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The company’s first-in-class oral small molecule linsitinib met its primary endpoint, showing statistically significant proptosis reduction with a favorable safety profile.
The world’s first oral small molecule solution for thyroid eye disease (TED) has passed its first test with flying colors.
On Tuesday, Sling Therapeutics (Ann Arbor, MI, USA) rolled out positive topline results for its candidate IGF-1R inhibitor linsitinib in the Phase IIb/III LIDS trial.
According to the company, linsitinib met its primary endpoint of statistically significant protopsis reduction—the percentage of proptosis responders at week 24, who were defined as exhibiting a minimum two-millimeter reduction from baseline (PRR). PRR percentages were reported as 52% (p=0.01).
The drug also demonstrated a favorable safety profile in areas of concern typical to IGF-1R inhibition, including hearing loss, glycemic control issues and menstrual cycle concerns.
“The positive data from this trial establish the clinical significance of linsitinib and represent the first ever successful clinical trial of an oral small molecule for the treatment of TED,” said Ryan Zeidan, PhD, president and CEO of Sling Therapeutics.
“We believe linsitinib can be a potential new treatment option that could enable a broader number of physicians across multiple therapeutic disciplines to treat patients diagnosed with TED. We are excited to continue our clinical program and are on track to initiate our confirmatory Phase III registrational trial later this year.”
Trial details
The LIDS Phase IIb/III trial is a randomized, double-masked placebo-controlled study designed to evaluate the safety, efficacy and pharmacokinetics of linsitinib in patients with active, moderate-to-severe TED.
Ninety (90) patients at 35 sites in five countries were randomized 1:1:1 and were given either linsitinib 150 mg BID, linsitinib 75 mg BID or placebo for 24 weeks. It is the 150 mg BID dose that showed the aforementioned statistical significance (54% PRR, p=0.01).
In addition to a lack of hyperglycemia, menstrual cycle changes and hearing adverse events, no QTc prolongation was observed.
For more details on topline result read-outs, head over to Sling Therapeutics’ press release here. The company plans on reporting the full results at an unspecified upcoming medical event.
What’s next
On the back of these results, Sling has reported that it is engaging with relevant regulatory agencies to talk about the details of an upcoming confirmatory Phase III trial. The trial is on track for 2025.
Dr. Raymond Douglas, a professor at Ceders-Sinai Medical Center and chief scientific officer at Sling Therapeutics, believes that the reported results presage an important shift in the way TED is treated.
“TED is a debilitating auto-immune disorder with limited options available for patients today. Patients must currently choose between an invasive orbital surgery or eight infusions over 24 weeks, which can be inconvenient and time-consuming and pose serious potential risks,” he said.
“In this trial, patients demonstrated significant improvement in disease with no drug-related hearing impairments or significant hyperglycemia. These side effects are the largest barriers for current medical treatments, making linsitinib an important potential new therapy for patients with TED. As a practicing physician, it makes sense to start a new patient’s treatment journey with an oral therapy that shows an early response that increases over time.”