCT05276063) enrolled 90 adults whose TED began within the previous 12 months, with proptosis of at least 3 mm and a Clinical Activity Score (CAS) of at least 4. Participants were randomized in a 1:1:1 ratio to receive linsitinib 75 mg twice daily (BID), linsitinib 150 mg BID or placebo for 24 weeks.

The primary endpoint was the proportion of patients achieving a reduction in proptosis of at least 2 mm from baseline at Week 24. The 150 mg BID group achieved a responder rate of 51.7%, compared with 18.8% for placebo (p=0.010). The 75 mg BID group recorded a response rate of 38.9% (p=0.09 versus placebo). The prespecified statistical significance threshold was p<0.0125 for each dose.

The higher dose therefore met the reported statistical threshold, whereas the lower dose did not. Although both linsitinib groups showed numerically higher response rates than placebo, the results do not establish comparative efficacy against other active TED treatments.

Durability After Treatment: Encouraging but Preliminary

A key finding from the presentation was the persistence of proptosis response after treatment ended. Twenty pooled linsitinib-treated patients who had achieved a proptosis response at Week 24 entered a 48-week off-drug follow-up period.

In this post-hoc analysis, 95% maintained their response at Weeks 36, 48 and 60, while 82% retained their response at Week 72, 48 weeks after treatment completion.

Disease activity and patient-reported quality of life also showed favourable trends during follow-up. Mean CAS declined from 1.2 at Week 24 to 0.8 at Week 72, while mean overall Graves’ Ophthalmopathy Quality of Life (GO-QoL) scores increased from 74.0 to 95.2.

These findings suggest that proptosis response and improvements in disease activity and quality of life may persist after linsitinib treatment ends. However, the durability analysis included only 20 selected Week 24 responders and was post hoc. The results therefore cannot establish the likelihood of sustained benefit among all treated patients or demonstrate that the same durability would occur in a broader TED population.

Safety Profile and Treatment Discontinuations

Most adverse events (AEs) were reported as mild to moderate and reversible. In the 150 mg BID group, the most common treatment-emergent AEs occurring in more than 10% of patients in any arm were diarrhoea, headache and nausea (20.7% each), fatigue (17.2%), increased alanine aminotransferase (ALT) and hyperhidrosis (13.8% each), and muscle spasms and increased aspartate aminotransferase (AST) (10.3% each).

Serious AEs occurred in 3.2% of placebo recipients, none of the 75 mg group and 6.9% of the 150 mg group. Treatment discontinuations were reported in 16.7%, 20.0% and 33.3% of the placebo, 75 mg and 150 mg groups, respectively. The discontinuation rate was therefore highest in the 150 mg group, an important consideration when interpreting the higher dose’s efficacy results.

Hyperglycaemia occurred in one patient in each linsitinib arm. One report each of hypoacusis and tinnitus in the 150 mg group was assessed as unrelated to treatment. The presentation also reported no menstrual changes or encephalopathy.

During the off-drug follow-up period, no treatment-related AEs, serious AEs or AEs leading to discontinuation were reported. These observations are reassuring within the reported study, but the sample size and follow-up findings do not establish the absence of uncommon or delayed adverse effects.

Phase 3 ORBIT Trial Will Test Confirmatory Evidence

Sling Therapeutics announced in September 2026 that the first patients had been dosed in its global Phase 3 ORBIT pivotal trial, following a successful end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA). The trial is actively enrolling adults with moderate to severe active TED.

ORBIT is a randomized, double-masked, placebo-controlled study expected to enroll approximately 130 participants. Patients are being randomized in a 1:1 ratio to receive oral linsitinib 150 mg BID or placebo for 24 weeks. The primary endpoint is the proportion of proptosis responders at Week 24, defined as a reduction of at least 2 mm in proptosis in the study eye without a corresponding worsening in the fellow eye. The study also includes secondary assessments of proptosis, CAS and GO-QoL. An open-label extension is planned after the 24-week controlled treatment period.

Linsitinib is an oral small-molecule inhibitor of intracellular insulin-like growth factor 1 receptor (IGF-1R) signalling. IGF-1R is implicated in the inflammation, tissue expansion and proptosis associated with TED. Linsitinib has received FDA Fast Track designation but remains investigational for TED.

The LIDS findings provide a rationale for further evaluation, particularly the statistically significant Week 24 response with the 150 mg dose and the persistence of improvement among selected responders. ORBIT will help determine whether the efficacy and safety findings can be confirmed in a larger pivotal study. The available results do not establish regulatory approval or comparative superiority over existing therapies.

Reference

Sling Therapeutics Presents Data from Phase 2b/3 LIDS Clinical Trial Demonstrating Durability of Linsitinib in Thyroid Eye Disease at ASOPRS 57th Annual Fall Scientific Symposium, Sling Therapeutics,  October 9, 2026.

A Phase 2b, Study of Linsitinib in Subjects with Active, Moderate to Severe Thyroid Eye Disease (TED) (LIDS), ClinicalTrials.gov ID NCT05276063