Sling Therapeutics, Inc. has released positive topline safety and efficacy findings from a phase 2b/3 clinical trial evaluating linsitinib, a small-molecule therapy, for the treatment of thyroid eye disease (TED).
First up: this company.
Launched in 2022 and based in Ann Arbor, Michigan, the late-stage biopharmaceutical company is currently focused on the ophthalmology space—TED, specifically—as well as two undisclosed diseases in the endocrinology and rare disease space (still in the preclinical phase).
- Its lead investigational candidate: Linsitinib, an oral small molecule
Let’s get some details on this therapeutic, please.
Referred to as a “convenient oral small molecule,” linsitinib is designed to be taken twice a day (BID) and has a short half-life—intended to enable easier management of adverse events (AEs), according to Sling.
How it works: By blocking insulin-like growth factor 1 receptor (IGF-IR), known to be overexpressed in TED and the only “clinically validated” target for treatment of the disease.
- Some background: When activated, IGF-IR can cause such symptoms as inflammation and proptosis that are characteristic of TED.
So how does this stack up to other TED treatments?
Amgen’s Tepezza (teprotumumab-trbw), a monoclonal (mAb) IGF-IR antibody that reduces disease activity, proptosis, and diplopia, is the first and currently only FDA-approved treatment for TED.
- Its recommended dosage: 10 mg/kg intravenously injected into the arm followed by a second 20 mg/kg injection every 3 weeks for seven additional infusions (with each ranging from 60 to 90 minutes).
- Compare this to linsitinib’s BID dosing schedule, and Sling may have an advantage over Amgen’s therapeutic.
Perhaps not for long, though: A randomized phase 3 trial evaluating Tepezza in a subcutaneous formulation (potentially enabling more rapid drug delivery) was initiated last year.
Interesting … now talk about linsitinib’s clinical data.
Before we get into the new phase 2b/3 findings, linsitinib has reportedly undergone clinical investigation for multiple diseases across 15 clinical trials with 900+ patients.
More recently, the company presented preclinical data in June 2023 from a mouse model of TED that demonstrated the small molecule’s ability to prevent disease progression.
The key takeaways: The data indicated that “linsitinib blocks the development of localized pathology in mice with early and late-stage TED, demonstrating potential as an effective TED treatment,” stated Ryan Zeidan, Sling’s CEO, in the company’s announcement.
- Specifically: Linsitinb was found to reduce the autoimmune response and limit the severity in both early and late stages of TED—opening the door to formulation and oral administration of the small molecule for human patients.
Nice! Now can we discuss this new trial?
Absolutely! The phase 2b LIDS trial (NCT05276063) is a randomized, double-masked, placebo-controlled study evaluating the safety and efficacy of linsitinib in TED patients.
- The participants: 90 patients (aged 18+) diagnosed with active, moderate to severe TED
- The setup: Participants randomized 1:1:1 to orally receive either:
- Linsitinib 150 mg (BID)
- Linsitinib 175 mg (BID)
- Placebo (BID)
- The duration: 24 weeks
- The outcome measures:
Next up: the findings.
To start: The study met its primary endpoint, with a statistically significant and meaningful PRR observed for patients (n = 29) in the 150 mg linsitinib group.
- PRR = 52% (p = 0.01) at Week 24
And how was linsitinib’s safety profile?
The therapeutic was “well-tolerated and consistent with the safety profile” of its previous clinical performance.
The following IGF-1R-targeted areas of interest were also noted for patients in the 150 mg linsitinib group:
- No reports of drug-related hearing impairment
- 0% tinnitus placebo-adjusted rate
- 3% rate of hyperglycemia
- 0% reports of menstrual cycle changes
See here for further safety details.
Why is this important?
Sling Chief Scientific Officer Raymond Douglas, MD, PhD, emphasized patients’ disease improvement 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,” he stated.
And looking at AEs specifically …
The majority of AEs were mild or moderate, reversible, and resolved quickly “upon treatment pause or discontinuation consistent with a shorter half-life treatment,” Sling reported.
Treatment-emergent AEs ≥ 10% included:
- Diarrhea (20.7%)
- Headache (20.7%)
- Fatigue (17.2%)
- ALT increase (17.2%)
- Hyperhidrosis (13.8%)
- AST increase (10.3%)
- Muscle spasms (10.3%)
So what’s significant about this data?
Sling President and CEO Ryan Zeidan, PhD, noted that the positive findings not only establish the clinical significance of linsitinib but also “represent the first ever clinical trial of an oral small molecule” for TED treatment.
- “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,” he stated.
A full data readout from the LIDS trial is expected to be presented at a future medical meeting later this year, according to the company.
And the next step for the therapeutic?
Sling reported it is currently engaging with regulatory authorities to discuss a confirmatory phase 3 trial design—expected to kick off later this year.
As always, stay tuned for updates on this!